@online{schubert_how_2018,
	title = {How working as a research technician can bolster your scientific career},
	rights = {2018 Nature},
	url = {http://www.nature.com/articles/d41586-018-05991-4},
	abstract = {A technician job can become a satisfying career — or act as a solid stepping stone.},
	titleaddon = {Nature},
	type = {News},
	author = {Schubert, Charlotte},
	urldate = {2018-08-23},
	date = {2018-08-21},
	doi = {10.1038/d41586-018-05991-4},
	file = {Snapshot:/home/jlagarde/Zotero/storage/8CZKWBR7/d41586-018-05991-4.html:text/html}
}

@article{fyshe_how_2018,
	title = {How to start a research lab},
	volume = {361},
	issn = {0036-8075},
	url = {http://science.sciencemag.org/content/361/6402/618?utm_campaign=toc_sci-mag_2018-08-09&et_rid=105413688&et_cid=2246786},
	doi = {10.1126/SCIENCE.361.6402.618},
	abstract = {As September approaches, a new cohort of junior faculty members are taking up their first positions as research group leaders. I was there 3 years ago, making career-shaping decisions—sometimes without much mentoring or support. I learned a lot in my first years—how to write a grant, manage rejection, and supervise students, to name just a few—and it was all trial by fire. Though I made it through and had some successes along the way, I certainly could have used advice about how to set up and run my lab. I've learned that my experience is the norm, which inspired me and a group of other early-career principal investigators to interview leaders in our fields about how they built successful research groups. Here are some of the lessons they shared. ![Figure][1]{\textbackslash}textless/img{\textbackslash}textgreater {ILLUSTRATION}: {ROBERT} {NEUBECKER} {FIND} {YOUR} {NICHE}. Before you even begin to interview for a faculty job, you need to decide what your lab's focus will be. You must be a pioneer, “carving out a niche for yourself that is unique, and where you'll be at the top of the heap,” says Margaret {McFall}-Ngai, a professor at the University of Hawaii at Manoa who was among the first to study squid-bacteria interactions. Identify how your skills intersect with the science that excites you, in the most promising uncharted territory. Plan big while identifying key publication checkpoints along the way. Your tenure case depends on it. {FIND} {YOUR} {PEOPLE}. Good science is done by talented people. “If you have an excellent person who wants to work with you, try to hire them at all costs, even if you have to spend the last of your money,” says Gregor Weihs, a professor of photonics at the University of Innsbruck in Austria. On the flip side, hiring the wrong people can be a real drain on the group. “Never hire just because you can,” Weihs says. Get to know prospective lab members by teaching graduate classes and taking on undergraduates for smaller projects, and use your network to find promising graduate students at other institutions. {IT} {PAYS} {TO} {WORK} {TOGETHER}. To secure major funding, “it's better to try and see if you can chase it together rather than all competing for the same buck,” says Melvyn Goodale, a professor of neuroscience at Western University in London, Canada, who helped form an 11-institution research consortium, the Canadian Action and Perception Network. If your goals are aligned with those of other labs, then it makes sense to work together on a joint application rather than against each other. Writing grant applications as a group can help spark new ideas, and many minds working together can increase your chance of success. Even if you don't get funded, writing a group grant can deepen your collaborative relationships for years to come. {BUILD} A {NETWORK}. To make connections when you're just starting out, you need to be your own marketing department. “It's not just doing the research; it's making it known,” says Yoshua Bengio, a professor at the University of Montreal in Canada who works on artificial intelligence. These days, a lot of networking is done online. Get on Twitter and follow your 10 favorite research labs. Look at who they follow to find more connections. Tweet about the work you publish and interesting papers you read to help people identify your niche and get to know your research brand. Finally, don't be afraid to reach out to senior faculty members to seek out mentoring, share your work, and ask for input on grant applications. Their feedback will be invaluable, and some day you will pay it forward to a new cohort of junior faculty members. There is knowledge and experience all around. You may be surprised at people's willingness to share it. [1]: pending:yes},
	pages = {618--618},
	number = {6402},
	journaltitle = {Science},
	author = {Fyshe, Alona},
	date = {2018-08},
	file = {Attachment:/home/jlagarde/Zotero/storage/H57HGG4X/Fyshe - 2018 - How to start a research lab.pdf:application/pdf}
}

@article{orsini_design_2018,
	title = {Design and {MinION} testing of a nanopore targeted gene sequencing panel for chronic lymphocytic leukemia},
	volume = {8},
	issn = {2045-2322},
	url = {http://www.nature.com/articles/s41598-018-30330-y},
	doi = {10.1038/s41598-018-30330-y},
	abstract = {We report a customized gene panel assay based on multiplex long-{PCR} followed by third generation sequencing on nanopore technology ({MinION}), designed to analyze five frequently mutated genes in chronic lymphocytic leukemia ({CLL}): {TP}53, {NOTCH}1, {BIRC}3, {SF}3B1 and {MYD}88. For this purpose, 12 patients were selected according to specific cytogenetic and molecular features significantly associated with their mutational status. In addition, simultaneous analysis of the targets genes was performed by molecular assays or Sanger Sequencing. Data analysis included mapping to the {GRCh}37 human reference genome, variant calling and annotation, and average sequencing depth/error rate analysis. The sequencing depth resulted on average higher for smaller amplicons, and the final breadth of coverage of the panel was 94.1\%. The error rate was about 6\% and 2\% for insertions/deletions and single nucleotide variants, respectively. Our gene panel allows analysis of the prognostically relevant genes in {CLL}, with two {PCRs} per patient. This strategy offers an easy and affordable workflow, although further advances are required to improve the accuracy of the technology and its use in the clinical field. Nevertheless, the rapid and constant development of nanopore technology, in terms of chemistry advances, more accurate basecallers and analysis software, offers promise for a wide use of {MinION} in the future.},
	pages = {11798},
	number = {1},
	journaltitle = {Scientific Reports},
	author = {Orsini, Paola and Minervini, Crescenzio F. and Cumbo, Cosimo and Anelli, Luisa and Zagaria, Antonella and Minervini, Angela and Coccaro, Nicoletta and Tota, Giuseppina and Casieri, Paola and Impera, Luciana and Parciante, Elisa and Brunetti, Claudia and Giordano, Annamaria and Specchia, Giorgina and Albano, Francesco},
	date = {2018-12},
	keywords = {Cancer genomics, Chronic lymphocytic leukaemia},
	file = {Attachment:/home/jlagarde/Zotero/storage/GJGVIQSA/Orsini et al. - 2018 - Design and MinION testing of a nanopore targeted gene sequencing panel for chronic lymphocytic leukemia.pdf:application/pdf}
}

@article{rang_squiggle_2018,
	title = {From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy},
	volume = {19},
	issn = {1474-760X},
	url = {https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1462-9},
	doi = {10.1186/s13059-018-1462-9},
	abstract = {Nanopore sequencing is a rapidly maturing technology delivering long reads in real time on a portable instrument at low cost. Not surprisingly, the community has rapidly taken up this new way of sequencing and has used it successfully for a variety of research applications. A major limitation of nanopore sequencing is its high error rate, which despite recent improvements to the nanopore chemistry and computational tools still ranges between 5\% and 15\%. Here, we review computational approaches determining the nanopore sequencing error rate. Furthermore, we outline strategies for translation of raw sequencing data into base calls for detection of base modifications and for obtaining consensus sequences.},
	pages = {90},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Rang, Franka J. and Kloosterman, Wigard P. and de Ridder, Jeroen},
	date = {2018-12},
	keywords = {Animal Genetics and Genomics, Bioinformatics, Evolutionary Biology, Human Genetics, Microbial Genetics and Genomics, Plant Genetics and Genomics},
	file = {Attachment:/home/jlagarde/Zotero/storage/SCDGRU2K/Rang, Kloosterman, de Ridder - 2018 - From squiggle to basepair computational approaches for improving nanopore sequencing read accuracy.pdf:application/pdf}
}

@article{wilton_terabase_2018,
	title = {The Terabase Search Engine: a large-scale relational database of short-read sequences},
	issn = {1367-4803},
	url = {https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/bty657/5057158},
	doi = {10.1093/bioinformatics/bty657},
	journaltitle = {Bioinformatics},
	author = {Wilton, Richard and Wheelan, Sarah J and Szalay, Alexander S and Salzberg, Steven L and Wren, Jonathan},
	editor = {Wren, Jonathan},
	date = {2018-07}
}

@article{tuck_distinctive_2018,
	title = {Distinctive features of {lincRNA} gene expression suggest widespread {RNA}-independent functions},
	volume = {1},
	issn = {2575-1077},
	url = {http://www.life-science-alliance.org/lookup/doi/10.26508/lsa.201800124},
	doi = {10.26508/lsa.201800124},
	abstract = {{\textbackslash}textlessp{\textbackslash}textgreater Eukaryotic genomes produce {RNAs} lacking protein-coding potential, with enigmatic roles. We integrated three approaches to study large intervening noncoding {RNA} ({lincRNA}) gene functions. First, we profiled mouse embryonic stem cells and neural precursor cells at single-cell resolution, revealing {lincRNAs} expressed in specific cell types, cell subpopulations, or cell cycle stages. Second, we assembled a transcriptome-wide atlas of nuclear {lincRNA} degradation by identifying targets of the exosome cofactor Mtr4. Third, we developed a reversible depletion system to separate the role of a {lincRNA} gene from that of its {RNA}. Our approach distinguished {lincRNA} loci functioning in {\textbackslash}textlessitalic{\textbackslash}textgreatertrans{\textbackslash}textless/italic{\textbackslash}textgreater from those modulating local gene expression. Some genes express stable and/or abundant {lincRNAs} in single cells, but many prematurely terminate transcription and produce {lincRNAs} rapidly degraded by the nuclear exosome. This suggests that besides {RNA}-dependent functions, {lincRNA} loci act as {DNA} elements or through transcription. Our integrative approach helps distinguish these mechanisms. {\textbackslash}textless/p{\textbackslash}textgreater},
	pages = {e201800124},
	number = {4},
	journaltitle = {Life Science Alliance},
	author = {Tuck, Alex C and Natarajan, Kedar Nath and Rice, Greggory M and Borawski, Jason and Mohn, Fabio and Rankova, Aneliya and Flemr, Matyas and Wenger, Alice and Nutiu, Razvan and Teichmann, Sarah and Bühler, Marc},
	date = {2018-08},
	file = {Attachment:/home/jlagarde/Zotero/storage/YU5SGCEX/Tuck et al. - 2018 - Distinctive features of lincRNA gene expression suggest widespread RNA-independent functions.pdf:application/pdf}
}

@article{gigante_picopore:_2017,
	title = {Picopore: A tool for reducing the storage size of Oxford Nanopore Technologies datasets without loss of functionality},
	volume = {6},
	issn = {2046-1402},
	url = {https://f1000research.com/articles/6-227/v3},
	doi = {10.12688/f1000research.11022.3},
	pages = {227},
	journaltitle = {F1000Research},
	author = {Gigante, Scott},
	date = {2017-09},
	file = {Attachment:/home/jlagarde/Zotero/storage/F3C584ND/Gigante - 2017 - Picopore A tool for reducing the storage size of Oxford Nanopore Technologies datasets without loss of functionality.pdf:application/pdf}
}

@article{zhang_interrogation_2018,
	title = {Interrogation of nonconserved human adipose {lincRNAs} identifies a regulatory role of linc-{ADAL} in adipocyte metabolism.},
	volume = {10},
	issn = {1946-6242},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/29925637},
	doi = {10.1126/scitranslmed.aar5987},
	abstract = {Long intergenic noncoding {RNAs} ({lincRNAs}) have emerged as important modulators of cellular functions. Most {lincRNAs} are not conserved among mammals, raising the fundamental question of whether nonconserved adipose-expressed {lincRNAs} are functional. To address this, we performed deep {RNA} sequencing of gluteal subcutaneous adipose tissue from 25 healthy humans. We identified 1001 putative {lincRNAs} expressed in all samples through de novo reconstruction of noncoding transcriptomes and integration with existing {lincRNA} annotations. One hundred twenty {lincRNAs} had adipose-enriched expression, and 54 of these exhibited peroxisome proliferator-activated receptor γ ({PPARγ}) or {CCAAT}/enhancer binding protein α (C/{EBPα}) binding at their loci. Most of these adipose-enriched {lincRNAs} (∼85\%) were not conserved in mice, yet on average, they showed degrees of expression and binding of {PPARγ} and C/{EBPα} similar to those displayed by conserved {lincRNAs}. Most adipose {lincRNAs} differentially expressed (n = 53) in patients after bariatric surgery were nonconserved. The most abundant adipose-enriched {lincRNA} in our subcutaneous adipose data set, linc-{ADAL}, was nonconserved, up-regulated in adipose depots of obese individuals, and markedly induced during in vitro human adipocyte differentiation. We demonstrated that linc-{ADAL} interacts with heterogeneous nuclear ribonucleoprotein U ({hnRNPU}) and insulin-like growth factor 2 {mRNA} binding protein 2 ({IGF}2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis.},
	pages = {eaar5987},
	number = {446},
	journaltitle = {Science translational medicine},
	author = {Zhang, Xuan and Xue, Chenyi and Lin, Jennie and Ferguson, Jane F and Weiner, Amber and Liu, Wen and Han, Yumiao and Hinkle, Christine and Li, Wenjun and Jiang, Hongfeng and Gosai, Sager and Hachet, Melanie and Garcia, Benjamin A and Gregory, Brian D and Soccio, Raymond E and Hogenesch, John B and Seale, Patrick and Li, Mingyao and Reilly, Muredach P},
	date = {2018-06},
	pmid = {29925637},
	file = {Attachment:/home/jlagarde/Zotero/storage/IRFQXRSE/Zhang et al. - 2018 - Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabo.pdf:text/xml}
}

@article{kouno_c1_2018,
	title = {C1 {CAGE} detects transcription start sites and enhancer activity at single-cell resolution},
	url = {https://www.biorxiv.org/content/early/2018/05/25/330845},
	doi = {10.1101/330845},
	abstract = {Single-cell transcriptomic profiling is a powerful tool to explore cellular heterogeneity. However, most of these methods focus on the 3'-end of polyadenylated transcripts and provide only a partial view of the transcriptome. We introduce C1 {CAGE}, a method for the detection of transcript 5'-ends with an original sample multiplexing strategy in the C1 microfluidic system. We first quantified the performance of C1 {CAGE} and found it as accurate and sensitive as other methods in C1 system. We then used it to profile promoter and enhancer activities in the cellular response to {TGF}-beta of lung cancer cells and discovered subpopulations of cells differing in their response. We also describe enhancer {RNA} dynamics revealing transcriptional bursts in subsets of cells with transcripts arising from either strand within a single-cell in a mutually exclusive manner, which was validated using single molecule fluorescence in-situ hybridization.},
	pages = {330845},
	journaltitle = {{bioRxiv}},
	author = {Kouno, Tsukasa and Moody, Jonathan and Kwon, Andrew and Shibayama, Youtaro and Kato, Sachi and Huang, Yi and Böttcher, Michael and Motakis, Efthymios and Mendez, Mickaël and Severin, Jessica and Luginbühl, Joachim and Abugessaisa, Imad and Hasegawa, Akira and Takizawa, Satoshi and Arakawa, Takahiro and Furuno, Masaaki and Ramalingam, Naveen and West, Jay and Suzuki, Harukazu and Kasukawa, Takeya and Lassmann, Timo and Hon, Chung-Chau and Arner, Erik and Carninci, Piero and Plessy, Charles and Shin, Jay W},
	date = {2018-05},
	file = {Attachment:/home/jlagarde/Zotero/storage/CRMQUTN9/Kouno et al. - 2018 - C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution.pdf:application/pdf}
}

@article{uszczynska-ratajczak_towards_2018,
	title = {Towards a complete map of the human long non-coding {RNA} transcriptome},
	issn = {14710064},
	doi = {10.1038/s41576-018-0017-y},
	abstract = {© 2018 Macmillan Publishers Ltd., part of Springer Nature Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single-gene to genome-wide scales and from basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding {RNAs} ({lncRNAs}), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of {lncRNAs} expressed throughout a human lifetime.},
	journaltitle = {Nature Reviews Genetics},
	author = {Uszczynska-Ratajczak, B. and Lagarde, J. and Frankish, A. and Guigó, R. and Johnson, R.},
	date = {2018}
}

@article{tramontano_nutritional_2018,
	title = {Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies},
	issn = {2058-5276},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/29556107 http://www.nature.com/articles/s41564-018-0123-9},
	doi = {10.1038/s41564-018-0123-9},
	abstract = {Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences. We identify mucin utilizers and species inhibited by amino acids and short-chain fatty acids. Our analysis also uncovers media for in vitro studies wherein growth capacity correlates well with in vivo abundance. Further value of the underlying resource is demonstrated by correcting pathway gaps in available genome-scale metabolic models of gut microorganisms. Together, the media resource and the extracted knowledge on growth abilities widen experimental and computational access to the gut microbiota.},
	journaltitle = {Nature Microbiology},
	author = {Tramontano, Melanie and Andrejev, Sergej and Pruteanu, Mihaela and Klünemann, Martina and Kuhn, Michael and Galardini, Marco and Jouhten, Paula and Zelezniak, Aleksej and Zeller, Georg and Bork, Peer and Typas, Athanasios and Patil, Kiran Raosaheb},
	date = {2018-03},
	pmid = {29556107}
}

@article{dunham_integrated_2012,
	title = {An integrated encyclopedia of {DNA} elements in the human genome},
	volume = {489},
	issn = {14764687},
	doi = {10.1038/nature11247},
	abstract = {The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of {DNA} Elements ({ENCODE}) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80\% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. © 2012 Macmillan Publishers Limited. All rights reserved.},
	number = {7414},
	journaltitle = {Nature},
	author = {Dunham, I. and Kundaje, A. and Aldred, S.F. and Collins, P.J. and Davis, C.A. and Doyle, F. and Epstein, C.B. and Frietze, S. and Harrow, J. and Kaul, R. and Khatun, J. and Lajoie, B.R. and Landt, S.G. and Lee, B.-K. and Pauli, F. and Rosenbloom, K.R. and Sabo, P. and Safi, A. and Sanyal, A. and Shoresh, N. and Simon, J.M. and Song, L. and Trinklein, N.D. and Altshuler, R.C. and Birney, E. and Brown, J.B. and Cheng, C. and Djebali, S. and Dong, X. and Ernst, J. and Furey, T.S. and Gerstein, M. and Giardine, B. and Greven, M. and Hardison, R.C. and Harris, R.S. and Herrero, J. and Hoffman, M.M. and Iyer, S. and Kellis, M. and Kheradpour, P. and Lassmann, T. and Li, Q. and Lin, X. and Marinov, G.K. and Merkel, A. and Mortazavi, A. and Parker, S.C.J. and Reddy, T.E. and Rozowsky, J. and Schlesinger, F. and Thurman, R.E. and Wang, J. and Ward, L.D. and Whitfield, T.W. and Wilder, S.P. and Wu, W. and Xi, H.S. and Yip, K.Y. and Zhuang, J. and Bernstein, B.E. and Green, E.D. and Gunter, C. and Snyder, M. and Pazin, M.J. and Lowdon, R.F. and Dillon, L.A.L. and Adams, L.B. and Kelly, C.J. and Zhang, J. and Wexler, J.R. and Good, P.J. and Feingold, E.A. and Crawford, G.E. and Dekker, J. and Elnitski, L. and Farnham, P.J. and Giddings, M.C. and Gingeras, T.R. and Guigó, R. and Hubbard, T.J. and Kent, W.J. and Lieb, J.D. and Margulies, E.H. and Myers, R.M. and Stamatoyannopoulos, J.A. and Tenenbaum, S.A. and Weng, Z. and White, K.P. and Wold, B. and Yu, Y. and Wrobel, J. and Risk, B.A. and Gunawardena, H.P. and Kuiper, H.C. and Maier, C.W. and Xie, L. and Chen, X. and Mikkelsen, T.S. and Gillespie, S. and Goren, A. and Ram, O. and Zhang, X. and Wang, L. and Issner, R. and Coyne, M.J. and Durham, T. and Ku, M. and Truong, T. and Eaton, M.L. and Dobin, A. and Tanzer, A. and Lagarde, J. and Lin, W. and Xue, C. and Williams, B.A. and Zaleski, C. and Röder, M. and Kokocinski, F. and Abdelhamid, R.F. and Alioto, T. and Antoshechkin, I. and Baer, M.T. and Batut, P. and Bell, I. and Bell, K. and Chakrabortty, S. and Chrast, J. and Curado, J. and Derrien, T. and Drenkow, J. and Dumais, E. and Dumais, J. and Duttagupta, R. and Fastuca, M. and Fejes-Toth, K. and Ferreira, P. and Foissac, S. and Fullwood, M.J. and Gao, H. and Gonzalez, D. and Gordon, A. and Howald, C. and Jha, S. and Johnson, R. and Kapranov, P. and King, B. and Kingswood, C. and Li, G. and Luo, O.J. and Park, E. and Preall, J.B. and Presaud, K. and Ribeca, P. and Robyr, D. and Ruan, X. and Sammeth, M. and Sandhu, K.S. and Schaeffer, L. and See, L.-H. and Shahab, A. and Skancke, J. and Suzuki, A.M. and Takahashi, H. and Tilgner, H. and Trout, D. and Walters, N. and Wang, H. and Hayashizaki, Y. and Reymond, A. and Antonarakis, S.E. and Hannon, G.J. and Ruan, Y. and Carninci, P. and Sloan, C.A. and Learned, K. and Malladi, V.S. and Wong, M.C. and Barber, G.P. and Cline, M.S. and Dreszer, T.R. and Heitner, S.G. and Karolchik, D. and Kirkup, V.M. and Meyer, L.R. and Long, J.C. and Maddren, M. and Raney, B.J. and Grasfeder, L.L. and Giresi, P.G. and Battenhouse, A. and Sheffield, N.C. and Showers, K.A. and London, D. and Bhinge, A.A. and Shestak, C. and Schaner, M.R. and Kim, S.K. and Zhang, Z.Z. and Mieczkowski, P.A. and Mieczkowska, J.O. and Liu, Z. and {McDaniell}, R.M. and Ni, Y. and Rashid, N.U. and Kim, M.J. and Adar, S. and Zhang, Z. and Wang, T. and Winter, D. and Keefe, D. and Iyer, V.R. and Zheng, M. and Wang, P. and Gertz, J. and Vielmetter, J. and Partridge, E.C. and Varley, K.E. and Gasper, C. and Bansal, A. and Pepke, S. and Jain, P. and Amrhein, H. and Bowling, K.M. and Anaya, M. and Cross, M.K. and Muratet, M.A. and Newberry, K.M. and {McCue}, K. and Nesmith, A.S. and Fisher-Aylor, K.I. and Pusey, B. and {DeSalvo}, G. and Parker, S.L. and Balasubramanian, S. and Davis, N.S. and Meadows, S.K. and Eggleston, T. and Newberry, J.S. and Levy, S.E. and Absher, D.M. and Wong, W.H. and Blow, M.J. and Visel, A. and Pennachio, L.A. and Petrykowska, H.M. and Abyzov, A. and Aken, B. and Barrell, D. and Barson, G. and Berry, A. and Bignell, A. and Boychenko, V. and Bussotti, G. and Davidson, C. and Despacio-Reyes, G. and Diekhans, M. and Ezkurdia, I. and Frankish, A. and Gilbert, J. and Gonzalez, J.M. and Griffiths, E. and Harte, R. and Hendrix, D.A. and Hunt, T. and Jungreis, I. and Kay, M. and Khurana, E. and Leng, J. and Lin, M.F. and Loveland, J. and Lu, Z. and Manthravadi, D. and Mariotti, M. and Mudge, J. and Mukherjee, G. and Notredame, C. and Pei, B. and Rodriguez, J.M. and Saunders, G. and Sboner, A. and Searle, S. and Sisu, C. and Snow, C. and Steward, C. and Tapanari, E. and Tress, M.L. and Van Baren, M.J. and Washietl, S. and Wilming, L. and Zadissa, A. and Zhang, Z. and Brent, M. and Haussler, D. and Valencia, A. and Addleman, N. and Alexander, R.P. and Auerbach, R.K. and Balasubramanian, S. and Bettinger, K. and Bhardwaj, N. and Boyle, A.P. and Cao, A.R. and Cayting, P. and Charos, A. and Cheng, Y. and Eastman, C. and Euskirchen, G. and Fleming, J.D. and Grubert, F. and Habegger, L. and Hariharan, M. and Harmanci, A. and Iyengar, S. and Jin, V.X. and Karczewski, K.J. and Kasowski, M. and Lacroute, P. and Lam, H. and Lamarre-Vincent, N. and Lian, J. and Lindahl-Allen, M. and Min, R. and Miotto, B. and Monahan, H. and Moqtaderi, Z. and Mu, X.J. and O'Geen, H. and Ouyang, Z. and Patacsil, D. and Raha, D. and Ramirez, L. and Reed, B. and Shi, M. and Slifer, T. and Witt, H. and Wu, L. and Xu, X. and Yan, K.-K. and Yang, X. and Struhl, K. and Weissman, S.M. and Penalva, L.O. and Karmakar, S. and Bhanvadia, R.R. and Choudhury, A. and Domanus, M. and Ma, L. and Moran, J. and Victorsen, A. and Auer, T. and Centanin, L. and Eichenlaub, M. and Gruhl, F. and Heermann, S. and Hoeckendorf, B. and Inoue, D. and Kellner, T. and Kirchmaier, S. and Mueller, C. and Reinhardt, R. and Schertel, L. and Schneider, S. and Sinn, R. and Wittbrodt, B. and Wittbrodt, J. and Jain, G. and Balasundaram, G. and Bates, D.L. and Byron, R. and Canfield, T.K. and Diegel, M.J. and Dunn, D. and Ebersol, A.K. and Frum, T. and Garg, K. and Gist, E. and Hansen, R.S. and Boatman, L. and Haugen, E. and Humbert, R. and Johnson, A.K. and Johnson, E.M. and Kutyavin, T.V. and Lee, K. and Lotakis, D. and Maurano, M.T. and Neph, S.J. and Neri, F.V. and Nguyen, E.D. and Qu, H. and Reynolds, A.P. and Roach, V. and Rynes, E. and Sanchez, M.E. and Sandstrom, R.S. and Shafer, A.O. and Stergachis, A.B. and Thomas, S. and Vernot, B. and Vierstra, J. and Vong, S. and Wang, H. and Weaver, M.A. and Yan, Y. and Zhang, M. and Akey, J.M. and Bender, M. and Dorschner, M.O. and Groudine, M. and {MacCoss}, M.J. and Navas, P. and Stamatoyannopoulos, G. and Beal, K. and Brazma, A. and Flicek, P. and Johnson, N. and Lukk, M. and Luscombe, N.M. and Sobral, D. and Vaquerizas, J.M. and Batzoglou, S. and Sidow, A. and Hussami, N. and Kyriazopoulou-Panagiotopoulou, S. and Libbrecht, M.W. and Schaub, M.A. and Miller, W. and Bickel, P.J. and Banfai, B. and Boley, N.P. and Huang, H. and Li, J.J. and Noble, W.S. and Bilmes, J.A. and Buske, O.J. and Sahu, A.D. and Kharchenko, P.V. and Park, P.J. and Baker, D. and Taylor, J. and Lochovsky, L.},
	date = {2012},
	keywords = {Human, Genomics, {DNA}, Sequence Analysis, Animals, Genetic, Genome, Humans, Promoter Regions, Proteins, Proteins: genetics, Regulatory Sequences, {RNA}, Transcription, Binding Sites, Exons, Nucleic Acid, Alleles, Binding Sites: genetics, Chromatin, Chromatin Immunoprecipitation, Chromatin: genetics, Chromatin: metabolism, Chromosomes, Deoxyribonuclease I, Deoxyribonuclease I: metabolism, {DNA} Footprinting, {DNA} Methylation, {DNA} Methylation: genetics, {DNA}-Binding Proteins, {DNA}-Binding Proteins: metabolism, {DNA}: genetics, Encyclopedias as Topic, Exons: genetics, Genetic Predisposition to Disease, Genetic Predisposition to Disease: genetics, Genetic Variation, Genetic Variation: genetics, Genetic: genetics, Genome-Wide Association Study, Histones, Histones: chemistry, Histones: metabolism, Human: genetics, Human: metabolism, Mammals, Mammals: genetics, Molecular Sequence Annotation, Neoplasms, Neoplasms: genetics, Nucleic Acid: genetics, Polymorphism, Single Nucleotide, Single Nucleotide: genetics, Transcription Factors, Transcription Factors: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/IP5XLPEQ/Bernstein et al. - 2012 - An integrated encyclopedia of DNA elements in the human genome.pdf:application/pdf}
}

@article{myers_users_2011,
	title = {A user's guide to the Encyclopedia of {DNA} elements ({ENCODE})},
	volume = {9},
	issn = {15457885},
	doi = {10.1371/journal.pbio.1001046},
	abstract = {The mission of the Encyclopedia of {DNA} Elements ({ENCODE}) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The {ENCODE} Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and {DNA} methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of {ENCODE} data to interpret the human genome. © 2011 The {ENCODE} Project Consortium. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},
	number = {4},
	journaltitle = {{PLoS} Biology},
	author = {Myers, R.M. and Stamatoyannopoulos, J. and Snyder, M. and Dunham, I. and Hardison, R.C. and Bernstein, B.E. and Gingeras, T.R. and Kent, W.J. and Birney, E. and Wold, B. and Crawford, G.E. and Epstein, C.B. and Shoresh, N. and Ernst, J. and Mikkelsen, T.S. and Kheradpour, P. and Zhang, X. and Wang, L. and Issner, R. and Coyne, M.J. and Durham, T. and Ku, M. and Truong, T. and Ward, L.D. and Altshuler, R.C. and Lin, M.F. and Kellis, M. and Davis, C.A. and Kapranov, P. and Dobin, A. and Zaleski, C. and Schlesinger, F. and Batut, P. and Chakrabortty, S. and Jha, S. and Lin, W. and Drenkow, J. and Wang, H. and Bell, K. and Bell, I. and Gao, H. and Dumais, E. and Dumais, J. and Antonarakis, S.E. and Ucla, C. and Borel, C. and Guigo, R. and Djebali, S. and Lagarde, J. and Kingswood, C. and Ribeca, P. and Sammeth, M. and Alioto, T. and Merkel, A. and Tilgner, H. and Carninci, P. and Hayashizaki, Y. and Lassmann, T. and Takahashi, H. and Abdelhamid, R.F. and Hannon, G. and Fejes, K. and Preall, J. and Gordon, A. and Sotirova, V. and Reymond, A. and Howald, C. and Graison, E.A.Y. and Chrast, J. and Ruan, Y. and Ruan, X. and Shahab, A. and Poh, W.T. and Wei, C.-L. and Furey, T.S. and Boyle, A.P. and Sheffield, N.C. and Song, L. and Shibata, Y. and Vales, T. and Winter, D. and Zhang, Z. and London, D. and Wang, T. and Keefe, D. and Iyer, V.R. and Lee, B.-K. and {McDaniell}, R.M. and Liu, Z. and Battenhouse, A. and Bhinge, A.A. and Lieb, J.D. and Grasfeder, L.L. and Showers, K.A. and Giresi, P.G. and Kim, S.K.C. and Shestak, C. and Pauli, F. and Reddy, T.E. and Gertz, J. and Partridge, E.C. and Jain, P. and Sprouse, R.O. and Bansal, A. and Pusey, B. and Muratet, M.A. and Varley, K.E. and Bowling, K.M. and Newberry, K.M. and Nesmith, A.S. and Dilocker, J.A. and Parker, S.L. and Waite, L.L. and Thibeault, K. and Roberts, K. and Absher, D.M. and Mortazavi, A. and Williams, B. and Marinov, G. and Trout, D. and King, B. and {McCue}, K. and Kirilusha, A. and {DeSalvo}, G. and Fisher, K. and Amrhein, H. and Pepke, S. and Vielmetter, J. and Sherlock, G. and Sidow, A. and Batzoglou, S. and Rauch, R. and Kundaje, A. and Libbrecht, M. and Margulies, E.H. and Parker, S.C.J. and Elnitski, L. and Green, E.D. and Hubbard, T. and Harrow, J. and Searle, S. and Kokocinski, F. and Aken, B. and Frankish, A. and Hunt, T. and Despacio-Reyes, G. and Kay, M. and Mukherjee, G. and Bignell, A. and Saunders, G. and Boychenko, V. and Brent, M. and van Baren, M.J. and Brown, R.H. and Gerstein, M. and Khurana, E. and Balasubramanian, S. and Lam, H. and Cayting, P. and Robilotto, R. and Lu, Z. and Derrien, T. and Tanzer, A. and Knowles, D.G. and Mariotti, M. and Haussler, D. and Harte, R. and Diekhans, M. and Lin, M. and Valencia, A. and Tress, M. and Landt, S.G. and Raha, D. and Shi, M. and Euskirchen, G. and Grubert, F. and Kasowski, M. and Lian, J. and Lacroute, P. and Xu, Y. and Monahan, H. and Patacsil, D. and Slifer, T. and Yang, X. and Charos, A. and Reed, B. and Wu, L. and Auerbach, R.K. and Habegger, L. and Hariharan, M. and Rozowsky, J. and Abyzov, A. and Weissman, S.M. and Struhl, K. and Lamarre-Vincent, N. and Lindahl-Allen, M. and Miotto, B. and Moqtaderi, Z. and Fleming, J.D. and Newburger, P. and Farnham, P.J. and Frietze, S. and O'Geen, H. and Xu, X. and Blahnik, K.R. and Cao, A.R. and Iyengar, S. and Kaul, R. and Thurman, R.E. and Wang, H. and Navas, P.A. and Sandstrom, R. and Sabo, P.J. and Weaver, M. and Canfield, T. and Lee, K. and Neph, S. and Roach, V. and Reynolds, A. and Johnson, A. and Rynes, E. and Giste, E. and Vong, S. and Neri, J. and Frum, T. and Nguyen, E.D. and Ebersol, A.K. and Sanchez, M.E. and Sheffer, H.H. and Lotakis, D. and Haugen, E. and Humbert, R. and Kutyavin, T. and Shafer, T. and Noble, W.S. and Dekker, J. and Lajoie, B.R. and Sanyal, A. and Rosenbloom, K.R. and Dreszer, T.R. and Raney, B.J. and Barber, G.P. and Meyer, L.R. and Sloan, C.A. and Malladi, V.S. and Cline, M.S. and Learned, K. and Swing, V.K. and Zweig, A.S. and Rhead, B. and Fujita, P.A. and Roskin, K. and Karolchik, D. and Kuhn, R.M. and Wilder, S.P. and Sobral, D. and Herrero, J. and Beal, K. and Lukk, M. and Brazma, A. and Vaquerizas, J.M. and Luscombe, N.M. and Bickel, P.J. and Boley, N. and Brown, J.B. and Li, Q. and Huang, H. and Sboner, A. and Yip, K.Y. and Cheng, C. and Yan, K.-K. and Bhardwaj, N. and Wang, J. and Lochovsky, L. and Jee, J. and Gibson, T. and Leng, J. and Du, J. and Harris, R.S. and Song, G. and Miller, W. and Suh, B. and Paten, B. and Hoffman, M.M. and Buske, O.J. and Weng, Z. and Dong, X. and Wang, J. and Xi, H. and Tenenbaum, S.A. and Doyle, F. and Chittur, S. and Penalva, L.O. and Tullius, T.D. and White, K.P. and Karmakar, S. and Victorsen, A. and Jameel, N. and Bild, N. and Grossman, R.L. and Collins, P.J. and Trinklein, N.D. and Giddings, M.C. and Khatun, J. and Maier, C. and Wang, T. and Whitfield, T.W. and Chen, X. and Yu, Y. and Gunawardena, H. and Feingold, E.A. and Lowdon, R.F. and Dillon, L.A.L. and Good, P.J. and Risk, B.},
	date = {2011}
}

@article{birney_identification_2007,
	title = {Identification and analysis of functional elements in 1\% of the human genome by the {ENCODE} pilot project},
	volume = {447},
	issn = {00280836},
	doi = {10.1038/nature05874},
	abstract = {We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1\% of the human genome as part of the pilot phase of the {ENCODE} Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with {DNA} replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function. ©2007 Nature Publishing Group.},
	number = {7146},
	journaltitle = {Nature},
	author = {Birney, E. and Stamatoyannopoulos, J.A. and Dutta, A. and Guigó, R. and Gingeras, T.R. and Margulies, E.H. and Weng, Z. and Snyder, M. and Dermitzakis, E.T. and Thurman, R.E. and Kuehn, M.S. and Taylor, C.M. and Neph, S. and Koch, C.M. and Asthana, S. and Malhotra, A. and Adzhubei, I. and Greenbaum, J.A. and Andrews, R.M. and Flicek, P. and Boyle, P.J. and Cao, H. and Carter, N.P. and Clelland, G.K. and Davis, S. and Day, N. and Dhami, P. and Dillon, S.C. and Dorschner, M.O. and Fiegler, H. and Giresi, P.G. and Goldy, J. and Hawrylycz, M. and Haydock, A. and Humbert, R. and James, K.D. and Johnson, B.E. and Johnson, E.M. and Frum, T.T. and Rosenzweig, E.R. and Karnani, N. and Lee, K. and Lefebvre, G.C. and Navas, P.A. and Neri, F. and Parker, S.C.J. and Sabo, P.J. and Sandstrom, R. and Shafer, A. and Vetrie, D. and Weaver, M. and Wilcox, S. and Yu, M. and Collins, F.S. and Dekker, J. and Lieb, J.D. and Tullius, T.D. and Crawford, G.E. and Sunyaev, S. and Noble, W.S. and Dunham, I. and Denoeud, F. and Reymond, A. and Kapranov, P. and Rozowsky, J. and Zheng, D. and Castelo, R. and Frankish, A. and Harrow, J. and Ghosh, S. and Sandelin, A. and Hofacker, I.L. and Baertsch, R. and Keefe, D. and Dike, S. and Cheng, J. and Hirsch, H.A. and Sekinger, E.A. and Lagarde, J. and Abril, J.F. and Shahab, A. and Flamm, C. and Fried, C. and Hackermüller, J. and Hertel, J. and Lindemeyer, M. and Missal, K. and Tanzer, A. and Washietl, S. and Korbel, J. and Emanuelsson, O. and Pedersen, J.S. and Holroyd, N. and Taylor, R. and Swarbreck, D. and Matthews, N. and Dickson, M.C. and Thomas, D.J. and Weirauch, M.T. and Gilbert, J. and Drenkow, J. and Bell, I. and Zhao, X. and Srinivasan, K.G. and Sung, W.-K. and Ooi, H.S. and Chiu, K.P. and Foissac, S. and Alioto, T. and Brent, M. and Pachter, L. and Tress, M.L. and Valencia, A. and Choo, S.W. and Choo, C.Y. and Ucla, C. and Manzano, C. and Wyss, C. and Cheung, E. and Clark, T.G. and Brown, J.B. and Ganesh, M. and Patel, S. and Tammana, H. and Chrast, J. and Henrichsen, C.N. and Kai, C. and Kawai, J. and Nagalakshmi, U. and Wu, J. and Lian, Z. and Lian, J. and Newburger, P. and Zhang, X. and Bickel, P. and Mattick, J.S. and Carninci, P. and Hayashizaki, Y. and Weissman, S. and Hubbard, T. and Myers, R.M. and Rogers, J. and Stadler, P.F. and Lowe, T.M. and Wei, C.-L. and Ruan, Y. and Struhl, K. and Gerstein, M. and Antonarakis, S.E. and Fu, Y. and Green, E.D. and Karaöz, U. and Siepel, A. and Taylor, J. and Liefer, L.A. and Wetterstrand, K.A. and Good, P.J. and Feingold, E.A. and Guyer, M.S. and Cooper, G.M. and Asimenos, G. and Dewey, C.N. and Hou, M. and Nikolaev, S. and Montoya-Burgos, J.I. and Löytynoja, A. and Whelan, S. and Pardi, F. and Massingham, T. and Huang, H. and Zhang, N.R. and Holmes, I. and Mullikin, J.C. and Ureta-Vidal, A. and Paten, B. and Seringhaus, M. and Church, D. and Rosenbloom, K. and Kent, W.J. and Stone, E.A. and Batzoglou, S. and Goldman, N. and Hardison, R.C. and Haussler, D. and Miller, W. and Sidow, A. and Trinklein, N.D. and Zhang, Z.D. and Barrera, L. and Stuart, R. and King, D.C. and Ameur, A. and Enroth, S. and Bieda, M.C. and Kim, J. and Bhinge, A.A. and Jiang, N. and Liu, J. and Yao, F. and Vega, V.B. and Lee, C.W.H. and Ng, P. and Yang, A. and Moqtaderi, Z. and Zhu, Z. and Xu, X. and Squazzo, S. and Oberley, M.J. and Inman, D. and Singer, M.A. and Richmond, T.A. and Munn, K.J. and Rada-Iglesias, A. and Wallerman, O. and Komorowski, J. and Fowler, J.C. and Couttet, P. and Bruce, A.W. and Dovey, O.M. and Ellis, P.D. and Langford, C.F. and Nix, D.A. and Euskirchen, G. and Hartman, S. and Urban, A.E. and Kraus, P. and Van Calcar, S. and Heintzman, N. and Hoon Kim, T. and Wang, K. and Qu, C. and Hon, G. and Luna, R. and Glass, C.K. and Rosenfeld, M.G. and Aldred, S.F. and Cooper, S.J. and Halees, A. and Lin, J.M. and Shulha, H.P. and Zhang, X. and Xu, M. and Haidar, J.N.S. and Yu, Y. and Iyer, V.R. and Green, R.D. and Wadelius, C. and Farnham, P.J. and Ren, B. and Harte, R.A. and Hinrichs, A.S. and Trumbower, H. and Clawson, H. and Hillman-Jackson, J. and Zweig, A.S. and Smith, K. and Thakkapallayil, A. and Barber, G. and Kuhn, R.M. and Karolchik, D. and Armengol, L. and Bird, C.P. and De Bakker, P.I.W. and Kern, A.D. and Lopez-Bigas, N. and Martin, J.D. and Stranger, B.E. and Woodroffe, A. and Davydov, E. and Dimas, A. and Eyras, E. and Hallgrímsdóttir, I.B. and Huppert, J. and Zody, M.C. and Abecasis, G.R. and Estivill, X. and Bouffard, G.G. and Guan, X. and Hansen, N.F. and Idol, J.R. and Maduro, V.V.B. and Maskeri, B. and {McDowell}, J.C. and Park, M. and Thomas, P.J. and Young, A.C. and Blakesley, R.W. and Muzny, D.M. and Sodergren, E. and Wheeler, D.A. and Worley, K.C. and Jiang, H. and Weinstock, G.M. and Gibbs, R.A. and Graves, T. and Fulton, R. and Mardis, E.R. and Wilson, R.K. and Clamp, M. and Cuff, J. and Gnerre, S. and Jaffe, D.B. and Chang, J.L. and Lindblad-Toh, K. and Lander, E.S. and Koriabine, M. and Nefedov, M. and Osoegawa, K. and Yoshinaga, Y. and Zhu, B. and De Jong, P.J.},
	date = {2007}
}

@article{feingold_encode_2004,
	title = {The {ENCODE} ({ENCyclopedia} of {DNA} Elements) Project},
	volume = {306},
	issn = {00368075},
	doi = {10.1126/science.1105136},
	abstract = {The {ENCyclopedia} Of {DNA} Elements ({ENCODE}) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1\%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.},
	number = {5696},
	journaltitle = {Science},
	author = {Feingold, E.A. and Good, P.J. and Guyer, M.S. and Kamholz, S. and Liefer, L. and Wetterstrand, K. and Collins, F.S. and Gingeras, T.R. and Kampa, D. and Sekinger, E.A. and Cheng, J. and Hirsch, H. and Ghosh, S. and Zhu, Z. and Patel, S. and Piccolboni, A. and Yang, A. and Tammana, H. and Bekiranov, S. and Kapranov, P. and Harrison, R. and Church, G. and Struhl, K. and Ren, B. and Kim, T.H. and Barrera, L.O. and Qu, C. and van Calcar, S. and Luna, R. and Glass, C.K. and Rosenfeld, M.G. and Guigo, R. and Antonarakis, S.E. and Birney, E. and Brent, M. and Pachter, L. and Reymond, A. and Dermitzakis, E.T. and Dewey, C. and Keefe, D. and Denoeud, F. and Lagarde, J. and Ashurst, J. and Hubbard, T. and Wesselink, J.J. and Castelo, R. and Eyras, E. and Myers, R.M. and Sidow, A. and Batzoglou, S. and Trinklein, N.D. and Hartman, S.J. and Aldred, S.F. and Anton, E. and Schroeder, D.I. and Marticke, S.S. and Nguyen, L. and Schmutz, J. and Grimwood, J. and Dickson, M. and Cooper, G.M. and Stone, E.A. and Asimenos, G. and Brudno, M. and Dutta, A. and Karnani, N. and Taylor, C.M. and Kim, H.K. and Robins, G. and Stamatoyannopoulos, G. and Stamatoyannopoulos, J.A. and Dorschner, M. and Sabo, P. and Hawrylycz, M. and Humbert, R. and Wallace, J. and Yu, M. and Navas, P.A. and {McArthur}, M. and Noble, W.S. and Dunham, I. and Koch, C.M. and Andrews, R.M. and Clelland, G.K. and Wilcox, S. and Fowler, J.C. and James, K.D. and Groth, P. and Dovey, O.M. and Ellis, P.D. and Wraight, V.L. and Mungall, A.J. and Dhami, P. and Fiegler, H. and Langford, C.F. and Carter, N.P. and Vetrie, D. and Snyder, M. and Euskirchen, G. and Urban, A.E. and Nagalakshmi, U. and Rinn, J. and Popescu, G. and Bertone, P. and Hartman, S. and Rozowsky, J. and Emanuelsson, O. and Royce, T. and Chung, S. and Gerstein, M. and Lian, Z. and Lian, J. and Nakayama, Y. and Weissman, S. and Stolc, V. and Tongprasit, W. and Sethi, H. and Jones, S. and Marra, M. and Shin, H. and Schein, J. and Clamp, M. and Lindblad-Toh, K. and Chang, J. and Jaffe, D.B. and Kamal, M. and Lander, E.S. and Mikkelsen, T.S. and Vinson, J. and Zody, M.C. and de Jong, P.J. and Osoegawa, K. and Nefedov, M. and Zhu, B. and Baxevanis, A.D. and Wolfsberg, T.G. and Crawford, G.E. and Whittle, J. and Holt, I.E. and Vasicek, T.J. and Zhou, D. and Luo, S. and Green, E.D. and Bouffard, G.G. and Margulies, E.H. and Portnoy, M.E. and Hansen, N.F. and Thomas, P.J. and {McDowell}, J.C. and Maskeri, B. and Young, A.C. and Idol, J.R. and Blakesley, R.W. and Schuler, G. and Miller, W. and Hardison, R. and Elnitski, L. and Shah, P. and Salzberg, S.L. and Pertea, M. and Majoros, W.H. and Haussler, D. and Thomas, D. and Rosenbloom, K.R. and Clawson, H. and Siepel, A. and Kent, W.J. and Weng, Z. and Jin, S. and Halees, A. and Burden, H. and Karaoz, U. and Fu, Y. and Yu, Y. and Ding, C. and Cantor, C.R. and Kingston, R.E. and Dennis, J. and Green, R.D. and Singer, M.A. and Richmond, T.A. and Norton, J.E. and Farnham, P.J. and Oberley, M.J. and Inman, D.R. and {McCormick}, M.R. and Kim, H. and Middle, C.L. and Pirrung, M.C. and Fu, X.D. and Kwon, Y.S. and Ye, Z. and Dekker, J. and Tabuchi, T.M. and Gheldof, N. and Dostie, J. and Harvey, S.C.},
	date = {2004}
}

@article{gerstein_comparative_2014,
	title = {Comparative analysis of the transcriptome across distant species},
	volume = {512},
	issn = {14764687},
	doi = {10.1038/nature13424},
	abstract = {The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the {ENCODE} and {modENCODE} consortia have generated large amounts of matched {RNA}-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a â universal model' based on a single set of organism-independent parameters. © 2014 Macmillan Publishers Limited.},
	number = {7515},
	journaltitle = {Nature},
	author = {Gerstein, M.B. and Rozowsky, J. and Yan, K.-K. and Wang, D. and Cheng, C. and Brown, J.B. and Davis, C.A. and Hillier, L. and Sisu, C. and Li, J.J. and Pei, B. and Harmanci, A.O. and Duff, M.O. and Djebali, S. and Alexander, R.P. and Alver, B.H. and Auerbach, R. and Bell, K. and Bickel, P.J. and Boeck, M.E. and Boley, N.P. and Booth, B.W. and Cherbas, L. and Cherbas, P. and Di, C. and Dobin, A. and Drenkow, J. and Ewing, B. and Fang, G. and Fastuca, M. and Feingold, E.A. and Frankish, A. and Gao, G. and Good, P.J. and Guigó, R. and Hammonds, A. and Harrow, J. and Hoskins, R.A. and Howald, C. and Hu, L. and Huang, H. and Hubbard, T.J.P. and Huynh, C. and Jha, S. and Kasper, D. and Kato, M. and Kaufman, T.C. and Kitchen, R.R. and Ladewig, E. and Lagarde, J. and Lai, E. and Leng, J. and Lu, Z. and {MacCoss}, M. and May, G. and {McWhirter}, R. and Merrihew, G. and Miller, D.M. and Mortazavi, A. and Murad, R. and Oliver, B. and Olson, S. and Park, P.J. and Pazin, M.J. and Perrimon, N. and Pervouchine, D. and Reinke, V. and Reymond, A. and Robinson, G. and Samsonova, A. and Saunders, G.I. and Schlesinger, F. and Sethi, A. and Slack, F.J. and Spencer, W.C. and Stoiber, M.H. and Strasbourger, P. and Tanzer, A. and Thompson, O.A. and Wan, K.H. and Wang, G. and Wang, H. and Watkins, K.L. and Wen, J. and Wen, K. and Xue, C. and Yang, L. and Yip, K. and Zaleski, C. and Zhang, Y. and Zheng, H. and Brenner, S.E. and Graveley, B.R. and Celniker, S.E. and Gingeras, T.R. and Waterston, R.},
	date = {2014}
}

@article{stamatoyannopoulos_encyclopedia_2012,
	title = {An encyclopedia of mouse {DNA} elements (Mouse {ENCODE})},
	volume = {13},
	issn = {1474760X},
	doi = {10.1186/gb-2012-13-8-418},
	abstract = {To complement the human Encyclopedia of {DNA} Elements ({ENCODE}) project and to enable a broad range of mouse genomics efforts, the Mouse {ENCODE} Consortium is applying the same experimental pipelines developed for human {ENCODE} to annotate the mouse genome. © 2012 {BioMed} Central Ltd.},
	number = {8},
	journaltitle = {Genome Biology},
	author = {Stamatoyannopoulos, J.A. and Snyder, M. and Hardison, R. and Ren, B. and Gingeras, T. and Gilbert, D.M. and Groudine, M. and Bender, M. and Kaul, R. and Canfield, T. and Giste, E. and Johnson, A. and Zhang, M. and Balasundaram, G. and Byron, R. and Roach, V. and Sabo, P.J. and Sandstrom, R. and Stehling, A.S. and Thurman, R.E. and Weissman, S.M. and Cayting, P. and Hariharan, M. and Lian, J. and Cheng, Y. and Landt, S.G. and Ma, Z. and Wold, B.J. and Dekker, J. and Crawford, G.E. and Keller, C.A. and Wu, W. and Morrissey, C. and Kumar, S.A. and Mishra, T. and Jain, D. and Byrska-Bishop, M. and Blankenberg, D. and Lajoiel, B.R. and Jain, G. and Sanyal, A. and Chen, K.-B. and Denas, O. and Taylor, J. and Blobel, G.A. and Weiss, M.J. and Pimkin, M. and Deng, W. and Marinov, G.K. and Williams, B.A. and Fisher-Aylor, K.I. and Desalvo, G. and Kiralusha, A. and Trout, D. and Amrhein, H. and Mortazavi, A. and Edsall, L. and {McCleary}, D. and Kuan, S. and Shen, Y. and Yue, F. and Ye, Z. and Davis, C.A. and Zaleski, C. and Jha, S. and Xue, C. and Dobin, A. and Lin, W. and Fastuca, M. and Wang, H. and Guigo, R. and Djebali, S. and Lagarde, J. and Ryba, T. and Sasaki, T. and Malladi, V.S. and Cline, M.S. and Kirkup, V.M. and Learned, K. and Rosenbloom, K.R. and Kent, W.J. and Feingold, E.A. and Good, P.J. and Pazin, M. and Lowdon, R.F. and Adams, L.B.},
	date = {2012},
	keywords = {Chip-seq, Comparative genomics, Dnasei hypersensitive sites, Encode project, Histone modifications, Mouse genome, Rna-seq, Transcription factor binding sites, Transcriptome}
}

@article{djebali_landscape_2012,
	title = {Landscape of transcription in human cells},
	volume = {489},
	issn = {00280836},
	doi = {10.1038/nature11233},
	abstract = {Eukaryotic cells make many types of primary and processed {RNAs} that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these {RNAs} is not yet available and their characteristic subcellular localizations are also poorly understood. Because {RNA} represents the direct output of the genetic information encoded by genomes and a significant proportion of a cellĝ€™s regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated {RNAs}. These observations, taken together, prompt a redefinition of the concept of a gene. © 2012 Macmillan Publishers Limited. All rights reserved.},
	number = {7414},
	journaltitle = {Nature},
	author = {Djebali, S. and Davis, C.A. and Merkel, A. and Dobin, A. and Lassmann, T. and Mortazavi, A. and Tanzer, A. and Lagarde, J. and Lin, W. and Schlesinger, F. and Xue, C. and Marinov, G.K. and Khatun, J. and Williams, B.A. and Zaleski, C. and Rozowsky, J. and Röder, M. and Kokocinski, F. and Abdelhamid, R.F. and Alioto, T. and Antoshechkin, I. and Baer, M.T. and Bar, N.S. and Batut, P. and Bell, K. and Bell, I. and Chakrabortty, S. and Chen, X. and Chrast, J. and Curado, J. and Derrien, T. and Drenkow, J. and Dumais, E. and Dumais, J. and Duttagupta, R. and Falconnet, E. and Fastuca, M. and Fejes-Toth, K. and Ferreira, P. and Foissac, S. and Fullwood, M.J. and Gao, H. and Gonzalez, D. and Gordon, A. and Gunawardena, H. and Howald, C. and Jha, S. and Johnson, R. and Kapranov, P. and King, B. and Kingswood, C. and Luo, O.J. and Park, E. and Persaud, K. and Preall, J.B. and Ribeca, P. and Risk, B. and Robyr, D. and Sammeth, M. and Schaffer, L. and See, L.-H. and Shahab, A. and Skancke, J. and Suzuki, A.M. and Takahashi, H. and Tilgner, H. and Trout, D. and Walters, N. and Wang, H. and Wrobel, J. and Yu, Y. and Ruan, X. and Hayashizaki, Y. and Harrow, J. and Gerstein, M. and Hubbard, T. and Reymond, A. and Antonarakis, S.E. and Hannon, G. and Giddings, M.C. and Ruan, Y. and Wold, B. and Carninci, P. and Guig, R. and Gingeras, T.R.},
	date = {2012},
	keywords = {Transcriptome, Human, Genomics, {DNA}, Sequence Analysis, Genetic, Genome, Humans, Regulatory Sequences, {RNA}, {RNA} Splicing, Transcription, Exons, Gene Expression Profiling, Intergenic, Nucleic Acid, Alleles, Cell Line, {DNA}: genetics, Encyclopedias as Topic, Enhancer Elements, Exons: genetics, Genes, Genetic: genetics, Human: genetics, Intergenic: genetics, Molecular Sequence Annotation, Nucleic Acid: genetics, Polyadenylation, Protein Isoforms, Protein Isoforms: genetics, Repetitive Sequences, {RNA} Editing, Transcriptome: genetics, {RNA}: genetics, Polyadenylation: genetics, Genes: genetics, {RNA} Editing: genetics, {RNA} Splicing: genetics, {RNA}: biosynthesis},
	file = {Attachment:/home/jlagarde/Zotero/storage/XKEJQQVB/Djebali et al. - 2012 - Landscape of transcription in human cells.pdf:application/pdf}
}

@article{tress_implications_2007,
	title = {The implications of alternative splicing in the {ENCODE} protein complement},
	volume = {104},
	issn = {00278424},
	doi = {10.1073/pnas.0700800104},
	abstract = {Alternative premessenger {RNA} splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the {ENCODE} pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing. © 2007 by The National Academy of Sciences of the {USA}.},
	number = {13},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	author = {Tress, M.L. and Martelli, P.L. and Frankish, A. and Reeves, G.A. and Wesselink, J.J. and Yeats, C. and Ólason, P.Í. and Albrecht, M. and Hegyi, H. and Giorgetti, A. and Raimondo, D. and Lagarde, J. and Laskowski, R.A. and López, G. and Sadowski, M.I. and Watson, J.D. and Fariselli, P. and Rossi, I. and Nagy, A. and Kai, W. and Størling, Z. and Orsini, M. and Assenov, Y. and Blankenburg, H. and Huthmacher, C. and Ramírez, F. and Schlicker, A. and Denoued, F. and Jones, P. and Kerrien, S. and Orchard, S. and Antonarakis, S.E. and Reymond, A. and Birney, E. and Brunak, S. and Casadio, R. and Guigo, R. and Harrow, J. and Hermjakob, H. and Jones, D.T. and Lengauer, T. and Orengo, C.A. and Patthy, L. and Thornton, J.M. and Tramontano, A. and Valencia, A.},
	date = {2007},
	keywords = {Function, Human, Isoforms, Splice, Structure}
}

@article{steijger_assessment_2013,
	title = {Assessment of transcript reconstruction methods for {RNA}-seq},
	volume = {10},
	issn = {15487091},
	doi = {10.1038/nmeth.2714},
	abstract = {We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from {RNA}-seq data. Our results show that most algorithms are able to identify discrete transcript components with high success rates but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression-level estimates also varied widely across methods, even when based on similar transcript models. Consequently, the complexity of higher eukaryotic genomes imposes severe limitations on transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation {RNA}-seq data.},
	number = {12},
	journaltitle = {Nature Methods},
	author = {Steijger, T. and Abril, J.F. and Engström, P.G. and Kokocinski, F. and Akerman, M. and Alioto, T. and Ambrosini, G. and Antonarakis, S.E. and Behr, J. and Bertone, P. and Bohnert, R. and Bucher, P. and Cloonan, N. and Derrien, T. and Djebali, S. and Du, J. and Dudoit, S. and Gerstein, M. and Gingeras, T.R. and Gonzalez, D. and Grimmond, S.M. and Guigó, R. and Habegger, L. and Harrow, J. and Hubbard, T.J. and Iseli, C. and Jean, G. and Kahles, A. and Lagarde, J. and Leng, J. and Lefebvre, G. and Lewis, S. and Mortazavi, A. and Niermann, P. and Rätsch, G. and Reymond, A. and Ribeca, P. and Richard, H. and Rougemont, J. and Rozowsky, J. and Sammeth, M. and Sboner, A. and Schulz, M.H. and Searle, S.M.J. and Solorzano, N.D. and Solovyev, V. and Stanke, M. and Stevenson, B.J. and Stockinger, H. and Valsesia, A. and Weese, D. and White, S. and Wold, B.J. and Wu, J. and Wu, T.D. and Zeller, G. and Zerbino, D. and Zhang, M.Q.},
	date = {2013},
	keywords = {Sequence Analysis, Animals, Genome, Humans, {RNA}, {RNA} Splicing, Computational Biology, Exons, Gene Expression Profiling, Messenger, Algorithms, Caenorhabditis elegans, Computational Biology: methods, Drosophila melanogaster, Introns, Messenger: metabolism, {RNA} Splice Sites, {RNA}: methods, Software, {RNA}, Messenger, Sequence Analysis, {RNA}},
	file = {Attachment:/home/jlagarde/Zotero/storage/BE2CUCIR/Liu et al. - 2013 - A promoter-level mammalian expression atlas(7).pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/SPBP5N8B/Steijger et al. - 2013 - Assessment of transcript reconstruction methods for RNA-seq.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/M494PTF3/Steijger et al. - 2013 - Assessment of transcript reconstruction methods fo.pdf:application/pdf}
}

@article{djebali_evidence_2012,
	title = {Evidence for transcript networks composed of chimeric rnas in human cells},
	volume = {7},
	issn = {19326203},
	doi = {10.1371/journal.pone.0028213},
	abstract = {The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85\% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric {RNAs}. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an {RNA} network. © 2012 Djebali et al.},
	number = {1},
	journaltitle = {{PLoS} {ONE}},
	author = {Djebali, S. and Lagarde, J. and Kapranov, P. and Lacroix, V. and Borel, C. and Mudge, J.M. and Howald, C. and Foissac, S. and Ucla, C. and Chrast, J. and Ribeca, P. and Martin, D. and Murray, R.R. and Yang, X. and Ghamsari, L. and Lin, C. and Bell, I. and Dumais, E. and Drenkow, J. and Tress, M.L. and Gelpí, J.L. and Orozco, M. and Valencia, A. and van Berkum, N.L. and Lajoie, B.R. and Vidal, M. and Stamatoyannopoulos, J. and Batut, P. and Dobin, A. and Harrow, J. and Hubbard, T. and Dekker, J. and Frankish, A. and Salehi-Ashtiani, K. and Reymond, A. and Antonarakis, S.E. and Guigó, R. and Gingeras, T.R.},
	date = {2012}
}

@article{washietl_structured_2007,
	title = {Structured {RNAs} in the {ENCODE} selected regions of the human genome},
	volume = {17},
	issn = {10889051},
	doi = {10.1101/gr.5650707},
	abstract = {Functional {RNA} structures play an important role both in the context of noncoding {RNA} transcripts as well as regulatory elements in {mRNAs}. Here we present a computational study to detect functional {RNA} structures within the {ENCODE} regions of the human genome. Since structural {RNAs} in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic-stochastic context-free grammar ({EvoFold}) or energy directed folding ({RNAz} and {AlifoldZ}), yielding several thousand candidate structures (corresponding to ∼2.7\% of the {ENCODE} regions). {EvoFold} has its highest sensitivity in highly conserved and relatively {AU}-rich regions, while {RNAz} favors slightly {GC}-rich regions, resulting in a relatively small overlap between methods. Comparison with the {GENCODE} annotation points to functional {RNAs} in all genomic contexts, with a slightly increased density in 3′-{UTRs}. While we estimate a significant false discovery rate of ∼50\%-70\% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both {RNAz} and {EvoFold}, and an additional 239 {RNAz} or {EvoFold} predictions are supported by the (more stringent) {AlifoldZ} algorithm. Five hundred seventy {RNAz} structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by {RT}-{PCR} in six tissues, and expression could be verified in 43 cases (24.6\%). ©2007 by Cold Spring Harbor Laboratory Press.},
	number = {6},
	journaltitle = {Genome Research},
	author = {Washietl, S. and Pedersen, J.S. and Korbel, J.O. and Stocsits, C. and Gruber, A.R. and Hackermüller, J. and Hertel, J. and Lindemeyer, M. and Reiche, K. and Tanzer, A. and Ucla, C. and Wyss, C. and Antonarakis, S.E. and Denoeud, F. and Lagarde, J. and Drenkow, J. and Kapranov, P. and Gingeras, T.R. and Guigó, R. and Snyder, M. and Gerstein, M.B. and Reymond, A. and Hofacker, I.L. and Stadler, P.F.},
	date = {2007}
}

@article{denoeud_prominent_2007,
	title = {Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in {ENCODE} regions},
	volume = {17},
	issn = {10889051},
	doi = {10.1101/gr.5660607},
	abstract = {This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1\% of the human genome targeted by the Encyclopedia of {DNA} elements ({ENCODE}) pilot project using a combination of 5′ rapid amplification of {cDNA} ends ({RACE}) and high-density resolution tiling arrays. We identified previously unannotated and often tissue- or cell-line-specific transcribed fragments ({RACEfrags}), both 5′ distal to the annotated 5′ terminus and internal to the annotated gene bounds for the vast majority (81.5\%) of the tested genes. Half of the distal {RACEfrags} span large segments of genomic sequences away from the main portion of the coding transcript and often overlap with the upstream-annotated gene(s). Notably, at least 20\% of the resultant novel transcripts have changes in their open reading frames ({ORFs}), most of them fusing {ORFs} of adjacent transcripts. A significant fraction of distal {RACEfrags} show expression levels comparable to those of known exons of the same locus, suggesting that they are not part of very minority splice forms. These results have significant implications concerning (1) our current understanding of the architecture of protein-coding genes; (2) our views on locations of regulatory regions in the genome; and (3) the interpretation of sequence polymorphisms mapping to regions hitherto considered to be "noncoding," ultimately relating to the identification of disease-related sequence alterations. ©2007 by Cold Spring Harbor Laboratory Press.},
	number = {6},
	journaltitle = {Genome Research},
	author = {Denoeud, F. and Kapranov, P. and Ucla, C. and Frankish, A. and Castelo, R. and Drenkow, J. and Lagarde, J. and Alioto, T. and Manzano, C. and Chrast, J. and Dike, S. and Wyss, C. and Henrichsen, C.N. and Holroyd, N. and Dickson, M.C. and Taylor, R. and Hance, Z. and Foissac, S. and Myers, R.M. and Rogers, J. and Hubbard, T. and Harrow, J. and Guigó, R. and Gingeras, T.R. and Antonarakis, S.E. and Reymond, A.},
	date = {2007}
}

@article{djebali_efficient_2008,
	title = {Efficient targeted transcript discovery via array-based normalization of {RACE} libraries},
	volume = {5},
	issn = {15487091},
	doi = {10.1038/nmeth.1216},
	abstract = {Rapid amplification of {cDNA} ends ({RACE}) is a widely used approach for transcript identification. Random clone selection from the {RACE} mixture, however, is an ineffective sampling strategy if the dynamic range of transcript abundances is large. To improve sampling efficiency of human transcripts, we hybridized the products of the {RACE} reaction onto tiling arrays and used the detected exons to delineate a series of reverse-transcriptase ({RT})-{PCRs}, through which the original {RACE} transcript population was segregated into simpler transcript populations. We independently cloned the products and sequenced randomly selected clones. This approach, {RACEarray}, is superior to direct cloning and sequencing of {RACE} products because it specifically targets new transcripts and often results in overall normalization of transcript abundance. We show theoretically and experimentally that this strategy leads indeed to efficient sampling of new transcripts, and we investigated multiplexing the strategy by pooling {RACE} reactions from multiple interrogated loci before hybridization.},
	number = {7},
	journaltitle = {Nature Methods},
	author = {Djebali, S. and Kapranov, P. and Foissac, S. and Lagarde, J. and Reymond, A. and Ucla, C. and Wyss, C. and Drenkow, J. and Dumais, E. and Murray, R.R. and Lin, C. and Szeto, D. and Denoeud, F. and Calvo, M. and Frankish, A. and Harrow, J. and Makrythanasis, P. and Vidal, M. and Salehi-Ashtiani, K. and Antonarakis, S.E. and Gingeras, T.R. and Guigó, R.},
	date = {2008},
	keywords = {Human, {DNA}, Complementary, Genetic, Genome, Humans, {RNA}, Transcription, Exons, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Alternative Splicing, Chromosomes, Cloning, Complementary: genetics, Gene Expression Profiling: methods, Gene Library, Molecular, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis: methods, Protein Isoforms, Protein Isoforms: genetics, Reverse Transcriptase Polymerase Chain Reaction, Nucleic Acid Amplification Techniques, Nucleic Acid Amplification Techniques: methods, {RNA}: genetics, Pair 21, Pair 21: genetics, Pair 22, Pair 22: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/R78N9JQ9/Djebali et al. - 2008 - Efficient targeted transcript discovery via array-based normalization of RACE libraries.pdf:application/pdf}
}

@article{lagarde_extension_2016,
	title = {Extension of human {lncRNA} transcripts by {RACE} coupled with long-read high-throughput sequencing ({RACE}-Seq)},
	volume = {7},
	issn = {20411723},
	doi = {10.1038/ncomms12339},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) constitute a large, yet mostly uncharacterized fraction of the mammalian transcriptome. Such characterization requires a comprehensive, high-quality annotation of their gene structure and boundaries, which is currently lacking. Here we describe {RACE}-Seq, an experimental workflow designed to address this based on {RACE} (rapid amplification of {cDNA} ends) and long-read {RNA} sequencing. We apply {RACE}-Seq to 398 human {lncRNA} genes in seven tissues, leading to the discovery of 2,556 on-target, novel transcripts. About 60\% of the targeted loci are extended in either 5′ or 3′, often reaching genomic hallmarks of gene boundaries. Analysis of the novel transcripts suggests that {lncRNAs} are as long, have as many exons and undergo as much alternative splicing as protein-coding genes, contrary to current assumptions. Overall, we show that {RACE}-Seq is an effective tool to annotate an organism's deep transcriptome, and compares favourably to other targeted sequencing techniques.},
	journaltitle = {Nature Communications},
	author = {Lagarde, J. and Uszczynska-Ratajczak, B. and Santoyo-Lopez, J. and Gonzalez, J.M. and Tapanari, E. and Mudge, J.M. and Steward, C.A. and Wilming, L. and Tanzer, A. and Howald, C. and Chrast, J. and Vela-Boza, A. and Rueda, A. and Lopez-Domingo, F.J. and Dopazo, J. and Reymond, A. and Guigó, R. and Harrow, J.},
	date = {2016}
}

@article{harrow_gencode:_2006,
	title = {{GENCODE}: producing a reference annotation for {ENCODE}.},
	volume = {7 Suppl 1},
	issn = {14656914},
	abstract = {{BACKGROUND}: The {GENCODE} consortium was formed to identify and map all protein-coding genes within the {ENCODE} regions. This was achieved by a combination of initial manual annotation by the {HAVANA} team, experimental validation by the {GENCODE} consortium and a refinement of the annotation based on these experimental results. {RESULTS}: The {GENCODE} gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of {cDNA} ends ({RACE}) and {RT}-{PCR} were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 {RACE} products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the {GENCODE} annotation by attempting to validate all the predicted exon boundaries outside the {GENCODE} annotation. Out of 1,215 tested in a subset of the {ENCODE} regions, 14 novel exon pairs were validated, only two of them in intergenic regions. {CONCLUSION}: In total, 487 loci, of which 434 are coding, have been annotated as part of the {GENCODE} reference set available from the {UCSC} browser. Comparison of {GENCODE} annotation with {RefSeq} and {ENSEMBL} show only 40\% of {GENCODE} exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50\% of coding loci have been experimentally verified by 5' {RACE} for {EGASP} and the {GENCODE} collaboration is continuing to refine its annotation of 1\% human genome with the aid of experimental validation.},
	journaltitle = {Genome biology},
	author = {Harrow, J. and Denoeud, F. and Frankish, A. and Reymond, A. and Chen, C.K. and Chrast, J. and Lagarde, J. and Gilbert, J.G. and Storey, R. and Swarbreck, D. and Rossier, C. and Ucla, C. and Hubbard, T. and Antonarakis, S.E. and Guigo, R.},
	date = {2006},
	file = {Full Text:/home/jlagarde/Zotero/storage/Z7WP6AV2/Harrow et al. - 2006 - GENCODE producing a reference annotation for ENCO.pdf:application/pdf;GENCODE\: producing a reference annotation for ENCODE:/home/jlagarde/Zotero/storage/Z7AP62LL/harrow2006.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/GRC6RESY/gb-2006-7-s1-s4.html:text/html}
}

@article{kapusta_transposable_2013,
	title = {Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding {RNAs}.},
	volume = {9},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1003470},
	abstract = {Advances in vertebrate genomics have uncovered thousands of loci encoding long noncoding {RNAs} ({lncRNAs}). While progress has been made in elucidating the regulatory functions of {lncRNAs}, little is known about their origins and evolution. Here we explore the contribution of transposable elements ({TEs}) to the makeup and regulation of {lncRNAs} in human, mouse, and zebrafish. Surprisingly, {TEs} occur in more than two thirds of mature {lncRNA} transcripts and account for a substantial portion of total {lncRNA} sequence (∼30\% in human), whereas they seldom occur in protein-coding transcripts. While {TEs} contribute less to {lncRNA} exons than expected, several {TE} families are strongly enriched in {lncRNAs}. There is also substantial interspecific variation in the coverage and types of {TEs} embedded in {lncRNAs}, partially reflecting differences in the {TE} landscapes of the genomes surveyed. In human, {TE} sequences in {lncRNAs} evolve under greater evolutionary constraint than their non-{TE} sequences, than their intronic {TEs}, or than random {DNA}. Consistent with functional constraint, we found that {TEs} contribute signals essential for the biogenesis of many {lncRNAs}, including ∼30,000 unique sites for transcription initiation, splicing, or polyadenylation in human. In addition, we identified ∼35,000 {TEs} marked as open chromatin located within 10 kb upstream of {lncRNA} genes. The density of these marks in one cell type correlate with elevated expression of the downstream {lncRNA} in the same cell type, suggesting that these {TEs} contribute to cis-regulation. These global trends are recapitulated in several {lncRNAs} with established functions. Finally a subset of {TEs} embedded in {lncRNAs} are subject to {RNA} editing and predicted to form secondary structures likely important for function. In conclusion, {TEs} are nearly ubiquitous in {lncRNAs} and have played an important role in the lineage-specific diversification of vertebrate {lncRNA} repertoires.},
	pages = {e1003470},
	number = {4},
	journaltitle = {{PLoS} genetics},
	author = {Kapusta, Aurélie and Kronenberg, Zev and Lynch, Vincent J and Zhuo, Xiaoyu and Ramsay, {LeeAnn} and Bourque, Guillaume and Yandell, Mark and Feschotte, Cédric},
	editor = {Hoekstra, Hopi E.},
	date = {2013-04},
	pmid = {23637635},
	keywords = {Animals, Humans, Exons, Introns, {DNA} Transposable Elements, Vertebrates, {RNA}, Long Noncoding},
	file = {Full Text:/home/jlagarde/Zotero/storage/SLZU9SCE/Kapusta et al. - 2013 - Transposable elements are major contributors to th.pdf:application/pdf}
}

@article{anderson_micropeptide_2015,
	title = {A Micropeptide Encoded by a Putative Long Noncoding {RNA} Regulates Muscle Performance},
	volume = {160},
	issn = {00928674},
	doi = {10.1016/j.cell.2015.01.009},
	abstract = {Functional micropeptides can be concealed within {RNAs} that appear to be noncoding. We discovered a conserved micropeptide, which we named myoregulin ({MLN}), encoded by a skeletal muscle-specific {RNA} annotated as a putative long noncoding {RNA}. {MLN} shares structural and functional similarity with phospholamban ({PLN}) and sarcolipin ({SLN}), which inhibit {SERCA}, the membrane pump that controls muscle relaxation by regulating Ca(2+) uptake into the sarcoplasmic reticulum ({SR}). {MLN} interacts directly with {SERCA} and impedes Ca(2+) uptake into the {SR}. In contrast to {PLN} and {SLN}, which are expressed in cardiac and slow skeletal muscle in mice, {MLN} is robustly expressed in all skeletal muscle. Genetic deletion of {MLN} in mice enhances Ca(2+) handling in skeletal muscle and improves exercise performance. These findings identify {MLN} as an important regulator of skeletal muscle physiology and highlight the possibility that additional micropeptides are encoded in the many {RNAs} currently annotated as noncoding.},
	pages = {595--606},
	number = {4},
	journaltitle = {Cell},
	author = {Anderson, Douglas M. and Anderson, Kelly M. and Chang, Chi-Lun and Makarewich, Catherine A. and Nelson, Benjamin R. and {McAnally}, John R. and Kasaragod, Prasad and Shelton, John M. and Liou, Jen and Bassel-Duby, Rhonda and Olson, Eric N.},
	date = {2015-02},
	pmid = {25640239},
	keywords = {Animals, Base Sequence, Humans, Mice, Amino Acid Sequence, Male, Molecular Sequence Data, Myocardium, Sequence Alignment, {RNA}, Long Noncoding, Models, Molecular, Calcium, Calcium-Binding Proteins, Muscle Proteins, Muscle, Skeletal, Protein Structure, Secondary, Proteolipids, Sarcoplasmic Reticulum, Sarcoplasmic Reticulum Calcium-Transporting {ATPases}},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/8GBYVGQN/Anderson et al. - 2015 - A micropeptide encoded by a putative long noncodin.pdf:application/pdf}
}

@article{kong_cpc:_2007,
	title = {{CPC}: assess the protein-coding potential of transcripts using sequence features and support vector machine},
	volume = {35},
	issn = {1362-4962},
	doi = {10.1093/nar/gkm391},
	pages = {W345--W349},
	issue = {suppl\_2},
	journaltitle = {Nucleic Acids Research},
	author = {Kong, Lei and Zhang, Yong and Ye, Zhi-Qiang and Liu, Xiao-Qiao and Zhao, Shu-Qi and Wei, Liping and Gao, Ge},
	date = {2007-07},
	keywords = {Animals, Genetic, Mice, {RNA}, Transcription, Reproducibility of Results, Databases, Nucleic Acid, *Protein Biosynthesis, Computational Biology/*methods, Expressed Sequence Tags, Genetic Code, Genetic Variation, Genetic Vectors, Messenger/*genetics, Molecular Sequence Data, Proteins/*genetics, {RNA}/classification/*genetics}
}

@article{zhou_n_2016,
	title = {N 6 -Methyladenosine Modification in a Long Noncoding {RNA} Hairpin Predisposes Its Conformation to Protein Binding},
	doi = {10.1016/j.jmb.2015.08.021},
	abstract = {N 6 -Methyladenosine (m 6 A) is a reversible and abundant internal modification of messenger {RNA} ({mRNA}) and long noncoding {RNA} ({lncRNA}) with roles in {RNA} processing, transport, and stability. Although m 6 A does not preclude Watson–Crick base pairing, the N 6 -methyl group alters the stability of {RNA} secondary structure. Since changes in {RNA} structure can affect diverse cellular processes, the influence of m 6 A on {mRNA} and {lncRNA} structure has the potential to be an important mechanism for m 6 A function in the cell. Indeed, an m 6 A site in the {lncRNA} metastasis associated lung adenocarcinoma transcript 1 ({MALAT}1) was recently shown to induce a local change in structure that increases the accessibility of a U 5 -tract for recognition and binding by heterogeneous nuclear ribonucleoprotein C ({HNRNPC}). This m 6 A-dependent regulation of protein binding through a change in {RNA} structure, termed " m 6 A-switch " , affects transcriptome-wide {mRNA} abundance and alternative splicing. To further characterize this first example of an m 6 A-switch in a cellular {RNA}, we used nuclear magnetic resonance and Förster resonance energy transfer to demonstrate the effect of m 6 A on a 32-nucleotide {RNA} hairpin derived from the m 6 A-switch in {MALAT}1. The observed imino proton nuclear magnetic resonance resonances and Förster resonance energy transfer efficiencies suggest that m 6 A selectively destabilizes the portion of the hairpin stem where the U 5 -tract is located, increasing the solvent accessibility of the neighboring bases while maintaining the overall hairpin structure. The m 6 A-modified hairpin has a predisposed conformation that resembles the hairpin conformation in the {RNA}–{HNRNPC} complex more closely than the unmodified hairpin. The m 6 A-induced structural changes in the {MALAT}1 hairpin can serve as a model for a large family of m 6 A-switches that mediate the influence of m 6 A on cellular processes.},
	author = {Zhou, Katherine I and Parisien, Marc and Dai, Qing and Liu, Nian and Diatchenko, Luda and Sachleben, Joseph R and Pan, Tao},
	date = {2016}
}

@article{jain_oxford_2016,
	title = {The Oxford Nanopore {MinION}: delivery of nanopore sequencing to the genomics community},
	volume = {17},
	issn = {1474-760X},
	doi = {10.1186/s13059-016-1103-0},
	abstract = {Nanopore {DNA} strand sequencing has emerged as a competitive, portable technology. Reads exceeding 150 kilobases have been achieved, as have in-field detection and analysis of clinical pathogens. We summarize key technical features of the Oxford Nanopore {MinION}, the dominant platform currently available. We then discuss pioneering applications executed by the genomics community.},
	pages = {239},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Jain, Miten and Olsen, Hugh E. and Paten, Benedict and Akeson, Mark},
	date = {2016-12}
}

@article{the_rnacentral_consortium_rnacentral:_2017,
	title = {{RNAcentral}: a comprehensive database of non-coding {RNA} sequences},
	volume = {45},
	issn = {0305-1048},
	doi = {10.1093/nar/gkw1008},
	abstract = {{RNAcentral} is a database of non-coding {RNA} ({ncRNA}) sequences that aggregates data from specialised {ncRNA} resources and provides a single entry point for accessing {ncRNA} sequences of all {ncRNA} types from all organisms. Since its launch in 2014, {RNAcentral} has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from {MODOMICS} and {PDB}. We created new species-specific identifiers that refer to unique {RNA} sequences within a context of single species. The website has been subject to continuous improvements focusing on text and sequence similarity searches as well as genome browsing functionality. All {RNAcentral} data is provided for free and is available for browsing, bulk downloads, and programmatic access at http://rnacentral.org/.},
	pages = {D128--D134},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {{The RNAcentral Consortium}},
	date = {2017-01},
	pmid = {27794554}
}

@article{gibb_activation_2015,
	title = {Activation of an endogenous retrovirus-associated long non-coding {RNA} in human adenocarcinoma},
	volume = {7},
	issn = {1756-994X},
	doi = {10.1186/s13073-015-0142-6},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are emerging as molecules that significantly impact many cellular processes and have been associated with almost every human cancer. Compared to protein-coding genes, {lncRNA} genes are often associated with transposable elements, particularly with endogenous retroviral elements ({ERVs}). {ERVs} can have potentially deleterious effects on genome structure and function, so these elements are typically silenced in normal somatic tissues, albeit with varying efficiency. The aberrant regulation of {ERVs} associated with {lncRNAs} ({ERV}-{lncRNAs}), coupled with the diverse range of {lncRNA} functions, creates significant potential for {ERV}-{lncRNAs} to impact cancer biology. We used {RNA}-seq analysis to identify and profile the expression of a novel {lncRNA} in six large cohorts, including over 7,500 samples from The Cancer Genome Atlas ({TCGA}). We identified the tumor-specific expression of a novel {lncRNA} that we have named Endogenous {retroViral}-associated {ADenocarcinoma} {RNA} or ‘{EVADR}', by analyzing {RNA}-seq data derived from colorectal tumors and matched normal control tissues. Subsequent analysis of {TCGA} {RNA}-seq data revealed the striking association of {EVADR} with adenocarcinomas, which are tumors of glandular origin. Moderate to high levels of {EVADR} were detected in 25 to 53\% of colon, rectal, lung, pancreas and stomach adenocarcinomas (mean = 30 to 144 {FPKM}), and {EVADR} expression correlated with decreased patient survival (Cox regression; hazard ratio = 1.47, 95\% confidence interval = 1.06 to 2.04, P = 0.02). In tumor sites of non-glandular origin, {EVADR} expression was detectable at only very low levels and in less than 10\% of patients. For {EVADR}, a {MER}48 {ERV} element provides an active promoter to drive its transcription. Genome-wide, {MER}48 insertions are associated with nine {lncRNAs}, but none of the {MER}48-associated {lncRNAs} other than {EVADR} were consistently expressed in adenocarcinomas, demonstrating the specific activation of {EVADR}. The sequence and structure of the {EVADR} locus is highly conserved among Old World monkeys and apes but not New World monkeys or prosimians, where the {MER}48 insertion is absent. Conservation of the {EVADR} locus suggests a functional role for this novel {lncRNA} in humans and our closest primate relatives. Our results describe the specific activation of a highly conserved {ERV}-{lncRNA} in numerous cancers of glandular origin, a finding with diagnostic, prognostic and therapeutic implications.},
	pages = {22},
	number = {1},
	journaltitle = {Genome Medicine},
	author = {Gibb, Ewan A and Warren, René L and Wilson, Gavin W and Brown, Scott D and Robertson, Gordon A and Morin, Gregg B and Holt, Robert A and Djebali, S and Davis, {CA} and Merkel, A and Dobin, A and Lassmann, T and Mortazavi, A and Carninci, P and Kasukawa, T and Katayama, S and Gough, J and Frith, {MC} and Maeda, N and Kapranov, P and Laurent, G St and Raz, T and Ozsolak, F and Reynolds, {CP} and Sorensen, {PH} and Kapranov, P and Cheng, J and Dike, S and Nix, {DA} and Duttagupta, R and Willingham, {AT} and Derrien, T and Johnson, R and Bussotti, G and Tanzer, A and Djebali, S and Tilgner, H and Mercer, {TR} and Dinger, {ME} and Mattick, {JS} and Gibb, {EA} and Vucic, {EA} and Enfield, {KS} and Stewart, {GL} and Lonergan, {KM} and Kennett, {JY} and Castle, {JC} and Armour, {CD} and Lower, M and Haynor, D and Biery, M and Bouzek, H and Wu, {SC} and Kallin, {EM} and Zhang, Y and Tsai, {MC} and Manor, O and Wan, Y and Mosammaparast, N and Wang, {JK} and Lan, F and Kotake, Y and Nakagawa, T and Kitagawa, K and Suzuki, S and Liu, N and Kitagawa, M and Gutschner, T and Diederichs, S and Gibb, {EA} and Brown, {CJ} and Lam, {WL} and Huarte, M and Rinn, {JL} and Johnson, R and Guigo, R and Kapusta, A and Kronenberg, Z and Lynch, {VJ} and Zhuo, X and Ramsay, L and Bourque, G and Kelley, D and Rinn, J and Cohen, {CJ} and Lock, {WM} and Mager, {DL} and Lower, R and Lower, J and Kurth, R and Fort, A and Hashimoto, K and Yamada, D and Salimullah, M and Keya, {CA} and Saxena, A and Faulkner, {GJ} and Kimura, Y and Daub, {CO} and Wani, S and Plessy, C and Irvine, {KM} and Maksakova, {IA} and Mager, {DL} and Reiss, D and Stoye, {JP} and Kassiotis, G and Ruprecht, K and Mayer, J and Sauter, M and Roemer, K and Mueller-Lantzsch, N and Stauffer, Y and Theiler, G and Sperisen, P and Lebedev, Y and Jongeneel, {CV} and Santoni, {FA} and Guerra, J and Luban, J and Warren, {RL} and Freeman, {DJ} and Pleasance, S and Watson, P and Moore, {RA} and Cochrane, K and Dobin, A and Davis, {CA} and Schlesinger, F and Drenkow, J and Zaleski, C and Jha, S and Kim, D and Pertea, G and Trapnell, C and Pimentel, H and Kelley, R and Salzberg, {SL} and Trapnell, C and Williams, {BA} and Pertea, G and Mortazavi, A and Kwan, G and Baren, {MJ} and Warren, {RL} and Holt, {RA} and Altschul, {SF} and Gish, W and Miller, W and Myers, {EW} and Lipman, {DJ} and Mortazavi, A and Williams, {BA} and {McCue}, K and Schaeffer, L and Wold, B and Castellarin, M and Warren, {RL} and Freeman, {JD} and Dreolini, L and Krzywinski, M and Strauss, J and Wheeler, {TJ} and Clements, J and Eddy, {SR} and Hubley, R and Jones, {TA} and Jurka, J and Tamura, K and Stecher, G and Peterson, D and Filipski, A and Kumar, S and Waterhouse, {AM} and Procter, {JB} and Martin, {DM} and Clamp, M and Barton, {GJ} and Miller, W and Rosenbloom, K and Hardison, {RC} and Hou, M and Taylor, J and Raney, B and Kuhn, {RM} and Karolchik, D and Zweig, {AS} and Trumbower, H and Thomas, {DJ} and Thakkapallayil, A and Kong, L and Zhang, Y and Ye, {ZQ} and Liu, {XQ} and Zhao, {SQ} and Wei, L and Banfai, B and Jia, H and Khatun, J and Wood, E and Risk, B and Gundling, {WE} and Ma, J and Ward, {CC} and Jungreis, I and Slavoff, {SA} and Schwaid, {AG} and Neveu, J and Slavoff, {SA} and Mitchell, {AJ} and Schwaid, {AG} and Cabili, {MN} and Ma, J and Levin, {JZ} and Seo, {JS} and Ju, {YS} and Lee, {WC} and Shin, {JY} and Lee, {JK} and Bleazard, T and Budczies, J and Klauschen, F and Sinn, {BV} and Gyorffy, B and Schmitt, {WD} and Darb-Esfahani, S and Jurka, J and Kapitonov, {VV} and Klonowski, P and Walichiewicz, J and Smit, {AF} and Fromont-Racine, M and Bertrand, E and Pictet, R and Grange, T and Ha, {HS} and Chung, {WK} and Ahn, K and Bae, {JH} and Park, {SJ} and Moon, {JW} and Ge, P and Zhang, S and Subramanian, {RP} and Wildschutte, {JH} and Russo, C and Coffin, {JM} and Lander, {ES} and Linton, {LM} and Birren, B and Nusbaum, C and Zody, {MC} and Baldwin, J and Venter, {JC} and Adams, {MD} and Myers, {EW} and Li, {PW} and Mural, {RJ} and Sutton, {GG} and Kapitonov, V and Jurka, J and Springer, {MS} and Murphy, {WJ} and Eizirik, E and O'Brien, {SJ} and Marques, {AC} and Ponting, {CP} and Necsulea, A and Soumillon, M and Warnefors, M and Liechti, A and Daish, T and Zeller, U and Schuler, A and Ghanbarian, {AT} and Hurst, {LD} and Washietl, S and Kellis, M and Garber, M and Diederichs, S and Johnsson, P and Lipovich, L and Grander, D and Morris, {KV} and Lock, {FE} and Rebollo, R and Miceli-Royer, K and Gagnier, L and Kuah, S and Babaian, A and Laurent, G St and Shtokalo, D and Dong, B and Tackett, {MR} and Fan, X and Lazorthes, S and Loewer, S and Cabili, {MN} and Guttman, M and Loh, {YH} and Thomas, K and Park, {IH} and Lu, X and Sachs, F and Ramsay, L and Jacques, {PE} and Goke, J and Bourque, G},
	date = {2015-12}
}

@article{housman_methods_2016,
	title = {Methods for distinguishing between protein-coding and long noncoding {RNAs} and the elusive biological purpose of translation of long noncoding {RNAs}},
	volume = {1859},
	issn = {1874-9399},
	doi = {10.1016/J.BBAGRM.2015.07.017},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are a diverse class of {RNAs} with increasingly appreciated functions in vertebrates, yet much of their biology remains poorly understood. In particular, it is unclear to what extent the current catalog of over 10,000 annotated {lncRNAs} is indeed devoid of genes coding for proteins. Here we review the available computational and experimental schemes for distinguishing between coding and noncoding transcripts and assess the conclusions from their recent genome-wide applications. We conclude that the model most consistent with the available data is that a large number of mammalian {lncRNAs} undergo translation, but only a very small minority of such translation events results in stable and functional peptides. The outcomes of the majority of the translation events and their potential biological purposes remain an intriguing topic for future investigation. This article is part of a Special Issue entitled: Clues to long noncoding {RNA} taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.},
	pages = {31--40},
	number = {1},
	journaltitle = {Biochimica et Biophysica Acta ({BBA}) - Gene Regulatory Mechanisms},
	author = {Housman, Gali and Ulitsky, Igor},
	date = {2016-01}
}

@article{bussotti_improved_2016,
	title = {Improved definition of the mouse transcriptome via targeted {RNA} sequencing},
	volume = {26},
	issn = {1088-9051},
	doi = {10.1101/gr.199760.115},
	abstract = {Targeted {RNA} sequencing ({CaptureSeq}) uses oligonucleotide probes to capture {RNAs} for sequencing, providing enriched read coverage, accurate measurement of gene expression, and quantitative expression data. We applied {CaptureSeq} to refine transcript annotations in the current murine {GRCm}38 assembly. More than 23,000 regions corresponding to putative or annotated long noncoding {RNAs} ({lncRNAs}) and 154,281 known splicing junction sites were selected for targeted sequencing across five mouse tissues and three brain subregions. The results illustrate that the mouse transcriptome is considerably more complex than previously thought. We assemble more complete transcript isoforms than {GENCODE}, expand transcript boundaries, and connect interspersed islands of mapped reads. We describe a novel filtering pipeline that identifies previously unannotated but high-quality transcript isoforms. In this set, 911 {GENCODE} neighboring genes are condensed into 400 expanded gene models. Additionally, 594 {GENCODE} {lncRNAs} acquire an open reading frame ({ORF}) when their structure is extended with {CaptureSeq}. Finally, we validate our observations using current {FANTOM} and Mouse {ENCODE} resources.},
	pages = {705--716},
	number = {5},
	journaltitle = {Genome Research},
	author = {Bussotti, Giovanni and Leonardi, Tommaso and Clark, Michael B. and Mercer, Tim R. and Crawford, Joanna and Malquori, Lorenzo and Notredame, Cedric and Dinger, Marcel E. and Mattick, John S. and Enright, Anton J.},
	date = {2016-05},
	pmid = {27197243}
}

@article{gascoigne_pinstripe:_2012,
	title = {Pinstripe: a suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes},
	volume = {28},
	issn = {1367-4803},
	doi = {10.1093/bioinformatics/bts582},
	pages = {3042--3050},
	number = {23},
	journaltitle = {Bioinformatics},
	author = {Gascoigne, Dennis K. and Cheetham, Seth W. and Cattenoz, Pierre B. and Clark, Michael B. and Amaral, Paulo P. and Taft, Ryan J. and Wilhelm, Dagmar and Dinger, Marcel E. and Mattick, John S.},
	date = {2012-12},
	keywords = {*Software, Gene Expression Profiling/*methods, Genomics/*methods, Sequence Analysis, Genome, Humans, {RNA}, Messenger/genetics, Proteins/genetics, Exons, Databases, Open Reading Frames, Computational Biology/methods, Gene Library, Long Noncoding/genetics, Molecular Sequence Annotation, Protein, Proteomics/*methods}
}

@article{liu_single-cell_2016,
	title = {Single-cell analysis of long non-coding {RNAs} in the developing human neocortex},
	volume = {17},
	issn = {1474-760X},
	doi = {10.1186/s13059-016-0932-1},
	pages = {67},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Liu, Siyuan John and Nowakowski, Tomasz J. and Pollen, Alex A. and Lui, Jan H. and Horlbeck, Max A. and Attenello, Frank J. and He, Daniel and Weissman, Jonathan S. and Kriegstein, Arnold R. and Diaz, Aaron A. and Lim, Daniel A.},
	date = {2016-12}
}

@article{apweiler_uniprot:_2004,
	title = {{UniProt}: the Universal Protein knowledgebase},
	volume = {32},
	issn = {1362-4962},
	doi = {10.1093/nar/gkh131},
	abstract = {To provide the scientific community with a single, centralized, authoritative resource for protein sequences and functional information, the Swiss-Prot, {TrEMBL} and {PIR} protein database activities have united to form the Universal Protein Knowledgebase ({UniProt}) consortium. Our mission is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and query interfaces. The central database will have two sections, corresponding to the familiar Swiss-Prot (fully manually curated entries) and {TrEMBL} (enriched with automated classification, annotation and extensive cross-references). For convenient sequence searches, {UniProt} also provides several non-redundant sequence databases. The {UniProt} {NREF} ({UniRef}) databases provide representative subsets of the knowledgebase suitable for efficient searching. The comprehensive {UniProt} Archive ({UniParc}) is updated daily from many public source databases. The {UniProt} databases can be accessed online (http://www.uniprot.org) or downloaded in several formats (ftp://ftp.uniprot.org/pub). The scientific community is encouraged to submit data for inclusion in {UniProt}.},
	pages = {115D--119},
	number = {90001},
	journaltitle = {Nucleic Acids Research},
	author = {Apweiler, R. and Bairoch, Amos and Wu, Cathy H and Barker, Winona C and Boeckmann, Brigitte and Ferro, Serenella and Gasteiger, Elisabeth and Huang, Hongzhan and Lopez, Rodrigo and Magrane, Michele and Martin, Maria J and Natale, Darren A and O'Donovan, Claire and Redaschi, Nicole and Yeh, Lai-Su L},
	date = {2004-01},
	pmid = {14681372}
}

@article{gonzalez-porta_estimation_2012,
	title = {Estimation of alternative splicing variability in human populations},
	volume = {22},
	issn = {1088-9051},
	doi = {10.1101/gr.121947.111},
	abstract = {{DNA} arrays have been widely used to perform transcriptome-wide analysis of gene expression, and many methods have been developed to measure gene expression variability and to compare gene expression between conditions. Because {RNA}-seq is also becoming increasingly popular for transcriptome characterization, the possibility exists for further quantification of individual alternative transcript isoforms, and therefore for estimating the relative ratios of alternative splice forms within a given gene. Changes in splicing ratios, even without changes in overall gene expression, may have important phenotypic effects. Here we have developed statistical methodology to measure variability in splicing ratios within conditions, to compare it between conditions, and to identify genes with condition-specific splicing ratios. Furthermore, we have developed methodology to deconvolute the relative contribution of variability in gene expression versus variability in splicing ratios to the overall variability of transcript abundances. As a proof of concept, we have applied this methodology to estimates of transcript abundances obtained from {RNA}-seq experiments in lymphoblastoid cells from Caucasian and Yoruban individuals. We have found that protein-coding genes exhibit low splicing variability within populations, with many genes exhibiting constant ratios across individuals. When comparing these two populations, we have found that up to 10\% of the studied protein-coding genes exhibit population-specific splicing ratios. We estimate that ∼60\% of the total variability observed in the abundance of transcript isoforms can be explained by variability in transcription. A large fraction of the remaining variability can likely result from variability in splicing. Finally, we also detected that variability in splicing is uncommon without variability in transcription.},
	pages = {528--538},
	number = {3},
	journaltitle = {Genome Research},
	author = {Gonzalez-Porta, M. and Calvo, M. and Sammeth, M. and Guigo, R.},
	date = {2012-03},
	pmid = {22113879}
}

@article{kibbe_disease_2015,
	title = {Disease Ontology 2015 update: an expanded and updated database of human diseases for linking biomedical knowledge through disease data.},
	volume = {43},
	issn = {1362-4962},
	doi = {10.1093/nar/gku1011},
	abstract = {The current version of the Human Disease Ontology ({DO}) (http://www.disease-ontology.org) database expands the utility of the ontology for the examination and comparison of genetic variation, phenotype, protein, drug and epitope data through the lens of human disease. {DO} is a biomedical resource of standardized common and rare disease concepts with stable identifiers organized by disease etiology. The content of {DO} has had 192 revisions since 2012, including the addition of 760 terms. Thirty-two percent of all terms now include definitions. {DO} has expanded the number and diversity of research communities and community members by 50+ during the past two years. These community members actively submit term requests, coordinate biomedical resource disease representation and provide expert curation guidance. Since the {DO} 2012 {NAR} paper, there have been hundreds of term requests and a steady increase in the number of {DO} listserv members, twitter followers and {DO} website usage. {DO} is moving to a multi-editor model utilizing Protégé to curate {DO} in web ontology language. This will enable closer collaboration with the Human Phenotype Ontology, {EBI}'s Ontology Working Group, Mouse Genome Informatics and the Monarch Initiative among others, and enhance {DO}'s current asserted view and multiple inferred views through reasoning.},
	pages = {D1071--8},
	issue = {Database issue},
	journaltitle = {Nucleic acids research},
	author = {Kibbe, Warren A and Arze, Cesar and Felix, Victor and Mitraka, Elvira and Bolton, Evan and Fu, Gang and Mungall, Christopher J and Binder, Janos X and Malone, James and Vasant, Drashtti and Parkinson, Helen and Schriml, Lynn M},
	date = {2015-01},
	pmid = {25348409}
}

@article{ng_human_2012,
	title = {Human long non-coding {RNAs} promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors},
	volume = {31},
	issn = {02614189},
	doi = {10.1038/emboj.2011.459},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are a numerous class of newly discovered genes in the human genome, which have been proposed to be key regulators of biological processes, including stem cell pluripotency and neurogenesis. However, at present very little functional characterization of {lncRNAs} in human differentiation has been carried out. In the present study, we address this using human embryonic stem cells ({hESCs}) as a paradigm for pluripotency and neuronal differentiation. With a newly developed method, {hESCs} were robustly and efficiently differentiated into neurons, and we profiled the expression of thousands of {lncRNAs} using a custom-designed microarray. Some {hESC}-specific {lncRNAs} involved in pluripotency maintenance were identified, and shown to physically interact with {SOX}2, and {PRC}2 complex component, {SUZ}12. Using a similar approach, we identified {lncRNAs} required for neurogenesis. Knockdown studies indicated that loss of any of these {lncRNAs} blocked neurogenesis, and immunoprecipitation studies revealed physical association with {REST} and {SUZ}12. This study indicates that {lncRNAs} are important regulators of pluripotency and neurogenesis, and represents important evidence for an indispensable role of {lncRNAs} in human brain development.},
	pages = {522--533},
	number = {3},
	journaltitle = {The {EMBO} Journal},
	author = {Ng, Shi-Yan and Johnson, Rory and Stanton, Lawrence W},
	date = {2012-02},
	pmid = {22193719},
	keywords = {Humans, {RNA}, Oligonucleotide Array Sequence Analysis, Cell Differentiation/*genetics, Chromatin/*metabolism, Fluorescent Antibody Technique, Gene Knockdown Techniques, Neurons/*cytology, Transcription Factors/*metabolism, Untranslated/genetics/metabolism/*physiology}
}

@article{huarte_large_2010,
	title = {A large intergenic noncoding {RNA} induced by p53 mediates global gene repression in the p53 response},
	volume = {142},
	issn = {00928674},
	doi = {10.1016/j.cell.2010.06.040},
	abstract = {Recently, more than 1000 large intergenic noncoding {RNAs} ({lincRNAs}) have been reported. These {RNAs} are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of {lincRNAs} that are regulated by p53. One of these {lincRNAs} ({lincRNA}-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of {lincRNA}-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by {lincRNA}-p21 is mediated through the physical association with {hnRNP}-K. This interaction is required for proper genomic localization of {hnRNP}-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate {lincRNAs} that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes. {PaperFlick}: © 2010 Elsevier Inc.},
	pages = {409--419},
	number = {3},
	journaltitle = {Cell},
	author = {Huarte, Maite and Guttman, Mitchell and Feldser, David and Garber, Manuel and Koziol, Magdalena J and Kenzelmann-Broz, Daniela and Khalil, Ahmad M and Zuk, Or and Amit, Ido and Rabani, Michal and Attardi, Laura D and Regev, Aviv and Lander, Eric S and Jacks, Tyler and Rinn, John L},
	date = {2010-08},
	pmid = {20673990},
	keywords = {Animals, Genetic, Humans, Mice, {RNA}, Transcription, *Down-Regulation, Apoptosis, Heterogeneous-Nuclear Ribonucleoprotein K/metaboli, Molecular Sequence Data, Tumor Suppressor Protein p53/*metabolism, Untranslated/*metabolism},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/LNKDESZB/Huarte et al. - 2010 - A large intergenic non-coding RNA induced by p53 m.pdf:application/pdf}
}

@article{kasowski_variation_2010,
	title = {Variation in transcription factor binding among humans.},
	volume = {328},
	issn = {1095-9203},
	doi = {10.1126/science.1183621},
	abstract = {Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor ({TF}) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of {RNA} polymerase {II} ({PolII}) and a key regulator of immune responses, nuclear factor {kappaB} (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5\% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing {PolII} binding between humans and chimpanzee suggests extensive divergence in {TF} binding. Our results indicate that many differences in individuals and species occur at the level of {TF} binding, and they provide insight into the genetic events responsible for these differences.},
	pages = {232--5},
	number = {5975},
	journaltitle = {Science (New York, N.Y.)},
	author = {Kasowski, Maya and Grubert, Fabian and Heffelfinger, Christopher and Hariharan, Manoj and Asabere, Akwasi and Waszak, Sebastian M and Habegger, Lukas and Rozowsky, Joel and Shi, Minyi and Urban, Alexander E and Hong, Mi-Young and Karczewski, Konrad J and Huber, Wolfgang and Weissman, Sherman M and Gerstein, Mark B and Korbel, Jan O and Snyder, Michael},
	date = {2010-04},
	pmid = {20299548}
}

@article{carlevaro-fita_ancient_2017,
	title = {Ancient exapted transposable elements promote nuclear enrichment of long noncoding {RNAs}},
	doi = {10.1101/189753},
	abstract = {The sequence domains underlying long noncoding {RNA} ({lncRNA}) activities, including their characteristic nuclear enrichment, remain largely unknown. It has been proposed that these domains can originate from neofunctionalised fragments of transposable elements ({TEs}), otherwise known as {RIDLs} (Repeat Insertion Domains of Long Noncoding {RNA}). However, this concept remains largely untested, and just a handful of {RIDLs} have been identified. We present a transcriptome-wide map of putative {RIDLs} in human, using evidence from insertion frequency, strand bias and evolutionary conservation of sequence and structure. In the exons of {GENCODE} v21 {lncRNAs}, we identify 5374 {RIDLs} in 3566 loci. These are enriched in functionally-validated and disease-associated genes. This {RIDL} map was used to explore the relationship between {TEs} and {lncRNA} subcellular localisation. Using global localisation data from ten human cell lines, we uncover a dose-dependent relationship between nuclear/cytoplasmic distribution, and exonic {LINE}2 and {MIR} elements. This is observed in multiple cell types, and is unaffected by confounders of transcript length or expression. Experimental validation with engineered transgenes shows that L2b, {MIRb} and {MIRc} elements drive nuclear enrichment of their host {lncRNA}. Together these data suggest a global role for exonic {TEs} in regulating the subcellular localisation of {lncRNAs}.},
	pages = {189753},
	journaltitle = {{bioRxiv}},
	author = {Carlevaro-Fita, Joana and Das, Monalisa and Polidori, Taisia and Navarro, Carmen and Johnson, Rory},
	date = {2017-10}
}

@article{amandio_hotair_2016,
	title = {Hotair Is Dispensible for Mouse Development},
	volume = {12},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1006232},
	abstract = {Despite the crucial importance of Hox genes functions during animal development, the mechanisms that control their transcription in time and space are not yet fully understood. In this context, it was proposed that Hotair, a {lncRNA} transcribed from within the {HoxC} cluster regulates Hoxd gene expression in trans, through the targeting of Polycomb and consecutive transcriptional repression. This activity was recently supported by the skeletal phenotype of mice lacking Hotair function. However, other loss of function alleles at this locus did not elicit the same effects. Here, we re-analyze the molecular and phenotypic consequences of deleting the Hotair locus in vivo. In contrast with previous findings, we show that deleting Hotair has no detectable effect on Hoxd genes expression in vivo. In addition, we were unable to observe any significant morphological alteration in mice lacking the Hotair transcript. However, we find a subtle impact of deleting the Hotair locus upon the expression of the neighboring Hoxc11 and Hoxc12 genes in cis. Our results do not support any substantial role for Hotair during mammalian development in vivo. Instead, they argue in favor of a {DNA}-dependent effect of the Hotair deletion upon the transcriptional landscape in cis.},
	pages = {e1006232},
	number = {12},
	journaltitle = {{PLOS} Genetics},
	author = {Amândio, Ana Rita and Necsulea, Anamaria and Joye, Elisabeth and Mascrez, Bénédicte and Duboule, Denis},
	editor = {Barsh, Gregory S.},
	date = {2016-12},
	pmid = {27977683}
}

@article{gerrard_integrative_2016,
	title = {An integrative transcriptomic atlas of organogenesis in human embryos},
	volume = {5},
	issn = {2050-084X},
	doi = {10.7554/eLife.15657},
	abstract = {{\textbackslash}textlessp{\textbackslash}{textgreaterHuman} organogenesis is when severe developmental abnormalities commonly originate. However, understanding this critical embryonic phase has relied upon inference from patient phenotypes and assumptions from in vitro stem cell models and non-human vertebrates. We report an integrated transcriptomic atlas of human organogenesis. By lineage-guided principal components analysis, we uncover novel relatedness of particular developmental genes across different organs and tissues and identified unique transcriptional codes which correctly predicted the cause of many congenital disorders. By inference, our model pinpoints co-enriched genes as new causes of developmental disorders such as cleft palate and congenital heart disease. The data revealed more than 6000 novel transcripts, over 90\% of which fulfil criteria as long non-coding {RNAs} correlated with the protein-coding genome over megabase distances. Taken together, we have uncovered cryptic transcriptional programs used by the human embryo and established a new resource for the molecular understanding of human organogenesis and its associated disorders.{\textbackslash}textless/p{\textbackslash}textgreater},
	pages = {e15657},
	journaltitle = {{eLife}},
	author = {Gerrard, Dave T and Berry, Andrew A and Jennings, Rachel E and Piper Hanley, Karen and Bobola, Nicoletta and Hanley, Neil A},
	date = {2016-08}
}

@article{li_physiological_2014,
	title = {Physiological roles of long noncoding {RNAs}: insight from knockout mice.},
	volume = {24},
	issn = {1879-3088},
	doi = {10.1016/j.tcb.2014.06.003},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are a pervasive and recently recognized class of genes. {lncRNAs} have been proposed to modulate gene expression and nuclear architecture, but their physiological functions are still largely unclear. Several recent efforts to inactivate {lncRNA} genes in mouse models have shed light on their functions. Different genetic strategies have yielded specific lessons about the roles of {lncRNA} transcription, the {lncRNA} transcript itself, and underlying sequence elements. Current results indicate important functions for {lncRNAs} in organ development, immunity, organismal viability, and in human diseases.},
	pages = {594--602},
	number = {10},
	journaltitle = {Trends in cell biology},
	author = {Li, Lingjie and Chang, Howard Y},
	date = {2014-10},
	pmid = {25022466}
}

@article{ponjavic_functionality_2007,
	title = {Functionality or transcriptional noise? Evidence for selection within long noncoding {RNAs}},
	volume = {17},
	issn = {10889051},
	doi = {10.1101/gr.6036807},
	abstract = {Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent "transcriptional noise." Here, we describe an analysis of 3122 long and full-length, noncoding {RNAs} ("{macroRNAs}") from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding {RNAs} is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the {macroRNAs}' promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1\%-5.5\%) in these {macroRNAs} is comparable to the density of exons within protein-coding transcripts (5.2\%). These {macroRNAs}, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these {macroRNAs}' functions.},
	pages = {556--565},
	number = {5},
	journaltitle = {Genome Research},
	author = {Ponjavic, Jasmina and Ponting, Chris P. and Lunter, Gerton},
	date = {2007-03},
	pmid = {17387145},
	keywords = {{DNA}, Animals, Conserved Sequence, Genetic, Humans, Mice, Promoter Regions, {RNA}, *Transcription, Databases, Untranslated/*genetics, {RNA} Splice Sites, *Selection, Consensus Sequence, Intergenic/genetics, Point Mutation, Rats}
}

@article{jan_formation_2011,
	title = {Formation, regulation and evolution of Caenorhabditis elegans 3'{UTRs}},
	volume = {469},
	issn = {0028-0836},
	doi = {10.1038/nature09616},
	abstract = {Post-transcriptional gene regulation frequently occurs through elements in {mRNA} 3' untranslated regions ({UTRs}). Although crucial roles for 3'{UTR}-mediated gene regulation have been found in Caenorhabditis elegans, most C. elegans genes have lacked annotated 3'{UTRs}. Here we describe a high-throughput method for reliable identification of polyadenylated {RNA} termini, and we apply this method, called poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans 3'{UTRs}. Compared to standard methods also recently applied to C. elegans {UTRs}, 3P-Seq identified 8,580 additional {UTRs} while excluding thousands of shorter {UTR} isoforms that do not seem to be authentic. Analysis of this expanded and corrected data set suggested that the high A/U content of C. elegans 3'{UTRs} facilitated genome compaction, because the elements specifying cleavage and polyadenylation, which are A/U rich, can more readily emerge in A/U-rich regions. Indeed, 30\% of the protein-coding genes have {mRNAs} with alternative, partially overlapping end regions that generate another 10,480 cleavage and polyadenylation sites that had gone largely unnoticed and represent potential evolutionary intermediates of progressive {UTR} shortening. Moreover, a third of the convergently transcribed genes use palindromic arrangements of bidirectional elements to specify {UTRs} with convergent overlap, which also contributes to genome compaction by eliminating regions between genes. Although nematode 3'{UTRs} have median length only one-sixth that of mammalian 3'{UTRs}, they have twice the density of conserved {microRNA} sites, in part because additional types of seed-complementary sites are preferentially conserved. These findings reveal the influence of cleavage and polyadenylation on the evolution of genome architecture and provide resources for studying post-transcriptional gene regulation.},
	pages = {97--101},
	number = {7328},
	journaltitle = {Nature},
	author = {Jan, Calvin H. and Friedman, Robin C. and Ruby, J. Graham and Bartel, David P.},
	date = {2011-01},
	pmid = {21085120}
}

@article{lopez_disparate_2006,
	title = {The disparate nature of "intergenic" polyadenylation sites.},
	volume = {12},
	issn = {1355-8382},
	doi = {10.1261/rna.136206},
	abstract = {The termination of mature eukaryotic {mRNAs} occurs at specific polyadenylation sites located downstream from stop codons in the 3'-untranslated region ({UTR}). An accurate delineation of these sites is essential for the study of 3'-{UTR}-based gene regulation and for the design of pertinent probes for transcriptome analysis. Although typical poly(A) sites are located between 0 and 2 kb from the stop codon, {EST} sequence analyses have identified sites located at unexpectedly long ranges (5-10 kb) in a number of genes. Here we perform a complete mapping of {EST} and full-length {cDNA} sequences on the mouse and human genome to observe putative poly(A) sites extending beyond annotated 3'-ends and into the intergenic regions. We introduce several quality parameters for poly(A) site prediction and train a classification tree to associate P-values to predicted sites. We observe a higher than background level of high-scoring sites up to 12-15 kb past the stop codon, both in human and mouse. This leads to an estimate of about 5000 human genes having unreported 3'-end extensions and about 3500 novel polyadenylated transcripts lying in present "intergenic" regions. These high-scoring, long-range poly(A) sites corresponding to novel transcripts and gene extensions should be incorporated into current human and mouse gene repositories.},
	pages = {1794--801},
	number = {10},
	journaltitle = {{RNA} (New York, N.Y.)},
	author = {Lopez, Fabrice and Granjeaud, Samuel and Ara, Takeshi and Ghattas, Badih and Gautheret, Daniel},
	date = {2006-10},
	pmid = {16931874},
	keywords = {{DNA}, Animals, Base Sequence, Genetic, Humans, Mice, {RNA}, Transcription, Computational Biology, Binding Sites/genetics, Codon, Expressed Sequence Tags, Intergenic/genetics, 3' Untranslated Regions/chemistry/genetics/metabol, Messenger/*chemistry/*genetics/metabolism, Terminator/genetics}
}

@article{ruiz-orera_long_2014,
	title = {Long non-coding {RNAs} as a source of new peptides},
	volume = {3},
	issn = {2050-084X},
	doi = {10.7554/eLife.03523},
	abstract = {{\textbackslash}textlessp{\textbackslash}{textgreaterDeep} transcriptome sequencing has revealed the existence of many transcripts that lack long or conserved open reading frames ({ORFs}) and which have been termed long non-coding {RNAs} ({lncRNAs}). The vast majority of {lncRNAs} are lineage-specific and do not yet have a known function. In this study, we test the hypothesis that they may act as a repository for the synthesis of new peptides. We find that a large fraction of the {lncRNAs} expressed in cells from six different species is associated with ribosomes. The patterns of ribosome protection are consistent with the translation of short peptides. {lncRNAs} show similar coding potential and sequence constraints than evolutionary young protein coding sequences, indicating that they play an important role in de novo protein evolution.{\textbackslash}textless/p{\textbackslash}textgreater},
	pages = {e03523},
	journaltitle = {{eLife}},
	author = {Ruiz-Orera, Jorge and Messeguer, Xavier and Subirana, Juan Antonio and Alba, M Mar},
	date = {2014-09},
	pmid = {25233276},
	keywords = {Sequence Analysis, Animals, Genetic, Humans, Mice, {RNA}, Gene Expression Profiling, Drosophila melanogaster, *Protein Biosynthesis, Arabidopsis, Evolution, Long Noncoding/*genetics/metabolism, Molecular, Open Reading Frames/*genetics, Peptides/*genetics, Proteomics, Ribosomes/genetics/metabolism, Saccharomyces cerevisiae, Selection, Species Specificity, Zebrafish}
}

@article{ahn_transcriptional_2017,
	title = {Transcriptional landscape of epithelial and immune cell populations revealed through {FACS}-seq of healthy human skin},
	volume = {7},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-01468-y},
	abstract = {Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, {CD}4+ T effector cells, and {CD}8+ T effector cells from healthy skin samples, followed by {RNA}-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant {CD}8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types.},
	pages = {1343},
	number = {1},
	journaltitle = {Scientific Reports},
	author = {Ahn, Richard S. and Taravati, Keyon and Lai, Kevin and Lee, Kristina M. and Nititham, Joanne and Gupta, Rashmi and Chang, David S. and Arron, Sarah T. and Rosenblum, Michael and Liao, Wilson},
	date = {2017-12}
}

@article{cabili_localization_2015,
	title = {Localization and abundance analysis of human {lncRNAs} at single-cell and single-molecule resolution.},
	volume = {16},
	issn = {1474-760X},
	doi = {10.1186/s13059-015-0586-4},
	abstract = {{BACKGROUND} Long non-coding {RNAs} ({lncRNAs}) have been implicated in diverse biological processes. In contrast to extensive genomic annotation of {lncRNA} transcripts, far fewer have been characterized for subcellular localization and cell-to-cell variability. Addressing this requires systematic, direct visualization of {lncRNAs} in single cells at single-molecule resolution. {RESULTS} We use single-molecule {RNA}-{FISH} to systematically quantify and categorize the subcellular localization patterns of a representative set of 61 {lncRNAs} in three different cell types. Our survey yields high-resolution quantification and stringent validation of the number and spatial positions of these {lncRNA}, with an {mRNA} set for comparison. Using this highly quantitative image-based dataset, we observe a variety of subcellular localization patterns, ranging from bright sub-nuclear foci to almost exclusively cytoplasmic localization. We also find that the low abundance of {lncRNAs} observed from cell population measurements cannot be explained by high expression in a small subset of 'jackpot' cells. Additionally, nuclear {lncRNA} foci dissolve during mitosis and become widely dispersed, suggesting these {lncRNAs} are not mitotic bookmarking factors. Moreover, we see that divergently transcribed {lncRNAs} do not always correlate with their cognate {mRNA}, nor do they have a characteristic localization pattern. {CONCLUSIONS} Our systematic, high-resolution survey of {lncRNA} localization reveals aspects of {lncRNAs} that are similar to {mRNAs}, such as cell-to-cell variability, but also several distinct properties. These characteristics may correspond to particular functional roles. Our study also provides a quantitative description of {lncRNAs} at the single-cell level and a universally applicable framework for future study and validation of {lncRNAs}.},
	pages = {20},
	journaltitle = {Genome biology},
	author = {Cabili, Moran N and Dunagin, Margaret C and {McClanahan}, Patrick D and Biaesch, Andrew and Padovan-Merhar, Olivia and Regev, Aviv and Rinn, John L and Raj, Arjun},
	date = {2015-01},
	pmid = {25630241}
}

@article{alam_promoter_2014,
	title = {Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding {RNA} and Protein-Coding Genes},
	volume = {9},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0109443},
	abstract = {Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding {RNA} ({lncRNA}) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human {lncRNA} and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor ({TF}) proteins that significantly favor {lncRNA}, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of {lncRNA} genes, including several distinct transcription factor binding sites ({TFBS}). Experimental {DNase} I hypersensitive site profiles are consistent with active configurations of these {lncRNA} {TFBS} sets in diverse human cell types. {TFBS} {ChIP}-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several {TFs} known to be directly regulated by {lncRNAs}, we find that their putative {TFBSs} are enriched at {lncRNA} promoters, suggesting that the {TFs} and the {lncRNAs} may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate {lncRNA} expression levels independently of {mRNA} levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed {lncRNA} genes is warranted in the future.},
	pages = {e109443},
	number = {10},
	journaltitle = {{PLoS} {ONE}},
	author = {Alam, Tanvir and Medvedeva, Yulia A. and Jia, Hui and Brown, James B. and Lipovich, Leonard and Bajic, Vladimir B.},
	editor = {Mantovani, Roberto},
	date = {2014-10},
	pmid = {25275320},
	keywords = {Human, Genetic, Genome, Humans, {RNA}, Transcription, *Promoter Regions, Binding Sites, Chromatin/genetics, Gene Expression Regulation, Long Noncoding/*genetics, Messenger/genetics, Protein Binding, Proteins/genetics, Transcription Factors/metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/ATINZD6W/Alam et al. - 2014 - Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.pdf:application/pdf}
}

@article{volders_update_2015,
	title = {An update on {LNCipedia}: a database for annotated human {lncRNA} sequences},
	volume = {43},
	issn = {1362-4962},
	doi = {10.1093/nar/gku1060},
	abstract = {The human genome is pervasively transcribed, producing thousands of non-coding {RNA} transcripts. The majority of these transcripts are long non-coding {RNAs} ({lncRNAs}) and novel {lncRNA} genes are being identified at rapid pace. To streamline these efforts, we created {LNCipedia}, an online repository of {lncRNA} transcripts and annotation. Here, we present {LNCipedia} 3.0 (http://www.lncipedia.org), the latest version of the publicly available human {lncRNA} database. Compared to the previous version of {LNCipedia}, the database grew over five times in size, gaining over 90,000 new {lncRNA} transcripts. Assessment of the protein-coding potential of {LNCipedia} entries is improved with state-of-the art methods that include large-scale reprocessing of publicly available proteomics data. As a result, a high-confidence set of {lncRNA} transcripts with low coding potential is defined and made available for download. In addition, a tool to assess {lncRNA} gene conservation between human, mouse and zebrafish has been implemented.},
	pages = {D174--D180},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Volders, Pieter-Jan and Verheggen, Kenneth and Menschaert, Gerben and Vandepoele, Klaas and Martens, Lennart and Vandesompele, Jo and Mestdagh, Pieter},
	date = {2015-01},
	pmid = {25378313}
}

@article{loewer_large_2010,
	title = {Large intergenic non-coding {RNA}-{RoR} modulates reprogramming of human induced pluripotent stem cells.},
	volume = {42},
	issn = {1546-1718},
	doi = {10.1038/ng.710},
	abstract = {The conversion of lineage-committed cells to induced pluripotent stem cells ({iPSCs}) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding {RNAs} ({lincRNAs}) that occurs upon derivation of human {iPSCs} and identify numerous {lincRNAs} whose expression is linked to pluripotency. Among these, we defined ten {lincRNAs} whose expression was elevated in {iPSCs} compared with embryonic stem cells, suggesting that their activation may promote the emergence of {iPSCs}. Supporting this, our results indicate that these {lincRNAs} are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such {lincRNA} ({lincRNA}-{RoR}) modulates reprogramming, thus providing a first demonstration for critical functions of {lincRNAs} in the derivation of pluripotent stem cells.},
	pages = {1113--7},
	number = {12},
	journaltitle = {Nature genetics},
	author = {Loewer, Sabine and Cabili, Moran N and Guttman, Mitchell and Loh, Yuin-Han and Thomas, Kelly and Park, In Hyun and Garber, Manuel and Curran, Matthew and Onder, Tamer and Agarwal, Suneet and Manos, Philip D and Datta, Sumon and Lander, Eric S and Schlaeger, Thorsten M and Daley, George Q and Rinn, John L},
	date = {2010-12},
	pmid = {21057500},
	keywords = {Genetic, Humans, {RNA}, Transcription, Gene Expression Regulation, Transcription Factors/metabolism, Cluster Analysis, Embryonic Stem Cells/metabolism, Fibroblasts/metabolism, Gene Knockdown Techniques, Genetic Loci/genetics, Induced Pluripotent Stem Cells/*metabolism, Nuclear Reprogramming/*genetics, Open Reading Frames/genetics, Reverse Transcriptase Polymerase Chain Reaction, Untranslated/genetics/*metabolism}
}

@article{adams_blueprint_2012,
	title = {{BLUEPRINT} to decode the epigenetic signature written in blood},
	volume = {30},
	issn = {1087-0156},
	doi = {10.1038/nbt.2153},
	pages = {224--226},
	number = {3},
	journaltitle = {Nature Biotechnology},
	author = {Adams, David and Altucci, Lucia and Antonarakis, Stylianos E and Ballesteros, Juan and Beck, Stephan and Bird, Adrian and Bock, Christoph and Boehm, Bernhard and Campo, Elias and Caricasole, Andrea and Dahl, Fredrik and Dermitzakis, Emmanouil T and Enver, Tariq and Esteller, Manel and Estivill, Xavier and Ferguson-Smith, Anne and Fitzgibbon, Jude and Flicek, Paul and Giehl, Claudia and Graf, Thomas and Grosveld, Frank and Guigo, Roderic and Gut, Ivo and Helin, Kristian and Jarvius, Jonas and Küppers, Ralf and Lehrach, Hans and Lengauer, Thomas and Lernmark, \{{\textbackslash}textbackslash\}{AAke} and Leslie, David and Loeffler, Markus and Macintyre, Elizabeth and Mai, Antonello and Martens, Joost {HA} and Minucci, Saverio and Ouwehand, Willem H and Pelicci, Pier Giuseppe and Pendeville, Hèléne and Porse, Bo and Rakyan, Vardhman and Reik, Wolf and Schrappe, Martin and Schübeler, Dirk and Seifert, Martin and Siebert, Reiner and Simmons, David and Soranzo, Nicole and Spicuglia, Salvatore and Stratton, Michael and Stunnenberg, Hendrik G and Tanay, Amos and Torrents, David and Valencia, Alfonso and Vellenga, Edo and Vingron, Martin and Walter, Jörn and Willcocks, Spike},
	date = {2012-03},
	pmid = {22398613}
}

@article{verheggen_noncoding_2017,
	title = {Noncoding after All: Biases in Proteomics Data Do Not Explain Observed Absence of {lncRNA} Translation Products.},
	volume = {16},
	issn = {1535-3907},
	doi = {10.1021/acs.jproteome.7b00085},
	abstract = {Over the past decade, long noncoding {RNAs} ({lncRNAs}) have emerged as novel functional entities of the eukaryotic genome. However, the scientific community remains divided over the amount of true noncoding transcripts among the large number of unannotated transcripts identified by recent large scale and deep {RNA}-sequencing efforts. Here, we systematically exclude possible technical reasons underlying the absence of {lncRNA}-encoded proteins in mass spectrometry data sets, strongly suggesting that the large majority of {lncRNAs} is indeed not translated.},
	pages = {2508--2515},
	number = {7},
	journaltitle = {Journal of proteome research},
	author = {Verheggen, Kenneth and Volders, Pieter-Jan and Mestdagh, Pieter and Menschaert, Gerben and Van Damme, Petra and Gevaert, Kris and Martens, Lennart and Vandesompele, Jo},
	date = {2017-07},
	pmid = {28534634}
}

@article{saini_genomic_2007,
	title = {Genomic analysis of human {microRNA} transcripts.},
	volume = {104},
	issn = {0027-8424},
	doi = {10.1073/pnas.0703890104},
	abstract = {{MicroRNAs} ({miRNAs}) are important genetic regulators of development, differentiation, growth, and metabolism. The mammalian genome encodes approximately 500 known {miRNA} genes. Approximately 50\% are expressed from non-protein-coding transcripts, whereas the rest are located mostly in the introns of coding genes. Intronic {miRNAs} are generally transcribed coincidentally with their host genes. However, the nature of the primary transcript of intergenic {miRNAs} is largely unknown. We have performed a large-scale analysis of transcription start sites, polyadenylation signals, {CpG} islands, {EST} data, transcription factor-binding sites, and expression ditag data surrounding intergenic {miRNAs} in the human genome to improve our understanding of the structure of their primary transcripts. We show that a significant fraction of primary transcripts of intergenic {miRNAs} are 3-4 kb in length, with clearly defined 5' and 3' boundaries. We provide strong evidence for the complete transcript structure of a small number of human {miRNAs}.},
	pages = {17719--24},
	number = {45},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	author = {Saini, Harpreet Kaur and Griffiths-Jones, Sam and Enright, Anton James},
	date = {2007-11},
	pmid = {17965236}
}

@article{ma_discovery_2014,
	title = {Discovery of human {sORF}-encoded polypeptides ({SEPs}) in cell lines and tissue.},
	volume = {13},
	issn = {1535-3907},
	doi = {10.1021/pr401280w},
	abstract = {The existence of nonannotated protein-coding human short open reading frames ({sORFs}) has been revealed through the direct detection of their {sORF}-encoded polypeptide ({SEP}) products. The discovery of novel {SEPs} increases the size of the genome and the proteome and provides insights into the molecular biology of mammalian cells, such as the prevalent usage of non-{AUG} start codons. Through modifications of the existing {SEP}-discovery workflow, we discover an additional 195 {SEPs} in K562 cells and extend this methodology to identify novel human {SEPs} in additional cell lines and human tissue for a final tally of 237 new {SEPs}. These results continue to expand the human genome and proteome and demonstrate that {SEPs} are a ubiquitous class of nonannotated polypeptides that require further investigation.},
	pages = {1757--65},
	number = {3},
	journaltitle = {Journal of proteome research},
	author = {Ma, Jiao and Ward, Carl C and Jungreis, Irwin and Slavoff, Sarah A and Schwaid, Adam G and Neveu, John and Budnik, Bogdan A and Kellis, Manolis and Saghatelian, Alan},
	date = {2014-03},
	pmid = {24490786}
}

@article{gong_lncrnas_2011,
	title = {{lncRNAs} transactivate {STAU}1-mediated {mRNA} decay by duplexing with 3' {UTRs} via Alu elements.},
	volume = {470},
	issn = {1476-4687},
	doi = {10.1038/nature09701},
	abstract = {Staufen 1 ({STAU}1)-mediated messenger {RNA} decay ({SMD}) involves the degradation of translationally active {mRNAs} whose 3'-untranslated regions (3' {UTRs}) bind to {STAU}1, a protein that binds to double-stranded {RNA}. Earlier studies defined the {STAU}1-binding site within {ADP}-ribosylation factor 1 ({ARF}1) {mRNA} as a 19-base-pair stem with a 100-nucleotide apex. However, we were unable to identify comparable structures in the 3' {UTRs} of other targets of {SMD}. Here we show that {STAU}1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3' {UTR} of an {SMD} target and another Alu element in a cytoplasmic, polyadenylated long non-coding {RNA} ({lncRNA}). An individual {lncRNA} can downregulate a subset of {SMD} targets, and distinct {lncRNAs} can downregulate the same {SMD} target. These are previously unappreciated functions of non-coding {RNAs} and Alu elements. Not all {mRNAs} that contain an Alu element in the 3' {UTR} are targeted for {SMD} even in the presence of a complementary {lncRNA} that targets other {mRNAs} for {SMD}. Most known trans-acting {RNA} effectors consist of fewer than 200 nucleotides, and these include small nucleolar {RNAs} and {microRNAs}. Our finding that the binding of {STAU}1 to {mRNAs} can be transactivated by {lncRNAs} uncovers an unexpected strategy that cells use to recruit proteins to {mRNAs} and mediate the decay of these {mRNAs}. We name these {lncRNAs} half-{STAU}1-binding site {RNAs} (1/2-{sbsRNAs}).},
	pages = {284--8},
	number = {7333},
	journaltitle = {Nature},
	author = {Gong, Chenguang and Maquat, Lynne E},
	date = {2011-02},
	pmid = {21307942},
	keywords = {Human, Humans, {RNA}, Binding Sites, Computational Biology, Software, *Nucleic Acid Conformation, *{RNA} Stability, 3' Untranslated Regions/*genetics, Alu Elements/*genetics, Base Pairing, Chromosomes, Cytoskeletal Proteins/*metabolism, Double-Stranded/chemistry/genetics/metabolism, Down-Regulation, {HeLa} Cells, Immunoprecipitation, Pair 11/genetics, Plasminogen Activator Inhibitor 1/genetics, Poly A/genetics/metabolism, {RNA}-Binding Proteins/genetics/*metabolism, Substrate Specificity, Trans-Activators/metabolism, Transcriptional Activation/*genetics, Untranslated/chemistry/*genetics/metabolism}
}

@article{zhang_ontological_2017,
	title = {Ontological function annotation of long non-coding {RNAs} through hierarchical multi-label classification},
	issn = {1367-4803},
	doi = {10.1093/bioinformatics/btx833},
	journaltitle = {Bioinformatics},
	author = {Zhang, Jingpu and Zhang, Zuping and Wang, Zixiang and Liu, Yuting and Deng, Lei},
	date = {2017-12}
}

@article{kelley_transposable_2014,
	title = {Transposable elements modulate human {RNA} abundance and splicing via specific {RNA}-protein interactions},
	volume = {15},
	issn = {1474-760X},
	doi = {10.1186/s13059-014-0537-5},
	abstract = {{BACKGROUND} Transposable elements ({TEs}) have significantly influenced the evolution of transcriptional regulatory networks in the human genome. Post-transcriptional regulation of human genes by {TE}-derived sequences has been observed in specific contexts, but has yet to be systematically and comprehensively investigated. Here, we study a collection of 75 {CLIP}-Seq experiments mapping the {RNA} binding sites for a diverse set of 51 human proteins to explore the role of {TEs} in post-transcriptional regulation of human {mRNAs} and {lncRNAs} via {RNA}-protein interactions. {RESULTS} We detect widespread interactions between {RNA} binding proteins ({RBPs}) and many families of {TE}-derived sequence in the {CLIP}-Seq data. Further, alignment coverage peaks on specific positions of the {TE} consensus sequences, illuminating a diversity of {TE}-specific {RBP} binding motifs. Evidence of binding and conservation of these motifs in the nonrepetitive transcriptome suggests that {TEs} have generally appropriated existing sequence preferences of the {RBPs}. Depletion assays for numerous {RBPs} show that {TE}-derived binding sites affect transcript abundance and splicing similarly to nonrepetitive sites. However, in a few cases the effect of {RBP} binding depends on the specific {TE} family bound; for example, the ubiquitously expressed {RBP} {HuR} confers transcript stability unless bound to an Alu element. {CONCLUSIONS} Our meta-analysis suggests a widespread role for {TEs} in shaping {RNA}-protein regulatory networks in the human genome.},
	pages = {537},
	number = {12},
	journaltitle = {Genome Biology},
	author = {Kelley, David R and Hendrickson, David G and Tenen, Danielle and Rinn, John L},
	date = {2014-12},
	pmid = {25572935}
}

@article{buske_triplex-inspector:_2013,
	title = {Triplex-Inspector: an analysis tool for triplex-mediated targeting of genomic loci},
	volume = {29},
	issn = {1460-2059},
	doi = {10.1093/bioinformatics/btt315},
	abstract = {{SUMMARY} At the heart of many modern biotechnological and therapeutic applications lies the need to target specific genomic loci with pinpoint accuracy. Although landmark experiments demonstrate technological maturity in manufacturing and delivering genetic material, the genomic sequence analysis to find suitable targets lags behind. We provide a computational aid for the sophisticated design of sequence-specific ligands and selection of appropriate targets, taking gene location and genomic architecture into account. {AVAILABILITY} Source code and binaries are downloadable from www.bioinformatics.org.au/triplexator/inspector. {CONTACT} t.bailey@uq.edu.au {SUPPLEMENTARY} {INFORMATION} Supplementary data are available at Bioinformatics online.},
	pages = {1895--1897},
	number = {15},
	journaltitle = {Bioinformatics},
	author = {Buske, Fabian A. and Bauer, Denis C. and Mattick, John S. and Bailey, Timothy L.},
	date = {2013-08},
	pmid = {23740745}
}

@article{kaewsapsak_live-cell_2017,
	title = {Live-cell mapping of organelle-associated {RNAs} via proximity biotinylation combined with protein-{RNA} crosslinking},
	volume = {6},
	issn = {2050-084X},
	doi = {10.7554/eLife.29224},
	abstract = {{\textbackslash}textlessp{\textbackslash}{textgreaterThe} spatial organization of {RNA} within cells is a crucial factor influencing a wide range of biological functions throughout all kingdoms of life. However, a general understanding of {RNA} localization has been hindered by a lack of simple, high-throughput methods for mapping the transcriptomes of subcellular compartments. Here, we develop such a method, termed {APEX}-{RIP}, which combines peroxidase-catalyzed, spatially restricted in situ protein biotinylation with {RNA}-protein chemical crosslinking. We demonstrate that, using a single protocol, {APEX}-{RIP} can isolate {RNAs} from a variety of subcellular compartments, including the mitochondrial matrix, nucleus, cytosol, and endoplasmic reticulum ({ER}), with specificity and sensitivity that rival or exceed those of conventional approaches. We further identify candidate {RNAs} localized to mitochondria-{ER} junctions and nuclear lamina, two compartments that are recalcitrant to classical biochemical purification. Since {APEX}-{RIP} is simple, versatile, and does not require special instrumentation, we envision its broad application in a variety of biological contexts.{\textbackslash}textless/p{\textbackslash}textgreater},
	journaltitle = {{eLife}},
	author = {Kaewsapsak, Pornchai and Shechner, David Michael and Mallard, William and Rinn, John L and Ting, Alice Y},
	date = {2017-12},
	pmid = {29239719}
}

@article{marin-bejar_human_2017,
	title = {The human {lncRNA} {LINC}-{PINT} inhibits tumor cell invasion through a highly conserved sequence element},
	volume = {18},
	issn = {1474760X},
	doi = {10.1186/s13059-017-1331-y},
	abstract = {{BACKGROUND} It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding {RNAs} ({lncRNAs}). Many {lncRNAs} show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of {lncRNA} dictate their function. {RESULTS} Here we characterize the function of the p53-regulated human {lncRNA} {LINC}-{PINT} in cancer. We find that {LINC}-{PINT} is downregulated in multiple types of cancer and acts as a tumor suppressor {lncRNA} by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in {LINC}-{PINT} that is essential for its function. This sequence mediates a specific interaction with {PRC}2, necessary for the {LINC}-{PINT}-dependent repression of a pro-invasion signature of genes regulated by the transcription factor {EGR}1. {CONCLUSIONS} Our findings support a conserved functional co-dependence between {LINC}-{PINT} and {PRC}2 and lead us to propose a new mechanism where the {lncRNA} regulates the availability of free {PRC}2 at the proximity of co-regulated genomic loci.},
	pages = {202},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Marín-Béjar, Oskar and Mas, Aina M. and González, Jovanna and Martinez, Dannys and Athie, Alejandro and Morales, Xabier and Galduroz, Mikel and Raimondi, Ivan and Grossi, Elena and Guo, Shuling and Rouzaut, Ana and Ulitsky, Igor and Huarte, Maite},
	date = {2017-12},
	pmid = {29078818}
}

@article{ezkurdia_multiple_2014,
	title = {Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes.},
	volume = {23},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddu309},
	abstract = {Determining the full complement of protein-coding genes is a key goal of genome annotation. The most powerful approach for confirming protein-coding potential is the detection of cellular protein expression through peptide mass spectrometry ({MS}) experiments. Here, we mapped peptides detected in seven large-scale proteomics studies to almost 60\% of the protein-coding genes in the {GENCODE} annotation of the human genome. We found a strong relationship between detection in proteomics experiments and both gene family age and cross-species conservation. Most of the genes for which we detected peptides were highly conserved. We found peptides for {\textbackslash}textgreater96\% of genes that evolved before bilateria. At the opposite end of the scale, we identified almost no peptides for genes that have appeared since primates, for genes that did not have any protein-like features or for genes with poor cross-species conservation. These results motivated us to describe a set of 2001 potential non-coding genes based on features such as weak conservation, a lack of protein features, or ambiguous annotations from major databases, all of which correlated with low peptide detection across the seven experiments. We identified peptides for just 3\% of these genes. We show that many of these genes behave more like non-coding genes than protein-coding genes and suggest that most are unlikely to code for proteins under normal circumstances. We believe that their inclusion in the human protein-coding gene catalogue should be revised as part of the ongoing human genome annotation effort.},
	pages = {5866--78},
	number = {22},
	journaltitle = {Human molecular genetics},
	author = {Ezkurdia, Iakes and Juan, David and Rodriguez, Jose Manuel and Frankish, Adam and Diekhans, Mark and Harrow, Jennifer and Vazquez, Jesus and Valencia, Alfonso and Tress, Michael L},
	date = {2014-11},
	pmid = {24939910}
}

@article{brannan_product_1990,
	title = {The product of the H19 gene may function as an {RNA}.},
	volume = {10},
	issn = {0270-7306},
	abstract = {The mouse H19 gene was identified as an abundant hepatic fetal-specific {mRNA} under the transcriptional control of a trans-acting locus termed raf. The protein this gene encoded was not apparent from an analysis of its nucleotide sequence, since the {mRNA} contained multiple translation termination signals in all three reading frames. As a means of assessing which of the 35 small open reading frames might be important to the function of the gene, the human H19 gene was cloned and sequenced. Comparison of the two homologs revealed no conserved open reading frame. Cellular fractionation showed that H19 {RNA} is cytoplasmic but not associated with the translational machinery. Instead, it is located in a particle with a sedimentation coefficient of approximately 28S. Despite the fact that it is transcribed by {RNA} polymerase {II} and is spliced and polyadenylated, we suggest that the H19 {RNA} is not a classical {mRNA}. Instead, the product of this unusual gene may be an {RNA} molecule.},
	pages = {28--36},
	number = {1},
	journaltitle = {Molecular and cellular biology},
	author = {Brannan, C I and Dees, E C and Ingram, R S and Tilghman, S M},
	date = {1990-01},
	pmid = {1688465},
	keywords = {{DNA}, Animals, Base Sequence, Humans, Mice, Proteins, {RNA}, Amino Acid Sequence, Chickens, Cytoplasm, Genes, Molecular Sequence Data, Protein Biosynthesis, Ribosomes, {RNA} Polymerase {II}, Transcription, Genetic},
	file = {Full Text:/home/jlagarde/Zotero/storage/VEB4G9MR/Brannan et al. - 1990 - The product of the H19 gene may function as an RNA.pdf:application/pdf}
}

@article{guttman_modular_2012,
	title = {Modular regulatory principles of large non-coding {RNAs}},
	volume = {482},
	issn = {0028-0836},
	doi = {10.1038/nature10887},
	abstract = {It is clear that {RNA} has a diverse set of functions and is more than just a messenger between gene and protein. The mammalian genome is extensively transcribed, giving rise to thousands of non-coding transcripts. Whether all of these transcripts are functional is debated, but it is evident that there are many functional large non-coding {RNAs} ({ncRNAs}). Recent studies have begun to explore the functional diversity and mechanistic role of these large {ncRNAs}. Here we synthesize these studies to provide an emerging model whereby large {ncRNAs} might achieve regulatory specificity through modularity, assembling diverse combinations of proteins and possibly {RNA} and {DNA} interactions.},
	pages = {339--346},
	number = {7385},
	journaltitle = {Nature},
	author = {Guttman, Mitchell and Rinn, John L.},
	date = {2012-02},
	pmid = {22337053},
	keywords = {{RNA}, Chromatin/genetics, Gene Expression Regulation, {RNA}-Binding Proteins/metabolism, Untranslated/analysis/genetics/*metabolism}
}

@article{jaffe_developmental_2014,
	title = {Developmental regulation of human cortex transcription and its clinical relevance at single base resolution},
	volume = {18},
	issn = {1097-6256},
	doi = {10.1038/nn.3898},
	abstract = {Transcriptome analysis of human brain provides fundamental insight into development and disease, but it largely relies on existing annotation. We sequenced transcriptomes of 72 prefrontal cortex samples across six life stages and identified 50,650 differentially expression regions ({DERs}) associated with developmental and aging, agnostic of annotation. While many {DERs} annotated to non-exonic sequence (41.1\%), most were similarly regulated in cytosolic {mRNA} extracted from independent samples. The {DERs} were developmentally conserved across 16 brain regions and in the developing mouse cortex, and were expressed in diverse cell and tissue types. The {DERs} were further enriched for active chromatin marks and clinical risk for neurodevelopmental disorders such as schizophrenia. Lastly, we demonstrate quantitatively that these {DERs} associate with a changing neuronal phenotype related to differentiation and maturation. These data show conserved molecular signatures of transcriptional dynamics across brain development, have potential clinical relevance and highlight the incomplete annotation of the human brain transcriptome.},
	pages = {154--161},
	number = {1},
	journaltitle = {Nature Neuroscience},
	author = {Jaffe, Andrew E and Shin, Jooheon and Collado-Torres, Leonardo and Leek, Jeffrey T and Tao, Ran and Li, Chao and Gao, Yuan and Jia, Yankai and Maher, Brady J and Hyde, Thomas M and Kleinman, Joel E and Weinberger, Daniel R},
	date = {2014-12},
	pmid = {25501035}
}

@article{mackowiak_extensive_2015,
	title = {Extensive identification and analysis of conserved small {ORFs} in animals},
	volume = {16},
	issn = {1474-760X},
	doi = {10.1186/s13059-015-0742-x},
	abstract = {{BACKGROUND} There is increasing evidence that transcripts or transcript regions annotated as non-coding can harbor functional short open reading frames ({sORFs}). Loss-of-function experiments have identified essential developmental or physiological roles for a few of the encoded peptides (micropeptides), but genome-wide experimental or computational identification of functional {sORFs} remains challenging. {RESULTS} Here, we expand our previously developed method and present results of an integrated computational pipeline for the identification of conserved {sORFs} in human, mouse, zebrafish, fruit fly, and the nematode C. elegans. Isolating specific conservation signatures indicative of purifying selection on amino acid (rather than nucleotide) sequence, we identify about 2,000 novel small {ORFs} located in the untranslated regions of canonical {mRNAs} or on transcripts annotated as non-coding. Predicted {sORFs} show stronger conservation signatures than those identified in previous studies and are sometimes conserved over large evolutionary distances. The encoded peptides have little homology to known proteins and are enriched in disordered regions and short linear interaction motifs. Published ribosome profiling data indicate translation of more than 100 novel {sORFs}, and mass spectrometry data provide evidence for more than 70 novel candidates. {CONCLUSIONS} Taken together, we identify hundreds of previously unknown conserved {sORFs} in major model organisms. Our computational analyses and integration with experimental data show that these {sORFs} are expressed, often translated, and sometimes widely conserved, in some cases even between vertebrates and invertebrates. We thus provide an integrated resource of putatively functional micropeptides for functional validation in vivo.},
	pages = {179},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Mackowiak, Sebastian D. and Zauber, Henrik and Bielow, Chris and Thiel, Denise and Kutz, Kamila and Calviello, Lorenzo and Mastrobuoni, Guido and Rajewsky, Nikolaus and Kempa, Stefan and Selbach, Matthias and Obermayer, Benedikt},
	date = {2015-12},
	pmid = {26364619},
	keywords = {3' Untranslated Regions, Animals, Conserved Sequence, Humans, Mice, Exons, *Open Reading Frames, Amino Acid Motifs, Amino Acid Sequence, Codon, Peptides/chemistry, Protein Biosynthesis, Sequence Alignment, Terminator}
}

@article{li_starbase_2014,
	title = {{starBase} v2.0: decoding {miRNA}-{ceRNA}, {miRNA}-{ncRNA} and protein–{RNA} interaction networks from large-scale {CLIP}-Seq data},
	volume = {42},
	issn = {0305-1048},
	doi = {10.1093/nar/gkt1248},
	pages = {D92--D97},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Li, Jun-Hao and Liu, Shun and Zhou, Hui and Qu, Liang-Hu and Yang, Jian-Hua},
	date = {2014-01}
}

@article{hezroni_principles_2015,
	title = {Principles of Long Noncoding {RNA} Evolution Derived from Direct Comparison of Transcriptomes in 17 Species},
	volume = {11},
	issn = {22111247},
	doi = {10.1016/j.celrep.2015.04.023},
	abstract = {The inability to predict long noncoding {RNAs} from genomic sequence has impeded the use of comparative genomics for studying their biology. Here, we develop methods that use {RNA} sequencing ({RNA}-seq) data to annotate the transcriptomes of 16 vertebrates and the echinoid sea urchin, uncovering thousands of previously unannotated genes, most of which produce long intervening noncoding {RNAs} ({lincRNAs}). Although in each species, {\textbackslash}textgreater70\% of {lincRNAs} cannot be traced to homologs in species that diverged {\textbackslash}textgreater50 million years ago, thousands of human {lincRNAs} have homologs with similar expression patterns in other species. These homologs share short, 5'-biased patches of sequence conservation nested in exonic architectures that have been extensively rewired, in part by transposable element exonization. Thus, over a thousand human {lincRNAs} are likely to have conserved functions in mammals, and hundreds beyond mammals, but those functions require only short patches of specific sequences and can tolerate major changes in gene architecture.},
	pages = {1110--1122},
	number = {7},
	journaltitle = {Cell Reports},
	author = {Hezroni, Hadas and Koppstein, David and Schwartz, Matthew G. and Avrutin, Alexandra and Bartel, David P. and Ulitsky, Igor},
	date = {2015-05},
	pmid = {25959816},
	keywords = {Transcriptome, Sequence Analysis, Base Sequence, Conserved Sequence, Humans, {RNA}, Long Noncoding/*genetics, *Evolution, Conserved Sequence/genetics, Molecular, Transcriptome/*genetics, Evolution, Molecular, {RNA}, Long Noncoding, Sequence Analysis, {RNA}},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/DWY4U99V/Hezroni et al. - 2015 - Principles of long noncoding RNA evolution derived.pdf:application/pdf}
}

@article{nellore_human_2016,
	title = {Human splicing diversity and the extent of unannotated splice junctions across human {RNA}-seq samples on the Sequence Read Archive.},
	volume = {17},
	issn = {1474-760X},
	doi = {10.1186/s13059-016-1118-6},
	abstract = {{BACKGROUND} Gene annotations, such as those in {GENCODE}, are derived primarily from alignments of spliced {cDNA} sequences and protein sequences. The impact of {RNA}-seq data on annotation has been confined to major projects like {ENCODE} and Illumina Body Map 2.0. {RESULTS} We aligned 21,504 Illumina-sequenced human {RNA}-seq samples from the Sequence Read Archive ({SRA}) to the human genome and compared detected exon-exon junctions with junctions in several recent gene annotations. We found 56,861 junctions (18.6\%) in at least 1000 samples that were not annotated, and their expression associated with tissue type. Junctions well expressed in individual samples tended to be annotated. Newer samples contributed few novel well-supported junctions, with the vast majority of detected junctions present in samples before 2013. We compiled junction data into a resource called intropolis available at http://intropolis.rail.bio . We used this resource to search for a recently validated isoform of the {ALK} gene and characterized the potential functional implications of unannotated junctions with publicly available {TRAP}-seq data. {CONCLUSIONS} Considering only the variation contained in annotation may suffice if an investigator is interested only in well-expressed transcript isoforms. However, genes that are not generally well expressed and nonetheless present in a small but significant number of samples in the {SRA} are likelier to be incompletely annotated. The rate at which evidence for novel junctions has been added to the {SRA} has tapered dramatically, even to the point of an asymptote. Now is perhaps an appropriate time to update incomplete annotations to include splicing present in the now-stable snapshot provided by the {SRA}.},
	pages = {266},
	number = {1},
	journaltitle = {Genome biology},
	author = {Nellore, Abhinav and Jaffe, Andrew E and Fortin, Jean-Philippe and Alquicira-Hernández, José and Collado-Torres, Leonardo and Wang, Siruo and Phillips, Robert A and Karbhari, Nishika and Hansen, Kasper D and Langmead, Ben and Leek, Jeffrey T},
	date = {2016},
	pmid = {28038678},
	file = {Full Text:/home/jlagarde/Zotero/storage/NWRWGFE4/Nellore et al. - 2016 - Human splicing diversity and the extent of unannot.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/83S5HALN/s13059-016-1118-6.html:text/html}
}

@article{kapranov_large-scale_2002,
	title = {Large-Scale Transcriptional Activity in Chromosomes 21 and 22},
	volume = {296},
	issn = {00368075},
	doi = {10.1126/science.1068597},
	abstract = {The sequences of the human chromosomes 21 and 22 indicate that there are approximately 770 well-characterized and predicted genes. In this study, empirically derived maps identifying active areas of {RNA} transcription on these chromosomes have been constructed with the use of cytosolic polyadenylated {RNA} obtained from 11 human cell lines. Oligonucleotide arrays containing probes spaced on average every 35 base pairs along these chromosomes were used. When compared with the sequence annotations available for these chromosomes, it is noted that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized exons.},
	pages = {916--919},
	number = {5569},
	journaltitle = {Science},
	author = {Kapranov, P. and Cawley, Simon E and Drenkow, Jorg and Bekiranov, Stefan and Strausberg, Robert L and Fodor, Stephen P A and Gingeras, Thomas R},
	date = {2002-05},
	pmid = {11988577},
	keywords = {Humans, Computational Biology, Exons, Oligonucleotide Array Sequence Analysis, Cell Nucleus, Cell Line, Oligonucleotide Probes, Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, {RNA}, Messenger, Transcription, Genetic, Contig Mapping, Physical Chromosome Mapping, {DNA}, Complementary, Tumor Cells, Cultured, Cytosol, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 22, {DiGeorge} Syndrome}
}

@article{cabili_integrative_2011,
	title = {Integrative annotation of human large intergenic noncoding {RNAs} reveals global properties and specific subclasses},
	volume = {25},
	issn = {08909369},
	doi = {10.1101/gad.17446611},
	abstract = {Large intergenic noncoding {RNAs} ({lincRNAs}) are emerging as key regulators of diverse cellular processes. Determining the function of individual {lincRNAs} remains a challenge. Recent advances in {RNA} sequencing ({RNA}-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of {\textbackslash}textgreater8000 human {lincRNAs}. Our catalog unifies previously existing annotation sources with transcripts we assembled from {RNA}-seq data collected from ∼4 billion {RNA}-seq reads across 24 tissues and cell types. We characterize each {lincRNA} by a panorama of {\textbackslash}textgreater30 properties, including sequence, structural, transcriptional, and orthology features. We found that {lincRNA} expression is strikingly tissue-specific compared with coding genes, and that {lincRNAs} are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short {ORFs} and may serve as either {lincRNAs} or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human {lincRNAs} reveals the global properties of {lincRNAs} and will facilitate experimental studies and further functional classification of these genes.},
	pages = {1915--1927},
	number = {18},
	journaltitle = {Genes and Development},
	author = {Cabili, Moran and Trapnell, Cole and Goff, Loyal and Koziol, Magdalena and Tazon-Vega, Barbara and Regev, Aviv and Rinn, John L.},
	date = {2011-09},
	pmid = {21890647},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Genetic/genetics, Nucleic Acid, Alternative Splicing, Enhancer Elements, Genes, Molecular Sequence Annotation, Molecular Sequence Annotation/*methods, Overlapping, Sequence Homology, Untranslated/classification/*genetics, Enhancer Elements, Genetic, {RNA}, Untranslated, Sequence Homology, Nucleic Acid, Genes, Overlapping},
	file = {Full Text:/home/jlagarde/Zotero/storage/KM972KKM/Cabili et al. - 2011 - Integrative annotation of human large intergenic n.pdf:application/pdf}
}

@article{gtex_consortium_genotype-tissue_2013,
	title = {The Genotype-Tissue Expression ({GTEx}) project.},
	volume = {45},
	issn = {1546-1718},
	doi = {10.1038/ng.2653},
	abstract = {Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression ({GTEx}) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.},
	pages = {580--5},
	number = {6},
	journaltitle = {Nature genetics},
	author = {{GTEx} Consortium, The {GTEx}},
	date = {2013-06},
	pmid = {23715323}
}

@article{tan_cis_2017,
	title = {cis -Acting Complex-Trait-Associated {lincRNA} Expression Correlates with Modulation of Chromosomal Architecture},
	volume = {18},
	issn = {22111247},
	doi = {10.1016/j.celrep.2017.02.009},
	abstract = {Intergenic long noncoding {RNAs} ({lincRNAs}) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant {lincRNAs} ({TR}-{lincRNAs}) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain ({TAD}) boundaries provide evidence that {TR}-{lincRNAs} likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between {TR}-{lincRNA} abundance and intra-{TAD} {DNA}-{DNA} contacts. Our results provide insights into the molecular mode of action by which {TR}-{lincRNAs} contribute to complex human traits.},
	pages = {2280--2288},
	number = {9},
	journaltitle = {Cell Reports},
	author = {Tan, Jennifer Yihong and Smith, Adam Alexander Thil and Ferreira da Silva, Maria and Matthey-Doret, Cyril and Rueedi, Rico and Sönmez, Reyhan and Ding, David and Kutalik, Zoltán and Bergmann, Sven and Marques, Ana Claudia},
	date = {2017-02},
	pmid = {28249171}
}

@article{brockdorff_product_1992,
	title = {The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved {ORF} and located in the nucleus.},
	volume = {71},
	issn = {0092-8674},
	abstract = {The Xist gene maps to the X inactivation center region in both mouse and human, and previous analysis of the 3' end of the gene has demonstrated inactive X-specific expression, suggesting a possible role in X inactivation. We have now analyzed the entire mouse Xist gene. The mature inactive X-specific transcript is 15 kb in length and contains no conserved {ORF}. The Xist sequence contains a number of regions comprised of tandem repeats. Comparison with the human {XIST} gene demonstrates significant conservation of sequence and gene structure. Xist {RNA} is not associated with the translational machinery of the cell and is located almost exclusively in the nucleus. Together with conservation of inactive X-specific expression, these findings support a role for Xist in X inactivation, possibly as a functional {RNA} or as a chromatin organizer region.},
	pages = {515--26},
	number = {3},
	journaltitle = {Cell},
	author = {Brockdorff, N and Ashworth, A and Kay, G F and {McCabe}, V M and Norris, D P and Cooper, P J and Swift, S and Rastan, S},
	date = {1992-10},
	pmid = {1423610},
	keywords = {Animals, Base Sequence, Mice, Cell Nucleus, Gene Library, Molecular Sequence Data, Sequence Alignment, Transcription Factors, X Chromosome, {RNA}, Long Noncoding, {RNA}, Messenger, {RNA}, Untranslated, Repetitive Sequences, Nucleic Acid, Models, Biological, Dosage Compensation, Genetic}
}

@article{pruitt_refseq:_2014,
	title = {{RefSeq}: an update on mammalian reference sequences},
	volume = {42},
	issn = {0305-1048},
	doi = {10.1093/nar/gkt1114},
	abstract = {The National Center for Biotechnology Information ({NCBI}) Reference Sequence ({RefSeq}) database is a collection of annotated genomic, transcript and protein sequence records derived from data in public sequence archives and from computation, curation and collaboration (http://www.ncbi.nlm.nih.gov/refseq/). We report here on growth of the mammalian and human subsets, changes to {NCBI}'s eukaryotic annotation pipeline and modifications affecting transcript and protein records. Recent changes to {NCBI}'s eukaryotic genome annotation pipeline provide higher throughput, and the addition of {RNAseq} data to the pipeline results in a significant expansion of the number of transcripts and novel exons annotated on mammalian {RefSeq} genomes. Recent annotation changes include reporting supporting evidence for transcript records, modification of exon feature annotation and the addition of a structured report of gene and sequence attributes of biological interest. We also describe a revised protein annotation policy for alternatively spliced transcripts with more divergent predicted proteins and we summarize the current status of the {RefSeqGene} project.},
	pages = {D756--D763},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Pruitt, Kim D. and Brown, Garth R. and Hiatt, Susan M. and Thibaud-Nissen, Françoise and Astashyn, Alexander and Ermolaeva, Olga and Farrell, Catherine M. and Hart, Jennifer and Landrum, Melissa J. and {McGarvey}, Kelly M. and Murphy, Michael R. and O'Leary, Nuala A. and Pujar, Shashikant and Rajput, Bhanu and Rangwala, Sanjida H. and Riddick, Lillian D. and Shkeda, Andrei and Sun, Hanzhen and Tamez, Pamela and Tully, Raymond E. and Wallin, Craig and Webb, David and Weber, Janet and Wu, Wendy and {DiCuccio}, Michael and Kitts, Paul and Maglott, Donna R. and Murphy, Terence D. and Ostell, James M.},
	date = {2014-01},
	pmid = {24259432}
}

@article{khalil_many_2009,
	title = {Many human large intergenic noncoding {RNAs} associate with chromatin-modifying complexes and affect gene expression},
	volume = {106},
	issn = {0027-8424},
	doi = {10.1073/pnas.0904715106},
	pages = {11667--11672},
	number = {28},
	journaltitle = {Proceedings of the National Academy of Sciences},
	author = {Khalil, Ahmad M. and Guttman, Mitchell and Huarte, Maite and Garber, Manuel and Raj, Arjun and Rivea Morales, Dianali and Thomas, Kelly and Presser, Aviva and Bernstein, Bradley E. and van Oudenaarden, Alexander and Regev, Aviv and Lander, Eric S. and Rinn, John L.},
	date = {2009-07},
	keywords = {Genetic, Humans, {RNA}, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Chromatin/*genetics, *Epigenesis, *Models, Gene Expression Regulation/*genetics, Polycomb-Group Proteins, Repressor Proteins/genetics/*metabolism, Untranslated/*genetics/*metabolism}
}

@article{ounzain_carmen_2015,
	title = {{CARMEN}, a human super enhancer-associated long noncoding {RNA} controlling cardiac specification, differentiation and homeostasis.},
	volume = {89},
	issn = {1095-8584},
	doi = {10.1016/j.yjmcc.2015.09.016},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell ({CPC}) remain unexplored. To characterize the long noncoding transcriptome during human {CPC} cardiac differentiation, we profiled the {lncRNA} transcriptome in {CPCs} isolated from the human fetal heart and identified 570 {lncRNAs} that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers ({SE}) with their expression being correlated with proximal cardiac genes. One of the most upregulated {lncRNAs} was a {SE}-associated {lncRNA} that was named {CARMEN}, ({CAR})diac (M)esoderm (E)nhancer-associated (N)oncoding {RNA}. {CARMEN} exhibits {RNA}-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, {CARMEN} interacts with {SUZ}12 and {EZH}2, two components of the polycomb repressive complex 2 ({PRC}2). We demonstrate that {CARMEN} knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of {MIR}-143 and -145 expression, two {microRNAs} located proximal to the enhancer sequences. Importantly, {CARMEN} expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that {CARMEN} is a crucial regulator of cardiac cell differentiation and homeostasis.},
	pages = {98--112},
	issue = {Pt A},
	journaltitle = {Journal of molecular and cellular cardiology},
	author = {Ounzain, Samir and Micheletti, Rudi and Arnan, Carme and Plaisance, Isabelle and Cecchi, Dario and Schroen, Blanche and Reverter, Ferran and Alexanian, Michael and Gonzales, Christine and Ng, Shi Yan and Bussotti, Giovanni and Pezzuto, Iole and Notredame, Cedric and Heymans, Stephane and Guigó, Roderic and Johnson, Rory and Pedrazzini, Thierry},
	date = {2015-12},
	pmid = {26423156}
}

@article{lanzos_discovery_2017,
	title = {Discovery of Cancer Driver Long Noncoding {RNAs} across 1112 Tumour Genomes: New Candidates and Distinguishing Features},
	volume = {7},
	issn = {20452322},
	doi = {10.1038/srep41544},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) represent a vast unexplored genetic space that may hold missing drivers of tumourigenesis, but few such "driver {lncRNAs}" are known. Until now, they have been discovered through changes in expression, leading to problems in distinguishing between causative roles and passenger effects. We here present a different approach for driver {lncRNA} discovery using mutational patterns in tumour {DNA}. Our pipeline, {ExInAtor}, identifies genes with excess load of somatic single nucleotide variants ({SNVs}) across panels of tumour genomes. Heterogeneity in mutational signatures between cancer types and individuals is accounted for using a simple local trinucleotide background model, which yields high precision and low computational demands. We use {ExInAtor} to predict drivers from the {GENCODE} annotation across 1112 entire genomes from 23 cancer types. Using a stratified approach, we identify 15 high-confidence candidates: 9 novel and 6 known cancer-related genes, including {MALAT}1, {NEAT}1 and {SAMMSON}. Both known and novel driver {lncRNAs} are distinguished by elevated gene length, evolutionary conservation and expression. We have presented a first catalogue of mutated {lncRNA} genes driving cancer, which will grow and improve with the application of {ExInAtor} to future tumour genome projects.},
	pages = {41544},
	journaltitle = {Scientific Reports},
	author = {Lanzós, Andrés and Carlevaro-Fita, Joana and Mularoni, Loris and Reverter, Ferran and Palumbo, Emilio and Guigó, Roderic and Johnson, Rory},
	date = {2017-01},
	pmid = {28128360}
}

@article{hansen_biases_2010,
	title = {Biases in Illumina transcriptome sequencing caused by random hexamer priming},
	volume = {38},
	issn = {1362-4962},
	doi = {10.1093/nar/gkq224},
	pages = {e131--e131},
	number = {12},
	journaltitle = {Nucleic Acids Research},
	author = {Hansen, Kasper D. and Brenner, Steven E. and Dudoit, Sandrine},
	date = {2010-07}
}

@article{mas-ponte_lncatlas_2017,
	title = {{LncATLAS} database for subcellular localisation of long noncoding {RNAs}.},
	issn = {1469-9001},
	doi = {10.1261/rna.060814.117},
	abstract = {The subcellular localisation of long noncoding {RNAs} ({lncRNAs}) holds valuable clues to their molecular function. However, measuring localisation of newly-discovered {lncRNAs} involves time-consuming and costly experimental methods. We have created "{LncATLAS}", a comprehensive resource of {lncRNA} localisation in human cells based on {RNA}-sequencing datasets. Altogether, 6,768 {GENCODE}-annotated {lncRNAs} are represented across various compartments of 15 cell lines. We introduce "Relative concentration index" ({RCI}) as a useful measure of localisation derived from ensemble {RNAseq} measurements. {LncATLAS} is accessible through an intuitive and informative webserver, from which {lncRNAs} of interest are accessed using identifiers or names. Localisation is presented across cell types and organelles, and may be compared to the distribution of all other genes. Publication-quality figures and raw data tables are automatically generated with each query, and the entire dataset is also available to download. {LncATLAS} makes {lncRNA} subcellular localisation data available to the widest possible number of researchers. It is available at lncatlas.crg.eu.},
	pages = {rna.060814.117},
	journaltitle = {{RNA} (New York, N.Y.)},
	author = {Mas-Ponte, David and Carlevaro-Fita, Joana and Palumbo, Emilio and Hermoso Pulido, Toni and Guigo, Roderic and Johnson, Rory},
	date = {2017-04},
	pmid = {28386015},
	keywords = {{lncRNA}, Humans, Computational Biology, Cell Nucleus, Software, Cytoplasm, Molecular Sequence Annotation, Databases, Genetic, {RNA}, Long Noncoding, Sequence Analysis, {RNA}, chromatin, cytoplasm, long noncoding {RNA}, nucleus, subcellular localization},
	file = {Full Text:/home/jlagarde/Zotero/storage/ZDW2MKUZ/Mas-Ponte et al. - 2017 - LncATLAS database for subcellular localization of .pdf:application/pdf}
}

@article{lee_c._1993,
	title = {The C. elegans heterochronic gene lin-4 encodes small {RNAs} with antisense complementarity to lin-14.},
	volume = {75},
	issn = {0092-8674},
	abstract = {lin-4 is essential for the normal temporal control of diverse postembryonic developmental events in C. elegans. lin-4 acts by negatively regulating the level of {LIN}-14 protein, creating a temporal decrease in {LIN}-14 protein starting in the first larval stage (L1). We have cloned the C. elegans lin-4 locus by chromosomal walking and transformation rescue. We used the C. elegans clone to isolate the gene from three other Caenorhabditis species; all four Caenorhabditis clones functionally rescue the lin-4 null allele of C. elegans. Comparison of the lin-4 genomic sequence from these four species and site-directed mutagenesis of potential open reading frames indicated that lin-4 does not encode a protein. Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region ({UTR}) of lin-14 {mRNA}, suggesting that lin-4 regulates lin-14 translation via an antisense {RNA}-{RNA} interaction.},
	pages = {843--54},
	number = {5},
	journaltitle = {Cell},
	author = {Lee, R C and Feinbaum, R L and Ambros, V},
	date = {1993-12},
	pmid = {8252621}
}

@article{zhu_reverse_2001,
	title = {Reverse transcriptase template switching: a {SMART} approach for full-length {cDNA} library construction.},
	volume = {30},
	issn = {0736-6205},
	abstract = {Here, we describe a fast, simple method for constructing full-length {cDNA} libraries using {SMART} technology. This novel procedure uses the template-switching activity of Moloney murine leukemia virus ({MMLV}) reverse transcriptase to synthesize and anchor first-strand {cDNA} in one step. Following reverse transcription, three cycles of {PCR} are performed using a modified oligo({dT}) primer and an anchor primer to enrich the {cDNA} population for full-length sequences. Starting with 1 microgram human skeletal muscle poly(A)+ {RNA}, a {cDNA} library was constructed that contained 3 x 10(6) independent clones with an average insert size of 2 kb. Sequence analysis of 172 randomly selected clones showed that 77\% of {cDNA} clones corresponding to known genes contained intact open reading frames. The average length of complete open reading frames was 2.4 kb. Furthermore, 86\% of the full-length clones retained longer 5' {UTR} sequences than the longest 5' end deposited in the {GenBank} database. {cDNA} libraries generated using this method will be useful for accelerating the collection of {mRNA} 5' end sequence information, which is currently very limited in {GenBank}.},
	pages = {892--7},
	number = {4},
	journaltitle = {{BioTechniques}},
	author = {Zhu, Y Y and Machleder, E M and Chenchik, A and Li, R and Siebert, P D},
	date = {2001-04},
	pmid = {11314272}
}

@article{haerty_unexpected_2015,
	title = {Unexpected selection to retain high {GC} content and splicing enhancers within exons of multiexonic {lncRNA} loci},
	volume = {21},
	issn = {1355-8382},
	doi = {10.1261/rna.047324.114},
	abstract = {If sequencing was possible only for genomes, and not for {RNAs} or proteins, then functional protein-coding exons would be recognizable by their unusual patterns of nucleotide composition, specifically a high {GC} content across the body of exons, and an unusual nucleotide content near their edges. {RNAs} and proteins can, of course, be sequenced but the extent of functionality of intergenic long noncoding {RNAs} ({lncRNAs}) remains under question owing to their low nucleotide conservation. Inspired by the nucleotide composition patterns of protein-coding exons, we sought evidence for functionality across {lncRNA} loci from diverse species. We found that such patterns across multiexonic {lncRNA} loci mirror those of proteincoding genes, although to a lesser degree: Specifically, compared with introns, {lncRNA} exons are {GC} rich. Additionally we report evidence for the action of purifying selection to preserve exonic splicing enhancers within human multiexonic {lncRNAs} and nucleotide composition in fruit fly {lncRNAs}. Our findings provide evidence for selection for more efficient rates of transcription and splicing within {lncRNA} loci. Despite only a minor proportion of their {RNA} bases being constrained, multiexonic intergenic {lncRNAs} appear to require accurate splicing of their exons to transact their function.},
	pages = {320--332},
	number = {3},
	journaltitle = {{RNA}},
	author = {Haerty, Wilfried and Ponting, Chris P.},
	date = {2015-03},
	pmid = {25589248}
}

@article{bruford_devising_2015,
	title = {Devising a Consensus Framework for Validation of Novel Human Coding Loci.},
	volume = {14},
	issn = {1535-3907},
	doi = {10.1021/acs.jproteome.5b00688},
	abstract = {A report on the Wellcome Trust retreat on devising a consensus framework for the validation of novel human protein coding loci, held in Hinxton, U.K., May 11-13, 2015.},
	pages = {4945--8},
	number = {12},
	journaltitle = {Journal of proteome research},
	author = {Bruford, Elspeth A and Lane, Lydie and Harrow, Jennifer},
	date = {2015-12},
	pmid = {26367542}
}

@article{shao_scallop_2017,
	title = {Scallop Enables Accurate Assembly Of Transcripts Through Phasing-Preserving Graph Decomposition},
	doi = {10.1101/123612},
	abstract = {We introduce Scallop, an accurate, reference-based transcript assembler for {RNA}-seq data. Scallop significantly improves reconstruction of multi-exon and lowly expressed transcripts. On 10 human samples aligned with {STAR}, Scallop produces (on average) 35.7\% and 37.5\% more correct multi-exon transcripts than two leading transcript assemblers, {StringTie} and {TransComb}, respectively. For transcripts expressed at low levels in the same samples, Scallop assembles 65.2\% and 50.2\% more correct multi-exon transcripts than {StringTie} and {TransComb}, respectively. Scallop obtains this improvement through a novel algorithm that we prove preserves all phasing paths from reads (including paired-end reads), while also producing a parsimonious set of transcripts and minimizing coverage deviation.},
	pages = {123612},
	journaltitle = {doi.org},
	author = {Shao, Mingfu and Kingsford, Carl},
	date = {2017-04}
}

@article{kornienko_long_2016,
	title = {Long non-coding {RNAs} display higher natural expression variation than protein-coding genes in healthy humans.},
	volume = {17},
	issn = {1474-760X},
	doi = {10.1186/s13059-016-0873-8},
	abstract = {{BACKGROUND} Long non-coding {RNAs} ({lncRNAs}) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported {lncRNAs}, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to {mRNAs}. An unexplored factor potentially confounding {lncRNA} identification is inter-individual expression variability. Here, we characterize {lncRNA} natural expression variability in human primary granulocytes. {RESULTS} We annotate granulocyte {lncRNAs} and {mRNAs} in {RNA}-seq data from 10 healthy individuals, identifying multiple {lncRNAs} absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of {lncRNAs} relative to {mRNAs}. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that {lncRNAs} display significantly more inter-individual expression variability compared to {mRNAs}. We confirm this finding in two independent human datasets by analyzing multiple tissues from the {GTEx} project and lymphoblastoid cell lines from the {GEUVADIS} project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of {lncRNAs}, but minimally affects {mRNA} gene number. {CONCLUSIONS} A comprehensive annotation of {lncRNAs} is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general {lncRNA} feature to consider when creating a comprehensive annotation of human {lncRNAs} or proposing their use as prognostic or disease markers.},
	pages = {14},
	journaltitle = {Genome biology},
	author = {Kornienko, Aleksandra E and Dotter, Christoph P and Guenzl, Philipp M and Gisslinger, Heinz and Gisslinger, Bettina and Cleary, Ciara and Kralovics, Robert and Pauler, Florian M and Barlow, Denise P},
	date = {2016-01},
	pmid = {26821746}
}

@article{ashburner_gene_2000,
	title = {Gene Ontology: tool for the unification of biology},
	volume = {25},
	issn = {1061-4036},
	doi = {10.1038/75556},
	pages = {25--29},
	number = {1},
	journaltitle = {Nature Genetics},
	author = {Ashburner, Michael and Ball, Catherine A. and Blake, Judith A. and Botstein, David and Butler, Heather and Cherry, J. Michael and Davis, Allan P. and Dolinski, Kara and Dwight, Selina S. and Eppig, Janan T. and Harris, Midori A. and Hill, David P. and Issel-Tarver, Laurie and Kasarskis, Andrew and Lewis, Suzanna and Matese, John C. and Richardson, Joel E. and Ringwald, Martin and Rubin, Gerald M. and Sherlock, Gavin},
	date = {2000-05}
}

@article{fang_noncodev5:_2017,
	title = {{NONCODEV}5: a comprehensive annotation database for long non-coding {RNAs}},
	issn = {0305-1048},
	doi = {10.1093/nar/gkx1107},
	abstract = {{NONCODE} (http://www.bioinfo.org/noncode/) is a systematic database that is dedicated to presenting the most complete collection and annotation of non-coding {RNAs} ({ncRNAs}), especially long non-coding {RNAs} ({lncRNAs}). Since {NONCODE} 2016 was released two years ago, the amount of novel identified {ncRNAs} has been enlarged by the reduced cost of next-generation sequencing, which has produced an explosion of newly identified data. The third-generation sequencing revolution has also offered longer and more accurate annotations. Moreover, accumulating evidence confirmed by biological experiments has provided more comprehensive knowledge of {lncRNA} functions. The {ncRNA} data set was expanded by collecting newly identified {ncRNAs} from literature published over the past two years and integration of the latest versions of {RefSeq} and Ensembl. Additionally, pig was included in the database for the first time, bringing the total number of species to 17. The number of {lncRNAs} in {NONCODEv}5 increased from 527 336 to 548 640. {NONCODEv}5 also introduced three important new features: (i) human {lncRNA}-disease relationships and single nucleotide polymorphism-{lncRNA}-disease relationships were constructed; (ii) human exosome {lncRNA} expression profiles were displayed; (iii) the {RNA} secondary structures of {NONCODE} human transcripts were predicted. {NONCODEv}5 is also accessible through http://www.noncode.org/.},
	journaltitle = {Nucleic Acids Research},
	author = {Fang, {ShuangSang} and Zhang, {LiLi} and Guo, {JinCheng} and Niu, {YiWei} and Wu, Yang and Li, Hui and Zhao, {LianHe} and Li, {XiYuan} and Teng, {XueYi} and Sun, {XianHui} and Sun, Liang and Zhang, Michael Q. and Chen, {RunSheng} and Zhao, Yi},
	date = {2017-11},
	pmid = {29140524}
}

@article{quek_lncrnadb_2015,
	title = {{lncRNAdb} v2.0: expanding the reference database for functional long noncoding {RNAs}.},
	volume = {43},
	issn = {1362-4962},
	doi = {10.1093/nar/gku988},
	abstract = {Despite the prevalence of long noncoding {RNA} ({lncRNA}) genes in eukaryotic genomes, only a small proportion have been examined for biological function. {lncRNAdb}, available at http://lncrnadb.org, provides users with a comprehensive, manually curated reference database of 287 eukaryotic {lncRNAs} that have been described independently in the scientific literature. In addition to capturing a great proportion of the recent literature describing functions for individual {lncRNAs}, {lncRNAdb} now offers an improved user interface enabling greater accessibility to sequence information, expression data and the literature. The new features in {lncRNAdb} include the integration of Illumina Body Atlas expression profiles, nucleotide sequence information, a {BLAST} search tool and easy export of content via direct download or a {REST} {API}. {lncRNAdb} is now endorsed by {RNAcentral} and is in compliance with the International Nucleotide Sequence Database Collaboration.},
	pages = {D168--73},
	issue = {Database issue},
	journaltitle = {Nucleic acids research},
	author = {Quek, Xiu Cheng and Thomson, Daniel W and Maag, Jesper L V and Bartonicek, Nenad and Signal, Bethany and Clark, Michael B and Gloss, Brian S and Dinger, Marcel E},
	date = {2015-01},
	pmid = {25332394},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/S6E63LL5/Quek et al. - 2015 - lncRNAdb v2.0 expanding the reference database fo.pdf:application/pdf}
}

@article{hudson_international_2010,
	title = {International network of cancer genome projects},
	volume = {464},
	issn = {0028-0836},
	doi = {10.1038/nature08987},
	abstract = {The International Cancer Genome Consortium ({ICGC}) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.},
	pages = {993--998},
	number = {7291},
	journaltitle = {Nature},
	author = {Hudson, Thomas J. and Anderson, Warwick and Aretz, Axel and Barker, Anna D. and Bell, Cindy and Bernabé, Rosa R. and Bhan, M. K. and Calvo, Fabien and Eerola, Iiro and Gerhard, Daniela S. and Guttmacher, Alan and Guyer, Mark and Hemsley, Fiona M. and Jennings, Jennifer L. and Kerr, David and Klatt, Peter and Kolar, Patrik and Kusuda, Jun and Lane, David P. and Laplace, Frank and Lu, Youyong and Nettekoven, Gerd and Ozenberger, Brad and Peterson, Jane and Rao, T.S. and Remacle, Jacques and Schafer, Alan J. and Shibata, Tatsuhiro and Stratton, Michael R. and Vockley, Joseph G. and Watanabe, Koichi and Yang, Huanming and Yuen, Matthew M. F. and Knoppers (Leader), Bartha M. and Bobrow, Martin and Cambon-Thomsen, Anne and Dressler, Lynn G. and Dyke, Stephanie O. M. and Joly, Yann and Kato, Kazuto and Kennedy, Karen L. and Nicolás, Pilar and Parker, Michael J. and Rial-Sebbag, Emmanuelle and Romeo-Casabona, Carlos M. and Shaw, Kenna M. and Wallace, Susan and Wiesner, Georgia L. and Zeps, Nikolajs and Lichter (Leader), Peter and Biankin, Andrew V. and Chabannon, Christian and Chin, Lynda and Clément, Bruno and de Alava, Enrique and Degos, Françoise and Ferguson, Martin L. and Geary, Peter and Hayes, D. Neil and Hudson, Thomas J. and Johns, Amber L. and Kasprzyk, Arek and Nakagawa, Hidewaki and Penny, Robert and Piris, Miguel A. and Sarin, Rajiv and Scarpa, Aldo and Shibata, Tatsuhiro and van de Vijver, Marc and Futreal (Leader), P. Andrew and Aburatani, Hiroyuki and Bayés, Mónica and Bowtell, David D.L. and Campbell, Peter J. and Estivill, Xavier and Gerhard, Daniela S. and Grimmond, Sean M. and Gut, Ivo and Hirst, Martin and López-Otín, Carlos and Majumder, Partha and Marra, Marco and {McPherson}, John D. and Nakagawa, Hidewaki and Ning, Zemin and Puente, Xose S. and Ruan, Yijun and Shibata, Tatsuhiro and Stratton, Michael R. and Stunnenberg, Hendrik G. and Swerdlow, Harold and Velculescu, Victor E. and Wilson, Richard K. and Xue, Hong H. and Yang, Liu and Spellman (Leader), Paul T. and Bader, Gary D. and Boutros, Paul C. and Campbell, Peter J. and Flicek, Paul and Getz, Gad and Guigó, Roderic and Guo, Guangwu and Haussler, David and Heath, Simon and Hubbard, Tim J. and Jiang, Tao and Jones, Steven M. and Li, Qibin and López-Bigas, Nuria and Luo, Ruibang and Muthuswamy, Lakshmi and Francis Ouellette, B. F. and Pearson, John V. and Puente, Xose S. and Quesada, Victor and Raphael, Benjamin J. and Sander, Chris and Shibata, Tatsuhiro and Speed, Terence P. and Stein, Lincoln D. and Stuart, Joshua M. and Teague, Jon W. and Totoki, Yasushi and Tsunoda, Tatsuhiko and Valencia, Alfonso and Wheeler, David A. and Wu, Honglong and Zhao, Shancen and Zhou, Guangyu and Stein (Leader), Lincoln D. and Guigó, Roderic and Hubbard, Tim J. and Joly, Yann and Jones, Steven M. and Kasprzyk, Arek and Lathrop, Mark and López-Bigas, Nuria and Francis Ouellette, B. F. and Spellman, Paul T. and Teague, Jon W. and Thomas, Gilles and Valencia, Alfonso and Yoshida, Teruhiko and Kennedy (Leader), Karen L. and Axton, Myles and Dyke, Stephanie O. M. and Futreal, P. Andrew and Gerhard, Daniela S. and Gunter, Chris and Guyer, Mark and Hudson, Thomas J. and {McPherson}, John D. and Miller, Linda J. and Ozenberger, Brad and Shaw, Kenna M. and Kasprzyk (Leader), Arek and Stein (Leader), Lincoln D. and Zhang, Junjun and Haider, Syed A. and Wang, Jianxin and Yung, Christina K. and Cross, Anthony and Liang, Yong and Gnaneshan, Saravanamuttu and Guberman, Jonathan and Hsu, Jack and Bobrow (Leader), Martin and Chalmers, Don R. C. and Hasel, Karl W. and Joly, Yann and Kaan, Terry S. H. and Kennedy, Karen L. and Knoppers, Bartha M. and Lowrance, William W. and Masui, Tohru and Nicolás, Pilar and Rial-Sebbag, Emmanuelle and Lyman Rodriguez, Laura and Vergely, Catherine and Yoshida, Teruhiko and Grimmond (Leader), Sean M. and Biankin, Andrew V. and Bowtell, David D. L. and Cloonan, Nicole and {DeFazio}, Anna and Eshleman, James R. and Etemadmoghadam, Dariush and Gardiner, Brooke A. and Kench, James G. and Scarpa, Aldo and Sutherland, Robert L. and Tempero, Margaret A. and Waddell, Nicola J. and Wilson, Peter J. and {McPherson} (Leader), John D. and Gallinger, Steve and Tsao, Ming-Sound and Shaw, Patricia A. and Petersen, Gloria M. and Mukhopadhyay, Debabrata and Chin, Lynda and {DePinho}, Ronald A. and Thayer, Sarah and Muthuswamy, Lakshmi and Shazand, Kamran and Beck, Timothy and Sam, Michelle and Timms, Lee and Ballin, Vanessa and Lu (Leader), Youyong and Ji, Jiafu and Zhang, Xiuqing and Chen, Feng and Hu, Xueda and Zhou, Guangyu and Yang, Qi and Tian, Geng and Zhang, Lianhai and Xing, Xiaofang and Li, Xianghong and Zhu, Zhenggang and Yu, Yingyan and Yu, Jun and Yang, Huanming and Lathrop (Leader), Mark and Tost, Jörg and Brennan, Paul and Holcatova, Ivana and Zaridze, David and Brazma, Alvis and Egevad, Lars and Prokhortchouk, Egor and Elizabeth Banks, Rosamonde and Uhlén, Mathias and Cambon-Thomsen, Anne and Viksna, Juris and Ponten, Fredrik and Skryabin, Konstantin and Stratton (Leader), Michael R. and Futreal, P. Andrew and Birney, Ewan and Borg, Ake and Børresen-Dale, Anne-Lise and Caldas, Carlos and Foekens, John A. and Martin, Sancha and Reis-Filho, Jorge S. and Richardson, Andrea L. and Sotiriou, Christos and Stunnenberg, Hendrik G. and Thomas, Gilles and van de Vijver, Marc and van't Veer, Laura and Calvo (Leader), Fabien and Birnbaum, Daniel and Blanche, Hélène and Boucher, Pascal and Boyault, Sandrine and Chabannon, Christian and Gut, Ivo and Masson-Jacquemier, Jocelyne D. and Lathrop, Mark and Pauporté, Iris and Pivot, Xavier and Vincent-Salomon, Anne and Tabone, Eric and Theillet, Charles and Thomas, Gilles and Tost, Jörg and Treilleux, Isabelle and Calvo (Leader), Fabien and Bioulac-Sage, Paulette and Clément, Bruno and Decaens, Thomas and Degos, Françoise and Franco, Dominique and Gut, Ivo and Gut, Marta and Heath, Simon and Lathrop, Mark and Samuel, Didier and Thomas, Gilles and Zucman-Rossi, Jessica and Lichter (Leader), Peter and Eils (Leader), Roland and Brors, Benedikt and Korbel, Jan O. and Korshunov, Andrey and Landgraf, Pablo and Lehrach, Hans and Pfister, Stefan and Radlwimmer, Bernhard and Reifenberger, Guido and Taylor, Michael D. and von Kalle, Christof and Majumder (Leader), Partha P. and Sarin, Rajiv and Rao, T. S. and Bhan, M. K. and Scarpa (Leader), Aldo and Pederzoli, Paolo and Lawlor, Rita T. and Delledonne, Massimo and Bardelli, Alberto and Biankin, Andrew V. and Grimmond, Sean M. and Gress, Thomas and Klimstra, David and Zamboni, Giuseppe and Shibata (Leader), Tatsuhiro and Nakamura, Yusuke and Nakagawa, Hidewaki and Kusuda, Jun and Tsunoda, Tatsuhiko and Miyano, Satoru and Aburatani, Hiroyuki and Kato, Kazuto and Fujimoto, Akihiro and Yoshida, Teruhiko and Campo (Leader), Elias and López-Otín, Carlos and Estivill, Xavier and Guigó, Roderic and de Sanjosé, Silvia and Piris, Miguel A. and Montserrat, Emili and González-Díaz, Marcos and Puente, Xose S. and Jares, Pedro and Valencia, Alfonso and Himmelbaue, Heinz and Quesada, Victor and Bea, Silvia and Stratton (Leader), Michael R. and Futreal, P. Andrew and Campbell, Peter J. and Vincent-Salomon, Anne and Richardson, Andrea L. and Reis-Filho, Jorge S. and van de Vijver, Marc and Thomas, Gilles and Masson-Jacquemier, Jocelyne D. and Aparicio, Samuel and Borg, Ake and Børresen-Dale, Anne-Lise and Caldas, Carlos and Foekens, John A. and Stunnenberg, Hendrik G. and van't Veer, Laura and Easton, Douglas F. and Spellman, Paul T. and Martin, Sancha and Barker, Anna D. and Chin, Lynda and Collins, Francis S. and Compton, Carolyn C. and Ferguson, Martin L. and Gerhard, Daniela S. and Getz, Gad and Gunter, Chris and Guttmacher, Alan and Guyer, Mark and Hayes, D. Neil and Lander, Eric S. and Ozenberger, Brad and Penny, Robert and Peterson, Jane and Sander, Chris and Shaw, Kenna M. and Speed, Terence P. and Spellman, Paul T. and Vockley, Joseph G. and Wheeler, David A. and Wilson, Richard K. and Hudson (Chairperson), Thomas J. and Chin, Lynda and Knoppers, Bartha M. and Lander, Eric S. and Lichter, Peter and Stein, Lincoln D. and Stratton, Michael R. and Anderson, Warwick and Barker, Anna D. and Bell, Cindy and Bobrow, Martin and Burke, Wylie and Collins, Francis S. and Compton, Carolyn C. and {DePinho}, Ronald A. and Easton, Douglas F. and Futreal, P. Andrew and Gerhard, Daniela S. and Green, Anthony R. and Guyer, Mark and Hamilton, Stanley R. and Hubbard, Tim J. and Kallioniemi, Olli P. and Kennedy, Karen L. and Ley, Timothy J. and Liu, Edison T. and Lu, Youyong and Majumder, Partha and Marra, Marco and Ozenberger, Brad and Peterson, Jane and Schafer, Alan J. and Spellman, Paul T. and Stunnenberg, Hendrik G. and Wainwright, Brandon J. and Wilson, Richard K. and Yang, Huanming and Stunnenberg, Hendrik G and Wainwright, Brandon J and Wilson, Richard K and Yang, Huanming},
	date = {2010-04},
	pmid = {20393554},
	keywords = {Genomics, Genetic, Genome, Humans, Databases, *International Cooperation, {DNA} Methylation, {DNA} Mutational Analysis, {DNA} Mutational Analysis/trends, Genes, Genetics, Genomics/*organization \& administration/trends, Human/*genetics, Intellectual Property, International Cooperation, Medical/*organization \& administration/t, Mutation, Neoplasm/genetics, Neoplasms, Neoplasms/classification/*genetics/pathology/thera, Databases, Genetic, Genome, Human, Genetics, Medical, Genes, Neoplasm},
	file = {Full Text:/home/jlagarde/Zotero/storage/E53A9S8M/International Cancer Genome Consortium et al. - 2010 - International network of cancer genome projects.pdf:application/pdf}
}

@article{juul_non-coding_2017,
	title = {Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate},
	volume = {6},
	issn = {2050-084X},
	doi = {10.7554/eLife.21778},
	abstract = {{\textbackslash}textlessp{\textbackslash}{textgreaterNon}-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, {ncdDetect}, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using {ncdDetect}, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene ({CD}1A), where 5'{UTR} mutations correlate significantly with decreased survival in melanoma. Additionally, mutations in a base-excision-repair gene ({SMUG}1) correlate with a C-to-T mutational-signature. Overall, we find that a rich model of mutational heterogeneity facilitates non-coding driver identification and integrative analysis points to candidates of potential clinical relevance.{\textbackslash}textless/p{\textbackslash}textgreater},
	journaltitle = {{eLife}},
	author = {Juul, Malene and Bertl, Johanna and Guo, Qianyun and Nielsen, Morten Muhlig and Świtnicki, Micha\{{\textbackslash}textbackslash\}l and Hornshøj, Henrik and Madsen, Tobias and Hobolth, Asger and Pedersen, Jakob Skou},
	date = {2017-03},
	pmid = {28362259}
}

@article{eilbeck_sequence_2005,
	title = {The Sequence Ontology: a tool for the unification of genome annotations.},
	volume = {6},
	issn = {14656906},
	doi = {10.1186/gb-2005-6-5-r44},
	abstract = {The Sequence Ontology ({SO}) is a structured controlled vocabulary for the parts of a genomic annotation. {SO} provides a common set of terms and definitions that will facilitate the exchange, analysis and management of genomic data. Because {SO} treats part-whole relationships rigorously, data described with it can become substrates for automated reasoning, and instances of sequence features described by the {SO} can be subjected to a group of logical operations termed extensional mereology operators.},
	pages = {R44},
	number = {5},
	journaltitle = {Genome Biology},
	author = {Eilbeck, Karen and Lewis, Suzanna E and Mungall, Christopher J and Yandell, Mark and Stein, Lincoln and Durbin, Richard and Ashburner, Michael},
	date = {2005},
	pmid = {15892872}
}

@article{sen_rare_2017,
	title = {Rare Splice Variants in Long Non-Coding {RNAs}},
	volume = {3},
	issn = {2311-553X},
	doi = {10.3390/ncrna3030023},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) form a substantial component of the transcriptome and are involved in a wide variety of regulatory mechanisms. Compared to protein-coding genes, they are often expressed at low levels and are restricted to a narrow range of cell types or developmental stages. As a consequence, the diversity of their isoforms is still far from being recorded and catalogued in its entirety, and the debate is ongoing about what fraction of non-coding {RNAs} truly conveys biological function rather than being “junk”. Here, using a collection of more than 100 transcriptomes from related B cell lymphoma, we show that {lncRNA} loci produce a very defined set of splice variants. While some of them are so rare that they become recognizable only in the superposition of dozens or hundreds of transcriptome datasets and not infrequently include introns or exons that have not been included in available genome annotation data, there is still a very limited number of processing products for any given locus. The combined depth of our sequencing data is large enough to effectively exhaust the isoform diversity: the overwhelming majority of splice junctions that are observed at all are represented by multiple junction-spanning reads. We conclude that the human transcriptome produces virtually no background of {RNAs} that are processed at effectively random positions, but is—under normal circumstances—confined to a well defined set of splice variants.},
	pages = {23},
	number = {3},
	journaltitle = {Non-Coding {RNA}},
	author = {Sen, Rituparno and Doose, Gero and Stadler, Peter},
	date = {2017-07}
}

@article{ezkurdia_potential_2015,
	title = {The potential clinical impact of the release of two drafts of the human proteome.},
	volume = {12},
	issn = {1744-8387},
	doi = {10.1586/14789450.2015.1103186},
	abstract = {The authors have carried out an investigation of the two "draft maps of the human proteome" published in 2014 in Nature. The findings include an abundance of poor spectra, low-scoring peptide-spectrum matches and incorrectly identified proteins in both these studies, highlighting clear issues with the application of false discovery rates. This noise means that the claims made by the two papers - the identification of high numbers of protein coding genes, the detection of novel coding regions and the draft tissue maps themselves - should be treated with considerable caution. The authors recommend that clinicians and researchers do not use the unfiltered data from these studies. Despite this these studies will inspire further investigation into tissue-based proteomics. As long as this future work has proper quality controls, it could help produce a consensus map of the human proteome and improve our understanding of the processes that underlie health and disease.},
	pages = {579--93},
	number = {6},
	journaltitle = {Expert review of proteomics},
	author = {Ezkurdia, Iakes and Calvo, Enrique and Del Pozo, Angela and Vázquez, Jesús and Valencia, Alfonso and Tress, Michael L},
	date = {2015-11},
	pmid = {26496066}
}

@article{carrieri_long_2012,
	title = {Long non-coding antisense {RNA} controls Uchl1 translation through an embedded {SINEB}2 repeat.},
	volume = {491},
	issn = {1476-4687},
	doi = {10.1038/nature11508},
	abstract = {Most of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes protein-coding messenger {RNAs}, long non-coding {RNAs} ({lncRNAs}) and repetitive sequences, such as {SINEs} (short interspersed nuclear elements). A large percentage of {ncRNAs} are nuclear-enriched with unknown function. Antisense {lncRNAs} may form sense-antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and {mRNA} stability. Here we identify a nuclear-enriched {lncRNA} antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases. Antisense Uchl1 increases {UCHL}1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of {lncRNAs}. Antisense Uchl1 activity depends on the presence of a 5' overlapping sequence and an embedded inverted {SINEB}2 element. These features are shared by other natural antisense transcripts and can confer regulatory activity to an artificial antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as {mTORC}1 inhibition by rapamycin causes an increase in {UCHL}1 protein that is associated to the shuttling of antisense Uchl1 {RNA} from the nucleus to the cytoplasm. Antisense Uchl1 {RNA} is then required for the association of the overlapping sense protein-coding {mRNA} to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.},
	pages = {454--7},
	number = {7424},
	journaltitle = {Nature},
	author = {Carrieri, Claudia and Cimatti, Laura and Biagioli, Marta and Beugnet, Anne and Zucchelli, Silvia and Fedele, Stefania and Pesce, Elisa and Ferrer, Isidre and Collavin, Licio and Santoro, Claudio and Forrest, Alistair R R and Carninci, Piero and Biffo, Stefano and Stupka, Elia and Gustincich, Stefano},
	date = {2012-11},
	pmid = {23064229},
	keywords = {Animals, Humans, Mice, {RNA}, Anti-Bacterial Agents/pharmacology, Antisense/genetics/*metabolism, Cell Line, Male, Protein Biosynthesis, Protein Biosynthesis/drug effects/*genetics, Sequence Inversion, Short Interspersed Nucleotide Elements/*genetics, Sirolimus, Sirolimus/pharmacology, Ubiquitin Thiolesterase/*genetics/*metabolism, {RNA}, Antisense, Anti-Bacterial Agents, Short Interspersed Nucleotide Elements, Ubiquitin Thiolesterase}
}

@article{ingolia_ribosome_2011,
	title = {Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes},
	volume = {147},
	issn = {00928674},
	doi = {10.1016/j.cell.2011.10.002},
	abstract = {The ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep sequencing of ribosome-protected {mRNA} fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and unannotated translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both {AUG} and non-{AUG} codons, whose translation changes after differentiation. We also define a class of short, polycistronic ribosome-associated coding {RNAs} ({sprcRNAs}) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes.},
	pages = {789--802},
	number = {4},
	journaltitle = {Cell},
	author = {Ingolia, Nicholas T. and Lareau, Liana F. and Weissman, Jonathan S.},
	date = {2011-11},
	pmid = {22056041},
	keywords = {Genomics/*methods, Sequence Analysis, Animals, Mice, Open Reading Frames, Algorithms, *Protein Biosynthesis, Artificial Intelligence, Embryoid Bodies/cytology/metabolism, Embryonic Stem Cells/metabolism, Harringtonines/pharmacology, High-Throughput Nucleotide Sequencing/*methods, Kinetics, Peptide Chain Initiation, Ribosomes/*chemistry/drug effects, {RNA}/*analysis, {RNA}/*methods, Translational}
}

@article{byrne_nanopore_2017,
	title = {Nanopore long-read {RNAseq} reveals widespread transcriptional variation among the surface receptors of individual B cells},
	volume = {8},
	issn = {2041-1723},
	doi = {10.1038/ncomms16027},
	abstract = {Short-read {RNA}-seq is limited in its ability to resolve complex transcript isoforms since it cannot sequence full-length {cDNA}. Here the authors use Oxford Nanopore {MinION} and their Mandalorion analysis pipeline to measure complex isoforms in B1a cells.},
	pages = {16027},
	journaltitle = {Nature Communications},
	author = {Byrne, Ashley and Beaudin, Anna E. and Olsen, Hugh E. and Jain, Miten and Cole, Charles and Palmer, Theron and {DuBois}, Rebecca M. and Forsberg, E. Camilla and Akeson, Mark and Vollmers, Christopher},
	date = {2017-07}
}

@article{marques_chromatin_2013,
	title = {Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding {RNAs}},
	volume = {14},
	issn = {1465-6906},
	doi = {10.1186/gb-2013-14-11-r131},
	abstract = {{BACKGROUND} Mammalian transcriptomes contain thousands of long noncoding {RNAs} ({lncRNAs}). Some {lncRNAs} originate from intragenic enhancers which, when active, behave as alternative promoters producing transcripts that are processed using the canonical signals of their host gene. We have followed up this observation by analyzing intergenic {lncRNAs} to determine the extent to which they might also originate from intergenic enhancers. {RESULTS} We integrated high-resolution maps of transcriptional initiation and transcription to annotate a conservative set of intergenic {lncRNAs} expressed in mouse erythroblasts. We subclassified intergenic {lncRNAs} according to chromatin status at transcriptional initiation regions, defined by relative levels of histone H3K4 mono- and trimethylation. These transcripts are almost evenly divided between those arising from enhancer-associated ({elncRNA}) or promoter-associated ({plncRNA}) elements. These two classes of 5' capped and polyadenylated {RNA} transcripts are indistinguishable with regard to their length, number of exons or transcriptional orientation relative to their closest neighboring gene. Nevertheless, {elncRNAs} are more tissue-restricted, less highly expressed and less well conserved during evolution. Of considerable interest, we found that expression of {elncRNAs}, but not {plncRNAs}, is associated with enhanced expression of neighboring protein-coding genes during erythropoiesis. {CONCLUSIONS} We have determined globally the sites of initiation of intergenic {lncRNAs} in erythroid cells, allowing us to distinguish two similarly abundant classes of transcripts. Different correlations between the levels of {elncRNAs}, {plncRNAs} and expression of neighboring genes suggest that functional {lncRNAs} from the two classes may play contrasting roles in regulating the transcript abundance of local or distal loci.},
	pages = {R131},
	number = {11},
	journaltitle = {Genome Biology},
	author = {Marques, Ana C and Hughes, Jim and Graham, Bryony and Kowalczyk, Monika S and Higgs, Doug R and Ponting, Chris P},
	date = {2013-11},
	pmid = {24289259},
	keywords = {Transcriptome, {DNA}, Sequence Analysis, Animals, Genetic, Mice, Promoter Regions, {RNA}, Gene Expression Regulation, Messenger/genetics, *Transcription Initiation Site, Evolution, Genetic Loci, Histones/genetics, Inbred C57BL, Molecular, Protein Structure, Tertiary, Chromatin/*chemistry/genetics, Long Noncoding/*chemistry/genetics}
}

@article{benoit_bouvrette_cefra-seq_2018,
	title = {{CeFra}-seq reveals broad asymmetric {mRNA} and noncoding {RNA} distribution profiles in {\textbackslash}textlessi{\textbackslash}{textgreaterDrosophila}{\textbackslash}textless/i{\textbackslash}textgreater and human cells},
	volume = {24},
	issn = {1355-8382},
	doi = {10.1261/rna.063172.117},
	abstract = {Cells are highly asymmetrical, a feature that relies on the sorting of molecular constituents, including proteins, lipids, and nucleic acids, to distinct subcellular locales. The localization of {RNA} molecules is an important layer of gene regulation required to modulate localized cellular activities, although its global prevalence remains unclear. We combine biochemical cell fractionation with {RNA}-sequencing ({CeFra}-seq) analysis to assess the prevalence and conservation of {RNA} asymmetric distribution on a transcriptome-wide scale in Drosophila and human cells. This approach reveals that the majority (∼80\%) of cellular {RNA} species are asymmetrically distributed, whether considering coding or noncoding transcript populations, in patterns that are broadly conserved evolutionarily. Notably, a large number of Drosophila and human long noncoding {RNAs} and circular {RNAs} display enriched levels within specific cytoplasmic compartments, suggesting that these {RNAs} fulfill extra-nuclear functions. Moreover, fraction-specific {mRNA} populations exhibit distinctive sequence characteristics. Comparative analysis of {mRNA} fractionation profiles with that of their encoded proteins reveals a general lack of correlation in subcellular distribution, marked by strong cases of asymmetry. However, coincident distribution profiles are observed for {mRNA}/protein pairs related to a variety of functional protein modules, suggesting complex regulatory inputs of {RNA} localization to cellular organization.},
	pages = {98--113},
	number = {1},
	journaltitle = {{RNA}},
	author = {Benoit Bouvrette, Louis Philip and Cody, Neal A.L. and Bergalet, Julie and Lefebvre, Fabio Alexis and Diot, Cédric and Wang, Xiaofeng and Blanchette, Mathieu and Lécuyer, Eric},
	date = {2018-01},
	pmid = {29079635}
}

@article{sheik_mohamed_conserved_2010,
	title = {Conserved long noncoding {RNAs} transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells},
	volume = {16},
	issn = {1355-8382},
	doi = {10.1261/rna.1441510},
	abstract = {The genetic networks controlling stem cell identity are the focus of intense interest, due to their obvious therapeutic potential as well as exceptional relevance to models of early development. Genome-wide mapping of transcriptional networks in mouse embryonic stem cells ({mESCs}) reveals that many endogenous noncoding {RNA} molecules, including long noncoding {RNAs} ({lncRNAs}), may play a role in controlling the pluripotent state. We performed a genome-wide screen that combined full-length {mESC} transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key {mESC} transcription factors Oct4 and Nanog. We henceforth identified four {mESC}-expressed, conserved {lncRNA}-encoding genes residing proximally to active genomic binding sites of Oct4 and Nanog. Accordingly, these four genes have potential roles in pluripotency. We show that two of these {lncRNAs}, {AK}028326 (Oct4-activated) and {AK}141205 (Nanog-repressed), are direct targets of Oct4 and Nanog. Most importantly, we demonstrate that these {lncRNAs} are not merely controlled by {mESC} transcription factors, but that they themselves regulate developmental state: knockdown and overexpression of these transcripts lead to robust changes in Oct4 and Nanog {mRNA} levels, in addition to alterations in cellular lineage-specific gene expression and in the pluripotency of {mESCs}. We further characterize {AK}028326 as a co-activator of Oct4 in a regulatory feedback loop. These results for the first time implicate {lncRNAs} in the modulation of {mESC} pluripotency and expand the established {mESC} regulatory network model to include functional {lncRNAs} directly controlled by key {mESC} transcription factors.},
	pages = {324--337},
	number = {2},
	journaltitle = {{RNA}},
	author = {Sheik Mohamed, J. and Gaughwin, P. M. and Lim, B. and Robson, P. and Lipovich, L.},
	date = {2010-02},
	pmid = {20026622}
}

@article{seemann_identification_2017,
	title = {The identification and functional annotation of {RNA} structures conserved in vertebrates},
	volume = {27},
	issn = {1088-9051},
	doi = {10.1101/gr.208652.116},
	abstract = {Structured elements of {RNA} molecules are essential in, e.g., {RNA} stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved {RNA} structures ({CRSs}), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and {GC} content, we predict ∼516,000 human genomic regions containing {CRSs}. We find that a substantial fraction of human-mouse {CRS} regions (1) colocalize consistently with binding sites of the same {RNA} binding proteins ({RBPs}) or (2) are transcribed in corresponding tissues. Additionally, a {CaptureSeq} experiment revealed expression of many of our {CRS} regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, {qRT}-{PCR} and in vitro {RNA} structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 {CRS} regions are located near coding or long noncoding {RNA} genes or within enhancers. Structured ({CRS} overlapping) enhancer {RNAs} and extended 3' ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain {CRSs} support their {RNA}-mediated functionality.},
	pages = {1371--1383},
	number = {8},
	journaltitle = {Genome Research},
	author = {Seemann, Stefan E. and Mirza, Aashiq H. and Hansen, Claus and Bang-Berthelsen, Claus H. and Garde, Christian and Christensen-Dalsgaard, Mikkel and Torarinsson, Elfar and Yao, Zizhen and Workman, Christopher T. and Pociot, Flemming and Nielsen, Henrik and Tommerup, Niels and Ruzzo, Walter L. and Gorodkin, Jan},
	date = {2017-08},
	pmid = {28487280}
}

@article{carlevaro-fita_cytoplasmic_2016,
	title = {Cytoplasmic long noncoding {RNAs} are frequently bound to and degraded at ribosomes in human cells.},
	volume = {22},
	issn = {1469-9001},
	doi = {10.1261/rna.053561.115},
	abstract = {Recent footprinting studies have made the surprising observation that long noncoding {RNAs} ({lncRNAs}) physically interact with ribosomes. However, these findings remain controversial, and the overall proportion of cytoplasmic {lncRNAs} involved is unknown. Here we make a global, absolute estimate of the cytoplasmic and ribosome-associated population of stringently filtered {lncRNAs} in a human cell line using polysome profiling coupled to spike-in normalized microarray analysis. Fifty-four percent of expressed {lncRNAs} are detected in the cytoplasm. The majority of these (70\%) have {\textbackslash}textgreater50\% of their cytoplasmic copies associated with polysomal fractions. These interactions are lost upon disruption of ribosomes by puromycin. Polysomal {lncRNAs} are distinguished by a number of 5' {mRNA}-like features, including capping and 5'{UTR} length. On the other hand, nonpolysomal "free cytoplasmic" {lncRNAs} have more conserved promoters and a wider range of expression across cell types. Exons of polysomal {lncRNAs} are depleted of endogenous retroviral insertions, suggesting a role for repetitive elements in {lncRNA} localization. Finally, we show that blocking of ribosomal elongation results in stabilization of many associated {lncRNAs}. Together these findings suggest that the ribosome is the default destination for the majority of cytoplasmic long noncoding {RNAs} and may play a role in their degradation.},
	pages = {867--82},
	number = {6},
	journaltitle = {{RNA} (New York, N.Y.)},
	author = {Carlevaro-Fita, Joana and Rahim, Anisa and Guigó, Roderic and Vardy, Leah A and Johnson, Rory},
	date = {2016-04},
	pmid = {27090285}
}

@article{wucher_feelnc:_2017,
	title = {{FEELnc}: a tool for long non-coding {RNA} annotation and its application to the dog transcriptome},
	volume = {45},
	issn = {0305-1048},
	doi = {10.1093/nar/gkw1306},
	pages = {gkw1306},
	number = {8},
	journaltitle = {Nucleic Acids Research},
	author = {Wucher, Valentin and Legeai, Fabrice and Hédan, Benoît and Rizk, Guillaume and Lagoutte, L\{{\textbackslash}textbackslash\}a etitia and Leeb, Tosso and Jagannathan, Vidhya and Cadieu, Edouard and David, Audrey and Lohi, Hannes and Cirera, Susanna and Fredholm, Merete and Botherel, Nadine and Leegwater, Peter A.J. and Le Béguec, Céline and Fieten, Hille and Johnson, Jeremy and Alföldi, Jessica and André, Catherine and Lindblad-Toh, Kerstin and Hitte, Christophe and Derrien, Thomas},
	date = {2017-01}
}

@article{deveson_universal_2018,
	title = {Universal Alternative Splicing of Noncoding Exons},
	volume = {6},
	issn = {24054712},
	doi = {10.1016/j.cels.2017.12.005},
	abstract = {The human transcriptome is so large, diverse, and dynamic that, even after a decade of investigation by {RNA} sequencing ({RNA}-seq), we have yet to resolve its true dimensions. {RNA}-seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read {RNA}-seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome, identifying a fundamental distinction between protein-coding and noncoding gene content: almost every noncoding exon undergoes alternative splicing, producing a seemingly limitless variety of isoforms. Analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse, yet human splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a deeply conserved splicing code. We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory {RNAs} and a rich transcriptional reservoir for gene evolution.},
	pages = {245--255.e5},
	number = {2},
	journaltitle = {Cell Systems},
	author = {Deveson, Ira W. and Brunck, Marion E. and Blackburn, James and Tseng, Elizabeth and Hon, Ting and Clark, Tyson A. and Clark, Michael B. and Crawford, Joanna and Dinger, Marcel E. and Nielsen, Lars K. and Mattick, John S. and Mercer, Tim R.},
	date = {2018-02},
	pmid = {29396323}
}

@article{bray_near-optimal_2016,
	title = {Near-optimal probabilistic {RNA}-seq quantification},
	volume = {34},
	issn = {1087-0156},
	doi = {10.1038/nbt.3519},
	abstract = {We present kallisto, an {RNA}-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy. Kallisto pseudoaligns reads to a reference, producing a list of transcripts that are compatible with each read while avoiding alignment of individual bases. We use kallisto to analyze 30 million unaligned paired-end {RNA}-seq reads in {\textbackslash}textless10 min on a standard laptop computer. This removes a major computational bottleneck in {RNA}-seq analysis.},
	pages = {525--527},
	number = {5},
	journaltitle = {Nature Biotechnology},
	author = {Bray, Nicolas L and Pimentel, Harold and Melsted, Páll and Pachter, Lior},
	date = {2016-05},
	pmid = {27043002}
}

@article{kanitz_comparative_2015,
	title = {Comparative assessment of methods for the computational inference of transcript isoform abundance from {RNA}-seq data},
	volume = {16},
	issn = {1465-6906},
	doi = {10.1186/s13059-015-0702-5},
	abstract = {{BACKGROUND} Understanding the regulation of gene expression, including transcription start site usage, alternative splicing, and polyadenylation, requires accurate quantification of expression levels down to the level of individual transcript isoforms. To comparatively evaluate the accuracy of the many methods that have been proposed for estimating transcript isoform abundance from {RNA} sequencing data, we have used both synthetic data as well as an independent experimental method for quantifying the abundance of transcript ends at the genome-wide level. {RESULTS} We found that many tools have good accuracy and yield better estimates of gene-level expression compared to commonly used count-based approaches, but they vary widely in memory and runtime requirements. Nucleotide composition and intron/exon structure have comparatively little influence on the accuracy of expression estimates, which correlates most strongly with transcript/gene expression levels. To facilitate the reproduction and further extension of our study, we provide datasets, source code, and an online analysis tool on a companion website, where developers can upload expression estimates obtained with their own tool to compare them to those inferred by the methods assessed here. {CONCLUSIONS} As many methods for quantifying isoform abundance with comparable accuracy are available, a user's choice will likely be determined by factors such as the memory and runtime requirements, as well as the availability of methods for downstream analyses. Sequencing-based methods to quantify the abundance of specific transcript regions could complement validation schemes based on synthetic data and quantitative {PCR} in future or ongoing assessments of {RNA}-seq analysis methods.},
	pages = {150},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Kanitz, Alexander and Gypas, Foivos and Gruber, Andreas J. and Gruber, Andreas R. and Martin, Georges and Zavolan, Mihaela},
	date = {2015-12},
	pmid = {26201343}
}

@article{ning_lnc2cancer:_2016,
	title = {Lnc2Cancer: a manually curated database of experimentally supported {lncRNAs} associated with various human cancers},
	volume = {44},
	issn = {0305-1048},
	doi = {10.1093/nar/gkv1094},
	pages = {D980--D985},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Ning, Shangwei and Zhang, Jizhou and Wang, Peng and Zhi, Hui and Wang, Jianjian and Liu, Yue and Gao, Yue and Guo, Maoni and Yue, Ming and Wang, Lihua and Li, Xia},
	date = {2016-01}
}

@article{sauvageau_multiple_2013,
	title = {Multiple knockout mouse models reveal {lincRNAs} are required for life and brain development.},
	volume = {2},
	doi = {10.7554/eLife.01749},
	abstract = {Many studies are uncovering functional roles for long noncoding {RNAs} ({lncRNAs}), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of {lncRNAs} in various physiological conditions, we have developed a collection of 18 {lncRNA} knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc-Brn1b and linc-Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr(-/-) neonates, whereas linc-Brn1b(-/-) mutants displayed distinct abnormalities in the generation of upper layer {II}-{IV} neurons in the neocortex. This study demonstrates that {lncRNAs} play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of {lncRNA} molecules. {DOI}: http://dx.doi.org/10.7554/{eLife}.01749.001.},
	pages = {e01749},
	journaltitle = {{eLife}},
	author = {Sauvageau, Martin and Goff, Loyal A and Lodato, Simona and Bonev, Boyan and Groff, Abigail F and Gerhardinger, Chiara and Sanchez-Gomez, Diana B and Hacisuleyman, Ezgi and Li, Eric and Spence, Matthew and Liapis, Stephen C and Mallard, William and Morse, Michael and Swerdel, Mavis R and D'Ecclessis, Michael F and Moore, Jennifer C and Lai, Venus and Gong, Guochun and Yancopoulos, George D and Frendewey, David and Kellis, Manolis and Hart, Ronald P and Valenzuela, David M and Arlotta, Paola and Rinn, John L},
	date = {2013-12},
	pmid = {24381249}
}

@article{smith_reading_2017,
	title = {Reading canonical and modified nucleotides in 16S ribosomal {RNA} using nanopore direct {RNA} sequencing},
	doi = {10.1101/132274},
	abstract = {The ribosome small subunit is expressed in all living cells. It performs numerous essential functions during translation, including formation of the initiation complex and proofreading of base-pairs between {mRNA} codons and {tRNA} anticodons. The core constituent of the small ribosomal subunit is a ∼1.5 kb {RNA} strand in prokaryotes (16S {rRNA}) and a homologous ∼1.8 kb {RNA} strand in eukaryotes (18S {rRNA}). Traditional sequencing-by-synthesis ({SBS}) of {rRNA} genes or {rRNA} {cDNA} copies has achieved wide use as a "molecular chronometer" for phylogenetic studies [1], and as a tool for identifying infectious organisms in the clinic [2]. However, epigenetic modifications on {rRNA} are erased by {SBS} methods. Here we describe direct {MinION} nanopore sequencing of individual, full-length 16S {rRNA} absent reverse transcription or amplification. As little as 5 picograms (∼10 attomole) of E. coli 16S {rRNA} was detected in 4.5 micrograms of total human {RNA}. Nanopore ionic current traces that deviated from canonical patterns revealed conserved 16S {rRNA} base modifications, and a 7-methylguanosine modification that confers aminoglycoside resistance to some pathological E. coli strains. This direct {RNA} sequencing technology has promise for rapid identification of microbes in the environment and in patient samples.},
	pages = {132274},
	journaltitle = {{bioRxiv}},
	author = {Smith, Andrew M and Jain, Miten and Mulroney, Logan and Garalde, Daniel R and Akeson, Mark},
	date = {2017-04}
}

@article{sonnhammer_pfam:_1998,
	title = {Pfam: multiple sequence alignments and {HMM}-profiles of protein domains},
	volume = {26},
	issn = {13624962},
	doi = {10.1093/nar/26.1.320},
	pages = {320--322},
	number = {1},
	journaltitle = {Nucleic Acids Research},
	author = {Sonnhammer, E. and Eddy, Sean R. and Birney, Ewan and Bateman, Alex and Durbin, Richard},
	date = {1998-01}
}

@article{pegueroles_secondary_2016,
	title = {Secondary structure impacts patterns of selection in human {lncRNAs}},
	volume = {14},
	issn = {17417007},
	doi = {10.1186/s12915-016-0283-0},
	abstract = {{BACKGROUND} Metazoans transcribe many long non-coding {RNAs} ({lncRNAs}) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted {lncRNAs} is actually functional, and whether selection can effectively constrain {lncRNAs} in species with small effective population sizes such as human populations. {RESULTS} Here we evaluate signatures of selection in human {lncRNAs} using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized {lncRNAs}. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted {lncRNAs}. We found that {RNA} secondary structure constrains sequence variation in {lncRNAs}, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability. {CONCLUSIONS} Important implications of our results are that secondary structure plays a role in the functionality of {lncRNAs}, and that the set of predicted {lncRNAs} contains a large fraction of functional ones that may play key roles that remain to be discovered.},
	pages = {60},
	number = {1},
	journaltitle = {{BMC} Biology},
	author = {Pegueroles, Cinta and Gabaldón, Toni},
	date = {2016-12},
	pmid = {27457204}
}

@article{paraskevopoulou_diana-lncbase_2016,
	title = {{DIANA}-{LncBase} v2: indexing {microRNA} targets on non-coding transcripts},
	volume = {44},
	issn = {0305-1048},
	doi = {10.1093/nar/gkv1270},
	abstract = {{microRNAs} ({miRNAs}) are short non-coding {RNAs} ({ncRNAs}) that act as post-transcriptional regulators of coding gene expression. Long non-coding {RNAs} ({lncRNAs}) have been recently reported to interact with {miRNAs}. The sponge-like function of {lncRNAs} introduces an extra layer of complexity in the {miRNA} interactome. {DIANA}-{LncBase} v1 provided a database of experimentally supported and in silico predicted {miRNA} Recognition Elements ({MREs}) on {lncRNAs}. The second version of {LncBase} (www.microrna.gr/{LncBase}) presents an extensive collection of {miRNA}:{lncRNA} interactions. The significantly enhanced database includes more than 70 000 low and high-throughput, (in)direct {miRNA}:{lncRNA} experimentally supported interactions, derived from manually curated publications and the analysis of 153 {AGO} {CLIP}-Seq libraries. The new experimental module presents a 14-fold increase compared to the previous release. {LncBase} v2 hosts in silico predicted {miRNA} targets on {lncRNAs}, identified with the {DIANA}-{microT} algorithm. The relevant module provides millions of predicted {miRNA} binding sites, accompanied with detailed metadata and {MRE} conservation metrics. {LncBase} v2 caters information regarding cell type specific {miRNA}:{lncRNA} regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse. Database entries are also supported by accurate {lncRNA} expression information, derived from the analysis of more than 6 billion {RNA}-Seq reads.},
	pages = {D231--D238},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Paraskevopoulou, Maria D. and Vlachos, Ioannis S. and Karagkouni, Dimitra and Georgakilas, Georgios and Kanellos, Ilias and Vergoulis, Thanasis and Zagganas, Konstantinos and Tsanakas, Panayiotis and Floros, Evangelos and Dalamagas, Theodore and Hatzigeorgiou, Artemis G.},
	date = {2016-01},
	pmid = {26612864}
}

@article{lubelsky_sequences_2017,
	title = {Sequences enriched in Alu repeats drive nuclear localization of long {RNAs} in human cells},
	doi = {10.1101/189746},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are emerging as key players in multiple cellular pathways, but their modes of action, and how those are dictated by sequence remain elusive. While {lncRNAs} share most molecular properties with {mRNAs}, they are more likely to be enriched in the nucleus, a feature that is likely to be crucial for function of many {lncRNAs}, but whose molecular underpinnings remain largely unclear. In order identify elements that can force nuclear localization we screened libraries of short fragments tiled across nuclear {RNAs}, which were cloned into the untranslated regions of an efficiently exported {mRNA}. The screen identified a short sequence derived from Alu elements and found in many {mRNAs} and {lncRNAs} that increases nuclear accumulation and reduces overall expression levels. Measurements of the contribution of individual bases and short motifs to the element functionality identified a combination of {RCCTCCC} motifs that are bound by the abundant nuclear protein {HNRNPK}. Increased {HNRNPK} binding and C-rich motifs are predictive of substantial nuclear enrichment in both {lncRNAs} and {mRNAs}, and this mechanism is conserved across species. Our results thus detail a novel pathway for regulation of {RNA} accumulation and subcellular localization that has been co-opted to regulate the fate of transcripts that integrated Alu elements.},
	pages = {189746},
	journaltitle = {{bioRxiv}},
	author = {Lubelsky, Yoav and Ulitsky, Igor},
	date = {2017-09}
}

@article{liang_gene_2000,
	title = {Gene index analysis of the human genome estimates approximately 120,000 genes.},
	volume = {25},
	issn = {1061-4036},
	doi = {10.1038/76126},
	abstract = {Although sequencing of the human genome will soon be completed, gene identification and annotation remains a challenge. Early estimates suggested that there might be 60,000-100,000 (ref. 1) human genes, but recent analyses of the available data from {EST} sequencing projects have estimated as few as 45,000 (ref. 2) or as many as 140, 000 (ref. 3) distinct genes. The Chromosome 22 Sequencing Consortium estimated a minimum of 45,000 genes based on their annotation of the complete chromosome, although their data suggests there may be additional genes. The nearly 2,000,000 human {ESTs} in {dbEST} provide an important resource for gene identification and genome annotation, but these single-pass sequences must be carefully analysed to remove contaminating sequences, including those from genomic {DNA}, spurious transcription, and vector and bacterial sequences. We have developed a highly refined and rigorously tested protocol for cleaning, clustering and assembling {EST} sequences to produce high-fidelity consensus sequences for the represented genes (F.L. et al., manuscript submitted) and used this to create the {TIGR} Gene Indices-databases of expressed genes for human, mouse, rat and other species (http://www.tigr.org/tdb/tgi.html). Using highly refined and tested algorithms for {EST} analysis, we have arrived at two independent estimates indicating the human genome contains approximately 120,000 genes.},
	pages = {239--40},
	number = {2},
	journaltitle = {Nature genetics},
	author = {Liang, F and Holt, I and Pertea, G and Karamycheva, S and Salzberg, S L and Quackenbush, J},
	date = {2000-06},
	pmid = {10835646}
}

@article{yu_brwlda:_2017,
	title = {{BRWLDA}: bi-random walks for predicting {lncRNA}-disease associations},
	volume = {8},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.19588},
	abstract = {// Guoxian Yu 1 , Guangyuan Fu 1 , Chang Lu 1 , Yazhou Ren 2 and Jun Wang 1 1 College of Computer and Information Sciences, Southwest University, Chongqing, China 2 Big Data Research Center, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China Correspondence to: Guoxian Yu, email: gxyu@swu.edu.cn Jun Wang, email: kingjun@swu.edu.cn Keywords: {lncRNAs}, diseases, {lncRNA}-disease associations, bi-relational network, bi-random walk Received: May 25, 2017\ \ \ \  Accepted: June 19, 2017\ \ \ \  Published: July 26, 2017 {ABSTRACT} Increasing efforts have been done to figure out the association between {lncRNAs} and complex diseases. Many computational models construct various {lncRNA} similarity networks, disease similarity networks, along with known {lncRNA}-disease associations to infer novel associations. However, most of them neglect the structural difference between {lncRNAs} network and diseases network, hierarchical relationships between diseases and pattern of newly discovered associations. In this study, we developed a model that performs B i- R andom W alks to predict novel L {ncRNA}- D isease A ssociations ({BRWLDA} in short). This model utilizes multiple heterogeneous data to construct the {lncRNA} functional similarity network, and Disease Ontology to construct a disease network. It then constructs a directed bi-relational network based on these two networks and available {lncRNAs}-disease associations. Next, it applies bi-random walks on the network to predict potential associations. {BRWLDA} achieves reliable and better performance than other comparing methods not only on experiment verified associations, but also on the simulated experiments with masked associations. Case studies further demonstrate the feasibility of {BRWLDA} in identifying new {lncRNA}-disease associations.},
	pages = {60429--60446},
	number = {36},
	journaltitle = {Oncotarget},
	author = {Yu, Guoxian and Fu, Guangyuan and Lu, Chang and Ren, Yazhou and Wang, Jun and Yu, Guoxian and Fu, Guangyuan and Lu, Chang and Ren, Yazhou and Wang, Jun and Yu, Guoxian and Fu, Guangyuan and Lu, Chang and Ren, Yazhou and Wang, Jun},
	date = {2017-09}
}

@article{trapnell_transcript_2010,
	title = {Transcript assembly and quantification by {RNA}-Seq reveals unannotated transcripts and isoform switching during cell differentiation},
	volume = {28},
	issn = {1087-0156},
	doi = {10.1038/nbt.1621},
	abstract = {High-throughput {mRNA} sequencing ({RNA}-Seq) promises simultaneous transcript discovery and abundance estimation. However, this would require algorithms that are not restricted by prior gene annotations and that account for alternative transcription and splicing. Here we introduce such algorithms in an open-source software program called Cufflinks. To test Cufflinks, we sequenced and analyzed {\textbackslash}textgreater430 million paired 75-bp {RNA}-Seq reads from a mouse myoblast cell line over a differentiation time series. We detected 13,692 known transcripts and 3,724 previously unannotated ones, 62\% of which are supported by independent expression data or by homologous genes in other species. Over the time series, 330 genes showed complete switches in the dominant transcription start site ({TSS}) or splice isoform, and we observed more subtle shifts in 1,304 other genes. These results suggest that Cufflinks can illuminate the substantial regulatory flexibility and complexity in even this well-studied model of muscle development and that it can improve transcriptome-based genome annotation.},
	pages = {511--515},
	number = {5},
	journaltitle = {Nature Biotechnology},
	author = {Trapnell, Cole and Williams, Brian A and Pertea, Geo and Mortazavi, Ali and Kwan, Gordon and van Baren, Marijke J and Salzberg, Steven L and Wold, Barbara J and Pachter, Lior},
	date = {2010-05},
	pmid = {20436464},
	keywords = {Gene Expression Profiling/*methods, Sequence Analysis, Animals, Genome, Mice, {RNA}, Algorithms, Software, Cell Differentiation/*genetics, Cell Line, Oligonucleotide Array Sequence Analysis/*methods, Proto-Oncogene Proteins c-myc/genetics/metabolism, {RNA}/*methods, Messenger/*analysis/genetics/metabolism, Protein Isoforms/*genetics/metabolism}
}

@article{zhu_genome-scale_2016,
	title = {Genome-scale deletion screening of human long non-coding {RNAs} using a paired-guide {RNA} {CRISPR}–Cas9 library},
	volume = {34},
	issn = {1087-0156},
	doi = {10.1038/nbt.3715},
	abstract = {{CRISPR}-Cas9 screens have been widely adopted to analyze coding-gene functions, but high-throughput screening of non-coding elements using this method is more challenging because indels caused by a single cut in non-coding regions are unlikely to produce a functional knockout. A high-throughput method to produce deletions of non-coding {DNA} is needed. We report a high-throughput genomic deletion strategy to screen for functional long non-coding {RNAs} ({lncRNAs}) that is based on a lentiviral paired-guide {RNA} ({pgRNA}) library. Applying our screening method, we identified 51 {lncRNAs} that can positively or negatively regulate human cancer cell growth. We validated 9 of 51 {lncRNA} hits using {CRISPR}-Cas9-mediated genomic deletion, functional rescue, {CRISPR} activation or inhibition and gene-expression profiling. Our high-throughput {pgRNA} genome deletion method will enable rapid identification of functional mammalian non-coding elements.},
	pages = {1279--1286},
	number = {12},
	journaltitle = {Nature Biotechnology},
	author = {Zhu, Shiyou and Li, Wei and Liu, Jingze and Chen, Chen-Hao and Liao, Qi and Xu, Ping and Xu, Han and Xiao, Tengfei and Cao, Zhongzheng and Peng, Jingyu and Yuan, Pengfei and Brown, Myles and Liu, Xiaole Shirley and Wei, Wensheng},
	date = {2016-10},
	pmid = {27798563},
	keywords = {Humans, Chromosome Mapping, Gene Deletion, High-Throughput Nucleotide Sequencing, {RNA}, Long Noncoding, Sequence Analysis, {RNA}, Genome, Human, Genetic Testing, {CRISPR}-Cas Systems, Clustered Regularly Interspaced Short Palindromic Repeats},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/869MKCQR/Zhu et al. - 2016 - Genome-scale deletion screening of human long non-.pdf:application/pdf;Accepted Version:/home/jlagarde/Zotero/storage/Y9TI8YZD/Zhu et al. - 2016 - Genome-scale deletion screening of human long non-.pdf:application/pdf}
}

@article{ip_gomafu_2016,
	title = {Gomafu {lncRNA} knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine},
	volume = {6},
	issn = {2045-2322},
	doi = {10.1038/srep27204},
	abstract = {Gomafu {lncRNA} knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine},
	pages = {27204},
	number = {1},
	journaltitle = {Scientific Reports},
	author = {Ip, Joanna Y. and Sone, Masamitsu and Nashiki, Chieko and Pan, Qun and Kitaichi, Kiyoyuki and Yanaka, Kaori and Abe, Takaya and Takao, Keizo and Miyakawa, Tsuyoshi and Blencowe, Benjamin J. and Nakagawa, Shinichi},
	date = {2016-07}
}

@article{huang_peptide_2017,
	title = {A Peptide Encoded by a Putative {lncRNA} {HOXB}-{AS}3 Suppresses Colon Cancer Growth.},
	volume = {68},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2017.09.015},
	abstract = {A substantial fraction of eukaryotic transcripts are considered long non-coding {RNAs} ({lncRNAs}), which regulate various hallmarks of cancer. Here, we discovered that the {lncRNA} {HOXB}-{AS}3 encodes a conserved 53-aa peptide. The {HOXB}-{AS}3 peptide, not {lncRNA}, suppresses colon cancer ({CRC}) growth. Mechanistically, the {HOXB}-{AS}3 peptide competitively binds to the ariginine residues in {RGG} motif of {hnRNP} A1 and antagonizes the {hnRNP} A1-mediated regulation of pyruvate kinase M ({PKM}) splicing by blocking the binding of the ariginine residues in {RGG} motif of {hnRNP} A1 to the sequences flanking {PKM} exon 9, ensuring the formation of lower {PKM}2 and suppressing glucose metabolism reprogramming. {CRC} patients with low levels of {HOXB}-{AS}3 peptide have poorer prognoses. Our study indicates that the loss of {HOXB}-{AS}3 peptide is a critical oncogenic event in {CRC} metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an {lncRNA}.},
	pages = {171--184.e6},
	number = {1},
	journaltitle = {Molecular cell},
	author = {Huang, Jin-Zhou and Chen, Min and Chen, De and Gao, Xing-Cheng and Zhu, Song and Huang, Hongyang and Hu, Min and Zhu, Huifang and Yan, Guang-Rong},
	date = {2017-10},
	pmid = {28985503}
}

@article{de_kok_dd3pca3_2002,
	title = {{DD}3({PCA}3), a very sensitive and specific marker to detect prostate tumors.},
	volume = {62},
	issn = {0008-5472},
	abstract = {We identified {DD}3({PCA}3) as one of the most prostate cancer-specific genes at present (M. J. Bussemakers et al. Cancer Res., 59: 5975-5979, 1999). Consequently, {DD}3({PCA}3) is an interesting candidate for use as a diagnostic and/or prognostic marker. In this study we developed a method for the accurate quantification of {DD}3({PCA}3) {mRNA}, using real-time quantitative reverse transcription-{PCR}. {DD}3({PCA}3) was expressed at low levels in normal prostate but not in 21 selected other normal tissues, blood, or 39 tumor samples other than prostate. The diagnostic and prognostic value of {DD}3({PCA}3) in normal, hyperplastic, and malignant prostate tissues was determined and compared with another promising tumor marker for prostate cancer, telomerase reverse transcriptase ({hTERT} gene), the expression of which is related to telomerase activity. Sensitivity and specificity estimates for both genes were calculated as the area under the receiver-operating characteristics curve ({AUC}-{ROC}). {DD}3({PCA}3) ({AUC}-{ROC}, 0.98) demonstrated better diagnostic efficacy than {hTERT} ({AUC}-{ROC}, 0.88). Moreover, the median increase in {mRNA} expression in tumor tissues compared with nonmalignant prostate tissues was much higher for {DD}3({PCA}3) (34-fold) than for {hTERT} (6-fold). In tumor tissues, the median expression of {DD}3({PCA}3) was much higher than {hTERT} (5849 versus 10 normalized {mRNA} copies). A significant relationship was observed only between tumor stage and {hTERT} gene expression. We conclude that expression of the {DD}3({PCA}3) gene is a very sensitive and specific marker for the detection of prostate tumor cells in a high background of normal (prostate) cells. Consequently, {DD}3 measurements may be used for clinical application in prostate needle biopsies or bodily fluids such as blood, ejaculate, urine, or prostate massage fluid.},
	pages = {2695--8},
	number = {9},
	journaltitle = {Cancer research},
	author = {de Kok, Jacques B and Verhaegh, Gerald W and Roelofs, Rian W and Hessels, Daphne and Kiemeney, Lambertus A and Aalders, Tilly W and Swinkels, Dorine W and Schalken, Jack A},
	date = {2002-05},
	pmid = {11980670}
}

@article{oikonomopoulos_benchmarking_2016,
	title = {Benchmarking of the Oxford Nanopore {MinION} sequencing for quantitative and qualitative assessment of {cDNA} populations},
	volume = {6},
	issn = {2045-2322},
	doi = {10.1038/srep31602},
	abstract = {Benchmarking of the Oxford Nanopore {MinION} sequencing for quantitative and qualitative assessment of {cDNA} populations},
	pages = {31602},
	number = {1},
	journaltitle = {Scientific Reports},
	author = {Oikonomopoulos, Spyros and Wang, Yu Chang and Djambazian, Haig and Badescu, Dunarel and Ragoussis, Jiannis},
	date = {2016-10}
}

@article{wen_critical_2016,
	title = {Critical roles of long noncoding {RNAs} in Drosophila spermatogenesis.},
	volume = {26},
	issn = {1549-5469},
	doi = {10.1101/gr.199547.115},
	abstract = {Long noncoding {RNAs} ({lncRNAs}), a recently discovered class of cellular {RNAs}, play important roles in the regulation of many cellular developmental processes. Although {lncRNAs} have been systematically identified in various systems, most of them have not been functionally characterized in vivo in animal models. In this study, we identified 128 testis-specific Drosophila {lncRNAs} and knocked out 105 of them using an optimized three-component {CRISPR}/Cas9 system. Among the {lncRNA} knockouts, 33 (31\%) exhibited a partial or complete loss of male fertility, accompanied by visual developmental defects in late spermatogenesis. In addition, six knockouts were fully or partially rescued by transgenes in a trans configuration, indicating that those {lncRNAs} primarily work in trans Furthermore, gene expression profiles for five {lncRNA} mutants revealed that testis-specific {lncRNAs} regulate global gene expression, orchestrating late male germ cell differentiation. Compared with coding genes, the testis-specific {lncRNAs} evolved much faster. Moreover, {lncRNAs} of greater functional importance exhibited higher sequence conservation, suggesting that they are under constant evolutionary selection. Collectively, our results reveal critical functions of rapidly evolving testis-specific {lncRNAs} in late Drosophila spermatogenesis.},
	pages = {1233--44},
	number = {9},
	journaltitle = {Genome research},
	author = {Wen, Kejia and Yang, Lijuan and Xiong, Tuanlin and Di, Chao and Ma, Danhui and Wu, Menghua and Xue, Zhaoyu and Zhang, Xuedi and Long, Li and Zhang, Weimin and Zhang, Jiaying and Bi, Xiaolin and Dai, Junbiao and Zhang, Qiangfeng and Lu, Zhi John and Gao, Guanjun},
	date = {2016-09},
	pmid = {27516619}
}

@article{kanehisa_data_2014,
	title = {Data, information, knowledge and principle: back to metabolism in {KEGG}},
	volume = {42},
	issn = {0305-1048},
	doi = {10.1093/nar/gkt1076},
	pages = {D199--D205},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Kanehisa, Minoru and Goto, Susumu and Sato, Yoko and Kawashima, Masayuki and Furumichi, Miho and Tanabe, Mao},
	date = {2014-01}
}

@article{lagarde_high-throughput_2017,
	title = {High-throughput annotation of full-length long noncoding {RNAs} with capture long-read sequencing},
	volume = {49},
	issn = {1061-4036},
	doi = {10.1038/ng.3988},
	abstract = {Accurate annotation of genes and their transcripts is a foundation of genomics, but currently no annotation technique combines throughput and accuracy. As a result, reference gene collections remain incomplete-many gene models are fragmentary, and thousands more remain uncataloged, particularly for long noncoding {RNAs} ({lncRNAs}). To accelerate {lncRNA} annotation, the {GENCODE} consortium has developed {RNA} Capture Long Seq ({CLS}), which combines targeted {RNA} capture with third-generation long-read sequencing. Here we present an experimental reannotation of the {GENCODE} intergenic {lncRNA} populations in matched human and mouse tissues that resulted in novel transcript models for 3,574 and 561 gene loci, respectively. {CLS} approximately doubled the annotated complexity of targeted loci, outperforming existing short-read techniques. Full-length transcript models produced by {CLS} enabled us to definitively characterize the genomic features of {lncRNAs}, including promoter and gene structure, and protein-coding potential. Thus, {CLS} removes a long-standing bottleneck in transcriptome annotation and generates manual-quality full-length transcript models at high-throughput scales.},
	pages = {1731--1740},
	number = {12},
	journaltitle = {Nature Genetics},
	author = {Lagarde, Julien and Uszczynska-Ratajczak, Barbara and Carbonell, Silvia and Pérez-Lluch, Sílvia and Abad, Amaya and Davis, Carrie and Gingeras, Thomas R and Frankish, Adam and Harrow, Jennifer and Guigo, Roderic and Johnson, Rory},
	date = {2017-11},
	pmid = {29106417}
}

@article{guo_long_2013,
	title = {Long non-coding {RNAs} function annotation: a global prediction method based on bi-colored networks},
	volume = {41},
	issn = {1362-4962},
	doi = {10.1093/nar/gks967},
	pages = {e35--e35},
	number = {2},
	journaltitle = {Nucleic Acids Research},
	author = {Guo, Xingli and Gao, Lin and Liao, Qi and Xiao, Hui and Ma, Xiaoke and Yang, Xiaofei and Luo, Haitao and Zhao, Guoguang and Bu, Dechao and Jiao, Fei and Shao, Qixiang and Chen, {RunSheng} and Zhao, Yi},
	date = {2013-01}
}

@article{dinger_differentiating_2008,
	title = {Differentiating protein-coding and noncoding {RNA}: challenges and ambiguities.},
	volume = {4},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1000176},
	abstract = {The assumption that {RNA} can be readily classified into either protein-coding or non-protein-coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger {RNAs} ({mRNAs}), and readily distinguished from the small number of well-characterized non-protein-coding {RNAs} ({ncRNAs}), such as transfer, ribosomal, and spliceosomal {RNAs}. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between {mRNAs} and {ncRNAs} both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some {ncRNAs} may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some {RNAs} can function both as {mRNAs} and intrinsically as functional {ncRNAs}, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an {RNA} unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the {RNA} level and to encode proteins suggests a false dichotomy between {mRNAs} and {ncRNAs}. Therefore, the functionality of any transcript at the {RNA} level should not be discounted.},
	pages = {e1000176},
	number = {11},
	journaltitle = {{PLoS} computational biology},
	author = {Dinger, Marcel E and Pang, Ken C and Mercer, Tim R and Mattick, John S},
	editor = {{McEntyre}, Johanna},
	date = {2008-11},
	pmid = {19043537},
	keywords = {Genetic, {RNA}, Transcription, *Gene Expression Profiling, *Open Reading Frames, Computational Biology/*methods, Genomics/methods, Messenger/chemistry/*genetics, Untranslated/chemistry/*genetics}
}

@article{carlevaro-fita_unique_2017,
	title = {Unique genomic features and deeply-conserved functions of long non-coding {RNAs} in the Cancer {LncRNA} Census ({CLC})},
	doi = {10.1101/152769},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) that drive tumorigenesis are a growing focus of cancer genomics studies. To facilitate further discovery, we have created the “Cancer {LncRNA} Census” ({CLC}), a manually-curated and strictly-defined compilation of {lncRNAs} with causative roles in cancer. {CLC} has two principle applications: first, as a resource for training and benchmarking de novo identification methods; and second, as a dataset for studying the fundamental properties of these genes. {CLC} Version 1 comprises 122 {lncRNAs} implicated in 31 distinct cancers. {LncRNAs} are included based on functional or genetic evidence for different causative roles in cancer progression. All belong to the {GENCODE} reference annotation, to facilitate integration across projects and datasets. For each entry, the evidence type, biological activity (oncogene or tumour suppressor), source reference and cancer type are recorded. {CLC} genes are significantly enriched amongst de novo predicted driver genes from {PCAWG}. {CLC} genes are distinguished from other {lncRNAs} by a series of features consistent with biological function, including gene length, expression and sequence conservation of both exons and promoters. We identify a trend for {CLC} genes to be co-localised with known protein-coding cancer genes along the human genome. Finally, by integrating data from transposon-mutagenesis functional screens, we show that mouse orthologues of {CLC} genes tend also to be cancer driver genes. Thus {CLC} represents a valuable resource for research into long non-coding {RNAs} in cancer. Their evolutionary and genomic properties have implications for understanding disease mechanisms and point to conserved functions across ∼80 million years of evolution.},
	pages = {152769},
	journaltitle = {{bioRxiv}},
	author = {Carlevaro-Fita, Joana and Camaioni, Andres Arturo Lanzos and Feuerbach, Lars and Hong, Chen and Mas-Ponte, David and 2-5-9-14, - {PCAWG} Driver Identification Working Group and Guigo, Roderic and Pedersen, Jakob Skou and Johnson, Rory},
	date = {2017-06}
}

@article{mason_retinoic_2015,
	title = {Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb.},
	volume = {6},
	issn = {2041-9139},
	doi = {10.1186/s13227-015-0001-y},
	abstract = {{BACKGROUND} The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning. {RESULTS} Using transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction ({RT}-{qPCR}) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from {CS}16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid ({RA}) signalling as it is present in the retained interdigital tissue of Rdh10 (trex/trex) mice, which lack {RA}. Additionally, genes encoding {RA}-synthesising enzymes, Rdh10 and Aldh1a2, and the {RA} nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of {RA} signalling. {CONCLUSIONS} Mammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is {RA}-independent, and retention of interdigital webbing in bat wings is not due to the suppression of {RA}-induced cell death. Rather, {RA} signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth.},
	pages = {6},
	number = {1},
	journaltitle = {{EvoDevo}},
	author = {Mason, Mandy K and Hockman, Dorit and Curry, Lyle and Cunningham, Thomas J and Duester, Gregg and Logan, Malcolm and Jacobs, David S and Illing, Nicola},
	date = {2015-12},
	pmid = {25861444}
}

@article{di_iulio_human_2018,
	title = {The human noncoding genome defined by genetic diversity},
	issn = {1061-4036},
	url = {http://www.nature.com/articles/s41588-018-0062-7},
	doi = {10.1038/s41588-018-0062-7},
	abstract = {Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes. Constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions (21-fold when compared to the genome average). This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants and reconsider gene units at a larger scale.},
	pages = {1},
	journaltitle = {Nature Genetics},
	author = {di Iulio, Julia and Bartha, Istvan and Wong, Emily H. M. and Yu, Hung-Chun and Lavrenko, Victor and Yang, Dongchan and Jung, Inkyung and Hicks, Michael A. and Shah, Naisha and Kirkness, Ewen F. and Fabani, Martin M. and Biggs, William H. and Ren, Bing and Venter, J. Craig and Telenti, Amalio},
	date = {2018-02},
	keywords = {Animal Genetics and Genomics, Human Genetics, Agriculture, Biomedicine, Cancer Research, Gene Function, general},
	file = {Attachment:/home/jlagarde/Zotero/storage/AEUWEVV2/di Iulio et al. - 2018 - The human noncoding genome defined by genetic diversity.pdf:text/html}
}

@article{xie_soapdenovo-trans:_2014,
	title = {{SOAPdenovo}-Trans: De novo transcriptome assembly with short {RNA}-Seq reads},
	volume = {30},
	issn = {14602059},
	url = {https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btu077 http://www.ncbi.nlm.nih.gov/pubmed/24532719},
	doi = {10.1093/bioinformatics/btu077},
	abstract = {Motivation: Transcriptome sequencing has long been the favored method for quickly and inexpensively obtaining a large number of gene sequences from an organism with no reference genome. Owing to the rapid increase in throughputs and decrease in costs of next- generation sequencing, {RNA}-Seq in particular has become the method of choice. However, the very short reads (e.g. 2 × 90 bp paired ends) from next generation sequencing makes de novo assembly to recover complete or full-length transcript sequences an algorithmic challenge.\${\textbackslash}backslash\${nResults}: Here, we present {SOAPdenovo}-Trans, a de novo transcriptome assembler designed specifically for {RNA}-Seq. We evaluated its performance on transcriptome datasets from rice and mouse. Using as our benchmarks the known transcripts from these well-annotated genomes (sequenced a decade ago), we assessed how {SOAPdenovo}-Trans and two other popular transcriptome assemblers handled such practical issues as alternative splicing and variable expression levels. Our conclusion is that {SOAPdenovo}-Trans provides higher contiguity, lower redundancy and faster execution.\${\textbackslash}backslash\${nAvailability} and implementation: Source code and user manual are available at http://sourceforge.net/projects/soapdenovotrans/.\${\textbackslash}backslash\${nContact}: xieyl@genomics.cn or bgi-soap@googlegroups.com\${\textbackslash}backslash\${nSupplementary} information: Supplementary data are available at Bioinformatics online.},
	pages = {1660--1666},
	number = {12},
	journaltitle = {Bioinformatics},
	author = {Xie, Yinlong and Wu, Gengxiong and Tang, Jingbo and Luo, Ruibang and Patterson, Jordan and Liu, Shanlin and Huang, Weihua and He, Guangzhu and Gu, Shengchang and Li, Shengkang and Zhou, Xin and Lam, Tak Wah and Li, Yingrui and Xu, Xun and Wong, Gane Ka Shu and Wang, Jun},
	date = {2014-06},
	pmid = {24532719}
}

@article{grabherr_full-length_2011,
	title = {Full-length transcriptome assembly from {RNA}-Seq data without a reference genome},
	volume = {29},
	issn = {10870156},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21572440 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3571712 http://www.nature.com/articles/nbt.1883},
	doi = {10.1038/nbt.1883},
	abstract = {Massively parallel sequencing of {cDNA} has enabled deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here we present the Trinity method for de novo assembly of full-length transcripts and evaluate it on samples from fission yeast, mouse and whitefly, whose reference genome is not yet available. By efficiently constructing and analyzing sets of de Bruijn graphs, Trinity fully reconstructs a large fraction of transcripts, including alternatively spliced isoforms and transcripts from recently duplicated genes. Compared with other de novo transcriptome assemblers, Trinity recovers more full-length transcripts across a broad range of expression levels, with a sensitivity similar to methods that rely on genome alignments. Our approach provides a unified solution for transcriptome reconstruction in any sample, especially in the absence of a reference genome.},
	pages = {644--652},
	number = {7},
	journaltitle = {Nature Biotechnology},
	author = {Grabherr, Manfred G and Haas, Brian J and Yassour, Moran and Levin, Joshua Z and Thompson, Dawn A and Amit, Ido and Adiconis, Xian and Fan, Lin and Raychowdhury, Raktima and Zeng, Qiandong and Chen, Zehua and Mauceli, Evan and Hacohen, Nir and Gnirke, Andreas and Rhind, Nicholas and Di Palma, Federica and Birren, Bruce W and Nusbaum, Chad and Lindblad-Toh, Kerstin and Friedman, Nir and Regev, Aviv},
	date = {2011-07},
	pmid = {21572440}
}

@article{hayer_benchmark_2015,
	title = {Benchmark analysis of algorithms for determining and quantifying full-length {mRNA} splice forms from {RNA}-seq data},
	volume = {31},
	issn = {14602059},
	url = {https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btv488},
	doi = {10.1093/bioinformatics/btv488},
	abstract = {{MOTIVATION}: Because of the advantages of {RNA} sequencing ({RNA}-Seq) over microarrays, it is gaining widespread popularity for highly parallel gene expression analysis. For example, {RNA}-Seq is expected to be able to provide accurate identification and quantification of full-length splice forms. A number of informatics packages have been developed for this purpose, but short reads make it a difficult problem in principle. Sequencing error and polymorphisms add further complications. It has become necessary to perform studies to determine which algorithms perform best and which if any algorithms perform adequately. However, there is a dearth of independent and unbiased benchmarking studies. Here we take an approach using both simulated and experimental benchmark data to evaluate their accuracy. {RESULTS}: We conclude that most methods are inaccurate even using idealized data, and that no method is highly accurate once multiple splice forms, polymorphisms, intron signal, sequencing errors, alignment errors, annotation errors, and other complicating factors are present. These results point to the pressing need for further algorithm development. {AVAILABILITY}: Simulated data sets and other supporting information can be found at http://bioinf.itmat.upenn.edu/{BEERS}/bp2 {CONTACT}: hayer@upenn.edu.},
	pages = {3938--3945},
	number = {24},
	journaltitle = {Bioinformatics},
	author = {Hayer, Katharina E. and Pizarro, Angel and Lahens, Nicholas F. and Hogenesch, John B. and Grant, Gregory R.},
	date = {2015-09},
	pmid = {26338770},
	file = {Attachment:/home/jlagarde/Zotero/storage/TZ8DAB2P/Hayer et al. - 2015 - Benchmark analysis of algorithms for determining and quantifying full-length mRNA splice forms from RNA-seq data.pdf:application/pdf}
}

@article{marx_meet_2018,
	title = {Meet some code-breakers of noncoding {RNAs}},
	volume = {15},
	issn = {1548-7091},
	url = {http://www.nature.com/doifinder/10.1038/nmeth.4594},
	doi = {10.1038/nmeth.4594},
	pages = {103--106},
	number = {2},
	journaltitle = {Nature Methods},
	author = {Marx, Vivien},
	date = {2018-01}
}

@article{kopp_functional_2018,
	title = {Functional Classification and Experimental Dissection of Long Noncoding {RNAs}.},
	volume = {172},
	issn = {1097-4172},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/29373828},
	doi = {10.1016/j.cell.2018.01.011},
	abstract = {Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding {RNAs} ({lncRNAs}). At the same time, it is now appreciated that many types of {DNA} regulatory elements, such as enhancers and promoters, regularly initiate bi-directional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the {lncRNA} field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating {lncRNA} function. We categorize {lncRNA} loci into those that regulate gene expression in cis versus those that perform functions in trans and propose an experimental approach to dissect {lncRNA} activity based on these classifications. These strategies to further understand {lncRNAs} promise to reveal new and unanticipated biology with great potential to advance our understanding of normal physiology and disease.},
	pages = {393--407},
	number = {3},
	journaltitle = {Cell},
	author = {Kopp, Florian and Mendell, Joshua T},
	date = {2018-01},
	pmid = {29373828},
	keywords = {{lncRNA}, noncoding {RNA}},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/VWIWM93K/Kopp and Mendell - 2018 - Functional Classification and Experimental Dissect.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/4HK6JN9U/Kopp and Mendell - 2018 - Functional Classification and Experimental Dissect.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/SLG5WTPT/S0092-8674(18)30048-5.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/YBLTB588/S0092-8674(18)30048-5.html:text/html}
}

@article{weirather_comprehensive_2017,
	title = {Comprehensive comparison of Pacific Biosciences and Oxford Nanopore Technologies and their applications to transcriptome analysis.},
	volume = {6},
	issn = {2046-1402},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/28868132 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5553090},
	doi = {10.12688/f1000research.10571.2},
	abstract = {Background: Given the demonstrated utility of Third Generation Sequencing [Pacific Biosciences ({PacBio}) and Oxford Nanopore Technologies ({ONT})] long reads in many studies, a comprehensive analysis and comparison of their data quality and applications is in high demand. Methods: Based on the transcriptome sequencing data from human embryonic stem cells, we analyzed multiple data features of {PacBio} and {ONT}, including error pattern, length, mappability and technical improvements over previous platforms. We also evaluated their application to transcriptome analyses, such as isoform identification and quantification and characterization of transcriptome complexity, by comparing the performance of size-selected {PacBio}, non-size-selected {ONT} and their corresponding Hybrid-Seq strategies ({PacBio}+Illumina and {ONT}+Illumina). Results: {PacBio} shows overall better data quality, while {ONT} provides a higher yield. As with data quality, {PacBio} performs marginally better than {ONT} in most aspects for both long reads only and Hybrid-Seq strategies in transcriptome analysis. In addition, Hybrid-Seq shows superior performance over long reads only in most transcriptome analyses. Conclusions: Both {PacBio} and {ONT} sequencing are suitable for full-length single-molecule transcriptome analysis. As this first use of {ONT} reads in a Hybrid-Seq analysis has shown, both {PacBio} and {ONT} can benefit from a combined Illumina strategy. The tools and analytical methods developed here provide a resource for future applications and evaluations of these rapidly-changing technologies.},
	pages = {100},
	journaltitle = {F1000Research},
	author = {Weirather, Jason L and de Cesare, Mariateresa and Wang, Yunhao and Piazza, Paolo and Sebastiano, Vittorio and Wang, Xiu-Jie and Buck, David and Au, Kin Fai},
	date = {2017},
	pmid = {28868132},
	keywords = {Transcriptome, Oxford Nanopore Technologies, {PacBio}, Third Generation Sequencing}
}

@article{bartonicek_intergenic_2017,
	title = {Intergenic disease-associated regions are abundant in novel transcripts},
	volume = {18},
	issn = {1474-760X},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/29284497 https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1363-3},
	doi = {10.1186/s13059-017-1363-3},
	abstract = {{BACKGROUND} Genotyping of large populations through genome-wide association studies ({GWAS}) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a large proportion of {GWAS} single nucleotide polymorphisms ({SNPs}) and associated haplotype blocks are in intronic and intergenic regions, hindering their functional evaluation. While some of these risk-susceptibility regions encompass cis-regulatory sites, their transcriptional potential has never been systematically explored. {RESULTS} To detect rare tissue-specific expression, we employed the transcript-enrichment method {CaptureSeq} on 21 human tissues to identify 1775 multi-exonic transcripts from 561 intronic and intergenic haploblocks associated with 392 traits and diseases, covering 73.9 Mb (2.2\%) of the human genome. We show that a large proportion (85\%) of disease-associated haploblocks express novel multi-exonic non-coding transcripts that are tissue-specific and enriched for {GWAS} {SNPs} as well as epigenetic markers of active transcription and enhancer activity. Similarly, we captured transcriptomes from 13 melanomas, targeting nine melanoma-associated haploblocks, and characterized 31 novel melanoma-specific transcripts that include fusion proteins, novel exons and non-coding {RNAs}, one-third of which showed allelically imbalanced expression. {CONCLUSIONS} This resource of previously unreported transcripts in disease-associated regions ( http://gwas-captureseq.dingerlab.org ) should provide an important starting point for the translational community in search of novel biomarkers, disease mechanisms, and drug targets.},
	pages = {241},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Bartonicek, N. and Clark, M. B. and Quek, X. C. and Torpy, J. R. and Pritchard, A. L. and Maag, J. L. V. and Gloss, B. S. and Crawford, J. and Taft, R. J. and Hayward, N. K. and Montgomery, G. W. and Mattick, J. S. and Mercer, T. R. and Dinger, M. E.},
	date = {2017-12},
	pmid = {29284497}
}

@article{cheetham_rna-damid_2017,
	title = {{RNA}-{DamID} reveals cell-type-specific binding of {roX} {RNAs} at chromatin-entry sites},
	issn = {1545-9993},
	url = {http://www.nature.com/articles/s41594-017-0006-4 https://www.nature.com/articles/s41594-017-0006-4},
	doi = {10.1038/s41594-017-0006-4},
	abstract = {Thousands of long noncoding {RNAs} ({lncRNAs}) have been identified in eukaryotic genomes, many of which are expressed in spatially and temporally restricted patterns. Nonetheless, the roles of the majority of these transcripts are still unknown. One of the mechanisms by which {lncRNAs} function is through the modulation of chromatin states. To assess the functions of {lncRNAs}, we developed {RNA}-{DamID}, a novel approach that detects {lncRNA}–genome interactions in a cell-type-specific manner in vivo with high sensitivity and accuracy. Identifying the cell-type-specific genome occupancy of {lncRNAs} is vital to understanding their mechanisms of action in development and disease. We used {RNA}-{DamID} to investigate targeting of the {lncRNAs} in the Drosophila dosage-compensation complex ({DCC}) and show that initial targeting is cell-type specific.},
	pages = {1},
	journaltitle = {Nature Structural \& Molecular Biology 2017},
	author = {Cheetham, Seth W. and Brand, Andrea H.},
	date = {2017}
}

@article{krizanovic_evaluation_2017,
	title = {Evaluation of tools for long read {RNA}-seq splice-aware alignment},
	issn = {1367-4803},
	url = {https://github.com/kkrizanovic/RNAseqEval%0Ahttp://dx.doi.org/10.1101/126656%0Ahttp://biorxiv.org/content/early/2017/04/11/126656%0Ahttps://github.com/isovic/cgmemtime.git},
	doi = {10.1101/126656},
	abstract = {Motivation: High-throughput sequencing has transformed the study of gene expression levels through {RNA}-seq, a technique that is now routinely used by various fields, such as genetic research or diagnostics. The advent of third generation sequencing technologies providing significantly longer reads opens up new possibilities. However, the high error rates common to these technologies set new bioinformatics challenges for the gapped alignment of reads to their genomic origin. In this study, we have explored how currently available {RNA}-seq splice-aware alignment tools cope with increased read lengths and error rates. All tested tools were initially developed for short {NGS} reads, but some have claimed support for long {PacBio} or even {ONT} {MinION} reads. Results: The tools were tested on synthetic and real datasets from the {PacBio} and {ONT} {MinION} technologies, and both alignment quality and resource usage were compared across tools. The effect of error correction of long reads was explored, both using self-correction and correction with an external short reads dataset. A tool was developed for evaluating {RNA}-seq alignment results. This tool can be used to compare the alignment of simulated reads to their genomic origin, or to compare the alignment of real reads to a set of annotated transcripts. Our tests show that while some {RNA}-seq aligners were unable to cope with long error-prone reads, others produced overall good results. We further show that alignment accuracy can be improved using error-corrected reads.\${\textbackslash}backslash\$r\${\textbackslash}backslash\$n\${\textbackslash}backslash\$r\${\textbackslash}backslash\$n},
	pages = {1--14},
	journaltitle = {{bioRxiv}},
	author = {Krizanovic, Kresimir and Echchiki, Amina and Roux, Julien and Sikic, Mile},
	date = {2017-10},
	file = {Attachment:/home/jlagarde/Zotero/storage/IBXTR6HN/Krizanovic et al. - 2017 - Evaluation of tools for long read RNA-seq splice-aware alignment.pdf:application/pdf}
}

@article{hardwick_spliced_2016,
	title = {Spliced synthetic genes as internal controls in {RNA} sequencing experiments},
	volume = {13},
	issn = {15487105},
	url = {http://www.nature.com/doifinder/10.1038/nmeth.3958},
	doi = {10.1038/nmeth.3958},
	abstract = {{RNA} sequencing ({RNA}-seq) can be used to assemble spliced isoforms, quantify expressed genes and provide a global profile of the transcriptome. However, the size and diversity of the transcriptome, the wide dynamic range in gene expression and inherent technical biases confound {RNA}-seq analysis. We have developed a set of spike-in {RNA} standards, termed 'sequins' (sequencing spike-ins), that represent full-length spliced {mRNA} isoforms. Sequins have an entirely artificial sequence with no homology to natural reference genomes, but they align to gene loci encoded on an artificial in silico chromosome. The combination of multiple sequins across a range of concentrations emulates alternative splicing and differential gene expression, and it provides scaling factors for normalization between samples. We demonstrate the use of sequins in {RNA}-seq experiments to measure sample-specific biases and determine the limits of reliable transcript assembly and quantification in accompanying human {RNA} samples. In addition, we have designed a complementary set of sequins that represent fusion genes arising from rearrangements of the in silico chromosome to aid in cancer diagnosis. {RNA} sequins provide a qualitative and quantitative reference with which to navigate the complexity of the human transcriptome.},
	pages = {792--798},
	number = {9},
	journaltitle = {Nature Methods},
	author = {Hardwick, Simon A and Chen, Wendy Y and Wong, Ted and Deveson, Ira W and Blackburn, James and Andersen, Stacey B and Nielsen, Lars K and Mattick, John S and Mercer, Tim R},
	date = {2016-08},
	pmid = {27502218},
	keywords = {{RNA} sequencing, {RNA} splicing, Transcriptomics},
	file = {Attachment:/home/jlagarde/Zotero/storage/6K2FJ9N5/Hardwick et al. - 2016 - Spliced synthetic genes as internal controls in RNA sequencing experiments.pdf:text/html}
}

@article{nik-zainal_landscape_2016,
	title = {Landscape of somatic mutations in 560 breast cancer whole-genome sequences},
	volume = {534},
	issn = {0028-0836},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27135926 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4910866 http://www.nature.com/doifinder/10.1038/nature17676},
	doi = {10.1038/nature17676},
	abstract = {We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based {DNA} repair: one with deficient {BRCA}1 function, another with deficient {BRCA}1 or {BRCA}2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.},
	pages = {47--54},
	number = {7605},
	journaltitle = {Nature},
	author = {Nik-Zainal, Serena and Davies, Helen and Staaf, Johan and Ramakrishna, Manasa and Glodzik, Dominik and Zou, Xueqing and Martincorena, Inigo and Alexandrov, Ludmil B. and Martin, Sancha and Wedge, David C. and Van Loo, Peter and Ju, Young Seok and Smid, Marcel and Brinkman, Arie B. and Morganella, Sandro and Aure, Miriam R. and Lingj\{{\textbackslash}textbackslash\}a erde, Ole Christian and Langerød, Anita and Ringnér, Markus and Ahn, Sung-Min and Boyault, Sandrine and Brock, Jane E. and Broeks, Annegien and Butler, Adam and Desmedt, Christine and Dirix, Luc and Dronov, Serge and Fatima, Aquila and Foekens, John A. and Gerstung, Moritz and Hooijer, Gerrit K. J. and Jang, Se Jin and Jones, David R. and Kim, Hyung-Yong and King, Tari A. and Krishnamurthy, Savitri and Lee, Hee Jin and Lee, Jeong-Yeon and Li, Yilong and {McLaren}, Stuart and Menzies, Andrew and Mustonen, Ville and O'Meara, Sarah and Pauporté, Iris and Pivot, Xavier and Purdie, Colin A. and Raine, Keiran and Ramakrishnan, Kamna and Rodríguez-González, F. Germán and Romieu, Gilles and Sieuwerts, Anieta M. and Simpson, Peter T. and Shepherd, Rebecca and Stebbings, Lucy and Stefansson, Olafur A. and Teague, Jon and Tommasi, Stefania and Treilleux, Isabelle and Van den Eynden, Gert G. and Vermeulen, Peter and Vincent-Salomon, Anne and Yates, Lucy and Caldas, Carlos and van't Veer, Laura and Tutt, Andrew and Knappskog, Stian and Tan, Benita Kiat Tee and Jonkers, Jos and Borg, \{{\textbackslash}textbackslash\}{AAke} and Ueno, Naoto T. and Sotiriou, Christos and Viari, Alain and Futreal, P. Andrew and Campbell, Peter J. and Span, Paul N. and Van Laere, Steven and Lakhani, Sunil R. and Eyfjord, Jorunn E. and Thompson, Alastair M. and Birney, Ewan and Stunnenberg, Hendrik G. and van de Vijver, Marc J. and Martens, John W. M. and Børresen-Dale, Anne-Lise and Richardson, Andrea L. and Kong, Gu and Thomas, Gilles and Stratton, Michael R.},
	date = {2016-05},
	pmid = {27135926}
}

@article{burk_integrated_2017,
	title = {Integrated genomic and molecular characterization of cervical cancer},
	volume = {543},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature21386},
	doi = {10.1038/nature21386},
	abstract = {Cervical cancer is one of the main causes of cancer-related deaths worldwide, and 95\% of cases result from human papilloma virus ({HPV}) infection. The Cancer Genome Atlas Research Network now reports the genomic and molecular characterization of 228 primary cervical cancers. The authors identify significantly mutated genes and pathways that differ by cervical cancer subtype, and find that keratin-low squamous, keratin-high squamous and adenocarcinoma-rich clusters are marked by different {HPV} types and molecular features.},
	pages = {378--384},
	number = {7645},
	journaltitle = {Nature},
	author = {Burk, Robert D. and Chen, Zigui and Saller, Charles and Tarvin, Katherine and Carvalho, Andre L. and Scapulatempo-Neto, Cristovam and Silveira, Henrique C. and Fregnani, José H. and Creighton, Chad J. and Anderson, Matthew L. and Castro, Patricia and Wang, Sophia S. and Yau, Christina and Benz, Christopher and Robertson, A. Gordon and Mungall, Karen and Lim, Lynette and Bowlby, Reanne and Sadeghi, Sara and Brooks, Denise and Sipahimalani, Payal and Mar, Richard and Ally, Adrian and Clarke, Amanda and Mungall, Andrew J. and Tam, Angela and Lee, Darlene and Chuah, Eric and Schein, Jacqueline E. and Tse, Kane and Kasaian, Katayoon and Ma, Yussanne and Marra, Marco A. and Mayo, Michael and Balasundaram, Miruna and Thiessen, Nina and Dhalla, Noreen and Carlsen, Rebecca and Moore, Richard A. and Holt, Robert A. and Jones, Steven J. M. and Wong, Tina and Pantazi, Angeliki and Parfenov, Michael and Kucherlapati, Raju and Hadjipanayis, Angela and Seidman, Jonathan and Kucherlapati, Melanie and Ren, Xiaojia and Xu, Andrew W. and Yang, Lixing and Park, Peter J. and Lee, Semin and Rabeno, Brenda and Huelsenbeck-Dill, Lori and Borowsky, Mark and Cadungog, Mark and Iacocca, Mary and Petrelli, Nicholas and Swanson, Patricia and Ojesina, Akinyemi I. and Le, Xuan and Sandusky, George and Adebamowo, Sally N. and Akeredolu, Teniola and Adebamowo, Clement and Reynolds, Sheila M. and Shmulevich, Ilya and Shelton, Candace and Crain, Daniel and Mallery, David and Curley, Erin and Gardner, Johanna and Penny, Robert and Morris, Scott and Shelton, Troy and Liu, Jia and Lolla, Laxmi and Chudamani, Sudha and Wu, Ye and Birrer, Michael and {McLellan}, Michael D. and Bailey, Matthew H. and Miller, Christopher A. and Wyczalkowski, Matthew A. and Fulton, Robert S. and Fronick, Catrina C. and Lu, Charles and Mardis, Elaine R. and Appelbaum, Elizabeth L. and Schmidt, Heather K. and Fulton, Lucinda A. and Cordes, Matthew G. and Li, Tiandao and Ding, Li and Wilson, Richard K. and Rader, Janet S. and Behmaram, Behnaz and Uyar, Denise and Bradley, William and Wrangle, John and Pastore, Alessandro and Levine, Douglas A. and Dao, Fanny and Gao, Jianjiong and Schultz, Nikolaus and Sander, Chris and Ladanyi, Marc and Einstein, Mark and Teeter, Randall and Benz, Stephen and Wentzensen, Nicolas and Felau, Ina and Zenklusen, Jean C. and Bodelon, Clara and Demchok, John A. and Yang, Liming and Sheth, Margi and Ferguson, Martin L. and Tarnuzzer, Roy and Yang, Hannah and Schiffman, Mark and Zhang, Jiashan and Wang, Zhining and Davidsen, Tanja and Olaniyan, Olayinka and Hutter, Carolyn M. and Sofia, Heidi J. and Gordenin, Dmitry A. and Chan, Kin and Roberts, Steven A. and Klimczak, Leszek J. and Van Waes, Carter and Chen, Zhong and Saleh, Anthony D. and Cheng, Hui and Parfitt, Jeremy and Bartlett, John and Albert, Monique and Arnaout, Angel and Sekhon, Harman and Gilbert, Sebastien and Peto, Myron and Myers, Jerome and Harr, Jodi and Eckman, John and Bergsten, Julie and Tucker, Kelinda and Zach, Leigh Anne and Karlan, Beth Y. and Lester, Jenny and Orsulic, Sandra and Sun, Qiang and Naresh, Rashi and Pihl, Todd and Wan, Yunhu and Zaren, Howard and Sapp, Jennifer and Miller, Judy and Drwiega, Paul and Ojesina, Akinyemi I. and Murray, Bradley A. and Zhang, Hailei and Cherniack, Andrew D. and Sougnez, Carrie and Pedamallu, Chandra Sekhar and Lichtenstein, Lee and Meyerson, Matthew and Noble, Michael S. and Heiman, David I. and Voet, Doug and Getz, Gad and Saksena, Gordon and Kim, Jaegil and Shih, Juliann and Cho, Juok and Lawrence, Michael S. and Gehlenborg, Nils and Lin, Pei and Beroukhim, Rameen and Frazer, Scott and Gabriel, Stacey B. and Schumacher, Steven E. and Leraas, Kristen M. and Lichtenberg, Tara M. and Zmuda, Erik and Bowen, Jay and Frick, Jessica and Gastier-Foster, Julie M. and Wise, Lisa and Gerken, Mark and Ramirez, Nilsa C. and Danilova, Ludmila and Cope, Leslie and Baylin, Stephen B. and Salvesen, Helga B. and Vellano, Christopher P. and Ju, Zhenlin and Diao, Lixia and Zhao, Hao and Chong, Zechen and Ryan, Michael C. and Martinez-Ledesma, Emmanuel and Verhaak, Roeland G. and Averett Byers, Lauren and Yuan, Yuan and Chen, Ken and Ling, Shiyun and Mills, Gordon B. and Lu, Yiling and Akbani, Rehan and Seth, Sahil and Liang, Han and Wang, Jing and Han, Leng and Weinstein, John N. and Bristow, Christopher A. and Zhang, Wei and Mahadeshwar, Harshad S. and Sun, Huandong and Tang, Jiabin and Zhang, Jianhua and Song, Xingzhi and Protopopov, Alexei and Shaw, Kenna R. Mills and Chin, Lynda and Olabode, Oluwole and Ojesina, Akinyemi I. and {DiSaia}, Philip and Radenbaugh, Amie and Haussler, David and Zhu, Jingchun and Stuart, Josh and Chalise, Prabhakar and Koestler, Devin and Fridley, Brooke L. and Godwin, Andrew K. and Madan, Rashna and Ciriello, Giovanni and Martinez, Cathleen and Higgins, Kelly and Bocklage, Therese and Auman, J. Todd and Perou, Charles M. and Tan, Donghui and Parker, Joel S. and Hoadley, Katherine A. and Wilkerson, Matthew D. and Mieczkowski, Piotr A. and Skelly, Tara and Veluvolu, Umadevi and Hayes, D. Neil and Rathmell, W. Kimryn and Hoyle, Alan P. and Simons, Janae V. and Wu, Junyuan and Mose, Lisle E. and Soloway, Matthew G. and Balu, Saianand and Meng, Shaowu and Jefferys, Stuart R. and Bodenheimer, Tom and Shi, Yan and Roach, Jeffrey and Thorne, Leigh B. and Boice, Lori and Huang, Mei and Jones, Corbin D. and Zuna, Rosemary and Walker, Joan and Gunderson, Camille and Snowbarger, Carie and Brown, David and Moxley, Katherine and Moore, Kathleen and Andrade, Kelsi and Landrum, Lisa and Mannel, Robert and {McMeekin}, Scott and Johnson, Starla and Nelson, Tina and Elishaev, Esther and Dhir, Rajiv and Edwards, Robert and Bhargava, Rohit and Tiezzi, Daniel G. and Andrade, Jurandyr M. and Noushmehr, Houtan and Gilberto Carlotti, Carlos and Tirapelli, Daniela Pretti da Cunha and Weisenberger, Daniel J. and Van Den Berg, David J. and Maglinte, Dennis T. and Bootwalla, Moiz S. and Lai, Phillip H. and Triche, Timothy and Swisher, Elizabeth M. and Agnew, Kathy J. and Shelley, Carl Simon and Laird, Peter W. and Schwarz, Julie and Grigsby, Perry and Mutch, David},
	date = {2017-01},
	keywords = {Cervical cancer, Systems analysis},
	file = {Attachment:/home/jlagarde/Zotero/storage/4HEFA6TS/Burk et al. - 2017 - Integrated genomic and molecular characterization of cervical cancer.pdf:application/pdf}
}

@article{aldridge_1000_2008,
	title = {1000 Genomes project},
	volume = {26},
	issn = {1087-0156},
	url = {http://www.nature.com/doifinder/10.1038/nbt0308-256b},
	doi = {10.1038/nbt0308-256b},
	pages = {256--256},
	number = {3},
	journaltitle = {Nature Biotechnology},
	author = {Aldridge, Susan and Huggett, Brady and Jayaraman, {KS} and Melton, Lisa and Ratner, Mark and Siva, Nayanah},
	date = {2008-03}
}

@article{lek_analysis_2016,
	title = {Analysis of protein-coding genetic variation in 60,706 humans},
	volume = {536},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature19057},
	doi = {10.1038/nature19057},
	abstract = {As part of the Exome Aggregation Consortium ({ExAC}) project, Daniel {MacArthur} and colleagues report on the generation and analysis of high-quality exome sequencing data from 60,706 individuals of diverse ancestry. This provides the most comprehensive catalogue of human protein-coding genetic variation to date, yielding unprecedented resolution for the analysis of very rare variants across multiple human populations. The catalogue is freely accessible and provides a critical reference panel for the clinical interpretation of genetic variants and the discovery of disease-related genes.},
	pages = {285--291},
	number = {7616},
	journaltitle = {Nature},
	author = {Lek, Monkol and Karczewski, Konrad J. and Minikel, Eric V. and Samocha, Kaitlin E. and Banks, Eric and Fennell, Timothy and O'Donnell-Luria, Anne H. and Ware, James S. and Hill, Andrew J. and Cummings, Beryl B. and Tukiainen, Taru and Birnbaum, Daniel P. and Kosmicki, Jack A. and Duncan, Laramie E. and Estrada, Karol and Zhao, Fengmei and Zou, James and Pierce-Hoffman, Emma and Berghout, Joanne and Cooper, David N. and Deflaux, Nicole and {DePristo}, Mark and Do, Ron and Flannick, Jason and Fromer, Menachem and Gauthier, Laura and Goldstein, Jackie and Gupta, Namrata and Howrigan, Daniel and Kiezun, Adam and Kurki, Mitja I. and Moonshine, Ami Levy and Natarajan, Pradeep and Orozco, Lorena and Peloso, Gina M. and Poplin, Ryan and Rivas, Manuel A. and Ruano-Rubio, Valentin and Rose, Samuel A. and Ruderfer, Douglas M. and Shakir, Khalid and Stenson, Peter D. and Stevens, Christine and Thomas, Brett P. and Tiao, Grace and Tusie-Luna, Maria T. and Weisburd, Ben and Won, Hong-Hee and Yu, Dongmei and Altshuler, David M. and Ardissino, Diego and Boehnke, Michael and Danesh, John and Donnelly, Stacey and Elosua, Roberto and Florez, Jose C. and Gabriel, Stacey B. and Getz, Gad and Glatt, Stephen J. and Hultman, Christina M. and Kathiresan, Sekar and Laakso, Markku and {McCarroll}, Steven and {McCarthy}, Mark I. and {McGovern}, Dermot and {McPherson}, Ruth and Neale, Benjamin M. and Palotie, Aarno and Purcell, Shaun M. and Saleheen, Danish and Scharf, Jeremiah M. and Sklar, Pamela and Sullivan, Patrick F. and Tuomilehto, Jaakko and Tsuang, Ming T. and Watkins, Hugh C. and Wilson, James G. and Daly, Mark J. and {MacArthur}, Daniel G. and Ruano-Rubio, Valentin},
	date = {2016-08},
	keywords = {Genomics, Medical genetics}
}

@article{shao_accurate_2017,
	title = {Accurate assembly of transcripts through phase-preserving graph decomposition},
	volume = {35},
	issn = {15461696},
	url = {http://www.nature.com/doifinder/10.1038/nbt.4020},
	doi = {10.1038/nbt.4020},
	abstract = {Scallop improves identification of multi-exon and transcripts expressed at low levels by retaining phasing information during assembly.},
	pages = {1167--1169},
	number = {12},
	journaltitle = {Nature biotechnology},
	author = {Shao, Mingfu and Kingsford, Carl},
	date = {2017-11},
	pmid = {29131147},
	keywords = {{RNA} sequencing, Genome assembly algorithms},
	file = {Attachment:/home/jlagarde/Zotero/storage/G32F8FZ6/Shao, Kingsford - 2017 - Accurate assembly of transcripts through phase-preserving graph decomposition.pdf:text/html}
}

@article{chu_technologies_2015,
	title = {Technologies to probe functions and mechanisms of long noncoding {RNAs}},
	issn = {1545-9993},
	doi = {10.1038/nsmb.2921},
	abstract = {Thousands of long noncoding {RNAs} ({lncRNAs}) have been discovered, but their functional characterization has been slowed by a limited set of research tools. Here we review emerging {RNA}-centric methods to interrogate the intrinsic structure of {lncRNAs} as well as their genomic localization and biochemical partners. Understanding these technologies, including their advantages and caveats, and developing them in the future will be essential to progress from description to comprehension of the myriad roles of {lncRNAs}.},
	journaltitle = {Nature Structural \& Molecular Biology},
	author = {Chu, Ci and Spitale, Robert C and Chang, Howard Y},
	date = {2015},
	pmid = {25565030}
}

@article{blanchette_aligning_2004,
	title = {Aligning multiple genomic sequences with the threaded blockset aligner.},
	volume = {14},
	issn = {1088-9051},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15060014 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC383317},
	doi = {10.1101/gr.1933104},
	abstract = {We define a "threaded blockset," which is a novel generalization of the classic notion of a multiple alignment. A new computer program called {TBA} (for "threaded blockset aligner") builds a threaded blockset under the assumption that all matching segments occur in the same order and orientation in the given sequences; inversions and duplications are not addressed. {TBA} is designed to be appropriate for aligning many, but by no means all, megabase-sized regions of multiple mammalian genomes. The output of {TBA} can be projected onto any genome chosen as a reference, thus guaranteeing that different projections present consistent predictions of which genomic positions are orthologous. This capability is illustrated using a new visualization tool to view {TBA}-generated alignments of vertebrate Hox clusters from both the mammalian and fish perspectives. Experimental evaluation of alignment quality, using a program that simulates evolutionary change in genomic sequences, indicates that {TBA} is more accurate than earlier programs. To perform the dynamic-programming alignment step, {TBA} runs a stand-alone program called {MULTIZ}, which can be used to align highly rearranged or incompletely sequenced genomes. We describe our use of {MULTIZ} to produce the whole-genome multiple alignments at the Santa Cruz Genome Browser.},
	pages = {708--15},
	number = {4},
	journaltitle = {Genome research},
	author = {Blanchette, Mathieu and Kent, W James and Riemer, Cathy and Elnitski, Laura and Smit, Arian F A and Roskin, Krishna M and Baertsch, Robert and Rosenbloom, Kate and Clawson, Hiram and Green, Eric D and Haussler, David and Miller, Webb},
	date = {2004-04},
	pmid = {15060014},
	file = {Attachment:/home/jlagarde/Zotero/storage/2WHMUPMY/Blanchette et al. - 2004 - Aligning multiple genomic sequences with the threaded blockset aligner.pdf:application/pdf}
}

@article{tian_large-scale_2005,
	title = {A large-scale analysis of {mRNA} polyadenylation of human and mouse genes.},
	volume = {33},
	issn = {1362-4962},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15647503 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC546146},
	doi = {10.1093/nar/gki158},
	abstract = {{mRNA} polyadenylation is a critical cellular process in eukaryotes. It involves 3' end cleavage of nascent {mRNAs} and addition of the poly(A) tail, which plays important roles in many aspects of the cellular metabolism of {mRNA}. The process is controlled by various cis-acting elements surrounding the cleavage site, and their binding factors. In this study, we surveyed genome regions containing cleavage sites [herein called poly(A) sites], for 13,942 human and 11,155 mouse genes. We found that a great proportion of human and mouse genes have alternative polyadenylation ( approximately 54 and 32\%, respectively). The conservation of alternative polyadenylation type or polyadenylation configuration between human and mouse orthologs is statistically significant, indicating that alternative polyadenylation is widely employed by these two species to produce alternative gene transcripts. Genes belonging to several functional groups, indicated by their Gene Ontology annotations, are biased with respect to polyadenylation configuration. Many poly(A) sites harbor multiple cleavage sites (51.25\% human and 46.97\% mouse sites), leading to heterogeneous 3' end formation for transcripts. This implies that the cleavage process of polyadenylation is largely imprecise. Different types of poly(A) sites, with regard to their relative locations in a gene, are found to have distinct nucleotide composition in surrounding genomic regions. This large-scale study provides important insights into the mechanism of polyadenylation in mammalian species and represents a genomic view of the regulation of gene expression by alternative polyadenylation.},
	pages = {201--12},
	number = {1},
	journaltitle = {Nucleic acids research},
	author = {Tian, Bin and Hu, Jun and Zhang, Haibo and Lutz, Carol S},
	date = {2005},
	pmid = {15647503},
	keywords = {Human, Animals, Genome, Humans, Mice, Mice: genetics, {RNA}, Messenger, Messenger: metabolism, Messenger: chemistry, Polyadenylation, Mice: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/295LS86A/Tian et al. - 2005 - A large-scale analysis of mRNA polyadenylation of human and mouse genes.pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/43K4I68K/Tian et al. - 2005 - A large-scale analysis of mRNA polyadenylation of human and mouse genes.pdf:application/pdf}
}

@article{bunch_gene_2017,
	title = {Gene regulation of mammalian long non-coding {RNA}},
	issn = {1617-4615},
	url = {http://link.springer.com/10.1007/s00438-017-1370-9},
	doi = {10.1007/s00438-017-1370-9},
	pages = {1--15},
	journaltitle = {Molecular Genetics and Genomics},
	author = {Bunch, Heeyoun},
	date = {2017-09},
	file = {Attachment:/home/jlagarde/Zotero/storage/4S8SW8YL/Bunch - 2017 - Gene regulation of mammalian long non-coding RNA.pdf:application/pdf}
}

@article{zhao_noncode_2016,
	title = {{NONCODE} 2016: an informative and valuable data source of long non-coding {RNAs}},
	volume = {44},
	issn = {0305-1048},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26586799 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4702886 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkv1252},
	doi = {10.1093/nar/gkv1252},
	abstract = {{NONCODE} (http://www.bioinfo.org/noncode/) is an interactive database that aims to present the most complete collection and annotation of non-coding {RNAs}, especially long non-coding {RNAs} ({lncRNAs}). The recently reduced cost of {RNA} sequencing has produced an explosion of newly identified data. Revolutionary third-generation sequencing methods have also contributed to more accurate annotations. Accumulative experimental data also provides more comprehensive knowledge of {lncRNA} functions. In this update, {NONCODE} has added six new species, bringing the total to 16 species altogether. The {lncRNAs} in {NONCODE} have increased from 210 831 to 527,336. For human and mouse, the {lncRNA} numbers are 167,150 and 130,558, respectively. {NONCODE} 2016 has also introduced three important new features: (i) conservation annotation; (ii) the relationships between {lncRNAs} and diseases; and (iii) an interface to choose high-quality datasets through predicted scores, literature support and long-read sequencing method support. {NONCODE} is also accessible through http://www.noncode.org/.},
	pages = {D203--D208},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Zhao, Yi and Li, Hui and Fang, Shuangsang and Kang, Yue and Wu, Wei and Hao, Yajing and Li, Ziyang and Bu, Dechao and Sun, Ninghui and Zhang, Michael Q. and Chen, Runsheng},
	date = {2016-01},
	pmid = {26586799},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, Mice, {RNA}, Nucleic Acid, Disease, *Databases, Cattle, Disease/genetics, Long Noncoding/*genetics/metabolism, Molecular Sequence Annotation, Rats, {RNA}, Long Noncoding, Databases, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/SS9MNN7B/Zhao et al. - 2016 - NONCODE 2016 an informative and valuable data sou.pdf:application/pdf}
}

@article{hangauer_pervasive_2013,
	title = {Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding {RNAs}},
	volume = {9},
	issn = {1553-7404},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23818866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3688513 http://dx.plos.org/10.1371/journal.pgen.1003569},
	doi = {10.1371/journal.pgen.1003569},
	abstract = {Known protein coding gene exons compose less than 3\% of the human genome. The remaining 97\% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic {RNAs} are functional. Here we directly observed with a large set of {RNA}-seq data covering a wide array of human tissue types that the majority of the genome is indeed transcribed, corroborating recent observations by the {ENCODE} project. Furthermore, using de novo transcriptome assembly of this {RNA}-seq data, we found that intergenic regions encode far more long intergenic noncoding {RNAs} ({lincRNAs}) than previously described, helping to resolve the discrepancy between the vast amount of observed intergenic transcription and the limited number of previously known {lincRNAs}. In total, we identified tens of thousands of putative {lincRNAs} expressed at a minimum of one copy per cell, significantly expanding upon prior {lincRNA} annotation sets. These {lincRNAs} are specifically regulated and conserved rather than being the product of transcriptional noise. In addition, {lincRNAs} are strongly enriched for trait-associated {SNPs} suggesting a new mechanism by which intergenic trait-associated regions may function. These findings will enable the discovery and interrogation of novel intergenic functional elements.},
	pages = {e1003569},
	number = {6},
	journaltitle = {{PLoS} Genetics},
	author = {Hangauer, Matthew J. and Vaughn, Ian W. and {McManus}, Michael T.},
	editor = {Rinn, John L.},
	date = {2013-06},
	pmid = {23818866}
}

@article{trapnell_differential_2012,
	title = {Differential gene and transcript expression analysis of {RNA}-seq experiments with {TopHat} and Cufflinks},
	volume = {7},
	issn = {1754-2189},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22383036 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3334321 http://www.nature.com/doifinder/10.1038/nprot.2012.016},
	doi = {10.1038/nprot.2012.016},
	abstract = {Recent advances in high-throughput {cDNA} sequencing ({RNA}-seq) can reveal new genes and splice variants and quantify expression genome-wide in a single assay. The volume and complexity of data from {RNA}-seq experiments necessitate scalable, fast and mathematically principled analysis software. {TopHat} and Cufflinks are free, open-source software tools for gene discovery and comprehensive expression analysis of high-throughput {mRNA} sequencing ({RNA}-seq) data. Together, they allow biologists to identify new genes and new splice variants of known ones, as well as compare gene and transcript expression under two or more conditions. This protocol describes in detail how to use {TopHat} and Cufflinks to perform such analyses. It also covers several accessory tools and utilities that aid in managing data, including {CummeRbund}, a tool for visualizing {RNA}-seq analysis results. Although the procedure assumes basic informatics skills, these tools assume little to no background with {RNA}-seq analysis and are meant for novices and experts alike. The protocol begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations of analysis results. The protocol's execution time depends on the volume of transcriptome sequencing data and available computing resources but takes less than 1 d of computer time for typical experiments and approximately 1 h of hands-on time.},
	pages = {562--578},
	number = {3},
	journaltitle = {Nat Protoc},
	author = {Trapnell, Cole and Roberts, Adam and Goff, Loyal and Pertea, Geo and Kim, Daehwan and Kelley, David R and Pimentel, Harold and Salzberg, Steven L and Rinn, John L and Pachter, Lior},
	date = {2012-03},
	pmid = {22383036},
	keywords = {*Software, Complementary/*genetics, {DNA}, {DNA}/*methods, Gene Expression Profiling/*methods, Genetic Association Studies/*methods, Genomics/*methods, Sequence Analysis}
}

@article{carninci_transcriptional_2005,
	title = {The transcriptional landscape of the mammalian genome},
	volume = {309},
	issn = {1095-9203},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16141072 http://www.sciencemag.org/cgi/doi/10.1126/science.1112014},
	doi = {10.1126/science.1112014},
	abstract = {This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary {DNAs} derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.},
	pages = {1559--63},
	number = {5740},
	journaltitle = {Science (New York, N.Y.)},
	author = {Carninci, P and Kasukawa, T and Katayama, S and Gough, J and Frith, M C and Maeda, N and Oyama, R and Ravasi, T and Lenhard, B and Wells, C and Kodzius, R and Shimokawa, K and Bajic, V B and Brenner, S E and Batalov, S and Forrest, A R R and Zavolan, M and Davis, M J and Wilming, L G and Aidinis, V and Allen, J E and Ambesi-Impiombato, A and Apweiler, R and Aturaliya, R N and Bailey, T L and Bansal, M and Baxter, L and Beisel, K W and Bersano, T and Bono, H and Chalk, A M and Chiu, K P and Choudhary, V and Christoffels, A and Clutterbuck, D R and Crowe, M L and Dalla, E and Dalrymple, B P and de Bono, B and Della Gatta, G and di Bernardo, D and Down, T and Engstrom, P and Fagiolini, M and Faulkner, G and Fletcher, C F and Fukushima, T and Furuno, M and Futaki, S and Gariboldi, M and Georgii-Hemming, P and Gingeras, T R and Gojobori, T and Green, R E and Gustincich, S and Harbers, M and Hayashi, Y and Hensch, T K and Hirokawa, N and Hill, D and Huminiecki, L and Iacono, M and Ikeo, K and Iwama, A and Ishikawa, T and Jakt, M and Kanapin, A and Katoh, M and Kawasawa, Y and Kelso, J and Kitamura, H and Kitano, H and Kollias, G and Krishnan, S P T and Kruger, A and Kummerfeld, S K and Kurochkin, I V and Lareau, L F and Lazarevic, D and Lipovich, L and Liu, J and Liuni, S and McWilliam, S and Madan Babu, M and Madera, M and Marchionni, L and Matsuda, H and Matsuzawa, S and Miki, H and Mignone, F and Miyake, S and Morris, K and Mottagui-Tabar, S and Mulder, N and Nakano, N and Nakauchi, H and Ng, P and Nilsson, R and Nishiguchi, S and Nishikawa, S and Nori, F and Ohara, O and Okazaki, Y and Orlando, V and Pang, K C and Pavan, W J and Pavesi, G and Pesole, G and Petrovsky, N and Piazza, S and Reed, J and Reid, J F and Ring, B Z and Ringwald, M and Rost, B and Ruan, Y and Salzberg, S L and Sandelin, A and Schneider, C and Schönbach, C and Sekiguchi, K and Semple, C A M and Seno, S and Sessa, L and Sheng, Y and Shibata, Y and Shimada, H and Shimada, K and Silva, D and Sinclair, B and Sperling, S and Stupka, E and Sugiura, K and Sultana, R and Takenaka, Y and Taki, K and Tammoja, K and Tan, S L and Tang, S and Taylor, M S and Tegner, J and Teichmann, S A and Ueda, H R and van Nimwegen, E and Verardo, R and Wei, C L and Yagi, K and Yamanishi, H and Zabarovsky, E and Zhu, S and Zimmer, A and Hide, W and Bult, C and Grimmond, S M and Teasdale, R D and Liu, E T and Brusic, V and Quackenbush, J and Wahlestedt, C and Mattick, J S and Hume, D A and Kai, C and Sasaki, D and Tomaru, Y and Fukuda, S and Kanamori-Katayama, M and Suzuki, M and Aoki, J and Arakawa, T and Iida, J and Imamura, K and Itoh, M and Kato, T and Kawaji, H and Kawagashira, N and Kawashima, T and Kojima, M and Kondo, S and Konno, H and Nakano, K and Ninomiya, N and Nishio, T and Okada, M and Plessy, C and Shibata, K and Shiraki, T and Suzuki, S and Tagami, M and Waki, K and Watahiki, A and Okamura-Oho, Y and Suzuki, H and Kawai, J and Hayashizaki, Y and {FANTOM Consortium} and {RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group)}},
	date = {2005-09},
	pmid = {16141072},
	keywords = {Human, Genomics, {DNA}, 3' Untranslated Regions, Animals, Base Sequence, Complementary, Complementary: chemistry, Conserved Sequence, Genetic, Genome, Humans, Mice, Mice: genetics, Promoter Regions, Proteins, Proteins: genetics, Regulatory Sequences, Ribonucleic Acid, {RNA}, {RNA} Splicing, {RNA}: chemistry, {RNA}: classification, Terminator Regions, Transcription, Transcription Initiation Site, Untranslated, Untranslated: chemistry, Transcription, Genetic, Promoter Regions, Genetic, {RNA}, Untranslated, Genome, Human, {DNA}, Complementary, Regulatory Sequences, Ribonucleic Acid, Terminator Regions, Genetic}
}

@article{okonechnikov_qualimap_2016,
	title = {Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data},
	volume = {32},
	issn = {1367-4803},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26428292 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4708105 https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btv566 http://dx.doi.org/10.1093/bioinformatics/btv566},
	doi = {10.1093/bioinformatics/btv566},
	abstract = {Motivation: Detection of random errors and systematic biases is a crucial step of a robust pipeline for processing high-throughput sequencing ({HTS}) data. Bioinformatics software tools capable of performing this task are available, either for general analysis of {HTS} data or targeted to a specific sequencing technology. However, most of the existing {QC} instruments only allow processing of one sample at a time. Results: Qualimap 2 represents a next step in the {QC} analysis of {HTS} data. Along with comprehensive single-sample analysis of alignment data, it includes new modes that allow simultaneous processing and comparison of multiple samples. As with the first version, the new features are available via both graphical and command line interface. Additionally, it includes a large number of improvements proposed by the user community. Availability and implementation: The implementation of the software along with documentation is freely available at http://www.qualimap.org . Contact:meyer@mpiib-berlin.mpg.{deSupplementary} information: are available at Bioinformatics online.},
	pages = {292--294},
	number = {2},
	journaltitle = {Bioinformatics},
	author = {Okonechnikov, Konstantin and Conesa, Ana and García-Alcalde, Fernando},
	date = {2016-10},
	pmid = {26428292}
}

@article{guttman_chromatin_2009,
	title = {Chromatin signature reveals over a thousand highly conserved large non-coding {RNAs} in mammals},
	volume = {458},
	issn = {0028-0836},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19182780 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2754849 http://www.nature.com/doifinder/10.1038/nature07672},
	doi = {10.1038/nature07672},
	abstract = {There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most ({\textbackslash}textgreater95\%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding {RNAs} using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic {RNAs} across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding {RNAs} ({lincRNAs}) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95\% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each {lincRNA}, demonstrating a diverse range of roles for {lincRNAs} in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 {lincRNAs}, using cell-based assays. In particular, we demonstrate that specific {lincRNAs} are transcriptionally regulated by key transcription factors in these processes such as p53, {NFkappaB}, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional {lincRNAs} that are highly conserved and implicated in diverse biological processes.},
	pages = {223--227},
	number = {7235},
	journaltitle = {Nature},
	author = {Guttman, Mitchell and Amit, Ido and Garber, Manuel and French, Courtney and Lin, Michael F. and Feldser, David and Huarte, Maite and Zuk, Or and Carey, Bryce W. and Cassady, John P. and Cabili, Moran N. and Jaenisch, Rudolf and Mikkelsen, Tarjei S. and Jacks, Tyler and Hacohen, Nir and Bernstein, Bradley E. and Kellis, Manolis and Regev, Aviv and Rinn, John L. and Lander, Eric S.},
	date = {2009-03},
	pmid = {19182780},
	keywords = {{DNA}, Animals, Base Sequence, Conserved Sequence, Mice, Promoter Regions, {RNA}, Transcription Factors/metabolism, Exons, Intergenic, *Conserved Sequence/genetics, Cells, Chromatin/*genetics, Cultured, Exons/genetics, Genetic/genetics, Mammals/*genetics, Reproducibility of Results, {RNA}/*genetics, Chromatin, Mammals, Transcription Factors, Cells, Cultured, Promoter Regions, Genetic, {DNA}, Intergenic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/967CJ7D5/Guttman et al. - 2009 - Chromatin signature reveals over a thousand highly.pdf:application/pdf}
}

@article{jia_genome-wide_2010,
	title = {Genome-wide computational identification and manual annotation of human long noncoding {RNA} genes},
	volume = {16},
	issn = {1355-8382},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20587619 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2905748 http://rnajournal.cshlp.org/cgi/doi/10.1261/rna.1951310},
	doi = {10.1261/rna.1951310},
	abstract = {Experimental evidence suggests that half or more of the mammalian transcriptome consists of noncoding {RNA}. Noncoding {RNAs} are divided into short noncoding {RNAs} (including {microRNAs}) and long noncoding {RNAs} ({lncRNAs}). We defined complementary {DNAs} ({cDNAs}) lacking any positive-strand open reading frames ({ORFs}) longer than 30 amino acids, as well as {cDNAs} lacking any evidence of interspecies conservation of their longer-than-30-amino acid {ORFs}, as noncoding. We have identified 5446 {lncRNA} genes in the human genome from approximately 24,000 full-length {cDNAs}, using our new {ORF}-prediction pipeline. We combined them nonredundantly with {lncRNAs} from four published sources to derive 6736 {lncRNA} genes. In an effort to distinguish standalone and antisense {lncRNA} genes from database artifacts, we stratified our catalog of {lncRNAs} according to the distance between each {lncRNA} gene candidate and its nearest known protein-coding gene. We concurrently examined the protein-coding capacity of known genes overlapping with {lncRNAs}. Remarkably, 62\% of known genes with "hypothetical protein" names actually lacked protein-coding capacity. This study has greatly expanded the known human {lncRNA} catalog, increased its accuracy through manual annotation of {cDNA}-to-genome alignments, and revealed that a large set of hypothetical-protein genes in {GenBank} lacks protein-coding capacity. In addition, we have developed, independently of existing {NCBI} tools, command-line programs with high-throughput {ORF}-finding and {BLASTP}-parsing functionality, suitable for future automated assessments of protein-coding capacity of novel transcripts.},
	pages = {1478--1487},
	number = {8},
	journaltitle = {{RNA}},
	author = {Jia, H. and Osak, M. and Bogu, G. K. and Stanton, L. W. and Johnson, R. and Lipovich, L.},
	date = {2010-08},
	pmid = {20587619},
	keywords = {Human, {DNA}, Genome, Humans, {RNA}, Proteins/genetics, *Genome, Gene Expression Profiling, Complementary/chemistry/genetics, Databases, Nucleic Acid, Open Reading Frames, Untranslated/*genetics}
}

@article{batista_long_2013,
	title = {Long noncoding {RNAs}: cellular address codes in development and disease},
	volume = {152},
	issn = {1097-4172},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3651923&tool=pmcentrez&rendertype=abstract http://www.ncbi.nlm.nih.gov/pubmed/23498938},
	doi = {10.1016/j.cell.2013.02.012},
	abstract = {In biology as in real estate, location is a cardinal organizational principle that dictates the accessibility and flow of informational traffic. An essential question in nuclear organization is the nature of the address code–how objects are placed and later searched for and retrieved. Long noncoding {RNAs} ({lncRNAs}) have emerged as key components of the address code, allowing protein complexes, genes, and chromosomes to be trafficked to appropriate locations and subject to proper activation and deactivation. {lncRNA}-based mechanisms control cell fates during development, and their dysregulation underlies some human disorders caused by chromosomal deletions and translocations.},
	pages = {1298--1307},
	number = {6},
	journaltitle = {Cell},
	author = {Batista, Pedro J and Chang, Howard Y},
	date = {2013-03},
	pmid = {23498938},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation, Cell Nucleus, Cell Nucleus: chemistry, Cell Nucleus: genetics, Cell Nucleus/*chemistry/genetics, Disease, Disease: genetics, Disease/*genetics, Long Noncoding, Long Noncoding: chemistry, Long Noncoding: genetics, Long Noncoding: metabolism, Long Untranslated/*chemistry/genetics/metabol},
	file = {Attachment:/home/jlagarde/Zotero/storage/CGRTC9C7/Batista, Chang - 2013 - Long noncoding RNAs cellular address codes in development and disease.pdf:application/pdf}
}

@article{you_high-confidence_2017,
	title = {High-confidence coding and noncoding transcriptome maps},
	volume = {27},
	issn = {1549-5469},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/28396519},
	doi = {10.1101/gr.214288.116},
	abstract = {The advent of high-throughput {RNA} sequencing ({RNA}-seq) has led to the discovery of unprecedentedly immense transcriptomes encoded by eukaryotic genomes. However, the transcriptome maps are still incomplete partly because they were mostly reconstructed based on {RNA}-seq reads that lack their orientations (known as unstranded reads) and certain boundary information. Methods to expand the usability of unstranded {RNA}-seq data by predetermining the orientation of the reads and precisely determining the boundaries of assembled transcripts could significantly benefit the quality of the resulting transcriptome maps. Here, we present a high-performing transcriptome assembly pipeline, called {CAFE}, that significantly improves the original assemblies, respectively assembled with stranded and/or unstranded {RNA}-seq data, by orienting unstranded reads using the maximum likelihood estimation and by integrating information about transcription start sites and cleavage and polyadenylation sites. Applying large-scale transcriptomic data comprising 230 billion {RNA}-seq reads from the {ENCODE}, Human {BodyMap} 2.0, The Cancer Genome Atlas, and {GTEx} projects, {CAFE} enabled us to predict the directions of about 220 billion unstranded reads, which led to the construction of more accurate transcriptome maps, comparable to the manually curated map, and a comprehensive {lncRNA} catalog that includes thousands of novel {lncRNAs}. Our pipeline should not only help to build comprehensive, precise transcriptome maps from complex genomes but also to expand the universe of noncoding genomes.},
	pages = {1050--1062},
	number = {6},
	journaltitle = {Genome Res},
	author = {You, Bo-Hyun H and Yoon, Sang-Ho H and Nam, Jin-Wu W},
	date = {2017-04},
	pmid = {28396519},
	file = {Attachment:/home/jlagarde/Zotero/storage/R8ZQ3FPX/You, Yoon, Nam - 2017 - High-confidence coding and noncoding transcriptome maps.pdf:application/pdf}
}

@article{liu_regulation_1996,
	title = {Regulation of p21WAF1/{CIP}1 expression through mitogen-activated protein kinase signaling pathway},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8548769},
	abstract = {p21WAF1/{CIP}1 is a cyclin-dependent kinase inhibitor whose expression in mammalian tissues is highly induced in response to stress as well as during normal development and differentiation. Induction of p21WAF1/{CIP}1 in response to {DNA} damage occurs through a transcriptional mechanism that is dependent on the activation of the tumor suppressor protein p53. Recent evidence indicates that p21WAF1/{CIP}1 can also be induced independently of p53, but the signal transduction mechanisms involved in regulating p21WAF1/{CIP}1 expression in these situations have not been elucidated. In this study, we have addressed the role of the mitogen-activated protein kinase signaling pathway in the induction of p21WAF1/{CIP}1 in response to growth factor treatment. Using an experimental approach involving cotransfection of a p21WAF1/{CIP}1 promoter-luciferase construct with a variety of plasmids expressing dominant positive or dominant negative mutant proteins involved in this signaling pathway, we provide evidence to support a role for mitogen-activated protein kinase in the transcriptional activation of p21WAF1/{CIP}1 by growth factor stimulation.},
	pages = {31--35},
	number = {1},
	journaltitle = {Cancer Res},
	author = {Liu, Y and Martindale, J L and Gorospe, M and Holbrook, N J},
	date = {1996},
	pmid = {8548769},
	keywords = {Animals, Base Sequence, Humans, {RNA}, *Gene Expression Regulation, *Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases/genet, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/genetics/*metabolism, Dominant, Gene Transfer Techniques, Genes, {HeLa} Cells, Messenger/analysis, Mitogens/*pharmacology, Molecular Sequence Data, Mutation, {PC}12 Cells, Rats, Recessive}
}

@article{abraham_propagation_2010,
	title = {Propagation of human embryonic and induced pluripotent stem cells in an indirect co-culture system},
	volume = {393},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20117095},
	doi = {10.1016/j.bbrc.2010.01.101},
	abstract = {We have developed and validated a microporous poly(ethylene terephthalate) membrane-based indirect co-culture system for human pluripotent stem cell ({hPSC}) propagation, which allows real-time conditioning of the culture medium with human fibroblasts while maintaining the complete separation of the two cell types. The propagation and pluripotent characteristics of a human embryonic stem cell ({hESC}) line and a human induced pluripotent stem cell ({hiPSC}) line were studied in prolonged culture in this system. We report that {hPSCs} cultured on membranes by indirect co-culture with fibroblasts were indistinguishable by multiple criteria from {hPSCs} cultured directly on a fibroblast feeder layer. Thus this co-culture system is a significant advance in {hPSC} culture methods, providing a facile stem cell expansion system with continuous medium conditioning while preventing mixing of {hPSCs} and feeder cells. This membrane culture method will enable testing of novel feeder cells and differentiation studies using co-culture with other cell types, and will simplify stepwise changes in culture conditions for staged differentiation protocols.},
	pages = {211--216},
	number = {2},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Abraham, S and Sheridan, S D and Laurent, L C and Albert, K and Stubban, C and Ulitsky, I and Miller, B and Loring, J F and Rao, R R},
	date = {2010},
	pmid = {20117095},
	keywords = {Humans, Gene Expression Profiling, Cell Differentiation/genetics, Coculture Techniques/methods, Embryonic Stem Cells/cytology/metabolism/*physiolo, Induced Pluripotent Stem Cells/cytology/metabolism}
}

@article{zhang_identification_2015,
	title = {Identification of common genetic variants controlling transcript isoform variation in human whole blood},
	volume = {47},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25685889},
	doi = {10.1038/ng.3220},
	abstract = {An understanding of the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of common disease. The available evidence from splicing quantitative trait locus ({sQTL}) studies has been limited to small samples. We performed genome-wide screening to identify {SNPs} that might control {mRNA} splicing in whole blood collected from 5,257 Framingham Heart Study participants. We identified 572,333 cis {sQTLs} involving 2,650 unique genes. Many {sQTL}-associated genes (40\%) undergo alternative splicing. Using the National Human Genome Research Institute ({NHGRI}) genome-wide association study ({GWAS}) catalog, we determined that 528 unique {sQTLs} were significantly enriched for 8,845 {SNPs} associated with traits in previous {GWAS}. In particular, we found 395 (4.5\%) {GWAS} {SNPs} with evidence of cis {sQTLs} but not gene-level cis expression quantitative trait loci ({eQTLs}), suggesting that {sQTL} analysis could provide additional insights into the functional mechanism underlying {GWAS} results. Our findings provide an informative {sQTL} resource for further characterizing the potential functional roles of {SNPs} that control transcript isoforms relevant to common diseases.},
	pages = {345--352},
	number = {4},
	journaltitle = {Nat Genet},
	author = {Zhang, X and Joehanes, R and Chen, B H and Huan, T and Ying, S and Munson, P J and Johnson, A D and Levy, D and O'Donnell, C J},
	date = {2015},
	pmid = {25685889},
	keywords = {Transcriptome, Base Sequence, Humans, Gene Expression Profiling, *Polymorphism, Alternative Splicing/*genetics, Blood Cells/*metabolism, Disease/genetics, {DNA} Mutational Analysis, Genetic Predisposition to Disease, Genome-Wide Association Study, Protein Isoforms/*genetics, Quantitative Trait Loci/*genetics, {RNA} Splice Sites/genetics, Single Nucleotide}
}

@article{ragno_identification_2011,
	title = {Identification of small-molecule inhibitors of the {XendoU} endoribonucleases family},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21805647},
	doi = {10.1002/cmdc.201100281},
	abstract = {The {XendoU} family of enzymes includes several proteins displaying high sequence homology. The members characterized so far are endoribonucleases sharing similar biochemical properties and a common architecture in their active sites. Despite their similarities, these proteins are involved in distinct {RNA}-processing pathways in different organisms. The amphibian {XendoU} participates in the biosynthesis of small nucleolar {RNAs}, the human {PP}11 is supposed to play specialized roles in placental tissue, and {NendoU} has critical function in coronavirus replication. Notably, {XendoU} family members have been implicated in human pathologies such as cancer and respiratory diseases: {PP}11 is aberrantly expressed in various tumors, while {NendoU} activity has been associated with respiratory infections by pathogenic coronaviruses. The present study is aimed at identifying small molecules that may selectively interfere with these enzymatic activities. Combining structure-based virtual screening and experimental approaches, we identified four molecules that specifically inhibited the catalytic activity of {XendoU} and {PP}11 in the low micromolar range. Moreover, docking experiments strongly suggested that these compounds might also bind to the active site of {NendoU}, thus impairing the catalytic activity essential for the coronavirus life cycle. The identified compounds, while allowing deep investigation of the molecular functions of this enzyme family, may also represent leads for the development of new therapeutic tools.},
	pages = {1797--1805},
	number = {10},
	journaltitle = {{ChemMedChem}},
	author = {Ragno, R and Gioia, U and Laneve, P and Bozzoni, I and Mai, A and Caffarelli, E},
	date = {2011},
	pmid = {21805647},
	keywords = {Animals, Humans, Binding Sites, Catalytic Domain, Computer Simulation, Endoribonucleases/*antagonists \& inhibitors/metabo, Enzyme Activation/drug effects, Enzyme Inhibitors/*chemistry/pharmacology, Pregnancy Proteins/chemistry, Small Molecule Libraries/*chemistry/pharmacology, Xenopus laevis/metabolism, Xenopus Proteins/*antagonists \& inhibitors/metabol}
}

@article{salvatori_microrna-26a_2012,
	title = {The {microRNA}-26a target E2F7 sustains cell proliferation and inhibits monocytic differentiation of acute myeloid leukemia cells},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23096114},
	doi = {10.1038/cddis.2012.151},
	abstract = {Blocks in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia ({AML}) cells. 1,25-Dihydroxy-vitamin D3 ({VitD}3) arrests proliferation of {AML} cells and induces their differentiation into mature monocytes. In a previous study, we showed that {miR}-26a was induced upon {VitD}3-mediated monocytic differentiation. Here, we identify E2F7 as a novel target of {miR}-26a. We show that E2F7 significantly promotes cell cycle progression and inhibits monocytic differentiation of {AML} cells. We also demonstrate that E2F7 binds the cyclin-dependent kinase inhibitor p21({CIP}1/{WAF}1) (cyclin-dependent kinase inhibitor 1A) promoter repressing its expression. Moreover, interfering with E2F7 expression results in inhibition of c-Myc (v-myc myelocytomatosis viral oncogene homolog) transcriptional activity. This leads to the downregulation of c-Myc transcriptional target {miR}-17-92 cluster, whose expression has a well-defined role in contributing to block monocytic differentiation and sustain {AML} cell proliferation. Finally, we show that the expression of E2F7 is upregulated in primary blasts from {AML} patients. Thus, these findings indicate that the newly identified {miR}-26a target E2F7 might have an important role in monocytic differentiation and leukemogenesis.},
	pages = {e413},
	journaltitle = {Cell Death Dis},
	author = {Salvatori, B and Iosue, I and Mangiavacchi, A and Loddo, G and Padula, F and Chiaretti, S and Peragine, N and Bozzoni, I and Fazi, F and Fatica, A},
	date = {2012},
	pmid = {23096114},
	keywords = {Humans, Cells, Cultured, *Cell Differentiation, *Cell Proliferation, Acute/*genetics/metabolism/*phy, Cell Cycle, Cyclin-Dependent Kinase Inhibitor p21/genetics/met, E2F7 Transcription Factor/*genetics/metabolism, {HL}-60 Cells, Leukemia, {MicroRNAs}/*genetics/metabolism, Monocytes/*cytology/metabolism, Myeloid, U937 Cells}
}

@article{ritchie_comparison_2007,
	title = {A comparison of background correction methods for two-colour microarrays},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17720982},
	doi = {10.1093/bioinformatics/btm412},
	abstract = {{MOTIVATION}: Microarray data must be background corrected to remove the effects of non-specific binding or spatial heterogeneity across the array, but this practice typically causes other problems such as negative corrected intensities and high variability of low intensity log-ratios. Different estimators of background, and various model-based processing methods, are compared in this study in search of the best option for differential expression analyses of small microarray experiments. {RESULTS}: Using data where some independent truth in gene expression is known, eight different background correction alternatives are compared, in terms of precision and bias of the resulting gene expression measures, and in terms of their ability to detect differentially expressed genes as judged by two popular algorithms, {SAM} and limma {eBayes}. A new background processing method (normexp) is introduced which is based on a convolution model. The model-based correction methods are shown to be markedly superior to the usual practice of subtracting local background estimates. Methods which stabilize the variances of the log-ratios along the intensity range perform the best. The normexp+offset method is found to give the lowest false discovery rate overall, followed by morph and vsn. Like vsn, normexp is applicable to most types of two-colour microarray data. {AVAILABILITY}: The background correction methods compared in this article are available in the R package limma (Smyth, 2005) from http://www.bioconductor.org. {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available from http://bioinf.wehi.edu.au/resources/{webReferences}.html.},
	pages = {2700--2707},
	number = {20},
	journaltitle = {Bioinformatics},
	author = {Ritchie, M E and Silver, J and Oshlack, A and Holmes, M and Diyagama, D and Holloway, A and Smyth, G K},
	date = {2007},
	pmid = {17720982},
	keywords = {Reproducibility of Results, *Artifacts, Computer-Assisted/*methods, Fluorescence, Fluorescence/*methods, Image Enhancement/*methods, Image Interpretation, In Situ Hybridization, Microscopy, Multiphoton/*methods, Oligonucleotide Array Sequence Analysis/*methods, Sensitivity and Specificity}
}

@article{hirsch_dual_2015,
	title = {Dual Function of {DNA} Sequences: Protein-Coding Sequences Function as Transcriptional Enhancers},
	volume = {58},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26750601},
	doi = {10.1353/pbm.2015.0026},
	abstract = {Most of our genome comprises noncoding sequences that include diverse transcriptional regulatory elements, such as enhancers, while only ∼1.5\% of the genome codes for proteins. Nevertheless, {DNA} sequences that code for protein (exons) can also function as enhancers ({eExons}) that regulate transcription. Mutations in {eExons} can lead to multiple phenotypes due to their dual function. The prevalence of protein-coding sequences that possess transcriptional regulatory function (such as {eExons}) and the consequences of their mutations are not well described. Using advanced sequencing technologies, protein-coding sequences were analyzed for their potential regulatory function in mammalian cells and found to be overrepresented in the genome ({\textbackslash}textgreater6\%). Dissection of the enhancer activity of {eExons} at single nucleotide resolution in liver cells has demonstrated that: (1) most nucleotide changes with high impact effect are deleterious; (2) deleterious enhancer mutations are correlated with the location of transcription factor-binding sites; (3) synonymous and non-synonymous mutations have similar effects on enhancer activity; and (4) the transcription factor repertoire that controls the activity of enhancers differs across cell types, indicating differences in deleterious mutation profiles. Thus, {eExon} mutations can disrupt both protein structure and enhancer activity with differential effect across cell types, suggesting that a mutation in a gene could cause a phenotype that has nothing to do with its protein-coding function but is due to its additional hidden regulatory function.},
	pages = {182--195},
	number = {2},
	journaltitle = {Perspect Biol Med},
	author = {Hirsch, N and Birnbaum, R Y},
	date = {2015},
	pmid = {26750601},
	keywords = {Animals, Base Sequence, Genetic, Humans, Gene Expression Regulation, *Transcription, Exons, *Transcriptional Activation, {DNA}/genetics/*metabolism, Genotype, Mutation, Phenotype, Transcription Factors/genetics/*metabolism}
}

@article{cuff_extending_2011,
	title = {Extending {CATH}: increasing coverage of the protein structure universe and linking structure with function},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21097779},
	doi = {10.1093/nar/gkq1001},
	abstract = {{CATH} version 3.3 (class, architecture, topology, homology) contains 128,688 domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major focus on classifying structural genomics ({SG}) structures and transmembrane proteins, both of which are likely to add structural novelty to the database and therefore increase the coverage of protein fold space within {CATH}. For {CATH} version 3.4 we have significantly improved the presentation of sequence information and associated functional information for {CATH} superfamilies. The {CATH} superfamily pages now reflect both the functional and structural diversity within the superfamily and include structural alignments of close and distant relatives within the superfamily, annotated with functional information and details of conserved residues. A significantly more efficient search function for {CATH} has been established by implementing the search server Solr (http://lucene.apache.org/solr/). The {CATH} v3.4 webpages have been built using the Catalyst web framework.},
	pages = {D420--6},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Cuff, A L and Sillitoe, I and Lewis, T and Clegg, A B and Rentzsch, R and Furnham, N and Pellegrini-Calace, M and Jones, D and Thornton, J and Orengo, C A},
	date = {2011},
	pmid = {21097779},
	keywords = {*Databases, *Protein Structure, Phylogeny, Protein, Protein Folding, Proteins/chemistry/classification, Tertiary}
}

@article{king_evolution_1975,
	title = {Evolution at two levels in humans and chimpanzees.},
	volume = {188},
	pages = {107--116},
	number = {4184},
	journaltitle = {Science},
	author = {King, M C and Wilson, A C},
	date = {1975}
}

@article{novikova_structural_2012,
	title = {Structural architecture of the human long non-coding {RNA}, steroid receptor {RNA} activator},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22362738},
	doi = {10.1093/nar/gks071},
	abstract = {While functional roles of several long non-coding {RNAs} ({lncRNAs}) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human {lncRNA}, the steroid receptor {RNA} activator ({SRA}), 0.87 {kB} in size. The {SRA} {RNA} is a non-coding {RNA} that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of {SRA} are also expressed to produce proteins, making the {SRA} gene a unique bifunctional system. Our experimental findings ({SHAPE}, in-line, {DMS} and {RNase} V1 probing) reveal that this {lncRNA} has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the {SRA} gene at the {RNA} structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of {RNA} structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the {RNA} structural core rather than its translational product. We perform similar experiments on alternatively spliced {SRA} isoforms to assess their structural features.},
	pages = {5034--5051},
	number = {11},
	journaltitle = {Nucleic Acids Res},
	author = {Novikova, I V and Hennelly, S P and Sanbonmatsu, K Y},
	date = {2012},
	pmid = {22362738},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, Mice, {RNA}, Amino Acid Sequence, Carrier Proteins/biosynthesis/genetics, Evolution, Long Untranslated, Molecular, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Nucleotides/chemistry, Ribonucleases, Sequence Alignment, Untranslated/*chemistry}
}

@article{lee_structural_2008,
	title = {Structural differences of orthologous genes: insights from human-primate comparisons},
	volume = {92},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18606524},
	doi = {10.1016/j.ygeno.2008.05.006},
	abstract = {The genomic basis of phenotypic distinctions between humans and nonhuman primates remains insufficiently explained. We hypothesized that interspecies structural differences of orthologous genes can cause such distinctions and searched protein-coding genes conserved between humans and nonhuman primates for species-specific initial and terminal exons. We inferred gene structure differences from genomic locations where portions of primate transcripts aligned with the human genome outside of any human exons. Of 22,466 high-confidence {FANTOM}3 human transcriptional units, 7424 (33\%) had nonhuman primate full-length {cDNA} support. One hundred eighty-three of the loci contained 68,424 bp of sequence exonic in nonhuman primates but not humans. Fifty-four of 183 included species-specific portions of protein-coding regions. Six genes had evidence of intergenic splicing in a nonhuman primate but not in human. It is imperative that primate transcriptome projects be accelerated on par with genome projects to understand better interspecies gene structure distinctions.},
	pages = {134--143},
	number = {3},
	journaltitle = {Genomics},
	author = {Lee, T M and Lipovich, L},
	date = {2008},
	pmid = {18606524},
	keywords = {Human, {DNA}, Animals, Genome, Humans, {RNA} Splicing, Exons, *Genes, Complementary/genetics, Expressed Sequence Tags, Primates/*genetics, Sequence Alignment, Species Specificity}
}

@article{baker_resveratrol_2013,
	title = {Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24231106},
	doi = {10.1016/j.jnutbio.2013.08.009},
	abstract = {Resveratrol ({RSV}) is a plant polyphenol that exhibits several favorable effects on glucose homeostasis in adipocytes. Recent studies from our laboratory demonstrated that coplanar polychlorinated biphenyls ({PCBs}) that are ligands of the aryl hydrocarbon receptor impair glucose homeostasis in mice. {PCB}-induced impairment of glucose homeostasis was associated with augmented expression of inflammatory cytokines in adipose tissue, a site for accumulation of lipophilic {PCBs}. This study determined if {RSV} protects against {PCB}-77 induced impairment of glucose disposal in vitro and in vivo and if these beneficial effects are associated with enhanced nuclear factor erythoid 2-related factor 2 (Nrf2) signaling in adipose tissue. {PCB}-77 increased oxidative stress and abolished insulin stimulated 2-deoxy-d-glucose uptake in 3 T3-L1 adipocytes. These effects were restored by {RSV}, which resulted in a concentration-dependent increase in {NAD}(P)H:quinone oxidoreductase 1 ({NQO}1), the downstream target of Nrf2 signaling. We quantified glucose and insulin tolerance and components of Nrf2 and insulin signaling cascades in adipose tissue of male C57BL/6 mice administered vehicle or {PCB}-77 (50 mg/kg) and fed a diet with or without {resVida} (0.1\%, or 160 mg/kg per day). {PCB}-77 impaired glucose and insulin tolerance, and these effects were reversed by {RSV}. {PCB}-77 induced reductions in insulin signaling in adipose tissue were also abolished by {RSV}, which increased {NQO}1 expression. These results demonstrate that coplanar {PCB}-induced impairment of glucose homeostasis in mice can be prevented by {RSV}, potentially through stimulation of Nrf2 signaling and enhanced insulin stimulated glucose disposal in adipose tissue.},
	pages = {2168--2174},
	number = {12},
	journaltitle = {J Nutr Biochem},
	author = {Baker, N A and English, V and Sunkara, M and Morris, A J and Pearson, K J and Cassis, L A},
	date = {2013},
	pmid = {24231106}
}

@article{holdt_alu_2013,
	title = {Alu elements in {ANRIL} non-coding {RNA} at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23861667},
	doi = {10.1371/journal.pgen.1003588},
	abstract = {The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today. Chr9p21 encodes the long non-coding {RNA} ({ncRNA}) antisense non-coding {RNA} in the {INK}4 locus ({ANRIL}). {ANRIL} expression is associated with the Chr9p21 genotype and correlated with atherosclerosis severity. Here, we report on the molecular mechanisms through which {ANRIL} regulates target-genes in trans, leading to increased cell proliferation, increased cell adhesion and decreased apoptosis, which are all essential mechanisms of atherogenesis. Importantly, trans-regulation was dependent on Alu motifs, which marked the promoters of {ANRIL} target genes and were mirrored in {ANRIL} {RNA} transcripts. {ANRIL} bound Polycomb group proteins that were highly enriched in the proximity of Alu motifs across the genome and were recruited to promoters of target genes upon {ANRIL} over-expression. The functional relevance of Alu motifs in {ANRIL} was confirmed by deletion and mutagenesis, reversing trans-regulation and atherogenic cell functions. {ANRIL}-regulated networks were confirmed in 2280 individuals with and without coronary artery disease and functionally validated in primary cells from patients carrying the Chr9p21 risk allele. Our study provides a molecular mechanism for pro-atherogenic effects of {ANRIL} at Chr9p21 and suggests a novel role for Alu elements in epigenetic gene regulation by long {ncRNAs}.},
	pages = {e1003588},
	number = {7},
	journaltitle = {{PLoS} Genet},
	author = {Holdt, L M and Hoffmann, S and Sass, K and Langenberger, D and Scholz, M and Krohn, K and Finstermeier, K and Stahringer, A and Wilfert, W and Beutner, F and Gielen, S and Schuler, G and Gabel, G and Bergert, H and Bechmann, I and Stadler, P F and Thiery, J and Teupser, D},
	date = {2013},
	pmid = {23861667}
}

@article{zhang_diastereoselective_2013,
	title = {A diastereoselective oxa-Pictet-Spengler-based strategy for (+)-frenolicin B and epi-(+)-frenolicin B synthesis},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24151973},
	doi = {10.1021/ol4027649},
	abstract = {An efficient diastereoselective oxa-Pictet-Spengler reaction strategy was developed to construct benzoisochroman diastereomers. The utility of the reaction was demonstrated in the context of both the total synthesis of naturally occurring pyranonaphthoquinones (+)-frenolicin B and epi-(+)-frenolicin B as well as a range of frenolicin precursor analogs. The method is versatile and offers exquisite stereocontrol and, as such, offers a synthetic advance for the synthesis of pyranonaphthoquinone analogs.},
	pages = {5566--5569},
	number = {21},
	journaltitle = {Org Lett},
	author = {Zhang, Y and Wang, X and Sunkara, M and Ye, Q and Ponomereva, L V and She, Q B and Morris, A J and Thorson, J S},
	date = {2013},
	pmid = {24151973}
}

@article{ulitsky_detecting_2008,
	title = {Detecting pathways transcriptionally correlated with clinical parameters},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19642285},
	abstract = {The recent explosion in the number of clinical studies involving microarray data calls for novel computational methods for their dissection. Human protein interaction networks are rapidly growing and can assist in the extraction of functional modules from microarray data. We describe a novel methodology for extraction of connected network modules with coherent gene expression patterns that are correlated with a specific clinical parameter. Our approach suits both numerical (e.g., age or tumor size) and logical parameters (e.g., gender or mutation status). We demonstrate the method on a large breast cancer dataset, where we identify biologically-relevant modules related to nine clinical parameters including patient age, tumor size, and metastasis-free survival. Our method is capable of detecting disease-relevant pathways that could not be found using other methods. Our results support some previous hypotheses regarding the molecular pathways underlying diversity of breast tumors and suggest novel ones.},
	pages = {249--258},
	journaltitle = {Comput Syst Bioinformatics Conf},
	author = {Ulitsky, I and Shamir, R},
	date = {2008},
	pmid = {19642285},
	keywords = {Gene Expression Profiling/*methods, Humans, *Algorithms, *Models, *Signal Transduction, Biological, Biological/*analysis, Breast Neoplasms/*metabolism, Computer Simulation, Neoplasm Proteins/*analysis, Transcription Factors/*metabolism, Tumor Markers}
}

@article{giorgi_release_2001,
	title = {Release of U18 {snoRNA} from its host intron requires interaction of Nop1p with the Rnt1p endonuclease},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11726521},
	doi = {10.1093/emboj/20.23.6856},
	abstract = {An external stem, essential for the release of small nucleolar {RNAs} ({snoRNAs}) from their pre-{mRNAs}, flanks the majority of yeast intron-encoded {snoRNAs}. Even if this stem is not a canonical Rnt1p substrate, several experiments have indicated that the Rnt1p endonuclease is required for {snoRNA} processing. To identify the factors necessary for processing of intron-encoded {snoRNAs}, we have raised in vitro extracts able to reproduce such activity. We found that {snoRNP} factors are associated with the {snoRNA}- coding region throughout all the processing steps, and that mutants unable to assemble {snoRNPs} have a processing-deficient phenotype. Specific depletion of Nop1p completely prevents U18 {snoRNA} synthesis, but does not affect processing of a dicistronic {snoRNA}-coding unit that has a canonical Rnt1p site. Correct cleavage of intron-encoded U18 and {snR}38 {snoRNAs} can be reproduced in vitro by incubating together purified Nop1p and Rnt1p. Pull-down experiments showed that the two proteins interact physically. These data indicate that cleavage of U18, {snR}38 and possibly other intron-encoded {snoRNAs} is a regulated process, since the stem is cleaved by the Rnt1p endonuclease only when {snoRNP} assembly has occurred.},
	pages = {6856--6865},
	number = {23},
	journaltitle = {{EMBO} J},
	author = {Giorgi, C and Fatica, A and Nagel, R and Bozzoni, I},
	date = {2001},
	pmid = {11726521},
	keywords = {{RNA}, Protein Binding, *Introns, *Ribonucleoproteins, *Saccharomyces cerevisiae Proteins, {DNA} Primers/metabolism, Endoribonucleases/*metabolism, Fungal Proteins/*metabolism, Genes, Glutathione Transferase/metabolism, Mutation, Nuclear Proteins/*metabolism, Nucleic Acid Conformation, Phenotype, Recombinant Fusion Proteins/metabolism, Ribonuclease {III}, Small Nucleolar, Small Nucleolar/*metabolism}
}

@article{swaminathan_bach2_2013,
	title = {{BACH}2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23852341},
	doi = {10.1038/nm.3247},
	abstract = {The B cell-specific transcription factor {BACH}2 is required for affinity maturation of B cells. Here we show that Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin {VH}-{DJH} gene segments. After productive {VH}-{DJH} gene rearrangement, pre-B cell receptor signaling ends {BACH}2-mediated negative selection through B cell lymphoma 6 ({BCL}6)-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, the {BACH}2-mediated checkpoint control is compromised by deletions, rare somatic mutations and loss of its upstream activator, {PAX}5. Low levels of {BACH}2 expression in these patients represent a strong independent predictor of poor clinical outcome. In this study, we demonstrate that Bach2(+/+) pre-B cells resist leukemic transformation by Myc through Bach2-dependent upregulation of p53 and do not initiate fatal leukemia in transplant-recipient mice. Chromatin immunoprecipitation sequencing and gene expression analyses carried out by us revealed that {BACH}2 competes with {BCL}6 for promoter binding and reverses {BCL}6-mediated repression of p53 and other cell cycle checkpoint-control genes. These findings identify {BACH}2 as a crucial mediator of negative selection at the pre-B cell receptor checkpoint and a safeguard against leukemogenesis.},
	pages = {1014--1022},
	number = {8},
	journaltitle = {Nat Med},
	author = {Swaminathan, S and Huang, C and Geng, H and Chen, Z and Harvey, R and Kang, H and Ng, C and Titz, B and Hurtz, C and Sadiyah, M F and Nowak, D and Thoennissen, G B and Rand, V and Graeber, T G and Koeffler, H P and Carroll, W L and Willman, C L and Hall, A G and Igarashi, K and Melnick, A and Muschen, M},
	date = {2013},
	pmid = {23852341},
	keywords = {Animals, Mice, {RNA}, Gene Expression Regulation, B-Cell-Specific Activator Protein/metabolism, B-Lymphoid/metabolism/pathology, Basic-Leucine Zipper Transcription Factors/genetic, Cell Death, Cell Differentiation/genetics, Cell Survival/genetics, Cell Transformation, {DNA}-Binding Proteins/metabolism, Gene Deletion, Green Fluorescent Proteins/metabolism, Immunoglobulin mu-Chains/metabolism, Leukemic, Messenger/genetics/metabolism, Molecular Sequence Data, Neoplastic/pathology, Pre-B Cell Receptors/*metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma/gen, Precursor Cells, Proto-Oncogene Proteins c-myc/metabolism, {STAT}5 Transcription Factor/metabolism, Treatment Outcome, Tumor Suppressor Protein p53/*metabolism, V(D)J Recombination/genetics}
}

@article{huda_epigenetic_2011,
	title = {Epigenetic regulation of transposable element derived human gene promoters},
	volume = {475},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21215797},
	doi = {10.1016/j.gene.2010.12.010},
	abstract = {It was previously thought that epigenetic histone modifications of mammalian transposable elements ({TEs}) serve primarily to defend the genome against deleterious effects associated with their activity. However, we recently showed that, genome-wide, human {TEs} can also be epigenetically modified in a manner consistent with their ability to regulate host genes. Here, we explore the ability of {TE} sequences to epigenetically regulate individual human genes by focusing on the histone modifications of promoter sequences derived from {TEs}. We found 1520 human genes that initiate transcription from within {TE}-derived promoter sequences. We evaluated the distributions of eight histone modifications across these {TE}-promoters, within and between the {GM}12878 and K562 cell lines, and related their modification status with the cell-type specific expression patterns of the genes that they regulate. {TE}-derived promoters are significantly enriched for active histone modifications, and depleted for repressive modifications, relative to the genomic background. Active histone modifications of {TE}-promoters peak at transcription start sites and are positively correlated with increasing expression within cell lines. Furthermore, differential modification of {TE}-derived promoters between cell lines is significantly correlated with differential gene expression. {LTR}-retrotransposon derived promoters in particular play a prominent role in mediating cell-type specific gene regulation, and a number of these {LTR}-promoter genes are implicated in lineage-specific cellular functions. The regulation of human genes mediated by histone modifications targeted to {TE}-derived promoters is consistent with the ability of {TEs} to contribute to the epigenomic landscape in a way that provides functional utility to the host genome.},
	pages = {39--48},
	number = {1},
	journaltitle = {Gene},
	author = {Huda, A and Bowen, N J and Conley, A B and Jordan, I K},
	date = {2011},
	pmid = {21215797},
	keywords = {Epigenomics, Humans, Promoter Regions, *Epigenomics, Cell Line, {DNA} Transposable Elements, {DNA} Transposable Elements/*genetics, Genetic/*genetics, Genome-Wide Association Study, Histones, Histones/metabolism, Promoter Regions, Genetic}
}

@article{ulitsky_identification_2007,
	title = {Identification of functional modules using network topology and high-throughput data},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17408515},
	doi = {10.1186/1752-0509-1-8},
	abstract = {{BACKGROUND}: With the advent of systems biology, biological knowledge is often represented today by networks. These include regulatory and metabolic networks, protein-protein interaction networks, and many others. At the same time, high-throughput genomics and proteomics techniques generate very large data sets, which require sophisticated computational analysis. Usually, separate and different analysis methodologies are applied to each of the two data types. An integrated investigation of network and high-throughput information together can improve the quality of the analysis by accounting simultaneously for topological network properties alongside intrinsic features of the high-throughput data. {RESULTS}: We describe a novel algorithmic framework for this challenge. We first transform the high-throughput data into similarity values, (e.g., by computing pairwise similarity of gene expression patterns from microarray data). Then, given a network of genes or proteins and similarity values between some of them, we seek connected sub-networks (or modules) that manifest high similarity. We develop algorithms for this problem and evaluate their performance on the osmotic shock response network in S. cerevisiae and on the human cell cycle network. We demonstrate that focused, biologically meaningful and relevant functional modules are obtained. In comparison with extant algorithms, our approach has higher sensitivity and higher specificity. {CONCLUSION}: We have demonstrated that our method can accurately identify functional modules. Hence, it carries the promise to be highly useful in analysis of high throughput data.},
	pages = {8},
	journaltitle = {{BMC} Syst Biol},
	author = {Ulitsky, I and Shamir, R},
	date = {2007},
	pmid = {17408515},
	keywords = {{DNA}, Sequence Analysis, Genetic, Humans, Promoter Regions, *Algorithms, *Gene Regulatory Networks, *Metabolic Networks and Pathways, *Models, Biological, Cell Cycle/genetics, Cluster Analysis, Computer Simulation, Osmotic Pressure, Protein Interaction Mapping, Saccharomyces cerevisiae/genetics/metabolism, Systems Biology/*methods}
}

@article{fazi_heterochromatic_2007,
	title = {Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia},
	volume = {109},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17244680},
	doi = {10.1182/blood-2006-09-045781},
	abstract = {Alteration of lineage-specific transcriptional programs for hematopoiesis causes differentiation block and promotes leukemia development. Here, we show that {AML}1/{ETO}, the most common translocation fusion product in acute myeloid leukemia ({AML}), counteracts the activity of retinoic acid ({RA}), a transcriptional regulator of myelopoiesis. {AML}1/{ETO} participates in a protein complex with the {RA} receptor alpha ({RARalpha}) at {RA} regulatory regions on {RARbeta}2, which is a key {RA} target gene mediating {RA} activity/resistance in cells. At these sites, {AML}1/{ETO} recruits histone deacetylase, {DNA} methyltransferase, and {DNA}-methyl-{CpG} binding activities that promote a repressed chromatin conformation. The link among {AML}1/{ETO}, heterochromatic {RARbeta}2 repression, {RA} resistance, and myeloid differentiation block is indicated by the ability of either {siRNA}-{AML}1/{ETO} or the {DNA} methylation inhibitor 5-azacytidine to revert these epigenetic alterations and to restore {RA} differentiation response in {AML}1/{ETO} blasts. Finally, {RARbeta}2 is commonly silenced by hypermethylation in primary {AML} blasts but not in normal hematopoietic precursors, thus suggesting a role for the epigenetic repression of the {RA} signaling pathway in myeloid leukemogenesis.},
	pages = {4432--4440},
	number = {10},
	journaltitle = {Blood},
	author = {Fazi, F and Zardo, G and Gelmetti, V and Travaglini, L and Ciolfi, A and Di Croce, L and Rosa, A and Bozzoni, I and Grignani, F and Lo-Coco, F and Pelicci, P G and Nervi, C},
	date = {2007},
	pmid = {17244680},
	keywords = {Humans, Protein Binding, Cells, Cultured, *Gene Expression Regulation, *Gene Silencing, Acute Disease, Cell Differentiation/drug effects/genetics, Core Binding Factor Alpha 2 Subunit/antagonists \&, Fusion/antagonists \& inhibitors, Heterochromatin/*physiology, inhibitors/genetics/metabolism/physiology, Leukemia, Leukemic/drug effects, Myeloid/*genetics/metabolism/pathology, Oncogene Proteins, Receptors, Response Elements, Retinoic Acid/*genetics/metabolism, Retinoid X Receptors/metabolism, Signal Transduction/genetics, Transfection, Tretinoin/*metabolism/pharmacology, U937 Cells}
}

@article{nei_mathematical_1979,
	title = {Mathematical model for studying genetic variation in terms of restriction endonucleases},
	volume = {76},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/291943},
	abstract = {A mathematical model for the evolutionary change of restriction sites in mitochondrial {DNA} is developed. Formulas based on this model are presented for estimating the number of nucleotide substitutions between two populations or species. To express the degree of polymorphism in a population at the nucleotide level, a measure called "nucleotide diversity" is proposed.},
	pages = {5269--5273},
	number = {10},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Nei, M and Li, W H},
	date = {1979},
	pmid = {291943},
	keywords = {Base Sequence, *{DNA}, *{DNA} Restriction Enzymes, *Genetic Variation, Biological, Computers, Mathematics, Mitochondrial, Models}
}

@article{kim_ceramide-1-phosphate_2013,
	title = {Ceramide-1-phosphate regulates migration of multipotent stromal cells and endothelial progenitor cells–implications for tissue regeneration},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23193025},
	doi = {10.1002/stem.1291},
	abstract = {Ceramide-1-phosphate (C1P) is a bioactive lipid that, in contrast to ceramide, is an antiapoptotic molecule released from cells that are damaged and "leaky." As reported recently, C1P promotes migration of hematopoietic cells. In this article, we tested the hypothesis that C1P released upon tissue damage may play an underappreciated role in chemoattraction of various types of stem cells and endothelial cells involved in tissue/organ regeneration. We show for the first time that C1P is upregulated in damaged tissues and chemoattracts bone marrow ({BM})-derived multipotent stromal cells, endothelial progenitor cells, and very small embryonic-like stem cells. Furthermore, compared to other bioactive lipids, C1P more potently chemoattracted human umbilical vein endothelial cells and stimulated tube formation by these cells. C1P also promoted in vivo vascularization of Matrigel implants and stimulated secretion of stromal cell-derived factor-1 from {BM}-derived fibroblasts. Thus, our data demonstrate, for the first time, that C1P is a potent bioactive lipid released from damaged cells that potentially plays an important and novel role in recruitment of stem/progenitor cells to damaged organs and may promote their vascularization.},
	pages = {500--510},
	number = {3},
	journaltitle = {Stem Cells},
	author = {Kim, C and Schneider, G and Abdel-Latif, A and Mierzejewska, K and Sunkara, M and Borkowska, S and Ratajczak, J and Morris, A J and Kucia, M and Ratajczak, M Z},
	date = {2013},
	pmid = {23193025},
	keywords = {Animals, Humans, Mice, Cell Growth Processes/physiology, Cell Movement/*physiology, Ceramides/biosynthesis/*metabolism, Chemotactic Factors/biosynthesis/metabolism, Human Umbilical Vein Endothelial Cells/cytology/*m, Inbred C57BL, Mesenchymal Stromal Cells/cytology/*metabolism, Myocardial Ischemia/metabolism/pathology, Regeneration/*physiology, Regenerative Medicine/methods, Stem Cells/*cytology/metabolism, Up-Regulation}
}

@article{baker_protein_2001,
	title = {Protein structure prediction and structural genomics},
	volume = {294},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11588250},
	doi = {10.1126/science.1065659},
	abstract = {Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.},
	pages = {93--96},
	number = {5540},
	journaltitle = {Science},
	author = {Baker, D and Sali, A},
	date = {2001},
	pmid = {11588250},
	keywords = {Animals, Genetic, Humans, Binding Sites, Databases, Software, *Computational Biology, *Genomics, *Models, *Protein Conformation, Amino Acid Sequence, Computer Simulation, Factual, Internet, Molecular, Protein Folding, Protein Structure, Proteins/*chemistry/genetics/physiology, Sequence Alignment, Templates, Tertiary}
}

@article{yang_starbase:_2011,
	title = {{starBase}: a database for exploring {microRNA}-{mRNA} interaction maps from Argonaute {CLIP}-Seq and Degradome-Seq data},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21037263},
	doi = {10.1093/nar/gkq1056},
	abstract = {{MicroRNAs} ({miRNAs}) represent an important class of small non-coding {RNAs} ({sRNAs}) that regulate gene expression by targeting messenger {RNAs}. However, assigning {miRNAs} to their regulatory target genes remains technically challenging. Recently, high-throughput {CLIP}-Seq and degradome sequencing (Degradome-Seq) methods have been applied to identify the sites of Argonaute interaction and {miRNA} cleavage sites, respectively. In this study, we introduce a novel database, {starBase} ({sRNA} target Base), which we have developed to facilitate the comprehensive exploration of {miRNA}-target interaction maps from {CLIP}-Seq and Degradome-Seq data. The current version includes high-throughput sequencing data generated from 21 {CLIP}-Seq and 10 Degradome-Seq experiments from six organisms. By analyzing millions of mapped {CLIP}-Seq and Degradome-Seq reads, we identified approximately 1 million Ago-binding clusters and approximately 2 million cleaved target clusters in animals and plants, respectively. Analyses of these clusters, and of target sites predicted by 6 {miRNA} target prediction programs, resulted in our identification of approximately 400,000 and approximately 66,000 {miRNA}-target regulatory relationships from {CLIP}-Seq and Degradome-Seq data, respectively. Furthermore, two web servers were provided to discover novel {miRNA} target sites from {CLIP}-Seq and Degradome-Seq data. Our web implementation supports diverse query types and exploration of common targets, gene ontologies and pathways. The {starBase} is available at http://starbase.sysu.edu.cn/.},
	pages = {D202--9},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Yang, J H and Li, J H and Shao, P and Zhou, H and Chen, Y Q and Qu, L H},
	date = {2011},
	pmid = {21037263},
	keywords = {Genomics, Sequence Analysis, Animals, Humans, Mice, {RNA}, Binding Sites, Gene Expression Regulation, Nucleic Acid, Software, *Databases, Internet, Messenger/*chemistry/metabolism, {MicroRNAs}/*chemistry/metabolism, {RNA}-Binding Proteins/metabolism, User-Computer Interface}
}

@article{ruberti_characterization_1982,
	title = {Characterization of histone genes isolated from Xenopus laevis and Xenopus tropicalis genomic libraries},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6296782},
	abstract = {Using a {cDNA} clone for the histone H3 we have isolated, from two genomic libraries of Xenopus laevis and Xenopus tropicalis, clones containing four different histone gene clusters. The structural organization of X. laevis histone genes has been determined by restriction mapping, Southern blot hybridization and translation of the {mRNAs} which hybridize to the various restriction fragments. The arrangement of the histone genes in X. tropicalis has been determined by Southern analysis using X. laevis genomic fragments, containing individual genes, as probes. Histone genes are clustered in the genome of X. laevis and X. tropicalis and, compared to invertebrates, show a higher organization heterogeneity as demonstrated by structural analysis of the four genomic clones. In fact, the order of the genes within individual clusters is not conserved.},
	pages = {7543--7559},
	number = {23},
	journaltitle = {Nucleic Acids Res},
	author = {Ruberti, I and Fragapane, P and Pierandrei-Amaldi, P and Beccari, E and Amaldi, F and Bozzoni, I},
	date = {1982},
	pmid = {6296782},
	keywords = {{DNA}, Animals, Base Sequence, {RNA}, Messenger/genetics, *Cloning, *Genes, Amino Acid Sequence, {DNA} Restriction Enzymes, Histones/*genetics, Molecular, Nucleic Acid Hybridization, Recombinant/*analysis, Species Specificity, Xenopus}
}

@article{pierandrei-amaldi_ribosomal_1985,
	title = {Ribosomal protein production in normal and anucleolate Xenopus embryos: regulation at the posttranscriptional and translational levels},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/4016954},
	abstract = {We have studied the regulation of ribosomal protein (r-protein) synthesis in Xenopus anucleolate mutants, which lack the genes for {rRNA}. The accumulation of {mRNA} for the two r-proteins analyzed parallels the controls up to stage 30. This {mRNA} is mobilized onto polysomes and is translated as in normal embryos, but r-proteins are unstable in the absence of {rRNA} to assemble with. A translational control of rp-{mRNA} distribution between polysomes and {mRNPs} is observed, but this is not due to an autogenous regulation by r-proteins. After stage 30 the amount of rp-{mRNA} declines specifically in the mutants because the transcripts are unstable. Considering the temporal correlation between this event and the onset of r-protein synthesis we suggest that an autogenous control operates at the level of transcript stability.},
	pages = {317--323},
	number = {1},
	journaltitle = {Cell},
	author = {Pierandrei-Amaldi, P and Beccari, E and Bozzoni, I and Amaldi, F},
	date = {1985},
	pmid = {4016954},
	keywords = {Animals, Genetic, {RNA}, *Transcription, *Protein Biosynthesis, Cell Nucleolus/physiology, Messenger/biosynthesis/*genetics/metabolism, Mutation, Polyribosomes/metabolism, Ribosomal Proteins/*biosynthesis/genetics/metaboli, Ribosomal/genetics, Xenopus laevis/embryology}
}

@article{morera_[histopathological_2004,
	title = {[Histopathological changes at the surgical site in experimental animals following partial cricoid resection and thyrotracheal anastomosis]},
	volume = {55},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15253340},
	abstract = {{OBJECTIVE}: To study in an animal model the local healing process after partial cricoid resection with thyrotracheal anastomosis. {MATERIAL} {AND} {METHODS}: Partial cricoid resection with thyrotracheal anastomosis was performed in 17 New Zealand rabbits. Experimental animals were gradually sacrificed and the laryngotracheal complex was removed to proceed to a histopathological study. {RESULTS}: An acute inflammatory response followed by a chronic inflammatory process was found in the surgical site. Normal tissue architecture was established after an eight week period. Anteroposterior and transverse diameters at all levels of the upper respiratory tract were not significantly altered at any time along the healing process. Experimental animals remained free from symptoms during the follow-up period. {CONCLUSIONS}: These results support that partial cricoid resection with thyrotracheal anastomosis is a safe procedure for the treatment of severe laryngotracheal stenosis.},
	pages = {131--138},
	number = {3},
	journaltitle = {Acta Otorrinolaringol Esp},
	author = {Morera, E and Alvarez, H and Fontes, L and Gorospe, M and Bernaldez, R and Gavilan, J},
	date = {2004},
	pmid = {15253340},
	keywords = {Animals, Anastomosis, Cricoid Cartilage/*pathology/*surgery, Rabbits, Surgical/methods, Thyroid Gland/*pathology/*surgery, Trachea/*pathology/*surgery}
}

@article{bozzoni_replication_1981,
	title = {Replication of ribosomal {DNA} in Xenopus laevis},
	volume = {118},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7297565},
	abstract = {The study of the localization of the replication origins of {rDNA} in Xenopus laevis has been approached by two different methods. 1. The {DNA} of X. laevis larvae was fractionated by {CsCl} gradient centrifugation in bulk and ribosomal {DNA} and examined in the electron microscope. In bulk {DNA}, clusters of microbubbles, which are related with the origins of replication, appear to be spaced along the {DNA} molecules at intervals comparable with the size of the 'average' replicon of X. laevis. In ribosomal {DNA}, the distance between adjacent clusters is much shorter and corresponds to the size of the {rDNA} repeating unit. When ribosomal {DNA} was submitted to digestion with restriction enzymes (Eco {RI} and {HindIII}) the microbubbles are observed in the non-transcribed spacer-containing fragment. 2. Cultured cells of X. laevis were synchronized by mitotic selection and incubated with 5-fluoro-2-deoxyuridine for a time longer than the G1 phase. This treatment synchronizes the replicons and allows them to start replicating very slowly. It was thus possible to obtain a preferential labelling of the regions containing the origins. The analysis by gel electrophoresis of the Eco Ri-digested {rDNA} showed that the radioactivity was preferentially incorporated in the fragments which contain the non-transcribed spacer. The results of these two approaches indicate that the {rRNA} gene cluster consists of multiple units of replication, possibly one per gene unit. Furthermore they show that the origins of replication are localized into the non-transcribed spacer.},
	pages = {585--590},
	number = {3},
	journaltitle = {Eur J Biochem},
	author = {Bozzoni, I and Baldari, C T and Amaldi, F and Buongiorno-Nardelli, M},
	date = {1981},
	pmid = {7297565},
	keywords = {{DNA}, Animals, Binding Sites, *{DNA} Replication, Cell Line, Clone Cells, Recombinant/*biosynthesis, Ribosomal, Xenopus laevis}
}

@article{wehrspaun_brain-expressed_2014,
	title = {Brain-expressed 3'{UTR} extensions strengthen {miRNA} cross-talk between ion channel/transporter encoding {mRNAs}},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24616735},
	doi = {10.3389/fgene.2014.00041},
	abstract = {Why protein-coding genes express transcripts with longer 3'untranslated regions (3'{UTRs}) in the brain rather than in other tissues remains poorly understood. Given the established role of 3'{UTRs} in post-transcriptional regulation of transcript abundance and their recently highlighted contributions to {miRNA}-mediated cross-talk between {mRNAs}, we hypothesized that 3'{UTR} lengthening enhances coordinated expression between functionally-related genes in the brain. To test this hypothesis, we annotated 3'{UTRs} of human brain-expressed genes and found that transcripts encoding ion channels or transporters are specifically enriched among those genes expressing their longest 3'{UTR} extension in this tissue. These 3'{UTR} extensions have high density of response elements predicted for those {miRNAs} that are specifically expressed in the human frontal cortex ({FC}). Importantly, these {miRNA} response elements are more frequently shared among ion channel/transporter-encoding {mRNAs} than expected by chance. This indicates that {miRNA}-mediated cross-talk accounts, at least in part, for the observed coordinated expression of ion channel/transporter genes in the adult human brain. We conclude that extension of these genes' 3'{UTRs} enhances the {miRNA}-mediated cross-talk among their transcripts which post-transcriptionally regulates their {mRNAs}' relative levels.},
	pages = {41},
	journaltitle = {Front Genet},
	author = {Wehrspaun, C C and Ponting, C P and Marques, A C},
	date = {2014},
	pmid = {24616735}
}

@article{puttini_gene-mediated_2009,
	title = {Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19002166},
	doi = {10.1038/mt.2008.239},
	abstract = {Dystrophin mediates a physical link between the cytoskeleton of muscle fibers and the extracellular matrix, and its absence leads to muscle degeneration and dystrophy. In this article, we show that the lack of dystrophin affects the elasticity of individual fibers within muscle tissue explants, as probed using atomic force microscopy ({AFM}), providing a sensitive and quantitative description of the properties of normal and dystrophic myofibers. The rescue of dystrophin expression by exon skipping or by the ectopic expression of the utrophin analogue normalized the elasticity of dystrophic muscles, and these effects were commensurate to the functional recovery of whole muscle strength. However, a more homogeneous and widespread restoration of normal elasticity was obtained by the exon-skipping approach when comparing individual myofibers. {AFM} may thus provide a quantification of the functional benefit of gene therapies from live tissues coupled to single-cell resolution.},
	pages = {19--25},
	number = {1},
	journaltitle = {Mol Ther},
	author = {Puttini, S and Lekka, M and Dorchies, O M and Saugy, D and Incitti, T and Ruegg, U T and Bozzoni, I and Kulik, A J and Mermod, N},
	date = {2009},
	pmid = {19002166},
	keywords = {Animals, Mice, Animal/*genetics/physiopatholo, Atomic Force, Dependovirus/genetics, Dystrophin/*genetics, Elasticity, Genetic Therapy/*methods, Genetic Vectors/administration \& dosage/genetics, Inbred C57BL, Inbred mdx, Male, Microscopy, Muscle, Muscular Dystrophy, Skeletal/*metabolism/*physiopathology}
}

@article{romano_different_2010,
	title = {Different sets of {QTLs} influence fitness variation in yeast},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20160707},
	doi = {10.1038/msb.2010.1},
	abstract = {Most of the phenotypes in nature are complex and are determined by many quantitative trait loci ({QTLs}). In this study we identify gene sets that contribute to one important complex trait: the ability of yeast cells to survive under alkali stress. We carried out an in-lab evolution ({ILE}) experiment, in which we grew yeast populations under increasing alkali stress to enrich for beneficial mutations. The populations acquired different sets of affecting alleles, showing that evolution can provide alternative solutions to the same challenge. We measured the contribution of each allele to the phenotype. The sum of the effects of the {QTLs} was larger than the difference between the ancestor phenotype and the evolved strains, suggesting epistatic interactions between the {QTLs}. In parallel, a clinical isolated strain was used to map natural {QTLs} affecting growth at high {pH}. In all, 17 candidate regions were found. Using a predictive algorithm based on the distances in protein-interaction networks, candidate genes were defined and validated by gene disruption. Many of the {QTLs} found by both methods are not directly implied in {pH} homeostasis but have more general, and often regulatory, roles.},
	pages = {346},
	journaltitle = {Mol Syst Biol},
	author = {Romano, G H and Gurvich, Y and Lavi, O and Ulitsky, I and Shamir, R and Kupiec, M},
	date = {2010},
	pmid = {20160707},
	keywords = {Reproducibility of Results, Algorithms, *Quantitative Trait Loci, Antiporters/genetics, Cation Transport Proteins/genetics, Chromosome Mapping, Culture Media/metabolism, Directed Molecular Evolution/*methods, Genetic Fitness/*genetics, Homeostasis/genetics, Hydrogen-Ion Concentration, Mutation, Phenotype, Saccharomyces cerevisiae Proteins/genetics, Saccharomyces cerevisiae/*genetics, Systems Biology/methods}
}

@article{westbrook_genetic_2005,
	title = {A genetic screen for candidate tumor suppressors identifies {REST}},
	volume = {121},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15960972},
	doi = {10.1016/j.cell.2005.03.033},
	abstract = {Tumorigenesis is a multistep process characterized by a myriad of genetic and epigenetic alterations. Identifying the causal perturbations that confer malignant transformation is a central goal in cancer biology. Here we report an {RNAi}-based genetic screen for genes that suppress transformation of human mammary epithelial cells. We identified genes previously implicated in proliferative control and epithelial cell function including two established tumor suppressors, {TGFBR}2 and {PTEN}. In addition, we uncovered a previously unrecognized tumor suppressor role for {REST}/{NRSF}, a transcriptional repressor of neuronal gene expression. Array-{CGH} analysis identified {REST} as a frequent target of deletion in colorectal cancer. Furthermore, we detect a frameshift mutation of the {REST} gene in colorectal cancer cells that encodes a dominantly acting truncation capable of transforming epithelial cells. Cells lacking {REST} exhibit increased {PI}(3)K signaling and are dependent upon this pathway for their transformed phenotype. These results implicate {REST} as a human tumor suppressor and provide a novel approach to identifying candidate genes that suppress the development of human cancer.},
	pages = {837--848},
	number = {6},
	journaltitle = {Cell},
	author = {Westbrook, T F and Martin, E S and Schlabach, M R and Leng, Y and Liang, A C and Feng, B and Zhao, J J and Roberts, T M and Mandel, G and Hannon, G J and Depinho, R A and Chin, L and Elledge, S J},
	date = {2005},
	pmid = {15960972},
	keywords = {Humans, Cells, Cultured, Cell Line, Epithelial Cells/physiology, Genes, Genetic Testing/*methods, Phosphatidylinositol 3-Kinases/antagonists \& inhib, Repressor Proteins/pharmacology/*physiology, {RNA} Interference/physiology, Signal Transduction/drug effects/physiology, Transcription Factors/pharmacology/*physiology, Transforming Growth Factor beta/physiology, Tumor, Tumor Suppressor/*physiology}
}

@article{tominaga_competitive_2011,
	title = {Competitive regulation of nucleolin expression by {HuR} and {miR}-494},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21859890},
	doi = {10.1128/MCB.05955-11},
	abstract = {The {RNA}-binding protein ({RBP}) nucleolin promotes the expression of several proliferative proteins. Nucleolin levels are high in cancer cells, but the mechanisms that control nucleolin expression are unknown. Here, we show that nucleolin abundance is controlled posttranscriptionally via factors that associate with its 3' untranslated region (3'{UTR}). The {RBP} {HuR} was found to interact with the nucleolin ({NCL}) 3'{UTR} and specifically promoted nucleolin translation without affecting nucleolin {mRNA} levels. In human cervical carcinoma {HeLa} cells, analysis of a traceable {NCL} 3'{UTR} bearing {MS}2 {RNA} hairpins revealed that {NCL} {RNA} was mobilized to processing bodies ({PBs}) after silencing {HuR}, suggesting that the repression of nucleolin translation may occur in {PBs}. Immunoprecipitation of {MS}2-tagged {NCL} 3'{UTR} was used to screen for endogenous repressors of nucleolin synthesis. This search identified {miR}-494 as a {microRNA} that potently inhibited nucleolin expression, enhanced {NCL} {mRNA} association with argonaute-containing complexes, and induced {NCL} {RNA} transport to {PBs}. Importantly, {miR}-494 and {HuR} functionally competed for modulation of nucleolin expression. Moreover, the promotion of cell growth previously attributed to {HuR} was due in part to the {HuR}-elicited increase in nucleolin expression. Our collective findings indicate that nucleolin expression is positively regulated by {HuR} and negatively regulated via competition with {miR}-494.},
	pages = {4219--4231},
	number = {20},
	journaltitle = {Mol Cell Biol},
	author = {Tominaga, K and Srikantan, S and Lee, E K and Subaran, S S and Martindale, J L and Abdelmohsen, K and Gorospe, M},
	date = {2011},
	pmid = {21859890},
	keywords = {Humans, {RNA}, Messenger/genetics, *3' Untranslated Regions, *Gene Expression Regulation, Antigens, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, {MicroRNAs}/*genetics, Neoplasms/*genetics, Neoplastic, Phosphoproteins/*genetics, {RNA}-Binding Proteins/*genetics, Surface/*genetics}
}

@article{jeon_yy1_2011,
	title = {{YY}1 tethers Xist {RNA} to the inactive X nucleation center},
	volume = {146},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21729784},
	doi = {10.1016/j.cell.2011.06.026},
	abstract = {The long noncoding Xist {RNA} inactivates one X chromosome in the female mammal. Current models posit that Xist induces silencing as it spreads along X and recruits Polycomb complexes. However, the mechanisms for Xist loading and spreading are currently unknown. Here, we define the nucleation center for Xist {RNA} and show that {YY}1 docks Xist particles onto the X chromosome. {YY}1 is a "bivalent" protein, capable of binding both {RNA} and {DNA} through different sequence motifs. Xist's exclusive attachment to the inactive X is determined by an epigenetically regulated trio of {YY}1 sites as well as allelic origin. Specific {YY}1-to-{RNA} and {YY}1-to-{DNA} contacts are required to load Xist particles onto X. {YY}1 interacts with Xist {RNA} through Repeat C. We propose that {YY}1 acts as adaptor between regulatory {RNA} and chromatin targets.},
	pages = {119--133},
	number = {1},
	journaltitle = {Cell},
	author = {Jeon, Y and Lee, J T},
	date = {2011},
	pmid = {21729784},
	keywords = {Animals, Mice, {RNA}, *X Chromosome Inactivation, Female, Long Untranslated, Polycomb-Group Proteins, Repressor Proteins/metabolism, Transgenes, Untranslated/chemistry/*metabolism, X Chromosome/*genetics, {YY}1 Transcription Factor/*metabolism}
}

@article{earnshaw_esperanto_2013,
	title = {Esperanto for histones: {CENP}-A, not {CenH}3, is the centromeric histone H3 variant},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23580138},
	doi = {10.1007/s10577-013-9347-y},
	abstract = {The first centromeric protein identified in any species was {CENP}-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein {CenH}3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.},
	pages = {101--106},
	number = {2},
	journaltitle = {Chromosome Res},
	author = {Earnshaw, W C and Allshire, R C and Black, B E and Bloom, K and Brinkley, B R and Brown, W and Cheeseman, I M and Choo, K H and Copenhaver, G P and Deluca, J G and Desai, A and Diekmann, S and Erhardt, S and Fitzgerald-Hayes, M and Foltz, D and Fukagawa, T and Gassmann, R and Gerlich, D W and Glover, D M and Gorbsky, G J and Harrison, S C and Heun, P and Hirota, T and Jansen, L E and Karpen, G and Kops, G J and Lampson, M A and Lens, S M and Losada, A and Luger, K and Maiato, H and Maddox, P S and Margolis, R L and Masumoto, H and {McAinsh}, A D and Mellone, B G and Meraldi, P and Musacchio, A and Oegema, K and O'Neill, R J and Salmon, E D and Scott, K C and Straight, A F and Stukenberg, P T and Sullivan, B A and Sullivan, K F and Sunkel, C E and Swedlow, J R and Walczak, C E and Warburton, P E and Westermann, S and Willard, H F and Wordeman, L and Yanagida, M and Yen, T J and Yoda, K and Cleveland, D W},
	date = {2013},
	pmid = {23580138},
	keywords = {Humans, Autoantigens/*genetics/metabolism, Centromere, Chromosomal Proteins, Histones/*genetics/metabolism, Kinetochores, Non-Histone/*genetics/metabo, Scleroderma, Systemic/genetics, Terminology as Topic}
}

@article{horvath_real-time_2007,
	title = {Real-time magnetic resonance imaging guidance for cardiovascular procedures},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18395633},
	doi = {10.1053/j.semtcvs.2007.10.006},
	abstract = {Magnetic resonance imaging ({MRI}) of the cardiovascular system has proven to be an invaluable diagnostic tool. Given the ability to allow for real-time imaging, {MRI} guidance of intraoperative procedures can provide superb visualization, which can facilitate a variety of interventions and minimize the trauma of the operations as well. In addition to the anatomic detail, {MRI} can provide intraoperative assessment of organ and device function. Instruments and devices can be marked to enhance visualization and tracking, all of which is an advance over standard X-ray or ultrasonic imaging.},
	pages = {330--335},
	number = {4},
	journaltitle = {Semin Thorac Cardiovasc Surg},
	author = {Horvath, K A and Li, M and Mazilu, D and Guttman, M A and {McVeigh}, E R},
	date = {2007},
	pmid = {18395633},
	keywords = {Humans, *Magnetic Resonance Imaging/methods, Aortic Coarctation/surgery, Cardiac Catheterization/methods, Cardiovascular Diseases/*surgery, Cardiovascular Surgical Procedures/*methods, Computer-Assisted/*instrumentation, Heart Valve Prosthesis, Stents, Surgery, Time Factors}
}

@article{filippini_u86_2001,
	title = {U86, a novel {snoRNA} with an unprecedented gene organization in yeast},
	volume = {288},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11594746},
	doi = {10.1006/bbrc.2001.5720},
	abstract = {The Xenopus laevis Nop56 gene ({XNOP}56), coding for a {snoRNP}-specific factor, belongs to the 5'-{TOP} gene family. {XNOP}56, as many 5'-{TOP} genes, contains an intron-encoded {snoRNA}. This previously unidentified {RNA}, named U86, was found as a highly conserved species in yeast and human. While in human it is also encoded in an intron of the {hNop}56 gene, in yeast it has an unprecedented gene organization: it is encoded inside an open-reading frame. Both in X. laevis and yeast, the synthesis of U86 {snoRNA} appears to be alternative to that of the cotranscribed {mRNA}. Despite the overall homology, the three U86 {snoRNAs} do not show strong conservation of the sequence upstream from the box D and none of them displays significant sequence complementarity to {rRNA} or {snRNA} sequences, suggesting a role different from that of methylation.},
	pages = {16--21},
	number = {1},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Filippini, D and Renzi, F and Bozzoni, I and Caffarelli, E},
	date = {2001},
	pmid = {11594746},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, {RNA}, {RNA} Splicing, Nucleic Acid, Open Reading Frames, Introns, *Genes, *Saccharomyces cerevisiae Proteins, *Xenopus Proteins, Fungal, Molecular Sequence Data, Nuclear Proteins/*genetics, Saccharomyces cerevisiae/*genetics, Sequence Homology, Small Nucleolar/*genetics, Xenopus/genetics}
}

@article{koonin_structure_2002,
	title = {The structure of the protein universe and genome evolution},
	volume = {420},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12432406},
	doi = {10.1038/nature01256},
	abstract = {Despite the practically unlimited number of possible protein sequences, the number of basic shapes in which proteins fold seems not only to be finite, but also to be relatively small, with probably no more than 10,000 folds in existence. Moreover, the distribution of proteins among these folds is highly non-homogeneous – some folds and superfamilies are extremely abundant, but most are rare. Protein folds and families encoded in diverse genomes show similar size distributions with notable mathematical properties, which also extend to the number of connections between domains in multidomain proteins. All these distributions follow asymptotic power laws, such as have been identified in a wide variety of biological and physical systems, and which are typically associated with scale-free networks. These findings suggest that genome evolution is driven by extremely general mechanisms based on the preferential attachment principle.},
	pages = {218--223},
	number = {6912},
	journaltitle = {Nature},
	author = {Koonin, E V and Wolf, Y I and Karev, G P},
	date = {2002},
	pmid = {12432406},
	keywords = {Genetic, *Genome, Databases, *Evolution, *Protein Folding, Models, Molecular, Protein, Protein Structure, Proteins/*chemistry/classification/genetics, Proteome, Proteomics, Tertiary}
}

@article{xiao_polyamines_2007,
	title = {Polyamines regulate the stability of activating transcription factor-2 {mRNA} through {RNA}-binding protein {HuR} in intestinal epithelial cells},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17804813},
	doi = {10.1091/mbc.E07-07-0675},
	abstract = {Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the {RNA}-binding protein {HuR}, which stabilizes its target transcripts such as nucleophosmin and p53 {mRNAs}. The activating transcription factor-2 ({ATF}-2) {mRNA} encodes a member of the {ATF}/{CRE}-binding protein family of transcription factors and was computationally predicted to be a target of {HuR}. Here, we show that polyamines negatively regulate {ATF}-2 expression posttranscriptionally and that polyamine depletion stabilizes {ATF}-2 {mRNA} by enhancing the interaction of the 3'-untranslated region ({UTR}) of {ATF}-2 with cytoplasmic {HuR}. Decreasing cellular polyamines by inhibiting ornithine decarboxylase ({ODC}) with alpha-difluoromethylornithine increased the levels of {ATF}-2 {mRNA} and protein, whereas increasing polyamines by ectopic {ODC} overexpression repressed {ATF}-2 expression. Polyamine depletion did not alter transcription via the {ATF}-2 gene promoter but increased the stability of {ATF}-2 {mRNA}. Increased cytoplasmic {HuR} in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous {ATF}-2 {mRNA} and specifically bound to 3'-{UTR} of {ATF}-2 {mRNA} on multiple nonoverlapping 3'-{UTR} segments. Adenovirus-mediated {HuR} overexpression elevated {ATF}-2 {mRNA} and protein levels, whereas {HuR} silencing rendered the {ATF}-2 {mRNA} unstable and prevented increases in {ATF}-2 {mRNA} and protein. Furthermore, inhibition of {ATF}-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-alpha and cycloheximide. These results indicate that polyamines modulate the stability of {ATF}-2 {mRNA} by altering cytoplasmic {HuR} levels and that polyamine-modulated {ATF}-2 expression plays a critical role in regulating epithelial apoptosis.},
	pages = {4579--4590},
	number = {11},
	journaltitle = {Mol Biol Cell},
	author = {Xiao, L and Rao, J N and Zou, T and Liu, L and Marasa, B S and Chen, J and Turner, D J and Zhou, H and Gorospe, M and Wang, J Y},
	date = {2007},
	pmid = {17804813},
	keywords = {Animals, Promoter Regions, {RNA}, Gene Expression Regulation, Messenger/genetics, Protein Binding, Genetic/genetics, 3' Untranslated Regions/genetics, Activating Transcription Factor 2/*genetics/metabo, Antigens, Apoptosis, Cell Line, Cytoplasm/metabolism, Epithelial Cells/drug effects/*metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Intestines/*metabolism, Molecular Sequence Data, Polyamines/*metabolism, Rats, {RNA} Stability/*genetics, {RNA}-Binding Proteins/genetics/*metabolism, Small Interfering/genetics, Surface/genetics/*metabolism, Transcriptional Activation/genetics}
}

@article{kretz_suppression_2012,
	title = {Suppression of progenitor differentiation requires the long noncoding {RNA} {ANCR}},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22302877},
	doi = {10.1101/gad.182121.111},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) regulate diverse processes, yet a potential role for {lncRNAs} in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare {lncRNA} expression in epidermal progenitor populations versus differentiating cells. We identified {ANCR} (anti-differentiation {ncRNA}) as an 855-base-pair {lncRNA} down-regulated during differentiation. Depleting {ANCR} in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. In epidermis, {ANCR} loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The {ANCR} {lncRNA} is thus required to enforce the undifferentiated cell state within epidermis.},
	pages = {338--343},
	number = {4},
	journaltitle = {Genes Dev},
	author = {Kretz, M and Webster, D E and Flockhart, R J and Lee, C S and Zehnder, A and Lopez-Pajares, V and Qu, K and Zheng, G X and Chow, J and Kim, G E and Rinn, J L and Chang, H Y and Siprashvili, Z and Khavari, P A},
	date = {2012},
	pmid = {22302877},
	keywords = {Transcriptome, {RNA}, Gene Expression Regulation, Cells, Cultured, *Cell Differentiation, Developmental, Epidermis/cytology, Keratinocytes/*cytology, Long Untranslated, {RNA} Interference, Stem Cells/*cytology, Untranslated/genetics/*metabolism}
}

@article{mazan-mamczarz_identification_2009,
	title = {Identification of a signature motif in target {mRNAs} of {RNA}-binding protein {AUF}1},
	volume = {37},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19033365},
	doi = {10.1093/nar/gkn929},
	abstract = {The ubiquitous {RNA}-binding protein {AUF}1 promotes the degradation of some target {mRNAs}, but increases the stability and translation of other targets. Here, we isolated {AUF}1-associated {mRNAs} by immunoprecipitation of ({AUF}1-{RNA}) ribonucleoprotein ({RNP}) complexes from {HeLa} cells, identified them using microarrays, and used them to elucidate a signature motif shared among {AUF}1 target transcripts. The predicted {AUF}1 motif (29-39 nucleotides) contained 79\% As and Us, consistent with the {AU}-rich sequences of reported {AUF}1 targets. Importantly, 10 out of 15 previously reported {AUF}1 target {mRNAs} contained the {AUF}1 motif. The predicted interactions between {AUF}1 and target {mRNAs} were recapitulated in vitro using biotinylated {RNAs}. Interestingly, further validation of predicted {AUF}1 target transcripts revealed that {AUF}1 associates with both the pre-{mRNA} and the mature {mRNA} forms. The consequences of {AUF}1 binding to 10 predicted target {mRNAs} were tested by silencing {AUF}1, which elevated the steady-state levels of only four {mRNAs}, and by overexpressing {AUF}1, which also lowered the levels of only four {mRNAs}. In total, we have identified a signature motif in {AUF}1 target {mRNAs}, have found that {AUF}1 also associates with the corresponding pre-{mRNAs}, and have discovered that altering {AUF}1 levels alone only modifies the levels of subsets of target {mRNAs}.},
	pages = {204--214},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Mazan-Mamczarz, K and Kuwano, Y and Zhan, M and White, E J and Martindale, J L and Lal, A and Gorospe, M},
	date = {2009},
	pmid = {19033365},
	keywords = {Base Sequence, Humans, {RNA}, Binding Sites, Nucleic Acid, *{RNA} Stability, 3' Untranslated Regions/chemistry, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoprotein D/*metabol, Messenger/*chemistry/*metabolism, Molecular Sequence Data, Nucleic Acid Conformation, {RNA} Precursors/chemistry/metabolism, Sequence Homology}
}

@article{schmitz_interaction_2010,
	title = {Interaction of noncoding {RNA} with the {rDNA} promoter mediates recruitment of {DNMT}3b and silencing of {rRNA} genes},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20952535},
	doi = {10.1101/gad.590910},
	abstract = {Noncoding {RNAs} are important components of regulatory networks controlling the epigenetic state of chromatin. We analyzed the role of {pRNA} (promoter-associated {RNA}), a noncoding {RNA} that is complementary to the {rDNA} promoter, in mediating de novo {CpG} methylation of {rRNA} genes ({rDNA}). We show that {pRNA} interacts with the target site of the transcription factor {TTF}-I, forming a {DNA}:{RNA} triplex that is specifically recognized by the {DNA} methyltransferase {DNMT}3b. The results reveal a compelling new mechanism of {RNA}-dependent {DNA} methylation, suggesting that recruitment of {DNMT}3b by {DNA}:{RNA} triplexes may be a common and generally used pathway in epigenetic regulation.},
	pages = {2264--2269},
	number = {20},
	journaltitle = {Genes Dev},
	author = {Schmitz, K M and Mayer, C and Postepska, A and Grummt, I},
	date = {2010},
	pmid = {20952535},
	keywords = {{DNA}, Animals, Base Sequence, Humans, Mice, Promoter Regions, {RNA}, Gene Expression Regulation, Cell Line, Chromatin Immunoprecipitation, Confocal, {CpG} Islands/genetics, {DNA} (Cytosine-5-)-Methyltransferase/*genetics/meta, {DNA} Methylation, {DNA}-Binding Proteins/genetics/metabolism, {DNA}/chemistry/genetics, Genes, Genetic/*genetics, Green Fluorescent Proteins/genetics/metabolism, Microscopy, Molecular Sequence Data, Mutation, {NIH} 3T3 Cells, Nucleic Acid Conformation, Ribosomal/chemistry/*genetics, {rRNA}/*genetics, Untranslated/chemistry/genetics/*metabolism}
}

@article{wang_inhibition_2011,
	title = {Inhibition of activated pericentromeric {SINE}/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21862875},
	abstract = {Cellular aging is linked to deficiencies in efficient repair of {DNA} double strand breaks and authentic genome maintenance at the chromatin level. Aging poses a significant threat to adult stem cell function by triggering persistent {DNA} damage and ultimately cellular senescence. Senescence is often considered to be an irreversible process. Moreover, critical genomic regions engaged in persistent {DNA} damage accumulation are unknown. Here we report that 65\% of naturally occurring repairable {DNA} damage in self-renewing adult stem cells occurs within transposable elements. Upregulation of Alu retrotransposon transcription upon ex vivo aging causes nuclear cytotoxicity associated with the formation of persistent {DNA} damage foci and loss of efficient {DNA} repair in pericentric chromatin. This occurs due to a failure to recruit of condensin I and cohesin complexes. Our results demonstrate that the cytotoxicity of induced Alu repeats is functionally relevant for the human adult stem cell aging. Stable suppression of Alu transcription can reverse the senescent phenotype, reinstating the cells' self-renewing properties and increasing their plasticity by altering so-called "master" pluripotency regulators.},
	pages = {3016--3030},
	number = {17},
	journaltitle = {Cell Cycle},
	author = {Wang, J and Geesman, G J and Hostikka, S L and Atallah, M and Blackwell, B and Lee, E and Cook, P J and Pasaniuc, B and Shariat, G and Halperin, E and Dobke, M and Rosenfeld, M G and Jordan, I K and Lunyak, V V},
	date = {2011},
	pmid = {21862875},
	keywords = {Humans, *Alu Elements, *Cell Aging, *{DNA} Damage, *Transcriptional Activation, Adenosine Triphosphatases/metabolism, Adipose Tissue/cytology/metabolism, Adult Stem Cells/*cytology/metabolism, Cell Cycle Proteins/metabolism, Cell Nucleus/genetics/metabolism, Cell Proliferation, Centromere/genetics/metabolism, Chromatin/genetics/metabolism, Chromosomal Proteins, Chromosomes, {DNA} Repair, {DNA} Replication, {DNA}-Binding Proteins/metabolism, Fluorescent Antibody Technique, Histones/metabolism, Human/metabolism, Lentivirus/genetics/metabolism, Multiprotein Complexes/metabolism, Non-Histone/metabolism, Transfection}
}

@article{fumagalli_signatures_2011,
	title = {Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22072984},
	doi = {10.1371/journal.pgen.1002355},
	abstract = {Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of {SNPs} from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic {SNPs}, and particularly non-synonymous {SNPs} associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some susceptibility alleles for autoimmune diseases may be maintained in human population due to past selective processes.},
	pages = {e1002355},
	number = {11},
	journaltitle = {{PLoS} Genet},
	author = {Fumagalli, M and Sironi, M and Pozzoli, U and Ferrer-Admetlla, A and Pattini, L and Nielsen, R},
	date = {2011},
	pmid = {22072984},
	keywords = {Genetic, Humans, *Gene-Environment Interaction, Acclimatization/genetics, Adaptation, Biological Evolution, Biological/*genetics, Environment, Gene Frequency/*genetics, Genetic Drift, Genetic Variation, Genetic/*genetics, Genome-Wide Association Study, Genotype, Host-Pathogen Interactions/*genetics, Metabolic Networks and Pathways/*genetics, Models, Polymorphism, Selection, Single Nucleotide}
}

@article{vincenti_position_2007,
	title = {The position of yeast {snoRNA}-coding regions within host introns is essential for their biosynthesis and for efficient splicing of the host pre-{mRNA}},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17135484},
	doi = {10.1261/rna.251907},
	abstract = {Genomic location of sequences encoding small nucleolar {RNAs} ({snoRNAs}) is peculiar in all eukaryotes from yeast to mammals: most of them are encoded within the introns of host genes. In Saccharomyces cerevisiae, seven {snoRNAs} show this location. In this work we demonstrate that the position of {snoRNA}-coding regions with respect to splicing consensus sequences is critical: yeast strains expressing mutant constructs containing shorter or longer spacers (the regions between {snoRNA} ends and intron splice sites) show a drop in accumulation of U24 and U18 {snoRNAs}. Further mutational analysis demonstrates that altering the distance between the 3' end of the {snoRNA} and the branch point is the most important constraint for {snoRNA} biosynthesis, and that stable external stems, which are sometimes present in introns containing {snoRNAs}, can overcome the positional effect. Surprisingly enough, splicing of the host introns is clearly affected in most of these constructs indicating that, at least in S. cerevisiae, an incorrect location of {snoRNA}-coding sequences within the host intron is detrimental to the splicing process. This is different with respect to what was demonstrated in mammals, where the activity of the splicing machinery seems to be dominant with respect to the assembly of {snoRNPs}, and it is not affected by the location of {snoRNA} sequences. We also show that intronic box C/D {snoRNA} recognition and assembly of {snoRNPs} occur during transcription when splicing sequences are recognized.},
	pages = {138--150},
	number = {1},
	journaltitle = {{RNA}},
	author = {Vincenti, S and De Chiara, V and Bozzoni, I and Presutti, C},
	date = {2007},
	pmid = {17135484},
	keywords = {Genetic, {RNA}, Transcription, *{RNA} Splicing, Fungal/genetics/*metabolism, Introns/*genetics, Mutation, Nuclear Proteins/metabolism, Ribonucleoproteins, {RNA} Precursors/genetics/*metabolism, Saccharomyces cerevisiae Proteins/metabolism, Saccharomyces cerevisiae/*genetics, Small Nucleolar/*biosynthesis/genetics, Small Nucleolar/metabolism}
}

@article{bowen_exaptation_2007,
	title = {Exaptation of protein coding sequences from transposable elements},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18753790},
	doi = {10.1159/000107609},
	abstract = {The activity of transposable elements ({TEs}) has had a profound impact on the evolution of eukaryotic genomes. Once thought to be purely selfish genomic entities, {TEs} are now recognized to occupy a continuum of relationships, ranging from parasitic to mutualistic, with their host genomes. One of the many ways that {TEs} contribute to the function and evolution of the genomes in which they reside is through the donation of host protein coding sequences ({CDSs}). In this chapter, we will describe several notable examples of eukaryotic host {CDSs} that are derived from {TEs}. Despite the existence of a number of such well-established cases, the overall extent and significance of this phenomenon remains a matter of controversy. Genome-scale computational analyses have yielded vastly different estimates for the fraction of host {CDSs} that are derived from {TEs}. We explain how these seemingly contradictory findings are the result of specific ascertainment biases introduced by the different methods used to detect {TE}-related sequences. In light of this problem, we propose a comprehensive and systematic framework for definitively characterizing the contribution of {TEs} to eukaryotic {CDSs}.},
	pages = {147--162},
	journaltitle = {Genome Dyn},
	author = {Bowen, N J and Jordan, I K},
	date = {2007},
	pmid = {18753790},
	keywords = {Animals, Humans, {DNA} Transposable Elements/*genetics, Genome/genetics, Nucleic Acid/genetics, Open Reading Frames/*genetics, Repetitive Sequences}
}

@article{michienzi_inhibition_1998,
	title = {Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-{HIV} ribozymes in a human T lymphoblastoid cell line},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9551610},
	doi = {10.1089/hum.1998.9.5-621},
	abstract = {Human immunodeficiency virus ({HIV}) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the {HIV} life cycle, many different strategies have been developed including transdominant modifications of {HIV} proteins, {RNA} decoys, antisense {RNA}, ribozymes, and intracellular antibody fragments. In this paper, we have tested in a human T lymphoblastoid cell line the antiviral activity of ribozymes specifically designed to co-localize inside the nucleus with the Rev pre-{mRNA} before it is spliced and transported to the cytoplasm. This result was obtained by inserting the ribozyme in the spliceosomal U1 small nuclear {RNA} ({snRNA}) and in a derivative that has perfect complementarity with the 5' splice site of the Rev pre-{mRNA}. These ribozymes were tested in human T cell clones and were shown to be very efficient in inhibiting viral replication. Not only were the p24 levels in the culture medium drastically reduced but so were the intracellular {HIV} transcripts. Control disabled ribozymes enabled us to show the specificity of the ribozyme activity. Therefore, these constructs have potential utility for gene therapy of {HIV}-1 infection.},
	pages = {621--628},
	number = {5},
	journaltitle = {Hum Gene Ther},
	author = {Michienzi, A and Conti, L and Varano, B and Prislei, S and Gessani, S and Bozzoni, I},
	date = {1998},
	pmid = {9551610},
	keywords = {Genetic, Humans, {RNA}, Transcription, Anti-{HIV} Agents/*pharmacology, Catalytic/*genetics/*pharmacology, Chimera, Gene Dosage, Genetic Therapy, {HIV}-1/*drug effects/*physiology, Jurkat Cells, Rna, {RNA} Precursors/metabolism, Small Nuclear, Viral/analysis/metabolism, Virus Replication/*drug effects}
}

@article{li_ubiquitylation_2013,
	title = {Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I gamma by {HECTD}1 regulates focal adhesion dynamics and cell migration},
	volume = {126},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23572508},
	doi = {10.1242/jcs.117044},
	abstract = {Phosphatidylinositol 4-phosphate 5-kinase type I gamma ({PIPKIgamma}90) binds talin and localizes at focal adhesions ({FAs}). Phosphatidylinositol (4,5)-bisphosphate ({PIP}2) generated by {PIPKIgamma}90 is essential for {FA} formation and cell migration. On the other hand, {PIPKIgamma}90 and the beta-integrin tail compete for overlapping binding sites on talin. Enhanced {PIPKIgamma}90-talin interaction suppresses talin binding to the beta-integrin. It is unknown how {PIPKIgamma}90 is removed from the {PIPKIgamma}90-talin complex after on-site {PIP}2 production during cell migration. Here we show that {PIPKIgamma}90 is a substrate for {HECTD}1, an E3 ubiquitin ligase regulating cell migration. {HECTD}1 ubiquitinated {PIPKIgamma}90 at lysine 97 and resulted in {PIPKIgamma}90 degradation. Expression of the mutant {PIPKIgamma}90(K97R) enhanced {PIP}2 and {PIP}3 production, inhibited {FA} assembly and disassembly and inhibited cancer cell migration, invasion and metastasis. Interestingly, mutation at tryptophan 647 abolished the inhibition of {PIPKIgamma}90(K97R) on {FA} dynamics and partially rescued cancer cell migration and invasion. Thus, cycling {PIPKIgamma}90 ubiquitylation by {HECTD}1 and consequent degradation remove {PIPKIgamma}90 from talin after on-site {PIP}2 production, providing an essential regulatory mechanism for {FA} dynamics and cell migration.},
	pages = {2617--2628},
	issue = {Pt 12},
	journaltitle = {J Cell Sci},
	author = {Li, X and Zhou, Q and Sunkara, M and Kutys, M L and Wu, Z and Rychahou, P and Morris, A J and Zhu, H and Evers, B M and Huang, C},
	date = {2013},
	pmid = {23572508},
	keywords = {Animals, Humans, 5-Diphosphate/metabolism, Cell Line, Cell Movement/*physiology, {CHO} Cells, Cricetinae, Cricetulus, Focal Adhesions/*metabolism, {HEK}293 Cells, Integrin beta Chains/metabolism, Lysine/metabolism, Neoplasm Invasiveness, Neoplasm Metastasis, Phosphatidylinositol 4, Phosphotransferases (Alcohol Group Acceptor)/*meta, Talin/metabolism, Ubiquitin-Protein Ligases/*metabolism, Ubiquitination/*physiology}
}

@article{raval_real-time_2006,
	title = {Real-time {MRI} guided atrial septal puncture and balloon septostomy in swine},
	volume = {67},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16532499},
	doi = {10.1002/ccd.20579},
	abstract = {Cardiac perforation during atrial septal puncture ({ASP}) might be avoided by improved image guidance. X-ray fluoroscopy ({XRF}), which guides {ASP}, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real-time {MRI} ({rtMRI}) provides excellent tissue contrast in any orientation and may enable {ASP} and balloon atrial septostomy ({BAS}) in swine. Custom {MRI} catheters incorporated "active" (receiver antenna) and "passive" (iron or gadolinium) elements. Wholly {rtMRI}-guided transfemoral {ASP} and {BAS} were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded {MRI}. Successful {ASP} was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. {BAS} was successful in 9/10 animals. Antenna failure in a re-used needle led to inadvertent vena cava tear prior to {BAS} in 1 animal. {ASP} in the same animal was easily performed using a new needle. {rtMRI} illustrated clear device-tissue-lumen relationships in multiple orientations, and facilitated simple {ASP} and {BAS}. The mean procedure time was 19 +/- 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals. Interactive {rtMRI} permits rapid transcatheter {ASP} and {BAS} in swine. Further technical development may enable novel applications.},
	pages = {637--643},
	number = {4},
	journaltitle = {Catheter Cardiovasc Interv},
	author = {Raval, A N and Karmarkar, P V and Guttman, M A and Ozturk, C and Desilva, R and Aviles, R J and Wright, V J and Schenke, W H and Atalar, E and {McVeigh}, E R and Lederman, R J},
	date = {2006},
	pmid = {16532499},
	keywords = {Animals, *Angioplasty, *Surgery, Balloon, Cardiac Catheterization, Computer-Assisted, Coronary, Heart Atria/*surgery, Heart Septum/*surgery, Magnetic Resonance Imaging/*methods, Punctures/*methods, Swine}
}

@article{bradley_x--autosome_2004,
	title = {An X-to-autosome retrogene is required for spermatogenesis in mice},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15258580},
	doi = {10.1038/ng1390},
	abstract = {We identified the gene carrying the juvenile spermatogonial depletion mutation (jsd), a recessive spermatogenic defect mapped to mouse chromosome 1 (refs. 1,2). We localized jsd to a 272-kb region and resequenced this area to identify the underlying mutation: a frameshift that severely truncates the predicted protein product of a 2.3-kb genomic open reading frame. This gene, Utp14b, evidently arose through reverse transcription of an {mRNA} from an X-linked gene and integration of the resulting {cDNA} into an intron of an autosomal gene, whose promoter and 5' untranslated exons are shared with Utp14b. To our knowledge, Utp14b is the first protein-coding retrogene to be linked to a recessive mammalian phenotype. The X-linked progenitor of Utp14b is the mammalian ortholog of yeast Utp14, which encodes a protein required for processing of pre-{rRNA} and hence for ribosome assembly. Our findings substantiate the hypothesis that mammalian spermatogenesis is supported by autosomal retrogenes that evolved from X-linked housekeeping genes to compensate for silencing of the X chromosome during male meiosis. We find that Utp14b-like retrogenes arose independently and were conserved during evolution in at least four mammalian lineages. This recurrence implies a strong selective pressure, perhaps to enable ribosome assembly in male meiotic cells.},
	pages = {872--876},
	number = {8},
	journaltitle = {Nat Genet},
	author = {Bradley, J and Baltus, A and Skaletsky, H and Royce-Tolland, M and Dewar, K and Page, D C},
	date = {2004},
	pmid = {15258580},
	keywords = {Animals, Base Sequence, Conserved Sequence, Mice, Open Reading Frames, Chromosome Mapping, Frameshift Mutation, Inbred C57BL, Male, Molecular Sequence Data, Phylogeny, Sequence Alignment, Spermatogenesis/*genetics, X Chromosome}
}

@article{grant_fimo:_2011,
	title = {{FIMO}: scanning for occurrences of a given motif},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21330290},
	doi = {10.1093/bioinformatics/btr064},
	abstract = {A motif is a short {DNA} or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix. {RESULTS}: We describe Find Individual Motif Occurrences ({FIMO}), a software tool for scanning {DNA} or protein sequences with motifs described as position-specific scoring matrices. The program computes a log-likelihood ratio score for each position in a given sequence database, uses established dynamic programming methods to convert this score to a P-value and then applies false discovery rate analysis to estimate a q-value for each position in the given sequence. {FIMO} provides output in a variety of formats, including {HTML}, {XML} and several Santa Cruz Genome Browser formats. The program is efficient, allowing for the scanning of {DNA} sequences at a rate of 3.5 Mb/s on a single {CPU}. {AVAILABILITY} {AND} {IMPLEMENTATION}: {FIMO} is part of the {MEME} Suite software toolkit. A web server and source code are available at http://meme.sdsc.edu.},
	pages = {1017--1018},
	number = {7},
	journaltitle = {Bioinformatics},
	author = {Grant, C E and Bailey, T L and Noble, W S},
	date = {2011},
	pmid = {21330290},
	keywords = {Human, *Software, {DNA}/*methods, Sequence Analysis, Base Sequence, Conserved Sequence, Genetic, Genome, Humans, Binding Sites, Databases, *Amino Acid Motifs, {DNA}/*chemistry, Position-Specific Scoring Matrices, Protein/*methods, Repressor Proteins/metabolism}
}

@article{lorenz_viennarna_2011,
	title = {{ViennaRNA} Package 2.0},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22115189},
	doi = {10.1186/1748-7188-6-26},
	abstract = {{BACKGROUND}: Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties. {RESULTS}: The {ViennaRNA} Package has been a widely used compilation of {RNA} secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the Turner 2004 parameters, the pervasive use of multi-core {CPUs}, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying {RNAlib} and the interactive user programs. New features include an expanded repertoire of tools to assess {RNA}-{RNA} interactions and restricted ensembles of structures, additional output information such as centroid structures and maximum expected accuracy structures derived from base pairing probabilities, or z-scores for locally stable secondary structures, and support for input in fasta format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions. {CONCLUSIONS}: The {ViennaRNA} Package 2.0, supporting concurrent computations via {OpenMP}, can be downloaded from http://www.tbi.univie.ac.at/{RNA}.},
	pages = {26},
	journaltitle = {Algorithms Mol Biol},
	author = {Lorenz, R and Bernhart, S H and Honer Zu Siederdissen, C and Tafer, H and Flamm, C and Stadler, P F and Hofacker, I L},
	date = {2011},
	pmid = {22115189}
}

@article{mulvihill_protein_2011,
	title = {Protein interactions among Fe65, the low-density lipoprotein receptor-related protein, and the amyloid precursor protein},
	volume = {50},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21650223},
	doi = {10.1021/bi200508f},
	abstract = {The adapter protein Fe65 has been proposed to be the link between the intracellular domains of the amyloid precursor protein, {APP} ({AICD}), and the low-density lipoprotein receptor-related protein ({LRP}-{CT}). Functional linkage between these two proteins has been established, and mutations within {LRP}-{CT} affect the amount of Abeta produced from {APP}. Previous work showed that {AICD} binds to protein interaction domain 2 ({PID}2) of Fe65. Although the structure of {PID}1 was determined recently, all attempts to demonstrate {LRP}-{CT} binding to this domain failed. We used biophysical experiments and binding studies to investigate the binding among these three proteins. Full-length Fe65 bound more weakly to {AICD} than did N-terminally truncated forms; however, the intramolecular domain-domain interactions that had been proposed to inhibit binding could not be observed using amide H-D exchange. Surprisingly, when {LRP}-{CT} is phosphorylated at Tyr4507, it bound to Fe65 {PID}1 despite the fact that this domain belongs to the Dab-like subclass of {PIDs} that are not supposed to be phosphorylation-dependent. Mutation of a critical arginine abolished binding, providing further proof of the phosphorylation dependence. Fe65 {PID}1 thus provides a link between the Dab-like class and the {IRS}-like class of {PIDs} and is the first Dab-like family member to show phosphorylation-dependent binding.},
	pages = {6208--6216},
	number = {28},
	journaltitle = {Biochemistry},
	author = {Mulvihill, M M and Guttman, M and Komives, E A},
	date = {2011},
	pmid = {21650223},
	keywords = {Humans, Protein Binding, Amino Acid Sequence, Amyloid beta-Protein Precursor/*chemistry/metaboli, Binding, Competitive, Crystallography, {LDL}/*chemistry/metabolism, Molecular Sequence Data, Nerve Tissue Proteins/*chemistry/metabolism, Nuclear Proteins/*chemistry/metabolism, Phosphorylation, Phosphotyrosine/chemistry/metabolism, Protein Interaction Mapping, Protein Structure, Receptors, Tertiary, X-Ray}
}

@article{rogers_comparison_2013,
	title = {Comparison of perirectal versus rectal swabs for detection of asymptomatic carriers of toxigenic Clostridium difficile},
	volume = {51},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23926162},
	doi = {10.1128/JCM.01418-13},
	abstract = {For long-term care and spinal cord injury patients, the sensitivity, specificity, and positive and negative predictive values of perirectal versus rectal cultures for detection of asymptomatic carriers of Clostridium difficile were 95\%, 100\%, 100\%, and 97\%, respectively. Perirectal cultures provide an accurate method to detect asymptomatic carriers of C. difficile.},
	pages = {3421--3422},
	number = {10},
	journaltitle = {J Clin Microbiol},
	author = {Rogers, D S and Kundrapu, S and Sunkesula, V C and Donskey, C J},
	date = {2013},
	pmid = {23926162}
}

@article{mirza_effects_2014,
	title = {Effects of {GWAS}-associated genetic variants on {lncRNAs} within {IBD} and T1D candidate loci},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25144376},
	doi = {10.1371/journal.pone.0105723},
	abstract = {Long non-coding {RNAs} are a new class of non-coding {RNAs} that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease ({IBD}) and Type 1 Diabetes (T1D). Nearly 90\% of the phenotype-associated single-nucleotide polymorphisms ({SNPs}) identified by genome-wide association studies ({GWAS}) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding {RNAs} ({lncRNAs}) is poorly understood. Here, we systemically identified all annotated {IBD} and T1D loci-associated {lncRNAs}, and mapped nominally significant {GWAS}/{ImmunoChip} {SNPs} for {IBD} and T1D within these {lncRNAs}. Additionally, we identified tissue-specific cis-{eQTLs}, and strong linkage disequilibrium ({LD}) signals associated with these {SNPs}. We explored sequence and structure based attributes of these {lncRNAs}, and also predicted the structural effects of mapped {SNPs} within them. We also identified {lncRNAs} in {IBD} and T1D that are under recent positive selection. Our analysis identified putative {lncRNA} secondary structure-disruptive {SNPs} within and in close proximity (+/-5 kb flanking regions) of {IBD} and T1D loci-associated candidate genes, suggesting that these {RNA} conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of {lncRNA} secondary structure due to presence of {GWAS} {SNPs} provides valuable information that could be potentially useful for future structure-function studies on {lncRNAs}.},
	pages = {e105723},
	number = {8},
	journaltitle = {{PLoS} One},
	author = {Mirza, A H and Kaur, S and Brorsson, C A and Pociot, F},
	date = {2014},
	pmid = {25144376},
	keywords = {Animals, Humans, Mice, {RNA}, *Genetic Loci, *Genome-Wide Association Study, *Linkage Disequilibrium, *Polymorphism, Diabetes Mellitus, Female, Inflammatory Bowel Diseases/*genetics/metabolism, Long Noncoding/biosynthesis/*genetics, Male, Rats, Single Nucleotide, Type 1/*genetics/metabolism}
}

@article{gifford_transcriptional_2013,
	title = {Transcriptional and epigenetic dynamics during specification of human embryonic stem cells},
	volume = {153},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23664763},
	doi = {10.1016/j.cell.2013.04.037},
	abstract = {Differentiation of human embryonic stem cells ({hESCs}) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of {hESCs} representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and {RNA} sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in {DNA} methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated {hESCs}. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high {DNA} methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.},
	pages = {1149--1163},
	number = {5},
	journaltitle = {Cell},
	author = {Gifford, C A and Ziller, M J and Gu, H and Trapnell, C and Donaghey, J and Tsankov, A and Shalek, A K and Kelley, D R and Shishkin, A A and Issner, R and Zhang, X and Coyne, M and Fostel, J L and Holmes, L and Meldrim, J and Guttman, M and Epstein, C and Park, H and Kohlbacher, O and Rinn, J and Gnirke, A and Lander, E S and Bernstein, B E and Meissner, A},
	date = {2013},
	pmid = {23664763},
	keywords = {Genetic, Humans, *Transcription, *Epigenesis, Acetylation, Cell Differentiation, Chromatin/chemistry/metabolism, {DNA} Methylation, Embryonic Stem Cells/*metabolism, Enhancer Elements, Histones/metabolism, Methylation}
}

@article{schwanhausser_corrigendum:_2013,
	title = {Corrigendum: Global quantification of mammalian gene expression control},
	volume = {495},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23407496},
	doi = {10.1038/nature11848},
	pages = {126--127},
	number = {7439},
	journaltitle = {Nature},
	author = {Schwanhausser, B and Busse, D and Li, N and Dittmar, G and Schuchhardt, J and Wolf, J and Chen, W and Selbach, M},
	date = {2013},
	pmid = {23407496},
	keywords = {Animals, Humans, Mice, {RNA}, Reproducibility of Results, *Gene Expression Regulation, *Protein Biosynthesis, Blotting, Chromatography, Liquid, Mass Spectrometry, Messenger/analysis/genetics, {NIH} 3T3 Cells, Proteins/*analysis/genetics, Reference Standards, Sea Urchins/embryology/genetics, Western}
}

@article{srikantan_altered_2011,
	title = {Altered glycobiology of stem cells linked to age-related osteoarthritis},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21808096},
	abstract = {Comment on: Jiang et al. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases. Aging 2011; this issue. In this issue of Impact Aging, Jiang et al. report key differences in the patterns of expressed {mRNAs} in bone-marrow mesenchymal stem cells ({bmMSCs}) of young donors compared with old human donors.},
	pages = {663--664},
	number = {7},
	journaltitle = {Aging (Albany {NY})},
	author = {Srikantan, S and Gorospe, M},
	date = {2011},
	pmid = {21808096}
}

@article{lappalainen_transcriptome_2013,
	title = {Transcriptome and genome sequencing uncovers functional variation in humans},
	volume = {501},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24037378},
	doi = {10.1038/nature12531},
	abstract = {Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger {RNA} and {microRNA} from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project–the first uniformly processed high-throughput {RNA}-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.},
	pages = {506--511},
	number = {7468},
	journaltitle = {Nature},
	author = {Lappalainen, T and Sammeth, M and Friedlander, M R and t Hoen, P A and Monlong, J and Rivas, M A and Gonzalez-Porta, M and Kurbatova, N and Griebel, T and Ferreira, P G and Barann, M and Wieland, T and Greger, L and van Iterson, M and Almlof, J and Ribeca, P and Pulyakhina, I and Esser, D and Giger, T and Tikhonov, A and Sultan, M and Bertier, G and {MacArthur}, D G and Lek, M and Lizano, E and Buermans, H P and Padioleau, I and Schwarzmayr, T and Karlberg, O and Ongen, H and Kilpinen, H and Beltran, S and Gut, M and Kahlem, K and Amstislavskiy, V and Stegle, O and Pirinen, M and Montgomery, S B and Donnelly, P and {McCarthy}, M I and Flicek, P and Strom, T M and Lehrach, H and Schreiber, S and Sudbrak, R and Carracedo, A and Antonarakis, S E and Hasler, R and Syvanen, A C and van Ommen, G J and Brazma, A and Meitinger, T and Rosenstiel, P and Guigo, R and Gut, I G and Estivill, X and Dermitzakis, E T},
	date = {2013},
	pmid = {24037378},
	keywords = {Genome, Humans, {RNA}, Gene Expression Profiling, Exons/genetics, *High-Throughput Nucleotide Sequencing, *Sequence Analysis, Alleles, Cell Line, Genetic Variation/*genetics, Human/*genetics, Messenger/analysis/genetics, Polymorphism, Quantitative Trait Loci/genetics, Single Nucleotide/genetics, Transcriptome/*genetics, Transformed}
}

@article{perepelitsa-belancio_rna_2003,
	title = {{RNA} truncation by premature polyadenylation attenuates human mobile element activity},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14625551},
	doi = {10.1038/ng1269},
	abstract = {Long interspersed elements ({LINE}-1s, also called L1s) are the only active members of the autonomous, non-long terminal repeat ({LTR}) retrotransposon family, which reshapes mammalian genomes in many different ways. {LINE}-1 expression is low in most differentiated cells but high in some cancer cells, in testis and during embryonic development. To minimize the negative impact on their hosts' genomes, many mobile elements strategically limit their amplification potential, particularly in somatic cells. Here we show that the A-rich coding strand of the human {LINE}-1 contains multiple functional canonical and noncanonical polyadenylation (poly(A)) signals, resulting in truncation of full-length transcripts by premature polyadenylation. This attenuation lowers the rate of retrotransposition in assays using {HeLa} cells. It probably also increases the negative effects of {LINE}-1 insertions into genes.},
	pages = {363--366},
	number = {4},
	journaltitle = {Nat Genet},
	author = {Perepelitsa-Belancio, V and Deininger, P},
	date = {2003},
	pmid = {14625551},
	keywords = {Animals, Humans, Mice, {RNA}, *Long Interspersed Nucleotide Elements, *Polyadenylation, *Retroelements, Chickens, Fibroblasts/metabolism, {HeLa} Cells, Messenger/*genetics/*metabolism, Molecular Sequence Data, Mutagenesis, {NIH} 3T3 Cells, Poly A/*metabolism, Site-Directed}
}

@article{smith_widespread_2013,
	title = {Widespread purifying selection on {RNA} structure in mammals},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23847102},
	doi = {10.1093/nar/gkt596},
	abstract = {Evolutionarily conserved {RNA} secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus {RNA} structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, {RNAz} and {SISSIz}, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies {\textbackslash}textgreater4 million evolutionarily constrained {RNA} structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5-22\%). These predictions comprise 13.6\% of the human genome, 88\% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved {RNA} structure motifs in the long noncoding {RNA} {MALAT}1. This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.},
	pages = {8220--8236},
	number = {17},
	journaltitle = {Nucleic Acids Res},
	author = {Smith, M A and Gesell, T and Stadler, P F and Mattick, J S},
	date = {2013},
	pmid = {23847102},
	keywords = {Genomics, Base Sequence, Humans, Algorithms, Molecular Sequence Annotation, Molecular Sequence Data, Nucleic Acid Conformation, Evolution, Molecular, {RNA}, Long Noncoding, Genome, Human},
	file = {Full Text:/home/jlagarde/Zotero/storage/JLI7X4QS/Smith et al. - 2013 - Widespread purifying selection on RNA structure in.pdf:application/pdf}
}

@article{pogue_automated_2014,
	title = {Automated alerts coupled with antimicrobial stewardship intervention lead to decreases in length of stay in patients with gram-negative bacteremia},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24442074},
	doi = {10.1086/674849},
	abstract = {{OBJECTIVE}: To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia. {DESIGN}: Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011. {SETTING}: Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center. {PATIENTS}: All patients with monomicrobial gram-negative bacteremia during the study period. {INTERVENTION}: Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009). {RESULTS}: Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range ({IQR}), 2-24] vs 14 [{IQR}, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [{OR}], 0.73 [95\% confidence interval ({CI}), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay ({OR}, 0.76 [95\% {CI}, 0.66-0.86]) and infection-related mortality ({OR}, 0.24 [95\% {CI}, 0.08-0.76]). {CONCLUSIONS}: Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.},
	pages = {132--138},
	number = {2},
	journaltitle = {Infect Control Hosp Epidemiol},
	author = {Pogue, J M and Mynatt, R P and Marchaim, D and Zhao, J J and Barr, V O and Moshos, J and Sunkara, B and Chopra, T and Chidurala, S and Kaye, K S},
	date = {2014},
	pmid = {24442074}
}

@article{shi_downregulated_2015,
	title = {Downregulated Long Noncoding {RNA} {BANCR} Promotes the Proliferation of Colorectal Cancer Cells via Downregualtion of p21 Expression},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25928067},
	doi = {10.1371/journal.pone.0122679},
	abstract = {{BRAF} activated non-coding {RNA} ({BANCR}), a long non-coding {RNA} ({lncRNA}), is crucial for cell migration in melanoma cells and non-small cell lung cancer ({NSCLC}) cells. However, little is known regarding the role of this gene in the proliferation of colorectal cancer. Therefore, we investigated the involvement of {BANCR} in the proliferation of colorectal cancer cells. In this study, we show that {BANCR} expression was significantly down-regulated in colorectal cancer tissues compared with normal tissues, and overexpression of {BANCR} suppressed colorectal cancer cell growth in vitro and in vivo. We also determined that {pCDNA}-{BANCR}-mediated colorectal cancer cell proliferation was associated with induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21, and its effects were most likely posttranscriptional. Taken together, our findings suggest that down-regulation of {BANCR} contributes to the proliferation of colorectal cancer cells, at least in part, through the regulation of p21 protein.},
	pages = {e0122679},
	number = {4},
	journaltitle = {{PLoS} One},
	author = {Shi, Y and Liu, Y and Wang, J and Jie, D and Yun, T and Li, W and Yan, L and Wang, K and Feng, J},
	date = {2015},
	pmid = {25928067}
}

@article{brunelli_msx2_2004,
	title = {Msx2 and necdin combined activities are required for smooth muscle differentiation in mesoangioblast stem cells},
	volume = {94},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15155529},
	doi = {10.1161/01.RES.0000132747.12860.10},
	abstract = {Little is known about the molecular mechanism underlying specification and differentiation of smooth muscle ({SM}), and this is, at least in part, because of the few cellular systems available to study the acquisition of a {SM} phenotype in vitro. Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm, including {SM}. We performed a {DNA} microarray analysis of a mesoangioblast clone that spontaneously expresses an immature {SM} phenotype and compared it with a sister clone mainly composed of undifferentiated progenitor cells. This study allowed us to define a gene expression profile for "stem" cells versus smooth muscle cells ({SMCs}) in the absence of differentiation inducers such as transforming growth factor beta. Two transcription factors, msx2 and necdin, are expressed at least 100 times more in {SMCs} than in stem cells, are coexpressed in all {SMCs} and tissues, are induced by transforming growth factor beta, and, when coexpressed, induce a number of {SM} markers in mesoangioblast, fibroblast, and endothelial cell lines. Conversely, their downregulation through {RNA} interference results in a decreased expression of {SM} markers. These data support the hypothesis that Msx2 and necdin act as master genes regulating {SM} differentiation in at least a subset of {SMCs}.},
	pages = {1571--1578},
	number = {12},
	journaltitle = {Circ Res},
	author = {Brunelli, S and Tagliafico, E and De Angelis, F G and Tonlorenzi, R and Baesso, S and Ferrari, S and Niinobe, M and Yoshikawa, K and Schwartz, R J and Bozzoni, I and Cossu, G},
	date = {2004},
	pmid = {15155529},
	keywords = {Animals, Mice, {RNA}, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Cells, Cultured, *Gene Expression Regulation, Aorta/cytology/embryology, Cardiac/cytology, Cell Differentiation/genetics, Coculture Techniques, Developmental, {DNA}-Binding Proteins/genetics/*physiology, Homeodomain Proteins, Inbred C57BL, Mesenchymal Stromal Cells/*cytology/metabolism, Muscle, Muscle Proteins/*biosynthesis/genetics, Myocytes, Nerve Tissue Proteins/genetics/*physiology, Nuclear Proteins/genetics/*physiology, Rats, Recombinant Fusion Proteins/physiology, {RNA} Interference, Small Interfering/genetics, Smooth, Smooth Muscle/*cytology/metabolism, Transcriptional Activation, Transfection, Vascular}
}

@article{dobin_star:_2013,
	title = {{STAR}: ultrafast universal {RNA}-seq aligner},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23104886},
	doi = {10.1093/bioinformatics/bts635},
	abstract = {{MOTIVATION}: Accurate alignment of high-throughput {RNA}-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available {RNA}-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. {RESULTS}: To align our large ({\textbackslash}textgreater80 billon reads) {ENCODE} Transcriptome {RNA}-seq dataset, we developed the Spliced Transcripts Alignment to a Reference ({STAR}) software based on a previously undescribed {RNA}-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. {STAR} outperforms other aligners by a factor of {\textbackslash}textgreater50 in mapping speed, aligning to the human genome 550 million 2 x 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, {STAR} can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length {RNA} sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90\% success rate, corroborating the high precision of the {STAR} mapping strategy. {AVAILABILITY} {AND} {IMPLEMENTATION}: {STAR} is implemented as a standalone C++ code. {STAR} is free open source software distributed under {GPLv}3 license and can be downloaded from http://code.google.com/p/rna-star/.},
	pages = {15--21},
	number = {1},
	journaltitle = {Bioinformatics},
	author = {Dobin, A and Davis, C A and Schlesinger, F and Drenkow, J and Zaleski, C and Jha, S and Batut, P and Chaisson, M and Gingeras, T R},
	date = {2013},
	pmid = {23104886},
	keywords = {Human, *Software, Sequence Analysis, Genome, Humans, {RNA} Splicing, Gene Expression Profiling, Algorithms, Cluster Analysis, {RNA}/methods, Sequence Alignment/*methods}
}

@article{beletskii_pna_2001,
	title = {{PNA} interference mapping demonstrates functional domains in the noncoding {RNA} Xist},
	volume = {98},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11481485},
	doi = {10.1073/pnas.161173098},
	abstract = {The noncoding {RNA} Xist has been shown to be essential for X-chromosome inactivation and to coat the inactive X-chromosome (Xi). Thus, an important question in understanding the formation of Xi is whether the binding reaction of Xist is necessary for X-chromosome inactivation. In this article, we demonstrate the failure of X-chromosome silencing if the association of Xist with the X-chromosome is inhibited. The chromatin-binding region was functionally mapped and evaluated by using an approach for studying noncoding {RNA} function in living cells that we call peptide nucleic acid ({PNA}) interference mapping. In the reported experiments, a single 19-bp antisense cell-permeating {PNA} targeted against a particular region of Xist {RNA} caused the disruption of the Xi. The association of the Xi with macro-histone H2A is also disturbed by {PNA} interference mapping.},
	pages = {9215--9220},
	number = {16},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Beletskii, A and Hong, Y K and Pehrson, J and Egholm, M and Strauss, W M},
	date = {2001},
	pmid = {11481485},
	keywords = {Animals, Base Sequence, {RNA}, Female, Histones/metabolism, Long Untranslated, Male, Molecular Sequence Data, Peptide Nucleic Acids/*chemistry, {RNA}/chemistry/*metabolism, Transcription Factors/*chemistry/metabolism, Untranslated/*chemistry/metabolism, X Chromosome}
}

@article{sharan_network-based_2007,
	title = {Network-based prediction of protein function},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17353930},
	doi = {10.1038/msb4100129},
	abstract = {Functional annotation of proteins is a fundamental problem in the post-genomic era. The recent availability of protein interaction networks for many model species has spurred on the development of computational methods for interpreting such data in order to elucidate protein function. In this review, we describe the current computational approaches for the task, including direct methods, which propagate functional information through the network, and module-assisted methods, which infer functional modules within the network and use those for the annotation task. Although a broad variety of interesting approaches has been developed, further progress in the field will depend on systematic evaluation of the methods and their dissemination in the biological community.},
	pages = {88},
	journaltitle = {Mol Syst Biol},
	author = {Sharan, R and Ulitsky, I and Shamir, R},
	date = {2007},
	pmid = {17353930},
	keywords = {Algorithms, *Models, Cluster Analysis, Information Services, Proteins/*physiology, Theoretical}
}

@article{grossman_identifying_2013,
	title = {Identifying recent adaptations in large-scale genomic data},
	volume = {152},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23415221},
	doi = {10.1016/j.cell.2013.01.035},
	abstract = {Although several hundred regions of the human genome harbor signals of positive natural selection, few of the relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from the 1000 Genomes (1000G) Project and the composite of multiple signals ({CMS}) test, we investigated 412 candidate signals and leveraged functional annotation, protein structure modeling, epigenetics, and association studies to identify and extensively annotate candidate causal variants. The resulting catalog provides a tractable list for experimental follow-up; it includes 35 high-scoring nonsynonymous variants, 59 variants associated with expression levels of a nearby coding gene or {lincRNA}, and numerous variants associated with susceptibility to infectious disease and other phenotypes. We experimentally characterized one candidate nonsynonymous variant in Toll-like receptor 5 ({TLR}5) and show that it leads to altered {NF}-{kappaB} signaling in response to bacterial flagellin. {PAPERFLICK}:},
	pages = {703--713},
	number = {4},
	journaltitle = {Cell},
	author = {Grossman, S R and Andersen, K G and Shlyakhter, I and Tabrizi, S and Winnicki, S and Yen, A and Park, D J and Griesemer, D and Karlsson, E K and Wong, S H and Cabili, M and Adegbola, R A and Bamezai, R N and Hill, A V and Vannberg, F O and Rinn, J L and Lander, E S and Schaffner, S F and Sabeti, P C},
	date = {2013},
	pmid = {23415221},
	keywords = {Human, Animals, Humans, *Genome, *Genetic Techniques, *Genome-Wide Association Study, *Mutation, Bacteria/metabolism, Flagellin/metabolism, {HapMap} Project, {NF}-kappa B/metabolism, Quantitative Trait Loci, Regulatory Elements, Signal Transduction, Toll-Like Receptor 5/genetics/metabolism, Transcriptional}
}

@article{abdelmohsen_senescence-associated_2013,
	title = {Senescence-associated {lncRNAs}: senescence-associated long noncoding {RNAs}},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23758631},
	doi = {10.1111/acel.12115},
	abstract = {Noncoding {RNAs} include small transcripts, such as {microRNAs} and piwi-interacting {RNAs}, and a wide range of long noncoding {RNAs} ({lncRNAs}). Although many {lncRNAs} have been identified, only a small number of {lncRNAs} have been characterized functionally. Here, we sought to identify {lncRNAs} differentially expressed during replicative senescence. We compared {lncRNAs} expressed in proliferating, early-passage, 'young' human diploid {WI}-38 fibroblasts [population doubling ({PDL}) 20] with those expressed in senescent, late-passage, 'old' fibroblasts ({PDL} 52) by {RNA} sequencing ({RNA}-Seq). Numerous transcripts in all {lncRNA} groups (antisense {lncRNAs}, pseudogene-encoded {lncRNAs}, previously described {lncRNAs} and novel {lncRNAs}) were validated using reverse transcription ({RT}) and real-time, quantitative (q){PCR}. Among the novel senescence-associated {lncRNAs} ({SAL}-{RNAs}) showing lower abundance in senescent cells, {SAL}-{RNA}1 ({XLOC}\_023166) was found to delay senescence, because reducing {SAL}-{RNA}1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive beta-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel {lncRNAs} changes with senescence and suggests that {SAL}-{RNAs} play direct regulatory roles in this important cellular process.},
	pages = {890--900},
	number = {5},
	journaltitle = {Aging Cell},
	author = {Abdelmohsen, K and Panda, A and Kang, M J and Xu, J and Selimyan, R and Yoon, J H and Martindale, J L and De, S and Wood 3rd, W H and Becker, K G and Gorospe, M},
	date = {2013},
	pmid = {23758631}
}

@article{konkel_mobile_2010,
	title = {A mobile threat to genome stability: The impact of non-{LTR} retrotransposons upon the human genome},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20307669},
	doi = {10.1016/j.semcancer.2010.03.001},
	abstract = {It is now commonly agreed that the human genome is not the stable entity originally presumed. Deletions, duplications, inversions, and insertions are common, and contribute significantly to genomic structural variations ({SVs}). Their collective impact generates much of the inter-individual genomic diversity observed among humans. Not only do these variations change the structure of the genome; they may also have functional implications, e.g. altered gene expression. Some {SVs} have been identified as the cause of genetic disorders, including cancer predisposition. Cancer cells are notorious for their genomic instability, and often show genomic rearrangements at the microscopic and submicroscopic level to which transposable elements ({TEs}) contribute. Here, we review the role of {TEs} in genome instability, with particular focus on non-{LTR} retrotransposons. Currently, three non-{LTR} retrotransposon families - long interspersed element 1 (L1), {SVA} (short interspersed element ({SINE}-R), variable number of tandem repeats ({VNTR}), and Alu), and Alu (a {SINE}) elements - mobilize in the human genome, and cause genomic instability through both insertion- and post-insertion-based mutagenesis. Due to the abundance and high sequence identity of {TEs}, they frequently mislead the homologous recombination repair pathway into non-allelic homologous recombination, causing deletions, duplications, and inversions. While less comprehensively studied, non-{LTR} retrotransposon insertions and {TE}-mediated rearrangements are probably more common in cancer cells than in healthy tissue. This may be at least partially attributed to the commonly seen global hypomethylation as well as general epigenetic dysfunction of cancer cells. Where possible, we provide examples that impact cancer predisposition and/or development.},
	pages = {211--221},
	number = {4},
	journaltitle = {Semin Cancer Biol},
	author = {Konkel, M K and Batzer, M A},
	date = {2010},
	pmid = {20307669},
	keywords = {Humans, *Genome, Biological, {DNA} Breaks, {DNA} Methylation/genetics/physiology, Double-Stranded, Genetic/genetics/physiology, Genomic Instability/*genetics, Human/genetics, Insertional/methods/physiology, Models, Mutagenesis, Recombination, Retroelements/*physiology, Terminal Repeat Sequences/*genetics/physiology}
}

@article{matouk_h19_2007,
	title = {The H19 non-coding {RNA} is essential for human tumor growth},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17786216},
	doi = {10.1371/journal.pone.0000845},
	abstract = {{BACKGROUND}: Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding {RNAs} are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target. {METHODOLOGY}/{PRINCIPLE} {FINDINGS}: By controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular ({HCC}) and bladder carcinoma. Hypoxia upregulates the level of H19 {RNA}. Ablations of tumorigenicity of {HCC} and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57(kip2) induction. We identified a number of potential downstream targets of H19 {RNA}, including angiogenin and {FGF}18. {CONCLUSIONS}: H19 {RNA} harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy.},
	pages = {e845},
	number = {9},
	journaltitle = {{PLoS} One},
	author = {Matouk, I J and {DeGroot}, N and Mezan, S and Ayesh, S and Abu-lail, R and Hochberg, A and Galun, E},
	date = {2007},
	pmid = {17786216},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Oligonucleotide Array Sequence Analysis, Long Noncoding, Cell Division/*genetics, Cell Hypoxia, Cell Line, {DNA} Primers, Gene Knockdown Techniques, In Situ Hybridization, Nude, Reverse Transcriptase Polymerase Chain Reaction, Small Interfering, Tumor, Untranslated/genetics/*physiology, Urinary Bladder Neoplasms/genetics/*pathology}
}

@article{park_heterogeneous_2012,
	title = {Heterogeneous nuclear ribonucleoprotein C1/C2 controls the metastatic potential of glioblastoma by regulating {PDCD}4},
	volume = {32},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22907752},
	doi = {10.1128/MCB.00443-12},
	abstract = {{MicroRNAs} ({miRNAs}) have been implicated in the pathogenesis and progression of brain tumors. {miR}-21 is one of the most highly overexpressed {miRNAs} in glioblastoma multiforme ({GBM}), and its level of expression correlates with the tumor grade. Programmed cell death 4 ({PDCD}4) is a well-known {miR}-21 target and is frequently downregulated in glioblastomas in accordance with increased {miR}-21 expression. Downregulation of {miR}-21 or overexpression of {PDCD}4 can inhibit metastasis. Here, we investigate the role of heterogeneous nuclear ribonucleoprotein C1/C2 ({hnRNPC}) in the metastatic potential of the glioblastoma cell line T98G. {hnRNPC} bound directly to primary {miR}-21 (pri-{miR}-21) and promoted {miR}-21 expression in T98G cells. Silencing of {hnRNPC} lowered {miR}-21 levels, in turn increasing the expression of {PDCD}4, suppressing Akt and p70S6K activation, and inhibiting migratory and invasive activities. Silencing of {hnRNPC} reduced cell proliferation and enhanced etoposide-induced apoptosis. In support of a role for {hnRNPC} in the invasiveness of {GBM}, highly aggressive U87MG cells showed higher {hnRNPC} expression levels and {hnRNPC} abundance in tissue arrays and also showed elevated levels as a function of brain tumor grade. Taken together, our data indicate that {hnRNPC} controls the aggressiveness of {GBM} cells through the regulation of {PDCD}4, underscoring the potential usefulness of {hnRNPC} as a prognostic and therapeutic marker of {GBM}.},
	pages = {4237--4244},
	number = {20},
	journaltitle = {Mol Cell Biol},
	author = {Park, Y M and Hwang, S J and Masuda, K and Choi, K M and Jeong, M R and Nam, D H and Gorospe, M and Kim, H H},
	date = {2012},
	pmid = {22907752},
	keywords = {Humans, Gene Expression Regulation, 70-{kDa}/metabolism, Antineoplastic Agents, Apoptosis Regulatory Proteins/*biosynthesis, Apoptosis/drug effects, Brain Neoplasms/genetics/*pathology, Cell Line, Cell Movement/drug effects, Cell Proliferation/drug effects, Etoposide/pharmacology, Gene Silencing, Glioblastoma/genetics/*secondary, Heterogeneous-Nuclear Ribonucleoprotein Group C/ge, {MicroRNAs}/biosynthesis, Neoplasm Invasiveness, Neoplastic/drug effect, Oncogene Protein v-akt/metabolism, Phytogenic/pharmacology, Ribosomal Protein S6 Kinases, {RNA}-Binding Proteins/*biosynthesis, Tumor}
}

@article{martins_strategies_2013,
	title = {Strategies for outcrossing and genetic manipulation of Drosophila compound autosome stocks},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23316433},
	doi = {10.1534/g3.112.004481},
	abstract = {Among all organisms, Drosophila melanogaster has the most extensive well-characterized collection of large-scale chromosome rearrangements. Compound chromosomes, rearrangements in which homologous chromosome arms share a centromere, have proven especially useful in genetic-based surveys of the entire genome. However, their potential has not been fully realized because compound autosome stocks are refractile to standard genetic manipulations: if outcrossed, they yield inviable aneuploid progeny. Here we describe two strategies, cold-shock and use of the {bubR}1 mutant alleles, to produce nullo gametes through nondisjunction. These gametes are complementary to the compound chromosome-bearing gametes and thus produce viable progeny. Using these techniques, we created a compound chromosome two C(2){EN} stock bearing a red fluorescent protein-histone transgene, facilitating live analysis of these unusually long chromosomes.},
	pages = {1--4},
	number = {1},
	journaltitle = {G3 (Bethesda)},
	author = {Martins, T and Kotadia, S and Malmanche, N and Sunkel, C E and Sullivan, W},
	date = {2013},
	pmid = {23316433},
	keywords = {Animals, Genetic, Breeding/*methods, Cold-Shock Response, Crosses, Cytogenetic Analysis/methods, Drosophila melanogaster/*genetics, Gametogenesis/genetics/*physiology, Gene Transfer Techniques, Genetic/*genetics, Luminescent Proteins/genetics, Nondisjunction, Translocation}
}

@article{bellucci_predicting_2011,
	title = {Predicting protein associations with long noncoding {RNAs}},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21623348},
	doi = {10.1038/nmeth.1611},
	pages = {444--445},
	number = {6},
	journaltitle = {Nat Methods},
	author = {Bellucci, M and Agostini, F and Masin, M and Tartaglia, G G},
	date = {2011},
	pmid = {21623348},
	keywords = {Humans, {RNA}, Binding Sites, Gene Expression Profiling, Databases, Nucleic Acid, Algorithms, Endoribonucleases/chemistry/metabolism, Models, Molecular, Post-Transcriptional, Protein, Protein Structure, {RNA} Processing, {RNA}-Binding Proteins/chemistry/*metabolism, Secondary, Untranslated/genetics/*metabolism}
}

@article{onono_efficient_2013,
	title = {Efficient use of exogenous isoprenols for protein isoprenylation by {MDA}-{MB}-231 cells is regulated independently of the mevalonate pathway},
	volume = {288},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23908355},
	doi = {10.1074/jbc.M113.482307},
	abstract = {Mammalian cells can use exogenous isoprenols to generate isoprenoid diphosphate substrates for protein isoprenylation, but the mechanism, efficiency, and biological importance of this process are not known. We developed mass spectrometry-based methods using chemical probes and newly synthesized stable isotope-labeled tracers to quantitate incorporation of exogenously provided farnesol, geranylgeraniol, and unnatural analogs of these isoprenols containing an aniline group into isoprenoid diphosphates and protein isoprenylcysteines by cultured human cancer cell lines. We found that at exogenous isoprenol concentrations {\textbackslash}textgreater10 {muM}, this process can generate as much as 50\% of the cellular isoprenoid diphosphate pool used for protein isoprenylation. Mutational activation of p53 in {MDA}-{MB}-231 breast cancer cells up-regulates the mevalonate pathway to promote tumor invasiveness. p53 silencing or pharmacological inhibition of {HMG}-{CoA} reductase in these cells decreases protein isoprenylation from endogenously synthesized isoprenoids but enhances the use of exogenous isoprenols for this purpose, indicating that this latter process is regulated independently of the mevalonate pathway. Our observations suggest unique opportunities for design of cancer cell-directed therapies and may provide insights into mechanisms underlying pleiotropic therapeutic benefits and unwanted side effects of mevalonate pathway inhibition.},
	pages = {27444--27455},
	number = {38},
	journaltitle = {J Biol Chem},
	author = {Onono, F and Subramanian, T and Sunkara, M and Subramanian, K L and Spielmann, H P and Morris, A J},
	date = {2013},
	pmid = {23908355},
	keywords = {Humans, Antineoplastic Agents/pharmacokinetics/*pharmacolo, Cell Line, Diterpenes/pharmacokinetics/*pharmacology, Farnesol/analogs \& derivatives/pharmacokinetics/*p, Hydroxymethylglutaryl {CoA} Reductases/genetics/meta, Hydroxymethylglutaryl-{CoA} Reductase Inhibitors/pha, Mevalonic Acid/*metabolism, Mutation, Neoplasms/*drug therapy/genetics/metabolism/pathol, Polyisoprenyl Phosphates/*metabolism, Protein Prenylation/drug effects/genetics, Tumor, Tumor Suppressor Protein p53/genetics/metabolism}
}

@article{salous_mechanism_2013,
	title = {Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice},
	volume = {54},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23948545},
	doi = {10.1194/jlr.M039685},
	abstract = {Lysophosphatidic acid ({LPA}) is a bioactive lipid mediator. Concentrations of the major {LPA} species in mouse plasma decreased uniformly following administration of a potent selective inhibitor of the {LPA}-generating lysophospholipase D autotaxin, identifying an active mechanism for removal of {LPA} from the circulation. {LPA}, akylglycerol phosphate ({AGP}), sphingosine 1-phosphate (S1P), and a variety of structural mimetics of these lipids, including phosphatase-resistant phosphonate analogs of {LPA}, were rapidly eliminated (t1/2 {\textbackslash}textless 30 s) from the circulation of mice following intravenous administration of a single bolus dose without significant metabolism in situ in the blood. These lipids accumulated in the liver. Elimination of intravenously administered {LPA} was blunted by ligation of the hepatic circulation, and approximately 90\% of {LPA} administered through the portal vein was accumulated by the isolated perfused mouse liver at first pass. At early times following intravenous administration, more {LPA} was associated with a nonparenchymal liver cell fraction than with hepatocytes. Primary cultures of nonparenchymal liver cells rapidly assimilated exogenously provided {LPA}. Our results identify hepatic uptake as an important determinant of the bioavailability of {LPA} and bioactive lysophospholipid mimetics and suggest a mechanism to explain changes in circulating {LPA} levels that have been associated with liver dysfunction in humans.},
	pages = {2775--2784},
	number = {10},
	journaltitle = {J Lipid Res},
	author = {Salous, A K and Panchatcharam, M and Sunkara, M and Mueller, P and Dong, A and Wang, Y and Graf, G A and Smyth, S S and Morris, A J},
	date = {2013},
	pmid = {23948545}
}

@article{yoon_lincrna-p21_2012,
	title = {{LincRNA}-p21 suppresses target {mRNA} translation},
	volume = {47},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22841487},
	doi = {10.1016/j.molcel.2012.06.027},
	abstract = {Mammalian long intergenic noncoding {RNAs} ({lincRNAs}) are best known for modulating transcription. Here we report a posttranscriptional function for {lincRNA}-p21 as a modulator of translation. Association of the {RNA}-binding protein {HuR} with {lincRNA}-p21 favored the recruitment of let-7/Ago2 to {lincRNA}-p21, leading to lower {lincRNA}-p21 stability. Under reduced {HuR} levels, {lincRNA}-p21 accumulated in human cervical carcinoma {HeLa} cells, increasing its association with {JUNB} and {CTNNB}1 {mRNAs} and selectively lowering their translation. With elevated {HuR}, {lincRNA}-p21 levels declined, which in turn derepressed {JunB} and beta-catenin translation and increased the levels of these proteins. We propose that {HuR} controls translation of a subset of target {mRNAs} by influencing {lincRNA}-p21 levels. Our findings uncover a role for {lincRNA} as a posttranscriptional inhibitor of translation.},
	pages = {648--655},
	number = {4},
	journaltitle = {Mol Cell},
	author = {Yoon, J H and Abdelmohsen, K and Srikantan, S and Yang, X and Martindale, J L and De, S and Huarte, M and Zhan, M and Becker, K G and Gorospe, M},
	date = {2012},
	pmid = {22841487},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, Transcription, Long Noncoding/*genetics, Messenger/genetics, Cultured, *Protein Biosynthesis, *{RNA} Processing, beta Catenin/genetics/metabolism, Carboxypeptidases/genetics/metabolism, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens/genet, {MicroRNAs}/genetics, Molecular Sequence Data, Post-Transcriptional, Proteolysis, {RNA}-Binding Proteins/genetics/metabolism, Tumor Cells}
}

@article{melbye_symptoms_2012,
	title = {Symptoms of respiratory tract infection and associated care-seeking in subjects with and without obstructive lung disease; the Tromso Study: Tromso 6},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22958519},
	doi = {10.1186/1471-2466-12-51},
	abstract = {{BACKGROUND}: Respiratory tract infections ({RTIs}) may be more severe in those with asthma or {COPD} and these patients are more frequently in need of health care. The aim of the study was to describe the frequency of {RTI} symptoms in a general adult population and how care-seeking is associated with the presence of obstructive lung disease. {METHODS}: Cross-sectional data including spirometry and self-reported chronic diseases were collected among middle-aged and elderly subjects in the Tromso population survey (Tromso 6). Self- reported {RTI} symptoms, consultations and antibiotic use were the main outcome variables. Possible predictors of {RTI} symptoms were evaluated by multivariable logistic regression. {RESULTS}: Of the 6414 subjects included, 798 (12.4\%) reported {RTI} symptoms in the previous week. {RTI} symptoms were reported less frequently by subjects aged 75 years or above, than by those younger than 55 years ({OR} 0.5). Winter season ({OR} 1.28), current smoking ({OR} 1.60), low self-rated health ({OR} 1.26) and moderate to severe bronchial obstruction ({OR} 1.51), were also statistically significant independent predictors of {RTI} symptoms, but these variables did not predict {RTI} symptoms that had started within the previous seven days. Among subjects with {RTI} symptoms, 5.1\% also reported a consultation with a doctor. In those with bronchial obstruction by spirometry, who did not report asthma or {COPD}, this frequency was 2.4\%. Antibiotic treatment was reported by 7.4\% of the participants, among whom one third had consulted a doctor. Antibiotics were taken more frequently when asthma or {COPD} was reported (13.7\%), but not in subjects with bronchial obstruction who did not report these diseases (7.2\%). {CONCLUSIONS}: {RTI} symptoms seldom led to consultation with a doctor and not even in subjects with obstructive lung disease. This was in particular the case in subjects who did not know about their obstructive lung disease. Strategies for early diagnosis of {COPD} and providing health care to subjects with such disease cannot rely on their doctor visits due to respiratory symptoms.},
	pages = {51},
	journaltitle = {{BMC} Pulm Med},
	author = {Melbye, H and Joensen, L and Risor, M B and Halvorsen, P A},
	date = {2012},
	pmid = {22958519},
	keywords = {Humans, 80 and over, Adult, Aged, Chronic Obstructive/*diagnosis/, Cross-Sectional Studies, Female, Male, Middle Aged, Norway/epidemiology, Pulmonary Disease, Questionnaires, Regression Analysis, Respiratory Tract Infections/*diagnosis/*epidemiol, Spirometry}
}

@article{anastasiadou_epstein-barr_2010,
	title = {Epstein-Barr virus encoded {LMP}1 downregulates {TCL}1 oncogene through {miR}-29b},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19966860},
	doi = {10.1038/onc.2009.439},
	abstract = {Epstein-Barr virus ({EBV}) encoded latent membrane protein 1 ({LMP}1) is noted for its transforming potential. Yet, it also acts as a cytostatic and growth-relenting factor in Burkitt's lymphoma ({BL}) cells. The underlying molecular mechanisms of the growth inhibitory property of {LMP}1 have remained largely unknown. In this study, we show that {LMP}1 negatively regulates a major oncogene, {TCL}1, in diffuse large B-cell lymphoma ({DLBCL}) and {BL} cells. {MicroRNA} ({miR}) profiling of {LMP}1 transfectants showed that among others, {miR}-29b, is upregulated. {LMP}1 diminished {TCL}1 by inducing {miR}-29b through C-terminus activation region 1 ({CTAR}1) and {CTAR}2. {miR}-29b locked nucleic acid ({LNA}) antisense oligonucleotide transfection into {LMP}1-expressing cells reduced {miR}-29b expression and consequently reconstituted {TCL}1, suggesting that {LMP}1 negatively regulates {TCL}1 through {miR}-29b upregulation. The {miR}-29b increase by {LMP}1 was due to an increase in the cluster pri-{miR}-29b1-a transcription, derived from human chromosome 7. Using pharmacological inhibitors, we found that p38 mitogen-activated protein kinase-activating function of {LMP}1 is important for this effect. The ability of {LMP}1 to negatively regulate {TCL}1 through {miR}-29b might underlie its B-cell lymphoma growth antagonistic property. As {LMP}1 is also important for B-cell transformation, we suggest that the functional dichotomy of this viral protein may depend on a combination of levels of its expression, lineage and differentiation of the target cells and regulation of {miRs}, which then directs the outcome of the cellular response.},
	pages = {1316--1328},
	number = {9},
	journaltitle = {Oncogene},
	author = {Anastasiadou, E and Boccellato, F and Vincenti, S and Rosato, P and Bozzoni, I and Frati, L and Faggioni, A and Presutti, C and Trivedi, P},
	date = {2010},
	pmid = {19966860},
	keywords = {Humans, B-Cell/virology, Cell Line, Gene Expression Regulation/*drug effects, Herpesvirus 4, Human/chemistry/genetics/*metabolis, Lymphoma, {MicroRNAs}/*metabolism/pharmacology, Oncogenes/*drug effects/genetics, Proto-Oncogene Proteins/genetics/*metabolism, Signal Transduction/physiology, Tumor, Viral Matrix Proteins/*pharmacology}
}

@article{lopez_de_silanes_global_2004,
	title = {Global analysis of {HuR}-regulated gene expression in colon cancer systems of reducing complexity},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15473260},
	abstract = {{HuR}, a protein that binds to target {mRNAs} and can enhance their stability and translation, is increasingly recognized as a pivotal regulator of gene expression during cell division and tumorigenesis. We sought to identify collections of {HuR}-regulated {mRNAs} in colon cancer cells by systematic, {cDNA} array-based assessment of gene expression in three systems of varying complexity. First, comparison of gene expression profiles among tumors with different {HuR} abundance revealed highly divergent gene expression patterns, and virtually no changes in previously reported {HuR} target {mRNAs}. Assessment of gene expression patterns in a second system of reduced complexity, cultured colon cancer cells expressing different {HuR} levels, rendered more conserved sets of {HuR}-regulated {mRNAs}. However, the definitive identification of direct {HuR} target {mRNAs} required a third system of still lower complexity, wherein {HuR}-{RNA} complexes immunoprecipitated from colon cancer cells were subject to {cDNA} array hybridization to elucidate the endogenous {HuR}-bound {mRNAs}. Comparison of the transcript sets identified in each system revealed a strikingly limited overlap in {HuR}-regulated {mRNAs}. The data derived from this systematic analysis of {HuR}-regulated genes highlight the value of low-complexity, biochemical characterization of protein-{RNA} interactions. More importantly, however, the data underscore the broad usefulness of integrated approaches comprising systems of low complexity (protein-nucleic acid) and high complexity (cells, tumors) to comprehensively elucidate the gene regulatory events that underlie biological processes.},
	pages = {49--59},
	number = {1},
	journaltitle = {Gene Expr},
	author = {Lopez de Silanes, I and Fan, J and Galban, C J and Spencer, R G and Becker, K G and Gorospe, M},
	date = {2004},
	pmid = {15473260},
	keywords = {Animals, Humans, Mice, {RNA}, Oligonucleotide Array Sequence Analysis, Cultured, *Gene Expression Profiling, *Gene Expression Regulation, Antigens, Biological, Colonic Neoplasms/*metabolism, Down-Regulation, Hu Paraneoplastic Encephalomyelitis Antigens, Inbred {BALB} C, Male, Messenger/metabolism, Models, Neoplastic, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism, Tumor Cells, Up-Regulation}
}

@article{kaneko_dicer1_2011,
	title = {{DICER}1 deficit induces Alu {RNA} toxicity in age-related macular degeneration},
	volume = {471},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21297615},
	doi = {10.1038/nature09830},
	abstract = {Geographic atrophy ({GA}), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium ({RPE}) cell degeneration. Here we show that the {microRNA} ({miRNA})-processing enzyme {DICER}1 is reduced in the {RPE} of humans with {GA}, and that conditional ablation of Dicer1, but not seven other {miRNA}-processing enzymes, induces {RPE} degeneration in mice. {DICER}1 knockdown induces accumulation of Alu {RNA} in human {RPE} cells and Alu-like B1 and B2 {RNAs} in mouse {RPE}. Alu {RNA} is increased in the {RPE} of humans with {GA}, and this pathogenic {RNA} induces human {RPE} cytotoxicity and {RPE} degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 {RNAs} prevent {DICER}1 depletion-induced {RPE} degeneration despite global {miRNA} downregulation. {DICER}1 degrades Alu {RNA}, and this digested Alu {RNA} cannot induce {RPE} degeneration in mice. These findings reveal a {miRNA}-independent cell survival function for {DICER}1 involving retrotransposon transcript degradation, show that Alu {RNA} can directly cause human pathology, and identify new targets for a major cause of blindness.},
	pages = {325--330},
	number = {7338},
	journaltitle = {Nature},
	author = {Kaneko, H and Dridi, S and Tarallo, V and Gelfand, B D and Fowler, B J and Cho, W G and Kleinman, M E and Ponicsan, S L and Hauswirth, W W and Chiodo, V A and Kariko, K and Yoo, J W and Lee, D K and Hadziahmetovic, M and Song, Y and Misra, S and Chaudhuri, G and Buaas, F W and Braun, R E and Hinton, D R and Zhang, Q and Grossniklaus, H E and Provis, J M and Madigan, M C and Milam, A H and Justice, N L and Albuquerque, R J and Blandford, A D and Bogdanovich, S and Hirano, Y and Witta, J and Fuchs, E and Littman, D R and Ambati, B K and Rudin, C M and Chong, M M and Provost, P and Kugel, J F and Goodrich, J A and Dunaief, J L and Baffi, J Z and Ambati, J},
	date = {2011},
	pmid = {21297615},
	keywords = {Animals, Humans, Mice, Cells, Cultured, Alu Elements/*genetics, Antisense, Cell Death, Cell Survival, {DEAD}-box {RNA} Helicases/*deficiency/genetics/metabo, Gene Knockdown Techniques, Macular Degeneration/*genetics/*pathology, {MicroRNAs}/metabolism, Molecular Sequence Data, Oligonucleotides, Phenotype, Retinal Pigment Epithelium/enzymology/metabolism/p, Ribonuclease {III}/*deficiency/genetics/metabolism, {RNA}/*genetics/*metabolism}
}

@article{grammatikakis_modulation_2013,
	title = {Modulation of Cancer Traits by Tumor Suppressor {microRNAs}},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23325049},
	doi = {10.3390/ijms14011822},
	abstract = {{MicroRNAs} ({miRNAs}) are potent post-transcriptional regulators of gene expression. In mammalian cells, {miRNAs} typically suppress {mRNA} stability and/or translation through partial complementarity with target {mRNAs}. Each {miRNA} can regulate a wide range of {mRNAs}, and a single {mRNA} can be regulated by multiple {miRNAs}. Through these complex regulatory interactions, {miRNAs} participate in many cellular processes, including carcinogenesis. By altering gene expression patterns, cancer cells can develop specific phenotypes that allow them to proliferate, survive, secure oxygen and nutrients, evade immune recognition, invade other tissues and metastasize. At the same time, cancer cells acquire {miRNA} signature patterns distinct from those of normal cells; the differentially expressed {miRNAs} contribute to enabling the cancer traits. Over the past decade, several {miRNAs} have been identified, which functioned as oncogenic {miRNAs} ({oncomiRs}) or tumor-suppressive {miRNAs} ({TS}-{miRNAs}). In this review, we focus specifically on {TS}-{miRNAs} and their effects on well-established cancer traits. We also discuss the rising interest in {TS}-{miRNAs} in cancer therapy.},
	pages = {1822--1842},
	number = {1},
	journaltitle = {Int J Mol Sci},
	author = {Grammatikakis, I and Gorospe, M and Abdelmohsen, K},
	date = {2013},
	pmid = {23325049}
}

@article{morlando_role_2014,
	title = {The Role of Long Noncoding {RNAs} in the Epigenetic Control of Gene Expression},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24488863},
	doi = {10.1002/cmdc.201300569},
	abstract = {Recent advances in the methodologies employed to deeply analyse the complexity of transcriptomes have unveiled the existence of a new class of transcripts, long noncoding {RNAs} ({lncRNAs}). A significant amount of effort has been dedicated to the study of {lncRNAs}, and a large body of evidence now exists indicating their relevant role in different regulatory steps of gene expression. Given the role of epigenetics in disease development and progression, this Minireview focuses on {lncRNAs} involved in epigenetic control and provides an overview of the mechanisms used to guide epigenetic-modifying complexes to adjacent (cis-acting) or independent (trans-acting) genomic loci. Furthermore, it describes the activities of these transcripts in controlling the formation and spreading of heterochromatin domains. Just as other {RNA} molecules have found therapeutic application, though much remains to be elucidated about the structure and function of these {lncRNAs}, they too could hold potential as biomarkers, targets, and therapeutic agents.},
	pages = {505--510},
	number = {3},
	journaltitle = {{ChemMedChem}},
	author = {Morlando, M and Ballarino, M and Fatica, A and Bozzoni, I},
	date = {2014},
	pmid = {24488863}
}

@article{zheng_pancreatic_2016,
	title = {Pancreatic cancer risk variant in {LINC}00673 creates a {miR}-1231 binding site and interferes with {PTPN}11 degradation},
	volume = {48},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27213290},
	doi = {10.1038/ng.3568},
	abstract = {Genome-wide association studies have identified several loci associated with pancreatic cancer risk; however, the mechanisms by which genetic factors influence the development of sporadic pancreatic cancer remain largely unknown. Here, by using genome-wide association analysis and functional characterization, we identify a long intergenic noncoding {RNA} ({lincRNA}), {LINC}00673, as a potential tumor suppressor whose germline variation is associated with pancreatic cancer risk. {LINC}00673 is able to reinforce the interaction of {PTPN}11 with {PRPF}19, an E3 ubiquitin ligase, and promote {PTPN}11 degradation through ubiquitination, which causes diminished {SRC}-{ERK} oncogenic signaling and enhanced activation of the {STAT}1-dependent antitumor response. A G{\textbackslash}{textgreaterA} change at rs11655237 in exon 4 of {LINC}00673 creates a target site for {miR}-1231 binding, which diminishes the effect of {LINC}00673 in an allele-specific manner and thus confers susceptibility to tumorigenesis. These findings shed new light on the important role of {LINC}00673 in maintaining cell homeostasis and how its germline variation might confer susceptibility to pancreatic cancer.},
	pages = {747--757},
	number = {7},
	journaltitle = {Nat Genet},
	author = {Zheng, J and Huang, X and Tan, W and Yu, D and Du, Z and Chang, J and Wei, L and Han, Y and Wang, C and Che, X and Zhou, Y and Miao, X and Jiang, G and Yu, X and Yang, X and Cao, G and Zuo, C and Li, Z and Cheung, S T and Jia, Y and Zheng, X and Shen, H and Wu, C and Lin, D},
	date = {2016},
	pmid = {27213290}
}

@article{royce-tolland_-repeat_2010,
	title = {The A-repeat links {ASF}/{SF}2-dependent Xist {RNA} processing with random choice during X inactivation},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20657585},
	doi = {10.1038/nsmb.1877},
	abstract = {One X chromosome, selected at random, is silenced in each female mammalian cell. Xist encodes a noncoding {RNA} that influences the probability that the cis-linked X chromosome will be silenced. We found that the A-repeat, a highly conserved element within Xist, is required for the accumulation of spliced Xist {RNA}. In addition, the A-repeat is necessary for X-inactivation to occur randomly. In combination, our data suggest that normal Xist {RNA} processing is important in the regulation of random X-inactivation. We propose that modulation of Xist {RNA} processing may be part of the stochastic process that determines which X chromosome will be inactivated.},
	pages = {948--954},
	number = {8},
	journaltitle = {Nat Struct Mol Biol},
	author = {Royce-Tolland, M E and Andersen, A A and Koyfman, H R and Talbot, D J and Wutz, A and Tonks, I D and Kay, G F and Panning, B},
	date = {2010},
	pmid = {20657585},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Protein Binding, *{RNA} Processing, Alleles, Biological, Chromosomes, Female, {HeLa} Cells, Histones/metabolism, Long Untranslated, Male, Mammalian/metabolism, Messenger/genetics/metabolism, Models, Molecular Sequence Data, Nuclear Proteins/*metabolism, Nucleic Acid Conformation, Nucleic Acid/*genetics, Post-Transcriptional, Post-Translational, Protein Processing, Repetitive Sequences, {RNA}-Binding Proteins/*metabolism, Sequence Deletion/genetics, Untranslated/chemistry/*genetics, X Chromosome Inactivation/*genetics}
}

@article{beilharz_translational_2004,
	title = {Translational profiling: the genome-wide measure of the nascent proteome},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15355593},
	abstract = {Translation in eukaryotic cells is both physically and temporally separated from transcription. This provides cells with extended options to alter their proteome: (1) directly, by synchronizing translation with an altering transcriptional profile; (2) by imposing a changed translational control over transcripts already present in the transcriptome; or (3) by a combination of (1) and (2). In this paper, recent findings in the controlled translation of the transcriptome using microarray analyses are reviewed. A guide to the current technologies and data analysis is also provided, and future directions in the study of translational control as the interface between the transcriptome and the proteome are outlined. This survey is focused on the yeast Saccharomyces cerevisiae, but the topics covered have universal relevance to the control of translation in eukaryotic cells.},
	pages = {103--111},
	number = {2},
	journaltitle = {Brief Funct Genomic Proteomic},
	author = {Beilharz, T H and Preiss, T},
	date = {2004},
	pmid = {15355593},
	keywords = {{RNA}, Messenger/genetics, *Genome, Gene Expression Profiling, *Protein Biosynthesis, *Proteome}
}

@article{alba_inverse_2005,
	title = {Inverse relationship between evolutionary rate and age of mammalian genes},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15537804},
	doi = {10.1093/molbev/msi045},
	abstract = {A large number of genes is shared by all living organisms, whereas many others are unique to some specific lineages, indicating their different times of origin. The availability of a growing number of eukaryotic genomes allows us to estimate which mammalian genes are novel genes and, approximately, when they arose. In this article, we classify human genes into four different age groups and estimate evolutionary rates in human and mouse orthologs. We show that older genes tend to evolve more slowly than newer ones; that is, proteins that arose earlier in evolution currently have a larger proportion of sites subjected to negative selection. Interestingly, this property is maintained when a fraction of the fastest-evolving genes is excluded or when only genes belonging to a given functional class are considered. One way to explain this relationship is by assuming that genes maintain their functional constraints along all their evolutionary history, but the nature of more recent evolutionary innovations is such that the functional constraints operating on them are increasingly weaker. Alternatively, our results would also be consistent with a scenario in which the functional constraints acting on a gene would not need to be constant through evolution. Instead, starting from weak functional constraints near the time of origin of a gene-as supported by mechanisms proposed for the origin of orphan genes-there would be a gradual increase in selective pressures with time, resulting in fewer accepted mutations in older versus more novel genes.},
	pages = {598--606},
	number = {3},
	journaltitle = {Mol Biol Evol},
	author = {Alba, M M and Castresana, J},
	date = {2005},
	pmid = {15537804},
	keywords = {Human, {DNA}, Animals, Humans, Mice, *Genome, *Evolution, *Sequence Analysis, Molecular}
}

@article{marques_intergenic_2014,
	title = {Intergenic {lncRNAs} and the evolution of gene expression},
	volume = {27C},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24852186},
	doi = {10.1016/j.gde.2014.03.009},
	abstract = {Eukaryote genomes encode a surprisingly large number of noncoding transcripts. Around two-thirds of human transcribed loci do not encode protein, and many are intergenic and produce long ({\textbackslash}textgreater200 nucleotides) noncoding {RNAs} ({lncRNAs}). Extensive analyses using comparative genomics and transcriptomics approaches have established that {lncRNA} sequence and transcription tend to turn over rapidly during evolution. Our appreciation of the biological roles of {lncRNAs}, based only on a handful of transcripts with well-characterized functions, is that {lncRNAs} have diverse roles in regulating gene expression. These proposed roles together with their rapid rates of evolution suggest that {lncRNAs} could contribute to the divergent expression patterns observed among species and potentially to the origin of new traits.},
	pages = {48--53},
	journaltitle = {Curr Opin Genet Dev},
	author = {Marques, A C and Ponting, C P},
	date = {2014},
	pmid = {24852186}
}

@article{harrow_gencode:_2012,
	title = {{GENCODE}: the reference human genome annotation for The {ENCODE} Project},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22955987},
	doi = {10.1101/gr.135350.111},
	abstract = {The {GENCODE} Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The {GENCODE} 7 release contains 20,687 protein-coding and 9640 long noncoding {RNA} loci and has 33,977 coding transcripts not represented in {UCSC} genes and {RefSeq}. It also has the most comprehensive annotation of long noncoding {RNA} ({lncRNA}) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35\% of transcriptional start sites are supported by {CAGE} clusters and 62\% of protein-coding genes have annotated {polyA} sites. Over one-third of {GENCODE} protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 {RNA}-seq data identify 3689 new loci not currently in {GENCODE}, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. {GENCODE} 7 is publicly available from gencodegenes.org and via the Ensembl and {UCSC} Genome Browsers.},
	pages = {1760--1774},
	number = {9},
	journaltitle = {Genome Res},
	author = {Harrow, J and Frankish, A and Gonzalez, J M and Tapanari, E and Diekhans, M and Kokocinski, F and Aken, B L and Barrell, D and Zadissa, A and Searle, S and Barnes, I and Bignell, A and Boychenko, V and Hunt, T and Kay, M and Mukherjee, G and Rajan, J and Despacio-Reyes, G and Saunders, G and Steward, C and Harte, R and Lin, M and Howald, C and Tanzer, A and Derrien, T and Chrast, J and Walters, N and Balasubramanian, S and Pei, B and Tress, M and Rodriguez, J M and Ezkurdia, I and van Baren, J and Brent, M and Haussler, D and Kellis, M and Valencia, A and Reymond, A and Gerstein, M and Guigo, R and Hubbard, T J},
	date = {2012},
	pmid = {22955987},
	keywords = {Human, {DNA}, Genomics/*methods, Animals, Genetic, Humans, {RNA}, *Genome, Exons, Reproducibility of Results, Complementary/chemistry/genetics, Open Reading Frames, Long Noncoding, {RNA} Splice Sites, *Databases, *Molecular Sequence Annotation, Computational Biology/methods, Evolution, Genetic Loci, Internet, Models, Molecular, Pseudogenes, Quality Control, Untranslated Regions}
}

@article{iovino_loxp-containing_2005,
	title = {A {loxP}-containing pol {II} promoter for {RNA} interference is reversibly regulated by Cre recombinase},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17114926},
	abstract = {Several {DNA} vectors for {RNA} interference in mammalian cells have been described. These express a short hairpin {RNA} ({shRNA}) that is subsequently processed into mature small interfering {RNAs} ({siRNAs}). We previously developed the {siRNA}-expressing vector {psiUx} based on the {polII} promoter of the U1 small nuclear {RNA} gene. Here we describe the conversion of such construct into an inducible system. The starting construct {psiUStuff} contains a {loxP}-Stuffer-{loxP} cassette just upstream the transcription initiation site and does not express the {shRNA} until the two canonical {loxP} sites undergo Cre-mediated recombination. If sustained expression of the recombinase is maintained, transcription is repressed and {shRNA} synthesis is abolished. Therefore, in our system the Cre recombinase exhibits the dual function of activator and repressor allowing the on/off regulation of {siRNAs} production. Using a Cre recombinase whose transcription is under the control of a {tetOn} system, we show the temporally controlled expression of an {shRNA} directed towards the lamin A/C {mRNA}, as well as the regulated knockdown of its target.},
	pages = {86--92},
	number = {3},
	journaltitle = {{RNA} Biol},
	author = {Iovino, N and Denti, M A and Bozzoni, I and Cortese, R},
	date = {2005},
	pmid = {17114926},
	keywords = {Genetic, Humans, *Promoter Regions, *Genetic Techniques, *{RNA} Interference, {DNA} Polymerase {II}/*physiology, Gene Expression Regulation/*physiology, {HeLa} Cells, Integrases/*physiology, Recombination}
}

@article{cunningham_targeted_2006,
	title = {Targeted deletion of {MKK}4 in cancer cells: a detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss},
	volume = {66},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16740690},
	doi = {10.1158/0008-5472.CAN-06-0555},
	abstract = {Tumor-suppressors have commanded attention due to the selection for their inactivating mutations in human tumors. However, relatively little is understood about the inverse, namely, that tumors do not select for a large proportion of seemingly favorable mutations in tumor-suppressor genes. This could be explained by a detrimental phenotype accruing in a cell type-specific manner to most cells experiencing a biallelic loss. For example, {MKK}4, a tumor suppressor gene distinguished by a remarkably consistent mutational rate across diverse tumor types and an unusually high rate of loss of heterozygosity, has the surprisingly low rate of genetic inactivation of only approximately 5\%. To explore this incongruity, we engineered a somatic gene knockout of {MKK}4 in human cancer cells. Although the null cells resembled the wild-type cells regarding in vitro viability and proliferation in plastic dishes, there was a marked difference in a more relevant in vivo model of experimental metastasis and tumorigenesis. {MKK}4(-/-) clones injected i.v. produced fewer lung metastases than syngeneic {MKK}4-competent cells (P = 0.0034). These findings show how cell type-specific detrimental phenotypes can offer a paradoxical and yet key counterweight to the selective advantage attained by cells as they experiment with genetic null states during tumorigenesis, the resultant balance then determining the observed biallelic mutation rate for a given tumor-suppressor gene.},
	pages = {5560--5564},
	number = {11},
	journaltitle = {Cancer Res},
	author = {Cunningham, S C and Gallmeier, E and Hucl, T and Dezentje, D A and Calhoun, E S and Falco, G and Abdelmohsen, K and Gorospe, M and Kern, S E},
	date = {2006},
	pmid = {16740690},
	keywords = {Animals, Humans, Mice, Exons, *Genes, Cell Growth Processes/genetics, Cell Line, Enzyme Activation, Female, Gene Deletion, {MAP} Kinase Kinase 4/*deficiency/*genetics/metaboli, {MAP} Kinase Signaling System, Neoplasm Metastasis, Nude, p38 Mitogen-Activated Protein Kinases/metabolism, Pancreatic Neoplasms/*enzymology/*genetics/patholo, Phenotype, Tumor, Tumor Suppressor}
}

@article{lipovich_developmental_2013,
	title = {Developmental Changes in the Transcriptome of Human Cerebral Cortex Tissue: Long Noncoding {RNA} Transcripts},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23377288},
	doi = {10.1093/cercor/bhs414},
	abstract = {The human neocortex is characterized by protracted developmental intervals of synaptogenesis and myelination, which allow for an extended period of learning. The molecular basis of these and other postnatal developmental changes in the human cerebral cortex remain incompletely understood. Recently, a new large class of mammalian genes, encoding nonmessenger, long nonprotein-coding ribonucleic acid ({lncRNA}) molecules has been discovered. Although their function remains uncertain, numerous {lncRNAs} have primate-specific sequences and/or show evidence of rapid, lineage-specific evolution, making them potentially relevant to the evolution of unique human neural properties. To examine the hypothesis that {lncRNA} expression varies with age, potentially paralleling known developmental trends in synaptogenesis, myelination, and energetics, we quantified levels of nearly 6000 {lncRNAs} in 36 surgically resected human neocortical samples (primarily derived from temporal cortex) spanning infancy to adulthood. Our analysis identified 8 {lncRNA} genes with distinct developmental expression patterns. These {lncRNA} genes contained anthropoid-specific exons, as well as splice sites and polyadenylation signals that resided in primate-specific sequences. To our knowledge, our study is the first to describe developmental expression profiles of {lncRNA} in surgically resected in vivo human brain tissue. Future analysis of the functional relevance of these transcripts to neural development and energy metabolism is warranted.},
	journaltitle = {Cereb Cortex},
	author = {Lipovich, L and Tarca, A L and Cai, J and Jia, H and Chugani, H T and Sterner, K N and Grossman, L I and Uddin, M and Hof, P R and Sherwood, C C and Kuzawa, C W and Goodman, M and Wildman, D E},
	date = {2013},
	pmid = {23377288}
}

@article{mcallister_dck_2014,
	title = {{dCK} expression correlates with 5-fluorouracil efficacy and {HuR} cytoplasmic expression in pancreatic cancer: A dual-institutional follow-up with the {RTOG} 9704 trial},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24618665},
	abstract = {Deoxycytidine kinase ({dCK}) and human antigen R ({HuR}) have been associated with response to gemcitabine in small studies. The present study investigates the prognostic and predictive value of {dCK} and {HuR} expression levels for sensitivity to gemcitabine and 5-fluorouracil (5-{FU}) in a large phase {III} adjuvant trial with chemoradiation backbone in pancreatic ductal adenocarcinoma ({PDA}). The {dCK} and {HuR} expression levels were determined by immunohistochemistry on a tissue microarray of 165 resected {PDAs} from the Radiation Therapy Oncology Group ({RTOG}) 9704 trial. Association with overall survival ({OS}) and disease-free survival ({DFS}) status were analyzed using the log-rank test and the Cox proportional hazards model. Experiments with cultured {PDA} cells were performed to explore mechanisms linking {dCK} and {HuR} expression to drug sensitivity. {dCK} expression levels were associated with improved {OS} for all patients analyzed from {RTOG} 9704 ({HR}: 0.66, 95\% {CI} [0.47-0.93], P = 0.015). In a subset analysis based on treatment arm, the effect was restricted to patients receiving 5-{FU} ({HR}: 0.53, 95\% {CI} [0.33-0.85], P = 0.0078). Studies in cultured cells confirmed that {dCK} expression rendered cells more sensitive to 5-{FU}. {HuR} cytoplasmic expression was neither prognostic nor predictive of treatment response. Previous studies along with drug sensitivity and biochemical studies demonstrate that radiation interferes with {HuR}'s regulatory effects on {dCK}, and could account for the negative findings herein based on the clinical study design (i.e., inclusion of radiation). Finally, we demonstrate that 5-{FU} can increase {HuR} function by enhancing {HuR} translocation from the nucleus to the cytoplasm, similar to the effect of gemcitabine in {PDA} cells. For the first time, in the pre-treatment tumor samples, {dCK} and {HuR} cytoplasmic expression were strongly correlated (chi-square P = 0.015). This dual-institutional follow up study, in a multi-institutional {PDA} randomized clinical trial, observed that {dCK} expression levels were prognostic and had predictive value for sensitivity to 5-{FU}.},
	number = {6},
	journaltitle = {Cancer Biol Ther},
	author = {{McAllister}, F and Pineda, D M and Jimbo, M and Lal, S and Burkhart, R A and Moughan, J and Winter, K A and Abdelmohsen, K and Gorospe, M and de Jesus Acosta, A and Lankapalli, R H and Winter, J M and Yeo, C J and Witkiewicz, A K and Iacobuzio-Donahue, C A and Laheru, D and Brody, J R},
	date = {2014},
	pmid = {24618665}
}

@article{kuwano_analysis_2009,
	title = {Analysis of nitric oxide-stabilized {mRNAs} in human fibroblasts reveals {HuR}-dependent heme oxygenase 1 upregulation},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19289500},
	doi = {10.1128/MCB.01495-08},
	abstract = {We previously observed that nitric oxide ({NO}) exposure increases the stability of {mRNAs} encoding heme oxygenase 1 ({HO}-1) and {TIEG}-1 in human and mouse fibroblasts. Here, we have used microarrays to look broadly for changes in {mRNA} stability in response to {NO} treatment. Using human {IMR}-90 and mouse {NIH} 3T3 fibroblasts treated with actinomycin D to block de novo transcription, microarray analysis suggested that the stability of the majority of {mRNAs} was unaffected. Among the {mRNAs} that were stabilized by {NO} treatment, seven transcripts were found in both {IMR}-90 and {NIH} 3T3 cells ({CHIC}2, {GADD}45B, {HO}-1, {PTGS}2, {RGS}2, {TIEG}, and {ID}3) and were chosen for further analysis. All seven {mRNAs} showed at least one hit of a signature motif for the stabilizing {RNA}-binding protein ({RBP}) {HuR}; accordingly, ribonucleoprotein immunoprecipitation analysis revealed that all seven {mRNAs} associated with {HuR}. In keeping with a functional role of {HuR} in the response to {NO}, a measurable fraction of {HuR} increased in the cytoplasm following {NO} treatment. However, among the seven transcripts, only {HO}-1 {mRNA} showed a robust increase in the level of its association with {HuR} following {NO} treatment. In turn, {HO}-1 {mRNA} and protein levels were significantly reduced when {HuR} levels were silenced in {IMR}-90 cells, and they were elevated when {HuR} was overexpressed. In sum, our results indicate that {NO} stabilizes {mRNA} subsets in fibroblasts, identify {HuR} as an {RBP} implicated in the {NO} response, reveal that {HuR} alone is insufficient for stabilizing several {mRNAs} by {NO}, and show that {HO}-1 induction by {NO} is regulated by {HuR}.},
	pages = {2622--2635},
	number = {10},
	journaltitle = {Mol Cell Biol},
	author = {Kuwano, Y and Rabinovic, A and Srikantan, S and Gorospe, M and Demple, B},
	date = {2009},
	pmid = {19289500},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, *Gene Expression Regulation, *{RNA} Stability, Antigens, Cell Line, Enzymologic, Fibroblasts/cytology/*physiology, Heme Oxygenase-1/genetics/*metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/genetics/*metabolism, Molecular Sequence Data, Nitric Oxide/*metabolism, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism, Up-Regulation}
}

@article{xiao_mir-29b_2013,
	title = {{miR}-29b represses intestinal mucosal growth by inhibiting translation of cyclin-dependent kinase 2},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23904268},
	doi = {10.1091/mbc.E13-05-0287},
	abstract = {The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, and defects in the renewal process occur commonly in various disorders. {microRNAs} ({miRNAs}) posttranscriptionally regulate gene expression and are implicated in many aspects of cellular physiology. Here we investigate the role of {miRNA}-29b ({miR}-29b) in the regulation of normal intestinal mucosal growth and further validate its target {mRNAs}. {miRNA} expression profiling studies reveal that growth inhibition of the small intestinal mucosa is associated with increased expression of numerous {miRNAs}, including {miR}-29b. The simple systemic delivery of locked nucleic acid-modified, anti-{miR}-29b-reduced endogenous {miR}-29b levels in the small intestinal mucosa increases cyclin-dependent kinase 2 ({CDK}2) expression and stimulates mucosal growth. In contrast, overexpression of the {miR}-29b precursor in intestinal epithelial cells represses {CDK}2 expression and results in growth arrest in G1 phase. {miR}-29b represses {CDK}2 translation through direct interaction with the cdk2 {mRNA} via its 3'-untranslated region (3'-{UTR}), whereas point mutation of {miR}-29b binding site in the cdk2 3'-{UTR} prevents {miR}-29b-induced repression of {CDK}2 translation. These results indicate that {miR}-29b inhibits intestinal mucosal growth by repressing {CDK}2 translation.},
	pages = {3038--3046},
	number = {19},
	journaltitle = {Mol Biol Cell},
	author = {Xiao, L and Rao, J N and Zou, T and Liu, L and Cao, S and Martindale, J L and Su, W and Chung, H K and Gorospe, M and Wang, J Y},
	date = {2013},
	pmid = {23904268}
}

@article{sunkaraneni_computer_2013,
	title = {Computer or not? Use of image guidance during endoscopic sinus surgery for chronic rhinosinusitis at St Paul's Hospital, Vancouver, and meta-analysis},
	volume = {127},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23480580},
	doi = {10.1017/S0022215113000261},
	abstract = {{BACKGROUND}: The advantages and limitations of image guidance systems for endoscopic sinus surgery are unclear. We report our experience and present a meta-analysis of the evidence. {METHODS}: We performed a retrospective analysis of endoscopic sinus surgery procedures performed with versus without image guidance. A total of 355 cases was included. Primary outcomes included complication rates and time to revision surgery. A literature search was conducted to enable identification and analysis of studies of similar comparisons. {RESULTS}: Within 1.5 years of the index sinus surgical procedure, the risk of revision surgery was significantly higher for patients treated with non-assisted versus computer-assisted endoscopic sinus surgery (p = 0.001). Meta-analysis did not indicate a reduction in complications or revision surgery procedures with the use of image guidance systems, although the majority of included studies showed a non-significant reduction in revision surgery. {CONCLUSION}: Our study offers some evidence that computer-assisted endoscopic sinus surgery may delay residual disease and reduce the requirement for revision surgery. Although this finding was not borne out in the meta-analysis, the majority of identified studies demonstrated a trend towards fewer revision procedures after computer-assisted endoscopic sinus surgery. This type of surgery may offer other advantages that are not easily measurable.},
	pages = {368--377},
	number = {4},
	journaltitle = {J Laryngol Otol},
	author = {Sunkaraneni, V S and Yeh, D and Qian, H and Javer, A R},
	date = {2013},
	pmid = {23480580},
	keywords = {Humans, 80 and over, Adolescent, Adult, Aged, Canada, Chronic Disease, Computer-Assisted/*methods, Endoscopy/adverse effects/*methods, Female, Male, Middle Aged, Paranasal Sinuses/*surgery, Reoperation, Retrospective Studies, Sinusitis/*surgery, Surgery, Technology, Young Adult}
}

@article{ulitsky_identifying_2009,
	title = {Identifying functional modules using expression profiles and confidence-scored protein interactions},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19297352},
	doi = {10.1093/bioinformatics/btp118},
	abstract = {{MOTIVATION}: Microarray-based gene expression studies have great potential but are frequently difficult to interpret due to their overwhelming dimensions. Recent studies have shown that the analysis of expression data can be improved by its integration with protein interaction networks, but the performance of these analyses has been hampered by the uneven quality of the interaction data. {RESULTS}: We present Co-Expression Zone {ANalysis} using {NEtworks} ({CEZANNE}), a novel confidence-based method for extraction of functionally coherent co-expressed gene sets. {CEZANNE} uses probabilities for individual interactions, which can be computed by any available method. We propose a probabilistic model and a weighting scheme in which the likelihood of the connectivity of a subnetwork is related to the weight of its minimum cut. Applying {CEZANNE} to an expression dataset of {DNA} damage response in Saccharomyces cerevisiae, we recover both known and novel modules and predict novel protein functions. We show that {CEZANNE} outperforms previous methods for analysis of expression and interaction data. {AVAILABILITY}: {CEZANNE} is available as part of the {MATISSE} software at http://acgt.cs.tau.ac.il/matisse. {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at Bioinformatics online.},
	pages = {1158--1164},
	number = {9},
	journaltitle = {Bioinformatics},
	author = {Ulitsky, I and Shamir, R},
	date = {2009},
	pmid = {19297352},
	keywords = {Gene Expression Profiling/*methods, Oligonucleotide Array Sequence Analysis, Databases, Software, *Gene Expression, *Protein Interaction Mapping, {DNA} Damage, Protein, Proteins/chemistry/genetics, Saccharomyces cerevisiae/genetics/metabolism}
}

@article{marco-sola_efficient_2015,
	title = {Efficient Alignment of Illumina-Like High-Throughput Sequencing Reads with the {GEnomic} Multi-tool ({GEM}) Mapper},
	volume = {50},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26094690},
	doi = {10.1002/0471250953.bi1113s50},
	abstract = {Modern Illumina-like high-throughput sequencing machines allow the cheap decoding of great amounts of {DNA}. The {GEnomic} Multi-tool ({GEM}) mapper is one of the fastest and most sensitive methods known to date to align such data to a known genomic reference. This unit explains how to use it effectively. (c) 2015 by John Wiley \& Sons, Inc.},
	pages = {11 13 1--11 13 20},
	journaltitle = {Curr Protoc Bioinformatics},
	author = {Marco-Sola, S and Ribeca, P},
	date = {2015},
	pmid = {26094690}
}

@article{rederstorff_ex_2008,
	title = {Ex vivo correction of selenoprotein N deficiency in rigid spine muscular dystrophy caused by a mutation in the selenocysteine codon},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18025044},
	doi = {10.1093/nar/gkm1033},
	abstract = {Premature termination of translation due to nonsense mutations is a frequent cause of inherited diseases. Therefore, many efforts were invested in the development of strategies or compounds to selectively suppress this default. Selenoproteins are interesting candidates considering the idiosyncrasy of the amino acid selenocysteine (Sec) insertion mechanism. Here, we focused our studies on {SEPN}1, a selenoprotein gene whose mutations entail genetic disorders resulting in different forms of muscular diseases. Selective correction of a nonsense mutation at the Sec codon ({UGA} to {UAA}) was undertaken with a corrector {tRNA}(Sec) that was engineered to harbor a compensatory mutation in the anticodon. We demonstrated that its expression restored synthesis of a full-length selenoprotein N both in {HeLa} cells and in skin fibroblasts from a patient carrying the mutated Sec codon. Readthrough of the {UAA} codon was effectively dependent on the Sec insertion machinery, therefore being highly selective for this gene and unlikely to generate off-target effects. In addition, we observed that expression of the corrector {tRNA}(Sec) stabilized the mutated {SEPN}1 transcript that was otherwise more subject to degradation. In conclusion, our data provide interesting evidence that premature termination of translation due to nonsense mutations is amenable to correction, in the context of the specialized selenoprotein synthesis mechanism.},
	pages = {237--244},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Rederstorff, M and Allamand, V and Guicheney, P and Gartioux, C and Richard, P and Chaigne, D and Krol, A and Lescure, A},
	date = {2008},
	pmid = {18025044},
	keywords = {Humans, {RNA}, *Codon, Amino Acid-Specific/*genetics, Codon/chemistry, Fibroblasts/metabolism, {HeLa} Cells, Muscle Proteins/biosynthesis/*deficiency/*genetics, Muscular Atrophy, Nonsense, Selenocysteine/metabolism, Selenoproteins/biosynthesis/*deficiency/*genetics, Spinal/*genetics/metabolism, Transfer, Transgenes}
}

@article{dunker_sequences_2011,
	title = {Sequences and topology: intrinsic disorder in the evolving universe of protein structure},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21530236},
	doi = {10.1016/j.sbi.2011.04.002},
	pages = {379--381},
	number = {3},
	journaltitle = {Curr Opin Struct Biol},
	author = {Dunker, A K and Gough, J},
	date = {2011},
	pmid = {21530236},
	keywords = {*Amino Acid Sequence, *Evolution, Models, Molecular, Protein Binding/physiology, Proteins/*chemistry/*metabolism}
}

@article{charlesworth_fundamental_2009,
	title = {Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19204717},
	doi = {10.1038/nrg2526},
	abstract = {The effective size of a population, N(e), determines the rate of change in the composition of a population caused by genetic drift, which is the random sampling of genetic variants in a finite population. N(e) is crucial in determining the level of variability in a population, and the effectiveness of selection relative to drift. This article reviews the properties of N(e) in a variety of different situations of biological interest, and the factors that influence it. In particular, the action of selection means that N(e) varies across the genome, and advances in genomic techniques are giving new insights into how selection shapes N(e).},
	pages = {195--205},
	number = {3},
	journaltitle = {Nat Rev Genet},
	author = {Charlesworth, B},
	date = {2009},
	pmid = {19204717},
	keywords = {Animals, Humans, *Evolution, *Genetic Drift, *Genetics, *Population Density, Genetic Variation, Molecular, Population}
}

@article{kunarso_detailed_2008,
	title = {Detailed characterization of the mouse embryonic stem cell transcriptome reveals novel genes and intergenic splicing associated with pluripotency},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18400104},
	doi = {10.1186/1471-2164-9-155},
	abstract = {{BACKGROUND}: Transcriptional control of embryonic stem ({ES}) cell pluripotency has been a subject of intense study. Transcriptional regulators including Oct4 (Oct3/4 index), Sox2 and Nanog are fundamental for maintaining the undifferentiated state. However, the {ES} cell transcriptome is not limited to their targets, and exhibits considerable complexity when assayed with microarray, {MPSS}, {cDNA}/{EST} sequencing, and {SAGE} technologies. To identify novel genes associated with pluripotency, we globally searched for {ES} transcripts not corresponding to known genes, validated their sequences, determined their expression profiles, and employed {RNAi} to test their function. {RESULTS}: Gene Identification Signature ({GIS}) analysis, a {SAGE} derivative distinguished by paired 5' and 3' transcript end tags, identified 153 candidate novel transcriptional units ({TUs}) distinct from known genes in a mouse E14 {ES} {mRNA} library. We focused on 16 {TUs} free of artefacts and mapping discrepancies, five of which were validated by {RTPCR} product sequencing. Two of the {TUs} were revealed by annotation to represent novel protein-coding genes: a {PRY}-domain cluster member and a {KRAB}-domain zinc finger. The other three {TUs} represented intergenic splicing events involving adjacent, functionally unrelated protein-coding genes transcribed in the same orientation, with one event potentially encoding a fusion protein containing domains from both component genes (Clk2 and Scamp3). Expression profiling using embryonic samples and adult tissue panels confirmed that three of the {TUs} were unique to or most highly expressed in {ES} cells. Expression levels of all five {TUs} dropped dramatically during three distinct chemically induced differentiation treatments of {ES} cells in culture. However, {siRNA} knockdowns of the {TUs} did not alter {mRNA} levels of pluripotency or differentiation markers, and did not affect cell morphology. {CONCLUSION}: Transcriptome libraries retain considerable potential for novel gene discovery despite massive recent {cDNA} and {EST} sequencing efforts; {cDNA} and {EST} evidence for these {ES} cell {TUs} had been limited or absent. {RTPCR} and full-length sequencing remain essential in resolving the bottleneck between numerous candidate novel transcripts inferred from high-throughput sequencing and the small fraction that can be validated. {RNAi} results indicate that, despite their strong association with pluripotency, these five transcriptomic novelties may not be required for maintaining it.},
	pages = {155},
	journaltitle = {{BMC} Genomics},
	author = {Kunarso, G and Wong, K Y and Stanton, L W and Lipovich, L},
	date = {2008},
	pmid = {18400104},
	keywords = {{DNA}, Sequence Analysis, Animals, Genetic, Mice, Transcription, Transcription Factors/metabolism, *Gene Expression Profiling, *{RNA} Splicing, Embryonic Stem Cells/*metabolism, Pluripotent Stem Cells/*metabolism, {RNA} Interference}
}

@article{glazko_computational_2012,
	title = {Computational prediction of polycomb-associated long non-coding {RNAs}},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23028655},
	doi = {10.1371/journal.pone.0044878},
	abstract = {Among thousands of long non-coding {RNAs} ({lncRNAs}) only a small subset is functionally characterized and the functional annotation of {lncRNAs} on the genomic scale remains inadequate. In this study we computationally characterized two functionally different parts of human {lncRNAs} transcriptome based on their ability to bind the polycomb repressive complex, {PRC}2. This classification is enabled by the fact that while all {lncRNAs} constitute a diverse set of sequences, the classes of {PRC}2-binding and {PRC}2 non-binding {lncRNAs} possess characteristic combinations of sequence-structure patterns and, therefore, can be separated within the feature space. Based on the specific combination of features, we built several machine-learning classifiers and identified the {SVM}-based classifier as the best performing. We further showed that the {SVM}-based classifier is able to generalize on the independent data sets. We observed that this classifier, trained on the human {lncRNAs}, can predict up to 59.4\% of {PRC}2-binding {lncRNAs} in mice. This suggests that, despite the low degree of sequence conservation, many {lncRNAs} play functionally conserved biological roles.},
	pages = {e44878},
	number = {9},
	journaltitle = {{PLoS} One},
	author = {Glazko, G V and Zybailov, B L and Rogozin, I B},
	date = {2012},
	pmid = {23028655},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Binding Sites, *Computational Biology, Antisense/genetics/metabolism, Chromatin/genetics/metabolism, Double-Stranded/genetics/metabolism, Long Untranslated/genetics/*metabolism, Molecular Sequence Data, Polycomb Repressive Complex 2/*metabolism}
}

@article{park_aberrant_2004,
	title = {Aberrant methylation of integrin alpha4 gene in human gastric cancer cells},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14990990},
	doi = {10.1038/sj.onc.1207470},
	abstract = {Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been explored. In the present study, we found that the integrin alpha4 expression is lost in human gastric cancer cell lines and that this is recovered by treatment with {DNA} methyltransferase inhibitor, implying transcriptional silencing by {DNA} methylation. Methylation-specific {PCR} ({MSP}) and bisulfite genomic {DNA} sequencing demonstrated the {CpG} methylation-dependent silencing of integrin alpha4 expression in eight of nine (88.8\%) gastric cancer cell lines and in 84.7\% of 46 primary tumors. We also investigated whether the restoration of integrin alpha4 in integrin alpha4-inactivated cells affects their ability to invade extracellular matrix, using matrigel assays. Interestingly, integrin alpha4-stable transfectants had markedly less invasive ability than the parental cells. Taken together, these results suggest that the transcriptional repression of the integrin alpha4 gene is caused by aberrant {DNA} methylation, and that this may play an important role in human gastric carcinogenesis.},
	pages = {3474--3480},
	number = {19},
	journaltitle = {Oncogene},
	author = {Park, J and Song, S H and Kim, T Y and Choi, M C and Jong, H S and Lee, J W and Kim, N K and Kim, W H and Bang, Y J},
	date = {2004},
	pmid = {14990990},
	keywords = {Humans, *{DNA} Methylation, Cell Line, {CpG} Islands, Integrin alpha4/*genetics, Neoplasm Invasiveness, Stomach Neoplasms/etiology/*genetics/pathology, Tumor}
}

@article{alexandrov_deciphering_2013,
	title = {Deciphering signatures of mutational processes operative in human cancer},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23318258},
	doi = {10.1016/j.celrep.2012.12.008},
	abstract = {The genome of a cancer cell carries somatic mutations that are the cumulative consequences of the {DNA} damage and repair processes operative during the cellular lineage between the fertilized egg and the cancer cell. Remarkably, these mutational processes are poorly characterized. Global sequencing initiatives are yielding catalogs of somatic mutations from thousands of cancers, thus providing the unique opportunity to decipher the signatures of mutational processes operative in human cancer. However, until now there have been no theoretical models describing the signatures of mutational processes operative in cancer genomes and no systematic computational approaches are available to decipher these mutational signatures. Here, by modeling mutational processes as a blind source separation problem, we introduce a computational framework that effectively addresses these questions. Our approach provides a basis for characterizing mutational signatures from cancer-derived somatic mutational catalogs, paving the way to insights into the pathogenetic mechanism underlying all cancers.},
	pages = {246--259},
	number = {1},
	journaltitle = {Cell Rep},
	author = {Alexandrov, L B and Nik-Zainal, S and Wedge, D C and Campbell, P J and Stratton, M R},
	date = {2013},
	pmid = {23318258},
	keywords = {{DNA}, Sequence Analysis, Base Sequence, Genetic, Genome, Humans, Breast Neoplasms/genetics, Exome/genetics, Female, Human/genetics, Models, Molecular Sequence Data, Mutation/*genetics, Neoplasms/*genetics}
}

@article{s_effectiveness_2014,
	title = {Effectiveness of permethrin-treated clothing to prevent tick exposure in foresters in the central Appalachian region of the {USA}},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25290464},
	doi = {10.1080/09603123.2014.963033},
	abstract = {Outdoor workers are at risk from mosquito and tick bites and the extent to which exposures are linked to vector-borne disease is not understood. This pilot study characterizes for ester exposure to mosquitoes and ticks, and assesses effectiveness of permethrin-treated clothing for prevention of tick bites. Foresters (N = 34) from Kentucky, North Carolina, Ohio, Tennessee, Virginia, and West Virginia were placed into treatment (permethrin-treated clothing) or control (untreated clothing) groups. Foresters completed questionnaires about work-related tick/mosquito exposure and 454 ticks were collected/identified from May to June 2013. A time-weighted analysis based on information submitted by foresters about time working outdoors showed that control participants received a lower rate of tick exposure (0.15 tick bites/hour; 13 bites/person) compared to treatment participants (0.27 bites/hour; 21 bites/person). However, more control participants (85 \%) received at least one tick bite compared to treatment participants (52 \%). Outdoor workers should be aware of available protective measures, such as permethrin-treated clothing, that may mitigate occupational risks.},
	pages = {1--10},
	journaltitle = {Int J Environ Health Res},
	author = {S, L Richards and {JA}, G Balanay and J, W Harris},
	date = {2014},
	pmid = {25290464}
}

@article{peters_reduced_2004,
	title = {Reduced field of view and undersampled {PR} combined for interventional imaging of a fully dynamic field of view},
	volume = {51},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15065249},
	doi = {10.1002/mrm.20037},
	abstract = {Active catheter imaging was investigated using real-time undersampled projection reconstruction ({PR}) combined with the temporal filtering technique of reduced field of view ({rFOV}). Real-time {rFOV} processing was interactively enabled during highly undersampled catheter imaging, resulting in improved artifact suppression with better temporal resolution than that obtained by view-sharing. Imaging with 64 to 32 projections provided a resolution of 2 x 2 x 8 mm, and four to eight true frames per second. Image artifacts were reduced when {rFOV} processing was applied to the undersampled images. A comparison with Cartesian {rFOV} showed that {PR} image quality is less susceptible to aliasing that results from {rFOV} imaging with a wholly dynamic outer {FOV}. Simulations and {MRI} experiments demonstrated that {PR} {rFOV} provides significant artifact suppression, even for a fully dynamic {FOV}. The near doubling of temporal resolution that is possible with {PR} {rFOV} permits accurate monitoring of highly dynamic events, such as catheter movements, and arrhythmias, such as ventricular ectopy.},
	pages = {761--767},
	number = {4},
	journaltitle = {Magn Reson Med},
	author = {Peters, D C and Guttman, M A and Dick, A J and Raman, V K and Lederman, R J and {McVeigh}, E R},
	date = {2004},
	pmid = {15065249},
	keywords = {Animals, Aorta/pathology, Arrhythmias, Artifacts, Cardiac Catheterization/*methods, Cardiac/diagnosis, Computer-Assisted/methods, Heart Ventricles/pathology, Image Enhancement/*methods, Image Processing, Imaging, Interventional/*methods, Magnetic Resonance Imaging/*methods, Phantoms, Radiology, Swine, Ventricular Premature Complexes/diagnosis}
}

@article{tripathi_long_2013,
	title = {Long noncoding {RNA} {MALAT}1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-{MYB}},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23555285},
	doi = {10.1371/journal.pgen.1003368},
	abstract = {The long noncoding {MALAT}1 {RNA} is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that {MALAT}1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that {MALAT}1 modulates the expression of cell cycle genes and is required for G1/S and mitotic progression. Depletion of {MALAT}1 leads to activation of p53 and its target genes. The cell cycle defects observed in {MALAT}1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of {MALAT}1 activity. Furthermore, {MALAT}1-depleted cells display reduced expression of B-{MYB} (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-{MYB} pre-{mRNA} and aberrant alternative splicing. In human cells, {MALAT}1 promotes cellular proliferation by modulating the expression and/or pre-{mRNA} processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of {MALAT}1 in regulating cellular proliferation.},
	pages = {e1003368},
	number = {3},
	journaltitle = {{PLoS} Genet},
	author = {Tripathi, V and Shen, Z and Chakraborty, A and Giri, S and Freier, S M and Wu, X and Zhang, Y and Gorospe, M and Prasanth, S G and Lal, A and Prasanth, K V},
	date = {2013},
	pmid = {23555285},
	keywords = {Humans, Gene Expression Regulation, Oligonucleotide Array Sequence Analysis, *Neoplasms/genetics/metabolism, *{RNA}, Alternative Splicing, Cell Cycle Checkpoints/*genetics, Cell Cycle Proteins/*metabolism, Cell Proliferation, Long Noncoding/genetics/metabolism, Neoplastic, {RNA} Precursors/genetics/metabolism, Trans-Activators/*metabolism, Transcriptional Activation, Tumor Suppressor Protein p53/genetics/metabolism}
}

@article{doolittle_sixty_2013,
	title = {Sixty years of genome biology},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23651518},
	doi = {10.1186/gb-2013-14-4-113},
	abstract = {Sixty years after Watson and Crick published the double helix model of {DNA}'s structure, thirteen members of Genome Biology's Editorial Board select key advances in the field of genome biology subsequent to that discovery.},
	pages = {113},
	number = {4},
	journaltitle = {Genome Biol},
	author = {Doolittle, W F and Fraser, P and Gerstein, M B and Graveley, B R and Henikoff, S and Huttenhower, C and Oshlack, A and Ponting, C P and Rinn, J L and Schatz, M C and Ule, J and Weigel, D and Weinstock, G M},
	date = {2013},
	pmid = {23651518}
}

@article{velpula_proliposome_2013,
	title = {Proliposome powders for enhanced intestinal absorption and bioavailability of raloxifene hydrochloride: effect of surface charge},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22458264},
	doi = {10.3109/03639045.2012.670641},
	abstract = {The primary goal of the present study was to investigate the combined prospective of proliposomes and surface charge for the improved oral delivery of raloxifene hydrochloride ({RXH}). Keeping this objective, the present systematic study was focused to formulate proliposomes by varying the ratio of hydrogenated soyphosphatidylcholine and cholesterol. Furthermore, to assess the role of surface charge on improved absorption of {RXH}, anionic and cationic vesicles were prepared using dicetyl phosphate and stearylamine, respectively. The formulations were characterized for size, zeta potential and entrapment efficiency. The improved dissolution characteristics assessed from dissolution efficiency, mean dissolution rate were higher for proliposome formulations. The solid state characterization studies indicate the transformation of native crystalline form of the drug to amorphous and/or molecular state. The higher effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of proliposomes and cationic surface charge for augment in absorption across gastro intestinal barrier. To draw the conclusions, in vivo pharmacokinetic study carried out in rats indicate a threefold enhancement in the rate and extent of absorption of {RXH} from cationic proliposome formulation which unfurl the potential of proliposomes and role of cationic charge for improved oral delivery of {RXH}.},
	pages = {1895--1906},
	number = {12},
	journaltitle = {Drug Dev Ind Pharm},
	author = {Velpula, A and Jukanti, R and Janga, K Y and Sunkavalli, S and Bandari, S and Kandadi, P and Veerareddy, P R},
	date = {2013},
	pmid = {22458264}
}

@article{olanow_levodopa_2004,
	title = {Levodopa in the treatment of Parkinson's disease: current controversies},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15372588},
	doi = {10.1002/mds.20243},
	abstract = {Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease ({PD}) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in {PD} where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in {PD}. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in {MPTP} monkeys and {PD} patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.},
	pages = {997--1005},
	number = {9},
	journaltitle = {Mov Disord},
	author = {Olanow, C W and Agid, Y and Mizuno, Y and Albanese, A and Bonuccelli, U and Damier, P and De Yebenes, J and Gershanik, O and Guttman, M and Grandas, F and Hallett, M and Hornykiewicz, O and Jenner, P and Katzenschlager, R and Langston, W J and {LeWitt}, P and Melamed, E and Mena, M A and Michel, P P and Mytilineou, C and Obeso, J A and Poewe, W and Quinn, N and Raisman-Vozari, R and Rajput, A H and Rascol, O and Sampaio, C and Stocchi, F},
	date = {2004},
	pmid = {15372588},
	keywords = {Humans, Antiparkinson Agents/*adverse effects/pharmacokine, Corpus Striatum/drug effects/metabolism, Dopamine/drug effects/metabolism, Drug-Induced/etiology, Dyskinesia, Levodopa/*adverse effects/pharmacokinetics/therape, Parkinson Disease/*drug therapy, Receptors}
}

@article{lipovich_novel_2003,
	title = {Novel transcriptional units and unconventional gene pairs in the human genome: toward a sequence-level basis for primate-specific phenotypes?},
	volume = {68},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15338649},
	pages = {461--470},
	journaltitle = {Cold Spring Harb Symp Quant Biol},
	author = {Lipovich, L and King, M C},
	date = {2003},
	pmid = {15338649},
	keywords = {Human, {DNA}, Animals, Genetic, Humans, Mice, Promoter Regions, *Genome, *Transcription, Nucleic Acid, Chromosome Mapping, Chromosomes, Complementary/genetics, Expressed Sequence Tags, Multigene Family, Pair 22/genetics, Pair 5/genetics, Phenotype, Primates/genetics, Repetitive Sequences, Species Specificity}
}

@article{garber_high-throughput_2012,
	title = {A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals},
	volume = {47},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22940246},
	doi = {10.1016/j.molcel.2012.07.030},
	abstract = {Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors ({TF}) to {DNA}. Here, we develop a high-throughput Chromatin {ImmunoPrecipitation} ({HT}-{ChIP}) method to systematically map protein-{DNA} interactions. {HT}-{ChIP} was applied to define the dynamics of {DNA} binding by 25 {TFs} and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 {TF}-{DNA} interactions we find that {TFs} vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby {TF} networks are hierarchically organized into cell differentiation factors, factors that bind targets prior to stimulus to prime them for induction, and factors that regulate specific gene programs. Overlaying {HT}-{ChIP} data on gene-expression dynamics shows that many {TF}-{DNA} interactions are established prior to the stimuli, predominantly at immediate-early genes, and identified specific {TF} ensembles that coordinately regulate gene-induction.},
	pages = {810--822},
	number = {5},
	journaltitle = {Mol Cell},
	author = {Garber, M and Yosef, N and Goren, A and Raychowdhury, R and Thielke, A and Guttman, M and Robinson, J and Minie, B and Chevrier, N and Itzhaki, Z and Blecher-Gonen, R and Bornstein, C and Amann-Zalcenstein, D and Weiner, A and Friedrich, D and Meldrim, J and Ram, O and Cheng, C and Gnirke, A and Fisher, S and Friedman, N and Wong, B and Bernstein, B E and Nusbaum, C and Hacohen, N and Regev, A and Amit, I},
	date = {2012},
	pmid = {22940246},
	keywords = {Animals, Mice, Transcription Factors/metabolism, *Gene Expression Regulation, *High-Throughput Screening Assays, Chromatin Immunoprecipitation/*methods, Dendritic Cells/*metabolism, {DNA}/genetics/metabolism}
}

@article{beccari_sequences_1986,
	title = {Sequences coding for the ribosomal protein L14 in Xenopus laevis and Xenopus tropicalis; homologies in the 5' untranslated region are shared with other r-protein {mRNAs}},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3774540},
	abstract = {In the haploid genome of Xenopus laevis there are two genes coding for the r-protein L14. It is not known if they are located on the same chromosome. {cDNA} clones deriving from the transcripts of the two genes have been isolated from an oocyte messenger {cDNA} bank showing that they are both expressed. We have studied the structure of one of the L14 genes by Electron Microscopy, restriction mapping and sequencing. An allelic form of the L14 gene was also isolated. It contains a large deletion covering the 5' end region up to the middle of the third intron. The 5' end of the X. laevis L14 gene was compared to that of the corresponding gene in the closely related species X. tropicalis and found to be highly conserved. The L14 gene has multiple initiation sites, but the large majority of the transcripts start in the middle of a pyrimidine tract not preceded by a canonical {TATA} box as in other eukaryotic housekeeping genes. The X. laevis L1 and L14 genes have a common decanucleotide in the first exon in the same position with regard to the initiator {ATG} which just precedes the first intron. The decanucleotide shows homology with the X. laevis 18S {rRNA}.},
	pages = {7633--7646},
	number = {19},
	journaltitle = {Nucleic Acids Res},
	author = {Beccari, E and Mazzetti, P and Mileo, A and Bozzoni, I and Pierandrei-Amaldi, P and Amaldi, F},
	date = {1986},
	pmid = {3774540},
	keywords = {Animals, Genetic, {RNA}, Transcription, Nucleic Acid, *Base Sequence, *Sequence Homology, Amino Acid Sequence, Biological Evolution, {DNA}/isolation \& purification, Electron, Messenger/*analysis, Microscopy, Nucleotide Mapping, Ribosomal Proteins/analysis/*genetics, Xenopus laevis/*genetics, Xenopus/*genetics}
}

@article{lal_p16ink4a_2008,
	title = {p16({INK}4a) translation suppressed by {miR}-24},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18365017},
	doi = {10.1371/journal.pone.0001864},
	abstract = {{BACKGROUND}: Expression of the tumor suppressor p16({INK}4a) increases during aging and replicative senescence. {METHODOLOGY}/{PRINCIPAL} {FINDINGS}: Here, we report that the {microRNA} {miR}-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of {miR}-24, a {microRNA} that was predicted to associate with the p16 {mRNA} coding and 3'-untranslated regions. Ectopic {miR}-24 overexpression reduced p16 protein but not p16 {mRNA} levels. Conversely, introduction of antisense ({AS})-{miR}-24 blocked {miR}-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of {EGFP}-p16 reporter bearing the {miR}-24 target recognition sites. {CONCLUSIONS}/{SIGNIFICANCE}: Together, our results suggest that {miR}-24 represses the initiation and elongation phases of p16 translation.},
	pages = {e1864},
	number = {3},
	journaltitle = {{PLoS} One},
	author = {Lal, A and Kim, H H and Abdelmohsen, K and Kuwano, Y and Pullmann Jr., R and Srikantan, S and Subrahmanyam, R and Martindale, J L and Yang, X and Ahmed, F and Navarro, F and Dykxhoorn, D and Lieberman, J and Gorospe, M},
	date = {2008},
	pmid = {18365017},
	keywords = {Base Sequence, Humans, *Protein Biosynthesis, Cyclin-Dependent Kinase Inhibitor p16/*genetics, {DNA} Primers, {HeLa} Cells, {MicroRNAs}/*physiology, Mutagenesis, Site-Directed}
}

@article{marasa_microrna_2010,
	title = {{MicroRNA} profiling in human diploid fibroblasts uncovers {miR}-519 role in replicative senescence},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20606251},
	abstract = {{MicroRNAs} ({miRNAs}) are short non-coding {RNAs} that regulate diverse biological processes by controlling the pattern of expressed proteins. In mammalian cells, {miRNAs} partially complement their target sequences leading to {mRNA} degradation and/or decreased {mRNA} translation. Here, we have analyzed transcriptome-wide changes in {miRNAs} in senescent relative to early-passage {WI}-38 human diploid fibroblasts ({HDFs}). Among the {miRNAs} downregulated with senescence were members of the let-7 family, while upregulated {miRNAs} included {miR}-1204, {miR}-663 and {miR}-519. {miR}-519 was recently found to reduce tumor growth at least in part by lowering the abundance of the {RNA}-binding protein {HuR}. Overexpression of {miR}-519a in either {WI}-38 or human cervical carcinoma {HeLa} cells triggered senescence, as measured by monitoring beta-galactosidase activity and other senescence markers. These data suggest that {miR}-519 can suppress tumor growth by triggering senescence and that {miR}-519 elicits these actions by repressing {HuR} expression.},
	pages = {333--343},
	number = {6},
	journaltitle = {Aging (Albany {NY})},
	author = {Marasa, B S and Srikantan, S and Martindale, J L and Kim, M M and Lee, E K and Gorospe, M and Abdelmohsen, K},
	date = {2010},
	pmid = {20606251},
	keywords = {Humans, *Gene Expression Profiling, Blotting, Cell Aging/*genetics, Cell Line, Diploidy, Fibroblasts/*metabolism, {HeLa} Cells, {MicroRNAs}/*genetics/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Western}
}

@article{hawkins_transcriptional_2010,
	title = {Transcriptional regulation of Oct4 by a long non-coding {RNA} antisense to Oct4-pseudogene 5},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21151833},
	doi = {10.4161/trns.1.3.13332},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) have been shown to epigenetically regulate certain genes in human cells. Here we report evidence for the involvement of an antisense {lncRNA} in the transcriptional regulation of the pluripotency-associated factor Oct4. When an {lncRNA} antisense to Oct4-pseudogene 5 was suppressed, transcription of Oct4 and Oct4 pseudogenes 4 and 5 was observed to increase. This increase correlated with a loss of silent state epigenetic marks and the histone methyltransferase Ezh2 at the Oct4 promoter. We observed this {lncRNA} to interact with nucleolin and {PURA}, a 35 {kD} single-stranded {DNA} and {RNA} binding protein, and found that these proteins may act to negatively regulate this antisense transcript.},
	pages = {165--175},
	number = {3},
	journaltitle = {Transcription},
	author = {Hawkins, P G and Morris, K V},
	date = {2010},
	pmid = {21151833}
}

@article{mazan-mamczarz_en_2005,
	title = {En masse analysis of nascent translation using microarrays},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16060370},
	abstract = {We report a robust method for studying en masse changes in translation using {cDNA} arrays. The relative distribution of messenger {RNAs} ({mRNAs}) along polysome gradients was monitored by performing {cDNA} array analysis of each gradient fraction and quantifying the {mRNA} translational status by regression analysis. Using this strategy to study human carcinoma cells exposed to short-wavelength ultraviolet light ({UVC}), we identified a subset of 17 translationally induced {mRNAs} and a subset of 69 translationally repressed {mRNAs} following {UVC} irradiation. We describe an effective approach for globally investigating changes in protein biosynthesis.},
	pages = {61--62,64,66--67},
	number = {1},
	journaltitle = {Biotechniques},
	author = {Mazan-Mamczarz, K and Kawai, T and Martindale, J L and Gorospe, M},
	date = {2005},
	pmid = {16060370},
	keywords = {Gene Expression Profiling/*methods, Humans, Gene Expression Regulation, Cell Line, Colorectal Neoplasms/*metabolism, Neoplasm Proteins/*metabolism, Neoplastic, Oligonucleotide Array Sequence Analysis/*methods, Protein Biosynthesis/*physiology, Protein Modification, Proteome/genetics/*metabolism, Radiation Dosage, Translational/*physiology, Tumor, Ultraviolet Rays}
}

@article{mcveigh_real-time_2005,
	title = {Real-time, Interactive {MRI} for cardiovascular interventions},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16112512},
	doi = {10.1016/j.acra.2005.05.024},
	pages = {1121--1127},
	number = {9},
	journaltitle = {Acad Radiol},
	author = {{McVeigh}, E R and Guttman, M A and Kellman, P and Raval, A N and Lederman, R J},
	date = {2005},
	pmid = {16112512},
	keywords = {Animals, Humans, Cardiovascular Diseases/*therapy, Magnetic Resonance Imaging/instrumentation/*method}
}

@article{johnson_neurodegeneration_2012,
	title = {Neurodegeneration as an {RNA} disorder},
	volume = {99},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23063563},
	doi = {10.1016/j.pneurobio.2012.09.006},
	abstract = {Neurodegenerative diseases constitute one of the single most important public health challenges of the coming decades, and yet we presently have only a limited understanding of the underlying genetic, cellular and molecular causes. As a result, no effective disease-modifying therapies are currently available, and no method exists to allow detection at early disease stages, and as a result diagnoses are only made decades after disease pathogenesis, by which time the majority of physical damage has already occurred. Since the sequencing of the human genome, we have come to appreciate that the transcriptional output of the human genome is extremely rich in non-protein coding {RNAs} ({ncRNAs}). This heterogeneous class of transcripts is widely expressed in the nervous system, and is likely to play many crucial roles in the development and functioning of this organ. Most exciting, evidence has recently been presented that {ncRNAs} play central, but hitherto unappreciated roles in neurodegenerative processes. Here, we review the diverse available evidence demonstrating involvement of {ncRNAs} in neurodegenerative diseases, and discuss their possible implications in the development of therapies and biomarkers for these conditions.},
	pages = {293--315},
	number = {3},
	journaltitle = {Prog Neurobiol},
	author = {Johnson, R and Noble, W and Tartaglia, G G and Buckley, N J},
	date = {2012},
	pmid = {23063563},
	keywords = {Animals, Humans, {RNA}, Transcription, Gene Expression Regulation/genetics, Genetic/*genetics, {MicroRNAs}/genetics/metabolism, Neurodegenerative Diseases/*genetics/metabolism/ph, Trinucleotide Repeats/genetics, Untranslated/*genetics/physiology}
}

@article{ravina_role_2005,
	title = {The role of radiotracer imaging in Parkinson disease},
	volume = {64},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15668415},
	doi = {10.1212/01.WNL.0000149403.14458.7F},
	abstract = {Radiotracer imaging ({RTI}) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease ({PD}). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in {PD}: [18F]fluorodopa {PET}, (+)-[11C]dihydrotetrabenazine {PET}, [123I]beta-{CIT} {SPECT}, and [18F]fluorodeoxyglucose {PET}. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by {RTI} to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.},
	pages = {208--215},
	number = {2},
	journaltitle = {Neurology},
	author = {Ravina, B and Eidelberg, D and Ahlskog, J E and Albin, R L and Brooks, D J and Carbon, M and Dhawan, V and Feigin, A and Fahn, S and Guttman, M and Gwinn-Hardy, K and {McFarland}, H and Innis, R and Katz, R G and Kieburtz, K and Kish, S J and Lange, N and Langston, J W and Marek, K and Morin, L and Moy, C and Murphy, D and Oertel, W H and Oliver, G and Palesch, Y and Powers, W and Seibyl, J and Sethi, K D and Shults, C W and Sheehy, P and Stoessl, A J and Holloway, R},
	date = {2005},
	pmid = {15668415},
	keywords = {Humans, Biological Markers, Biotransformation, Blood-Brain Barrier, Carbon Radioisotopes/diagnostic use/pharmacokineti, Clinical Trials as Topic/methods, Cocaine/analogs \& derivatives/diagnostic use/pharm, Corpus Striatum/metabolism/*radionuclide imaging, Dihydroxyphenylalanine/analogs \& derivatives/diagn, Dopamine/metabolism, Emission-Computed, Fluorine Radioisotopes/diagnostic use/pharmacokine, Fluorodeoxyglucose F18/diagnostic use/pharmacokine, Forecasting, Iodine Radioisotopes/diagnostic use/pharmacokineti, Neurons/chemistry/radionuclide imaging, Parkinson Disease/diagnosis/*radionuclide imaging/, Positron-Emission Tomography, Prognosis, Radiopharmaceuticals/*diagnostic use/pharmacokinet, Receptors, Single-Photon, Substantia Nigra/metabolism/*radionuclide imaging, Tetrabenazine/analogs \& derivatives/diagnostic use, Tomography}
}

@article{lin_down-regulation_2000,
	title = {Down-regulation of cyclin D1 expression by prostaglandin A(2) is mediated by enhanced cyclin D1 {mRNA} turnover},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11027261},
	abstract = {Prostaglandin A(2) ({PGA}(2)), an experimental chemotherapeutic agent, causes growth arrest associated with decreased cyclin D1 expression in several cancer cell lines. Here, using human non-small-cell lung carcinoma H1299 cells, we investigated the mechanisms whereby {PGA}(2) down-regulates cyclin D1 expression. Transcription rates of the cyclin D1 gene, studied using a cyclin D1 promoter-luciferase construct and nuclear run-on assays, were not affected by {PGA}(2) treatment. Instead, the cyclin D1 {mRNA} was rendered unstable after exposure to {PGA}(2). Since the stability of labile {mRNA} is modulated through binding of proteins to specific {mRNA} sequences, we sought to identify protein(s) recognizing the cyclin D1 {mRNA}. In electrophoretic mobility-shift assays using radiolabeled {RNA} probes derived from different regions of cyclin D1 {mRNA}, we observed that (i) lysates prepared from {PGA}(2)-treated cells exhibited enhanced protein-cyclin D1 {RNA} complex formation; (ii) the kinetics of complex formation correlated closely with that of cyclin D1 {mRNA} loss; and (iii) binding occurred within a 390-base cyclin D1 3' untranslated region ({UTR}) (K12). This binding activity could be cross-linked, revealing proteins ranging from 30 to 47 {kDa}. The {RNA}-binding protein {AUF}1, previously associated with the degradation of target {mRNAs}, bound cyclin D1 {mRNA}, because anti-{AUF}1 antibodies were capable of supershifting or immunoprecipitating cyclin D1 {mRNA}-protein complexes. Finally, insertion of K12 in the 3'{UTR} of reporter genes markedly reduced the expression and half-life of the resulting chimeric {mRNAs} in transfected, {PGA}(2)-treated cells. Our data demonstrate that {PGA}(2) down-regulates cyclin D1 expression by decreasing cyclin D1 {mRNA} stability and implicates a 390-base element in the 3'{UTR} in this regulation.},
	pages = {7903--7913},
	number = {21},
	journaltitle = {Mol Cell Biol},
	author = {Lin, S and Wang, W and Wilson, G M and Yang, X and Brewer, G and Holbrook, N J and Gorospe, M},
	date = {2000},
	pmid = {11027261},
	keywords = {3' Untranslated Regions, Genetic, Humans, Promoter Regions, {RNA}, Transcription, Protein Binding, Cultured, *Down-Regulation, *Heterogeneous-Nuclear Ribonucleoprotein D, Blotting, Cell Division/drug effects, Cell Nucleus/metabolism, Cross-Linking Reagents/pharmacology, Cyclin D1/*genetics/*metabolism, Cytoplasm/metabolism, Dose-Response Relationship, Drug, Genes, Kinetics, Messenger/*metabolism, Models, Northern, Precipitin Tests, Prostaglandins A/genetics/*metabolism, Reporter, {RNA}-Binding Proteins/genetics/metabolism, {RNA}/metabolism, Subcellular Fractions, Time Factors, Transcriptional Activation, Transfection, Tumor Cells, Western}
}

@article{xiao_chromosomal_2013,
	title = {Chromosomal deletions and inversions mediated by {TALENs} and {CRISPR}/Cas in zebrafish},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23748566},
	doi = {10.1093/nar/gkt464},
	abstract = {Customized {TALENs} and Cas9/{gRNAs} have been used for targeted mutagenesis in zebrafish to induce indels into protein-coding genes. However, indels are usually not sufficient to disrupt the function of non-coding genes, gene clusters or regulatory sequences, whereas large genomic deletions or inversions are more desirable for this purpose. By injecting two pairs of {TALEN} {mRNAs} or two {gRNAs} together with Cas9 {mRNA} targeting distal {DNA} sites of the same chromosome, we obtained predictable genomic deletions or inversions with sizes ranging from several hundred bases to nearly 1 Mb. We have successfully achieved this type of modifications for 11 chromosomal loci by {TALENs} and 2 by Cas9/{gRNAs} with different combinations of {gRNA} pairs, including clusters of {miRNA} and protein-coding genes. Seven of eight {TALEN}-targeted lines transmitted the deletions and one transmitted the inversion through germ line. Our findings indicate that both {TALENs} and Cas9/{gRNAs} can be used as an efficient tool to engineer genomes to achieve large deletions or inversions, including fragments covering multiple genes and non-coding sequences. To facilitate the analyses and application of existing {ZFN}, {TALEN} and {CRISPR}/Cas data, we have updated our {EENdb} database to provide a chromosomal view of all reported engineered endonucleases targeting human and zebrafish genomes.},
	pages = {e141},
	number = {14},
	journaltitle = {Nucleic Acids Res},
	author = {Xiao, A and Wang, Z and Hu, Y and Wu, Y and Luo, Z and Yang, Z and Zu, Y and Li, W and Huang, P and Tong, X and Zhu, Z and Lin, S and Zhang, B},
	date = {2013},
	pmid = {23748566},
	keywords = {Animals, Genetic, Genome, {RNA}, Proteins/genetics, Databases, *Chromosome Deletion, *Chromosome Inversion, *Inverted Repeat Sequences, Endodeoxyribonucleases/*metabolism, Genetic Engineering/methods, Genetic Loci, Guide/chemistry, {MicroRNAs}/genetics, Zebrafish/*genetics}
}

@article{yu_chk2-dependent_2011,
	title = {Chk2-dependent {HuR} phosphorylation regulates occludin {mRNA} translation and epithelial barrier function},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21745814},
	doi = {10.1093/nar/gkr567},
	abstract = {Occludin is a transmembrane tight junction ({TJ}) protein that plays an important role in {TJ} assembly and regulation of the epithelial barrier function, but the mechanisms underlying its post-transcriptional regulation are unknown. The {RNA}-binding protein {HuR} modulates the stability and translation of many target {mRNAs}. Here, we investigated the role of {HuR} in the regulation of occludin expression and therefore in the intestinal epithelial barrier function. {HuR} bound the 3'-untranslated region of the occludin {mRNA} and enhanced occludin translation. {HuR} association with the occludin {mRNA} depended on Chk2-dependent {HuR} phosphorylation. Reduced {HuR} phosphorylation by Chk2 silencing or by reduction of Chk2 through polyamine depletion decreased {HuR}-binding to the occludin {mRNA} and repressed occludin translation, whereas Chk2 overexpression enhanced ({HuR}/occludin {mRNA}) association and stimulated occludin expression. In mice exposed to septic stress induced by cecal ligation and puncture, Chk2 levels in the intestinal mucosa decreased, associated with an inhibition of occludin expression and gut barrier dysfunction. These results indicate that {HuR} regulates occludin {mRNA} translation through Chk2-dependent {HuR} phosphorylation and that this influence is crucial for maintenance of the epithelial barrier integrity in the intestinal tract.},
	pages = {8472--8487},
	number = {19},
	journaltitle = {Nucleic Acids Res},
	author = {Yu, T X and Wang, P Y and Rao, J N and Zou, T and Liu, L and Xiao, L and Gorospe, M and Wang, J Y},
	date = {2011},
	pmid = {21745814},
	keywords = {3' Untranslated Regions, Animals, Mice, {RNA}, Cells, Cultured, *Gene Expression Regulation, *Protein Biosynthesis, Cell Membrane Permeability, Checkpoint Kinase 2, Hu Paraneoplastic Encephalomyelitis Antigens/*meta, Intestinal Mucosa/*metabolism, Male, Membrane Proteins/biosynthesis/*genetics, Messenger/metabolism, Occludin, Phosphorylation, Polyamines/metabolism, Protein-Serine-Threonine Kinases/*metabolism, Rats, Sepsis/enzymology/genetics}
}

@article{nielsen_scan_2005,
	title = {A scan for positively selected genes in the genomes of humans and chimpanzees},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15869325},
	doi = {10.1371/journal.pbio.0030170},
	abstract = {Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of {DNA} sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.},
	pages = {e170},
	number = {6},
	journaltitle = {{PLoS} Biol},
	author = {Nielsen, R and Bustamante, C and Clark, A G and Glanowski, S and Sackton, T B and Hubisz, M J and Fledel-Alon, A and Tanenbaum, D M and Civello, D and White, T J and J, J Sninsky and Adams, M D and Cargill, M},
	date = {2005},
	pmid = {15869325},
	keywords = {Human, Animals, Genetic, Humans, *Genome, Evolution, Likelihood Functions, Molecular, Pan troglodytes/*genetics, Polymerase Chain Reaction, Selection, Zinc Fingers/genetics}
}

@article{srikantan_translational_2011,
	title = {Translational control of {TOP}2A influences doxorubicin efficacy},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21768308},
	doi = {10.1128/MCB.05639-11},
	abstract = {The cellular abundance of topoisomerase {IIalpha} ({TOP}2A) critically maintains {DNA} topology after replication and determines the efficacy of {TOP}2 inhibitors in chemotherapy. Here, we report that the {RNA}-binding protein {HuR}, commonly overexpressed in cancers, binds to the {TOP}2A 3'-untranslated region (3'{UTR}) and increases {TOP}2A translation. Reducing {HuR} levels triggered the recruitment of {TOP}2A transcripts to {RNA}-induced silencing complex ({RISC}) components and to cytoplasmic processing bodies. Using a novel {MS}2-tagged {RNA} precipitation method, we identified {microRNA} {miR}-548c-3p as a mediator of these effects and further uncovered that the interaction of {miR}-548c-3p with the {TOP}2A 3'{UTR} repressed {TOP}2A translation by antagonizing the action of {HuR}. Lowering {TOP}2A by silencing {HuR} or by overexpressing {miR}-548c-3p selectively decreased {DNA} damage after treatment with the chemotherapeutic agent doxorubicin. In sum, {HuR} enhances {TOP}2A translation by competing with {miR}-548c-3p; their combined actions control {TOP}2A expression levels and determine the effectiveness of doxorubicin.},
	pages = {3790--3801},
	number = {18},
	journaltitle = {Mol Cell Biol},
	author = {Srikantan, S and Abdelmohsen, K and Lee, E K and Tominaga, K and Subaran, S S and Kuwano, Y and Kulshrestha, R and Panchakshari, R and Kim, H H and Yang, X and Martindale, J L and Marasa, B S and Kim, M M and Wersto, R P and Indig, F E and Chowdhury, D and Gorospe, M},
	date = {2011},
	pmid = {21768308},
	keywords = {3' Untranslated Regions, Humans, {RNA}, Gene Expression Regulation, Antibiotics, Antigens, Antineoplastic/pharmacology, {DNA} Damage/drug effects, {DNA} Topoisomerases, {DNA}-Binding Proteins/biosynthesis/*genetics, {DNA}/metabolism, Doxorubicin/*pharmacology, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/genetics/metabolism, {MicroRNAs}/genetics/metabolism, Neoplasm/biosynthesis/*genetics, Protein Biosynthesis, {RNA} Interference, {RNA}-Binding Proteins/antagonists \& inhibitors/bios, {RNA}-Induced Silencing Complex/metabolism, Small Interfering, Surface/genetics/*metabolism, Type {II}/biosynthesis/*genetics}
}

@article{bourque_transposable_2009,
	title = {Transposable elements in gene regulation and in the evolution of vertebrate genomes},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19914058},
	doi = {10.1016/j.gde.2009.10.013},
	abstract = {Repetitive {DNA} and in particular transposable elements have been intimately linked to eukaryotic genomes for millions of years. Once overlooked for being only a collection of selfish debris and a nuisance for sequence assembly, genomic repeats are now being recognized as a key driving force in genome evolution. Indeed, by changing the {DNA} landscape of genomes, transposable elements have been a rich source of innovation in genes, regulatory elements and genome structures. In this review, I will focus on recent advances that demonstrate that genomic repeats have had a global impact on vertebrate gene regulatory networks. I will also summarize results that show how transposable elements have been a major catalyst of structural rearrangements throughout evolution.},
	pages = {607--612},
	number = {6},
	journaltitle = {Curr Opin Genet Dev},
	author = {Bourque, G},
	date = {2009},
	pmid = {19914058},
	keywords = {Animals, Genome, Humans, Gene Expression Regulation, *Genome, *{DNA} Transposable Elements, *Evolution, *Gene Expression Regulation, {DNA} Transposable Elements, Molecular, Vertebrates, Vertebrates/*genetics, Evolution, Molecular}
}

@article{sunkara_role_2014,
	title = {Role of coronary artery calcium in cardiovascular risk assessment},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24345092},
	doi = {10.1586/14779072.2014.868305},
	abstract = {Coronary artery disease ({CAD}) is associated with substantial morbidity and mortality worldwide. Despite many advances in prevention and therapy for {CAD}, a third to one-half of cardiovascular events occur in those with no prior symptoms. Assessing subclinical disease using coronary artery calcium ({CAC}) has been shown to provide additional risk stratification and to improve prediction of cardiovascular events over traditional strategies such as the Framingham Risk Score. In this review, we aim to cover the current data available on utilization of {CAC} as a tool in the general population as well as in targeted subgroups such as those with diabetes and metabolic syndrome. For this review, the authors performed thorough Pubmed and Medline searches using keywords coronary artery calcification, X-ray computed tomography, multidetector computed tomography, {CAD}, diabetes mellitus and metabolic syndrome. Based on the authors' review of literature, they believe that {CAC} is an excellent risk stratification imaging modality, especially in patients with diabetes and metabolic syndrome; behavioral changes in patients and therapeutic interventions based on {CAC} scoring are cost-effective.},
	pages = {87--94},
	number = {1},
	journaltitle = {Expert Rev Cardiovasc Ther},
	author = {Sunkara, N and Wong, N D and Malik, S},
	date = {2014},
	pmid = {24345092}
}

@article{dong_inactivation_2012,
	title = {Inactivation of {MYO}5B promotes invasion and motility in gastric cancer cells},
	volume = {57},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22134786},
	doi = {10.1007/s10620-011-1989-z},
	abstract = {{BACKGROUND}: Loss of cell polarity and tissue disorganisation are hallmarks of cancer. {MYO}5B mutations disrupt epithelial cell polarity, suggesting that {MYO}5B may be involved in tumorigenesis. {METHODS}: We analyzed {MYO}5B expression in 70 gastric cancer tissues by immunohistochemistry using a tissue microarray method. Two related proteins, Rab11a and {TfR}, were also investigated. {RESULTS}: We found that the negative rate of {MYO}5B was 78.6 and 17.1\% in gastric cancer and normal gastric tissues (P {\textbackslash}textless 0.001), respectively. The {MYO}5B expression had a strong relationship with Rab11a expression (P = 0.002). We also found that inactivation by {siRNA} against {MYO}5B promoted the proliferation, invasion and migration of gastric cancer cells. {CONCLUSION}: The expression of {MYO}5B was downregulated in gastric cancer and inactivation of {MYO}5B may contribute to tumorigenesis. Therefore, {MYO}5B may become an important biomarker for gastric cancer in the future.},
	pages = {1247--1252},
	number = {5},
	journaltitle = {Dig Dis Sci},
	author = {Dong, W and Chen, X and Chen, P and Yue, D and Zhu, L and Fan, Q},
	date = {2012},
	pmid = {22134786},
	keywords = {Humans, {RNA}, *Cell Polarity, *Epithelial Cells/metabolism/pathology, *Myosin Heavy Chains/genetics/metabolism, *Myosin Type V/genetics/metabolism, *Stomach Neoplasms/genetics/metabolism/pathology, Antigens, {CD}/metabolism, Cell Line, Cell Movement, Cell Transformation, Down-Regulation, Female, Gene Expression, Immunohistochemistry, Lymphatic Metastasis, Male, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Invasiveness/*genetics, Neoplasm Staging, Neoplastic/genetics/metabolis, rab {GTP}-Binding Proteins/metabolism, Receptors, Small Interfering/metabolism, Stomach/pathology, Transferrin/metabolism, Tumor}
}

@article{de_marchis_rrp15p_2005,
	title = {Rrp15p, a novel component of pre-ribosomal particles required for 60S ribosome subunit maturation},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15769876},
	doi = {10.1261/rna.7200205},
	abstract = {In eukaryotes ribosome biogenesis required that {rRNAs} primary transcripts are assembled in pre-ribosomal particles and processed. Protein factors and pre-ribosomal complexes involved in this complex pathway are not completely depicted. The essential {ORF} {YPR}143W encodes in yeast for an uncharacterized protein product, named here Rrp15p. Cellular function of Rrp15p has not so far defined even if nucleolar location was referred. With the aim to define the possible role of this orphan gene, we performed {TAP}-tagging of Rrp15p and investigated its molecular association with known pre-ribosomal complexes. Comparative sucrose gradient sedimentation analyses of yeast lysates expressing the {TAP}-tagged Rrp15p, strongly indicated that this protein is a component of the pre-60S particles. Northern hybridization, primer extension and functional proteomics on {TAP}-affinity isolated complexes proved that Rrp15p predominately associated with pre-{rRNAs} and proteins previously characterized as components of early pre-60S ribosomal particles. Finally, depletion of Rrp15p inhibited the accumulation of 27S and 7S pre-{rRNAs} and 5.8S and 25S mature {rRNA}. These results provide the first indication that Rrp15p is a novel factor involved in the early maturation steps of the 60S subunits. Moreover, the identification of the protein kinase {CK}2 in the Rrp15p-containing pre-ribosomal particles here reported, sustains the link between ribosome synthesis and cell cycle progression.},
	pages = {495--502},
	number = {4},
	journaltitle = {{RNA}},
	author = {De Marchis, M L and Giorgi, A and Schinina, M E and Bozzoni, I and Fatica, A},
	date = {2005},
	pmid = {15769876},
	keywords = {Conserved Sequence, {RNA}, Databases, Amino Acid Sequence, Blotting, Mass, Matrix-Assisted Laser Desorpti, Molecular Sequence Data, Northern, Protein, Protein-Serine-Threonine Kinases/*genetics/isolati, Ribosomal Proteins, Ribosomal/genetics/*metabolism, Ribosomes/*metabolism, {RNA} Precursors/*genetics/metabolism, Saccharomyces cerevisiae Proteins/*genetics/isolat, Saccharomyces cerevisiae/genetics/growth \& develop, Spectrometry}
}

@article{furney_structural_2006,
	title = {Structural and functional properties of genes involved in human cancer},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16405732},
	doi = {10.1186/1471-2164-7-3},
	abstract = {{BACKGROUND}: One of the main goals of cancer genetics is to identify the causative elements at the molecular level leading to cancer. {RESULTS}: We have conducted an analysis of a set of genes known to be involved in cancer in order to unveil their unique features that can assist towards the identification of new candidate cancer genes. {CONCLUSION}: We have detected key patterns in this group of genes in terms of the molecular function or the biological process in which they are involved as well as sequence properties. Based on these features we have developed an accurate Bayesian classification model with which human genes have been scored for their likelihood of involvement in cancer.},
	pages = {3},
	journaltitle = {{BMC} Genomics},
	author = {Furney, S J and Higgins, D G and Ouzounis, C A and Lopez-Bigas, N},
	date = {2006},
	pmid = {16405732},
	keywords = {Animals, Conserved Sequence, Humans, Oligonucleotide Array Sequence Analysis, *Gene Expression Regulation, Amino Acid Sequence, Bayes Theorem, Neoplasm Proteins/chemistry/genetics, Neoplasms/*genetics, Neoplastic, Proteins/chemistry/genetics}
}

@article{paulsen_clinical_2001,
	title = {Clinical markers of early disease in persons near onset of Huntington's disease},
	volume = {57},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11524475},
	abstract = {{OBJECTIVE}: There is increasing evidence that neuron loss precedes the phenotypic expression of Huntington's disease ({HD}). As genes for late-onset neurodegenerative diseases are identified, the need for accurate assessment of phenoconversion (i.e., the transition from health to the disease phenotype) will be important. {METHODS}: Prospective longitudinal evaluation using the Unified Huntington's Disease Rating Scale ({UHDRS}) was conducted by Huntington Study Group members from 36 sites. There were 260 persons considered "at risk" for {HD} who initially did not have manifest disease and had at least one subsequent evaluation. Repeat {UHDRS} data, obtained an average of 2 years later, showed that 70 persons were given a diagnosis of definite {HD} based on the quantified neurologic examination. {RESULTS}: Baseline cognitive performances were consistently worse for the at-risk group who demonstrated conversion to a definitive diagnosis compared with those who did not. Longitudinal change scores showed that the at-risk group who did not demonstrate manifest disease during the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group demonstrating conversion to disease during the study declined across cognitive domains. {CONCLUSIONS}: Neuropsychological measures show impairment 2 years before the development of more manifest motor disease. Findings suggest that these brief cognitive measures administered over time may capture early striatal neural loss in {HD}.},
	pages = {658--662},
	number = {4},
	journaltitle = {Neurology},
	author = {Paulsen, J S and Zhao, H and Stout, J C and Brinkman, R R and Guttman, M and Ross, C A and Como, P and Manning, C and Hayden, M R and Shoulson, I},
	date = {2001},
	pmid = {11524475},
	keywords = {Humans, *Neuropsychological Tests, Adult, Cognition Disorders/diagnosis/*psychology, Female, Huntington Disease/diagnosis/*psychology, Male, Middle Aged, Prospective Studies}
}

@article{caffarelli_novel_1997,
	title = {A novel Mn++-dependent ribonuclease that functions in U16 {SnoRNA} processing in X. laevis},
	volume = {233},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9144568},
	doi = {10.1006/bbrc.1997.6487},
	abstract = {The intron-encoded U16 small nucleolar {RNA} ({snoRNA}) is a component of a new family of molecules which originate by processing of pre-{mRNA} in which they are contained. The mechanism of U16 {snoRNA} biosynthesis involves an initial step of endonucleolytic cleavage of the pre-{mRNA} with the release of a pre-{snoRNA} molecule; the subsequent step consists of exonucleolytic trimming that produces mature U16 molecules. In order to identify the molecular components involved in this peculiar biosynthetic pathway, we have undertaken the characterization of the endonucleolytic activity by biochemical fractionation of Xenopus laevis oocyte nuclear extract. In this paper we show the production of a protein fraction ({BSF}) which is highly enriched for a specific endonucleolytic activity that exactly reproduces the cleavage pattern of the U16-containing pre-{mRNA} identified in vivo in X. laevis oocytes and in unfractionated nuclear extract.},
	pages = {514--517},
	number = {2},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Caffarelli, E and Maggi, L and Fatica, A and Jiricny, J and Bozzoni, I},
	date = {1997},
	pmid = {9144568},
	keywords = {Animals, {RNA}, Manganese/*metabolism, Ribonucleases/*metabolism, Ribosomal Proteins/genetics, {RNA} Precursors/metabolism, Small Nuclear/*metabolism, Substrate Specificity, Xenopus laevis}
}

@article{gorospe_microregulators_2011,
	title = {{MicroRegulators} come of age in senescence},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21592610},
	doi = {10.1016/j.tig.2011.03.005},
	abstract = {Cellular senescence was first reported five decades ago as a state of long-term growth inhibition in viable, metabolically active cells cultured in vitro. However, evidence that senescence occurs in vivo and underlies pathophysiologic processes has only emerged over the past few years. Coincident with this increased knowledge, understanding of the mechanisms that control senescent-cell gene expression programs has also recently escalated. Such mechanisms include a prominent group of regulatory factors ({miRNA}), a family of small, noncoding {RNAs} that interact with select target {mRNAs} and typically repress their expression. Here, we review recent reports that {miRNAs} are key modulators of cellular senescence, and we examine their influence upon specific senescence-regulatory proteins. We discuss evidence that dysregulation of {miRNA}-governed senescence programs underlies age-associated diseases, including cancer.},
	pages = {233--241},
	number = {6},
	journaltitle = {Trends Genet},
	author = {Gorospe, M and Abdelmohsen, K},
	date = {2011},
	pmid = {21592610},
	keywords = {Animals, Humans, {RNA}, *Cell Aging, *Gene Expression Regulation, {MicroRNAs}/*genetics/metabolism, Post-Transcriptional, {RNA} Processing, Signal Transduction, Untranslated/genetics}
}

@article{sreedasyam_nn-propane-13-di-ylbis-2-amino-benzamide_2013,
	title = {N,N'-(Propane-1,3-di-yl)bis-(2-amino-benzamide)},
	volume = {69},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23723834},
	doi = {10.1107/S160053681300888X},
	abstract = {The title compound, C17H20N4O2, was prepared by the reaction between 1,3-di-amino-propane and isatoic anhydride in water. The carbonyl O atoms are involved in intra-molecular hydrogen bonding with the amine group and inter-molecular hydrogen bonding with an amide H atom of an adjacent mol-ecule. In the crystal, pairs of N-Hcdots, three dots, {centeredO} hydrogen bonds link mol-ecules into inversion dimers and further N-Hcdots, three dots, {centeredO} hydrogen bonds link the dimers into ladder-like chains along the a axis.},
	pages = {o673},
	issue = {Pt 5},
	journaltitle = {Acta Crystallogr Sect E Struct Rep Online},
	author = {Sreedasyam, J S and Sunkari, J and Kundha, S and Gundapaneni, R R},
	date = {2013},
	pmid = {23723834}
}

@article{gong_lncrnasnp:_2015,
	title = {{lncRNASNP}: a database of {SNPs} in {lncRNAs} and their potential functions in human and mouse},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25332392},
	doi = {10.1093/nar/gku1000},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) play key roles in various cellular contexts and diseases by diverse mechanisms. With the rapid growth of identified {lncRNAs} and disease-associated single nucleotide polymorphisms ({SNPs}), there is a great demand to study {SNPs} in {lncRNAs}. Aiming to provide a useful resource about {lncRNA} {SNPs}, we systematically identified {SNPs} in {lncRNAs} and analyzed their potential impacts on {lncRNA} structure and function. In total, we identified 495,729 and 777,095 {SNPs} in more than 30,000 {lncRNA} transcripts in human and mouse, respectively. A large number of {SNPs} were predicted with the potential to impact on the {miRNA}-{lncRNA} interaction. The experimental evidence and conservation of {miRNA}-{lncRNA} interaction, as well as {miRNA} expressions from {TCGA} were also integrated to prioritize the {miRNA}-{lncRNA} interactions and {SNPs} on the binding sites. Furthermore, by mapping {SNPs} to {GWAS} results, we found that 142 human {lncRNA} {SNPs} are {GWAS} {tagSNPs} and 197,827 {lncRNA} {SNPs} are in the {GWAS} linkage disequilibrium regions. All these data for human and mouse {lncRNAs} were imported into {lncRNASNP} database (http://bioinfo.life.hust.edu.cn/{lncRNASNP}/), which includes two sub-databases {lncRNASNP}-human and {lncRNASNP}-mouse. The {lncRNASNP} database has a user-friendly interface for searching and browsing through the {SNP}, {lncRNA} and {miRNA} sections.},
	pages = {D181--6},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Gong, J and Liu, W and Zhang, J and Miao, X and Guo, A Y},
	date = {2015},
	pmid = {25332392},
	keywords = {Animals, Humans, Mice, {RNA}, Nucleic Acid, *Databases, *Polymorphism, Genome-Wide Association Study, Internet, Long Noncoding/*chemistry/metabolism/physiolo, {MicroRNAs}/metabolism, Single Nucleotide}
}

@article{shack_activation_1999,
	title = {Activation of the cholesterol pathway and Ras maturation in response to stress},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10557091},
	doi = {10.1038/sj.onc.1203002},
	abstract = {All cells depend on sterols and isoprenoids derived from mevalonate ({MVA}) for growth, differentiation, and maintenance of homeostatic functions. In plants, environmental insults like heat and sunlight trigger the synthesis of isoprene, also derived from {MVA}, and this phenomenon has been associated with enhanced tolerance to heat. Here, we show that in human prostate adenocarcinoma {PC}-3M cells heat shock leads to activation of the {MVA} pathway. This is characterized by a dose- and time-dependent elevation in 3-hydroxy-3-methylglutaryl-coenzyme A reductase ({HMGR}) activity, enhanced sterol and isoprenoid synthesis, and increased protein prenylation. Furthermore, prenylation and subsequent membrane localization of Ras, a central player in cell signaling, was rapidly induced following heat stress. These effects were dose-dependent, augmented with repeated insults, and were prevented by culturing cells in the presence of lovastatin, a competitive inhibitor of {HMGR}. Enhanced Ras maturation by heat stress was also associated with a heightened activation of extracellular signal-regulated kinase ({ERK}), a key mediator of both mitogenic and stress signaling pathways, in response to subsequent growth factor stimulation. Thus, activation of the {MVA} pathway may constitute an important adaptive host response to stress, and have significant implications to carcinogenesis.},
	pages = {6021--6028},
	number = {44},
	journaltitle = {Oncogene},
	author = {Shack, S and Gorospe, M and Fawcett, T W and Hudgins, W R and Holbrook, N J},
	date = {1999},
	pmid = {10557091},
	keywords = {Humans, *Genes, Adenocarcinoma/drug therapy/etiology/*metabolism, Calcium-Calmodulin-Dependent Protein Kinases/metab, Cholesterol/*metabolism, Diterpenes/metabolism, Farnesol/metabolism, Heat-Shock Response/genetics, Hydroxymethylglutaryl {CoA} Reductases/drug effects/, Hydroxymethylglutaryl-{CoA} Reductase Inhibitors/pha, Hydroxymethylglutaryl-{CoA}-Reductases, Lovastatin/pharmacology, Male, Mevalonic Acid/metabolism, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases/metabolism, {NADP}-depende, Physiological/complications/*metabolism, Prostatic Neoplasms/drug therapy/etiology/*metabol, Protein Prenylation, ras, ras Proteins/genetics/metabolism, Sterols/biosynthesis, Stress}
}

@article{tsukada_enhanced_1993,
	title = {Enhanced proliferative potential in culture of cells from p53-deficient mice},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7504233},
	abstract = {Normal somatic cells are endowed with limited doubling potential in culture, and the process of immortalization is an inevitable step in neoplastic transformation of the cells. To examine the roles of p53 in this process, the cells of p53-deficient mice were examined for doubling potential. Fibroblast-like cells from a variety of tissues of these mice proliferated continuously without showing aging or crisis. The aneuploid cells overcome the population with passage, but cloning experiment indicated that chromosomal changes were not essential to this process. The enhanced proliferative potential in culture of cells from the p53-deficient mice was also observed in epithelial cells of lens, mammary glands and seminal vesicles and in neural precursor cells. Proliferation of bone marrow cells in response to stem cell factor was enhanced in long term culture, but not in in vitro colony assay; no permanent cell lines could be obtained. No effects of p53-deficiency were found in proliferation of cardiac muscle cells or hepatocytes.},
	pages = {3313--3322},
	number = {12},
	journaltitle = {Oncogene},
	author = {Tsukada, T and Tomooka, Y and Takai, S and Ueda, Y and Nishikawa, S and Yagi, T and Tokunaga, T and Takeda, N and Suda, Y and Abe, S and al, Et},
	date = {1993},
	pmid = {7504233},
	keywords = {Animals, Base Sequence, Mice, Cells, Cultured, Aneuploidy, Animal/cytology/embryology/metabol, Blotting, Bone Marrow Cells, Bone Marrow/metabolism, Cell Division/physiology, Chimera, Chromosomes/ultrastructure, Crystalline/cytology/embryology/metabolism, {DNA}/analysis/genetics, Epithelial Cells, Epithelium/embryology/metabolism, Female, Fibroblasts/*cytology/metabolism, Flow Cytometry, Hematopoietic Cell Growth Factors/pharmacology, Inbred C57BL, Inbred {CBA}, Karyotyping, Lens, Male, Mammary Glands, Molecular Sequence Data, Phenotype, Ploidies, Polymerase Chain Reaction, Seminal Vesicles/cytology/embryology/metabolism, Southern, Stem Cell Factor, Stem Cells/cytology/metabolism, Tumor Suppressor Protein p53/*deficiency/genetics/, Western}
}

@article{amato_sgk1_2009,
	title = {Sgk1 activates {MDM}2-dependent p53 degradation and affects cell proliferation, survival, and differentiation},
	volume = {87},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19756449},
	doi = {10.1007/s00109-009-0525-5},
	abstract = {Serum and glucocorticoid regulated kinase 1 (Sgk1) is a serine-threonine kinase that is activated by serum, steroids, insulin, vasopressin, and interleukin 2 at the transcriptional and post-translational levels. Sgk1 is also important in transduction of growth factors and steroid-dependent survival signals and may have a role in the development of resistance to cancer chemotherapy. In the present paper, we demonstrate that Sgk1 activates {MDM}2-dependent p53 ubiquitylation. The results were obtained in {RKO} cells and other cell lines by Sgk1-specific {RNA} silencing and were corroborated in an original mouse model as well as in transiently and in stably transfected {HeLa} cells expressing wild-type or dominant negative Sgk1 mutant. Sgk1 contributes to cell survival, cell-cycle progression, and epithelial de-differentiation. We also show that the effects of Sgk1 on the clonogenic potential of different cancer cells depend on the expression of wild-type p53. Since transcription of Sgk1 is activated by p53, we propose a finely tuned feedback model where Sgk1 down-regulates the expression of p53 by enhancing its mono- and polyubiquitylation.},
	pages = {1221--1239},
	number = {12},
	journaltitle = {J Mol Med (Berl)},
	author = {Amato, R and D'Antona, L and Porciatti, G and Agosti, V and Menniti, M and Rinaldo, C and Costa, N and Bellacchio, E and Mattarocci, S and Fuiano, G and Soddu, S and Paggi, M G and Lang, F and Perrotti, N},
	date = {2009},
	pmid = {19756449},
	keywords = {Animals, Humans, Mice, *Cell Differentiation, *Cell Proliferation, *Cell Survival, *Gene Expression Regulation, *Immediate-Early Proteins/genetics/metabolism, *Protein-Serine-Threonine Kinases/genetics/metabol, *Proto-Oncogene Proteins c-mdm2/genetics/metabolis, *Tumor Suppressor Protein p53/genetics/metabolism, Cell Death, Cell Line, {HeLa} Cells, Inbred {BALB} C, Male, Neoplastic, Signal Transduction, Transfection, Transgenic}
}

@article{baker_coplanar_2013,
	title = {Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice},
	volume = {121},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23099484},
	doi = {10.1289/ehp.1205421},
	abstract = {{BACKGROUND}: Previous studies demonstrated that coplanar polychlorinated biphenyls ({PCBs}) promote proinflammatory gene expression in adipocytes. {PCBs} are highly lipophilic and accumulate in adipose tissue, a site of insulin resistance in persons with type 2 diabetes. {OBJECTIVES}: We investigated the in vitro and in vivo effects of coplanar {PCBs} on adipose expression of tumor necrosis factor alpha ({TNF}-alpha) and on glucose and insulin homeostasis in lean and obese mice. {METHODS}: We quantified glucose and insulin tolerance, as well as {TNF}-alpha levels, in liver, muscle, and adipose tissue of male C57BL/6 mice administered vehicle, {PCB}-77, or {PCB}-126 and fed a low fat ({LF}) diet. Another group of mice administered vehicle or {PCB}-77 were fed a high fat ({HF}) diet for 12 weeks; the diet was then switched from {HF} to {LF} for 4 weeks to induce weight loss. We quantified glucose and insulin tolerance and adipose {TNF}-alpha expression in these mice. In addition, we used in vitro and in vivo studies to quantify aryl hydrocarbon receptor ({AhR})-dependent effects of {PCB}-77 on parameters of glucose homeostasis. {RESULTS}: Treatment with coplanar {PCBs} resulted in sustained impairment of glucose and insulin tolerance in mice fed the {LF} diet. In {PCB}-77-treated mice, {TNF}-alpha expression was increased in adipose tissue but not in liver or muscle. {PCB}-77 levels were strikingly higher in adipose tissue than in liver or serum. Antagonism of {AhR} abolished both in vitro and in vivo effects of {PCB}-77. In obese mice, {PCB}-77 had no effect on glucose homeostasis, but glucose homeostasis was impaired after weight loss. {CONCLUSIONS}: Coplanar {PCBs} impaired glucose homeostasis in lean mice and in obese mice following weight loss. Adipose-specific elevations in {TNF}-alpha expression by {PCBs} may contribute to impaired glucose homeostasis.},
	pages = {105--110},
	number = {1},
	journaltitle = {Environ Health Perspect},
	author = {Baker, N A and Karounos, M and English, V and Fang, J and Wei, Y and Stromberg, A and Sunkara, M and Morris, A J and Swanson, H I and Cassis, L A},
	date = {2013},
	pmid = {23099484},
	keywords = {Animals, Mice, Adipose Tissue/drug effects/metabolism, Glucose/*metabolism, Homeostasis/*drug effects, Inbred C57BL, Obese, Polychlorinated Biphenyls/*toxicity, Weight Loss/*physiology}
}

@article{washietl_fast_2005,
	title = {Fast and reliable prediction of noncoding {RNAs}},
	volume = {102},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15665081},
	doi = {10.1073/pnas.0409169102},
	abstract = {We report an efficient method for detecting functional {RNAs}. The approach, which combines comparative sequence analysis and structure prediction, already has yielded excellent results for a small number of aligned sequences and is suitable for large-scale genomic screens. It consists of two basic components: (i) a measure for {RNA} secondary structure conservation based on computing a consensus secondary structure, and (ii) a measure for thermodynamic stability, which, in the spirit of a z score, is normalized with respect to both sequence length and base composition but can be calculated without sampling from shuffled sequences. Functional {RNA} secondary structures can be identified in multiple sequence alignments with high sensitivity and high specificity. We demonstrate that this approach is not only much more accurate than previous methods but also significantly faster. The method is implemented in the program rnaz, which can be downloaded from www.tbi.univie.ac.at/∼wash/{RNAz}. We screened all alignments of length n {\textbackslash}textgreater or = 50 in the Comparative Regulatory Genomics database, which compiles conserved noncoding elements in upstream regions of orthologous genes from human, mouse, rat, Fugu, and zebrafish. We recovered all of the known noncoding {RNAs} and cis-acting elements with high significance and found compelling evidence for many other conserved {RNA} secondary structures not described so far to our knowledge.},
	pages = {2454--2459},
	number = {7},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Washietl, S and Hofacker, I L and Stadler, P F},
	date = {2005},
	pmid = {15665081},
	keywords = {{RNA}, Databases, Nucleic Acid, Algorithms, Software, Nucleic Acid Conformation, {RNA} Stability, Sequence Alignment, Sequence Alignment/statistics \& numerical data, Thermodynamics, Untranslated/chemistry/*genetics, {RNA}, Untranslated, Databases, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/TE4DJYHC/Washietl et al. - 2005 - Fast and reliable prediction of noncoding RNAs.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/8AF57PBW/Washietl et al. - 2005 - Fast and reliable prediction of noncoding RNAs.pdf:application/pdf}
}

@article{lopez_de_silanes_identification_2004,
	title = {Identification of a target {RNA} motif for {RNA}-binding protein {HuR}},
	volume = {101},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14981256},
	doi = {10.1073/pnas.0306453101},
	abstract = {{HuR}, a protein that binds to specific {mRNA} subsets, is increasingly recognized as a pivotal posttranscriptional regulator of gene expression. Here, {HuR} was immunoprecipitated under conditions that preserved {HuR}-{RNA} interactions, and {HuR}-bound target {mRNAs} were identified by {cDNA} array hybridization. Analysis of primary sequences and secondary structures shared among {HuR} targets led to the identification of a 17- to 20-base-long {RNA} motif rich in uracils. This {HuR} motif was found in almost all {mRNAs} previously reported to be {HuR} targets, was located preferentially within 3' untranslated regions of all unigene transcripts examined, and was conserved in {\textbackslash}textgreater50\% of human and mouse homologous genes. Importantly, the {HuR} motif allowed the successful prediction and subsequent validation of novel {HuR} targets from gene databases. This study describes an {HuR} target {RNA} motif and presents a general strategy for identifying target motifs for {RNA}-binding proteins.},
	pages = {2987--2992},
	number = {9},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Lopez de Silanes, I and Zhan, M and Lal, A and Yang, X and Gorospe, M},
	date = {2004},
	pmid = {14981256},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Binding Sites, Oligonucleotide Array Sequence Analysis, 3' Untranslated Regions/genetics, 5' Untranslated Regions/genetics, Antigens, Carcinoma, Cell Line, Colorectal Neoplasms, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/chemistry/*genetics/metabolism, Nucleic Acid Conformation, {RNA}-Binding Proteins/chemistry/*genetics/metabolis, Surface/chemistry/*genetics/metabolism, Tumor}
}

@article{huang_david_2007,
	title = {The {DAVID} Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17784955},
	doi = {10.1186/gb-2007-8-9-r183},
	abstract = {The {DAVID} Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.},
	pages = {R183},
	number = {9},
	journaltitle = {Genome Biol},
	author = {Huang, D W and Sherman, B T and Tan, Q and Collins, J R and Alvord, W G and Roayaei, J and Stephens, R and Baseler, M W and Lane, H C and Lempicki, R A},
	date = {2007},
	pmid = {17784955},
	keywords = {Genetic, Humans, Oligonucleotide Array Sequence Analysis, Databases, Algorithms, Software, *Gene Expression Profiling, *Genetic Techniques, *Genomics, Automated, Cluster Analysis, Computational Biology/methods, Data Interpretation, Models, Pattern Recognition, Statistical, Theoretical}
}

@article{kosiol_patterns_2008,
	title = {Patterns of positive selection in six Mammalian genomes},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18670650},
	doi = {10.1371/journal.pgen.1000144},
	abstract = {Genome-wide scans for positively selected genes ({PSGs}) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian {PSGs} to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of approximately 16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection ({FDR}{\textbackslash}textless0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified {PSGs} were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for {PSGs}, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible "selection histories" of each gene indicated that most {PSGs} have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that {PSGs} are expressed at significantly lower levels, and in a more tissue-specific manner, than non-{PSGs}. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for {PSGs}, but no evidence was found for an enrichment for {PSGs} among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.},
	pages = {e1000144},
	number = {8},
	journaltitle = {{PLoS} Genet},
	author = {Kosiol, C and Vinar, T and da Fonseca, R R and Hubisz, M J and Bustamante, C D and Nielsen, R and Siepel, A},
	date = {2008},
	pmid = {18670650},
	keywords = {Animals, Genetic, Humans, Mice, *Genome, Databases, *Evolution, *Selection, Bayes Theorem, Dogs, Gene Expression, Likelihood Functions, Macaca mulatta, Mammals/classification/*genetics, Molecular, Pan troglodytes, Phylogeny, Primates, Rats, Rodentia, Sequence Alignment}
}

@article{gracheva_ganglion-specific_2011,
	title = {Ganglion-specific splicing of {TRPV}1 underlies infrared sensation in vampire bats},
	volume = {476},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21814281},
	doi = {10.1038/nature10245},
	abstract = {Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation. In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal's face. Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate {TRPA}1 (transient receptor potential cation channel A1), to produce an infrared detector. Here we show that vampire bats tune a channel that is already heat-sensitive, {TRPV}1, by lowering its thermal activation threshold to about 30 degrees C. This is achieved through alternative splicing of {TRPV}1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, thereby maintaining a role for {TRPV}1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat Trpv1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs and moles), supporting a close phylogenetic relationship with bats. These findings reveal a novel molecular mechanism for physiological tuning of thermosensory nerve fibres.},
	pages = {88--91},
	number = {7358},
	journaltitle = {Nature},
	author = {Gracheva, E O and Cordero-Morales, J F and Gonzalez-Carcacia, J A and Ingolia, N T and Manno, C and Aranguren, C I and Weissman, J S and Julius, D},
	date = {2011},
	pmid = {21814281},
	keywords = {Animals, Humans, *Infrared Rays, Alternative Splicing/*genetics, Amino Acid Sequence, Cattle, Chiroptera/anatomy \& histology/classification/*gen, Face/anatomy \& histology/innervation, Feeding Behavior/physiology, {HEK}293 Cells, Hot Temperature, Molecular Sequence Data, Organ Specificity/genetics, Phylogeny, Predatory Behavior/physiology, Protein Isoforms/chemistry/genetics/metabolism, Protein Structure, Sensation/*physiology, Tertiary, Trigeminal Ganglion/*metabolism, {TRPV} Cation Channels/chemistry/*genetics/metabolis}
}

@article{criscione_transcriptional_2014,
	title = {Transcriptional landscape of repetitive elements in normal and cancer human cells},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25012247},
	doi = {10.1186/1471-2164-15-583},
	abstract = {{BACKGROUND}: Repetitive elements comprise at least 55\% of the human genome with more recent estimates as high as two-thirds. Most of these elements are retrotransposons, {DNA} sequences that can insert copies of themselves into new genomic locations by a "copy and paste" mechanism. These mobile genetic elements play important roles in shaping genomes during evolution, and have been implicated in the etiology of many human diseases. Despite their abundance and diversity, few studies investigated the regulation of endogenous retrotransposons at the genome-wide scale, primarily because of the technical difficulties of uniquely mapping high-throughput sequencing reads to repetitive {DNA}. {RESULTS}: Here we develop a new computational method called {RepEnrich} to study genome-wide transcriptional regulation of repetitive elements. We show that many of the Long Terminal Repeat retrotransposons in humans are transcriptionally active in a cell line-specific manner. Cancer cell lines display increased {RNA} Polymerase {II} binding to retrotransposons than cell lines derived from normal tissue. Consistent with increased transcriptional activity of retrotransposons in cancer cells we found significantly higher levels of L1 retrotransposon {RNA} expression in prostate tumors compared to normal-matched controls. {CONCLUSIONS}: Our results support increased transcription of retrotransposons in transformed cells, which may explain the somatic retrotransposition events recently reported in several types of cancers.},
	pages = {583},
	journaltitle = {{BMC} Genomics},
	author = {Criscione, S W and Zhang, Y and Thompson, W and Sedivy, J M and Neretti, N},
	date = {2014},
	pmid = {25012247},
	keywords = {Human, Sequence Analysis, Genome, Humans, {RNA}, Protein Binding, Cell Line, Chromatin Immunoprecipitation, Chromosome Mapping, {DNA} Transposable Elements/*genetics, {DNA}-Directed {RNA} Polymerases/metabolism, Male, Prostatic Neoplasms/genetics/pathology, {RNA}/genetics/metabolism, Tumor}
}

@article{fragapane_novel_1993,
	title = {A novel small nucleolar {RNA} (U16) is encoded inside a ribosomal protein intron and originates by processing of the pre-{mRNA}},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8335006},
	abstract = {We report that the third intron of the L1 ribosomal protein gene of Xenopus laevis encodes a previously uncharacterized small nucleolar {RNA} that we called U16. This {snRNA} is not independently transcribed; instead it originates by processing of the pre-{mRNA} in which it is contained. Its sequence, localization and biosynthesis are phylogenetically conserved: in the corresponding intron of the human L1 ribosomal protein gene a highly homologous region is found which can be released from the pre-{mRNA} by a mechanism similar to that described for the amphibian U16 {RNA}. The presence of a {snoRNA} inside an intron of the L1 ribosomal protein gene and the phylogenetic conservation of this gene arrangement suggest an important regulatory/functional link between these two components.},
	pages = {2921--2928},
	number = {7},
	journaltitle = {{EMBO} J},
	author = {Fragapane, P and Prislei, S and Michienzi, A and Caffarelli, E and Bozzoni, I},
	date = {1993},
	pmid = {8335006},
	keywords = {Animals, Base Sequence, Conserved Sequence, Genetic, Humans, {RNA}, Transcription, *Introns, *{RNA} Processing, Chromosomal Proteins, Dna, Messenger/metabolism, Molecular Sequence Data, Non-Histone/metabolism, Nucleic Acid Hybridization, Post-Transcriptional, Ribonucleoproteins/metabolism, Ribosomal Proteins/*genetics, {RNA} Precursors/*metabolism, Small Nuclear/*genetics, Xenopus laevis}
}

@article{gentleman_bioconductor:_2004,
	title = {Bioconductor: open software development for computational biology and bioinformatics},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15461798},
	doi = {10.1186/gb-2004-5-10-r80},
	abstract = {The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.},
	pages = {R80},
	number = {10},
	journaltitle = {Genome Biol},
	author = {Gentleman, R C and Carey, V J and Bates, D M and Bolstad, B and Dettling, M and Dudoit, S and Ellis, B and Gautier, L and Ge, Y and Gentry, J and Hornik, K and Hothorn, T and Huber, W and Iacus, S and Irizarry, R and Leisch, F and Li, C and Maechler, M and Rossini, A J and Sawitzki, G and Smith, C and Smyth, G and Tierney, L and Yang, J Y and Zhang, J},
	date = {2004},
	pmid = {15461798},
	keywords = {*Software, Reproducibility of Results, Computational Biology/*instrumentation/*methods, Internet}
}

@article{cesana_long_2011,
	title = {A long noncoding {RNA} controls muscle differentiation by functioning as a competing endogenous {RNA}},
	volume = {147},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22000014},
	doi = {10.1016/j.cell.2011.09.028},
	abstract = {Recently, a new regulatory circuitry has been identified in which {RNAs} can crosstalk with each other by competing for shared {microRNAs}. Such competing endogenous {RNAs} ({ceRNAs}) regulate the distribution of {miRNA} molecules on their targets and thereby impose an additional level of post-transcriptional regulation. Here we identify a muscle-specific long noncoding {RNA}, linc-{MD}1, which governs the time of muscle differentiation by acting as a {ceRNA} in mouse and human myoblasts. Downregulation or overexpression of linc-{MD}1 correlate with retardation or anticipation of the muscle differentiation program, respectively. We show that linc-{MD}1 "sponges" {miR}-133 and {miR}-133 [corrected] to regulate the expression of {MAML}1 and {MEF}2C, transcription factors that activate muscle-specific gene expression. Finally, we demonstrate that linc-{MD}1 exerts the same control over differentiation timing in human myoblasts, and that its levels are strongly reduced in Duchenne muscle cells. We conclude that the {ceRNA} network plays an important role in muscle differentiation.},
	pages = {358--369},
	number = {2},
	journaltitle = {Cell},
	author = {Cesana, M and Cacchiarelli, D and Legnini, I and Santini, T and Sthandier, O and Chinappi, M and Tramontano, A and Bozzoni, I},
	date = {2011},
	pmid = {22000014},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Long Noncoding, *Gene Expression Regulation, *Muscle Development, Developmental, {DNA}-Binding Proteins/genetics, Duchenne/embryology/metabolism, {MADS} Domain Proteins/genetics, {MEF}2 Transcription Factors, {MicroRNAs}/metabolism, Molecular Sequence Data, Muscle, Muscular Dystrophy, Myoblasts/metabolism, Myogenic Regulatory Factors/genetics, Nuclear Proteins/genetics, Post-Transcriptional, {RNA} Processing, Skeletal/*cytology/embryology/metabolism, Transcription Factors/genetics, Untranslated/*metabolism}
}

@article{do_aberrant_2014,
	title = {Aberrant {DNA} methylation of integrin alpha4 in human breast cancer},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24756760},
	doi = {10.1007/s13277-014-1952-7},
	abstract = {Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin alpha4 status is not clear. In this study, we investigated {DNA} methylation of integrin alpha4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin alpha4 methylation status. Integrin alpha4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 \%). In addition, {DNA} methylation of integrin alpha4 showed statistical correlation with {HER}2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and {TNM} status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin alpha4 in a heavily methylated breast cancer cell line ({ZR}-75) was restored by treatment with 5-aza-2'deoxycytidine, a {DNA} methyltransferase inhibitor, implying transcriptional silencing by {DNA} methylation. We observed that integrin alpha4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin alpha4 and {HER}2 are involved in the same signaling pathway. {DNA} methylation of integrin alpha4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.},
	pages = {7079--7084},
	number = {7},
	journaltitle = {Tumour Biol},
	author = {Do, S I and Ko, E and Kang, S Y and Lee, J E and Nam, S J and Cho, E Y and Kim, D H},
	date = {2014},
	pmid = {24756760},
	keywords = {Genetic, Humans, Promoter Regions, 80 and over, Adult, Aged, Biological/genetics, Breast Neoplasms/*genetics/pathology, {CpG} Islands/*genetics, {DNA} Methylation/*genetics, {ErbB}-2/metabolism, Female, Integrin alpha4/*genetics, Lymphatic Metastasis, {MCF}-7 Cells, Middle Aged, Neoplasm Staging, Prognosis, Receptor, Signal Transduction, Tumor Markers}
}

@article{ponting_smart:_1999,
	title = {{SMART}: identification and annotation of domains from signalling and extracellular protein sequences},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9847187},
	abstract = {{SMART} is a simple modular architecture research tool and database that provides domain identification and annotation on the {WWW} (http://coot.embl-heidelberg.de/{SMART}). The tool compares query sequences with its databases of domain sequences and multiple alignments whilst concurrently identifying compositionally biased regions such as signal peptide, transmembrane and coiled coil segments. Annotated and unannotated regions of the sequence can be used as queries in searches of sequence databases. The {SMART} alignment collection represents more than 250 signalling and extracellular domains. Each alignment is curated to assign appropriate domain boundaries and to ensure its quality. In addition, each domain is annotated extensively with respect to cellular localisation, species distribution, functional class, tertiary structure and functionally important residues.},
	pages = {229--232},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Ponting, C P and Schultz, J and Milpetz, F and Bork, P},
	date = {1999},
	pmid = {9847187},
	keywords = {*Databases, *Signal Transduction, Amino Acid, Amino Acid Sequence, Factual/trends, Information Storage and Retrieval, Internet, Membrane Proteins/chemistry/classification/metabol, Protein Sorting Signals, Protein Structure, Proteins/*chemistry/classification/*metabolism, Sequence Alignment, Sequence Homology, Tertiary, User-Computer Interface}
}

@article{he_noncode_2008,
	title = {{NONCODE} v2.0: decoding the non-coding},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18000000},
	doi = {10.1093/nar/gkm1011},
	abstract = {The {NONCODE} database is an integrated knowledge database designed for the analysis of non-coding {RNAs} ({ncRNAs}). Since {NONCODE} was first released 3 years ago, the number of known {ncRNAs} has grown rapidly, and there is growing recognition that {ncRNAs} play important regulatory roles in most organisms. In the updated version of {NONCODE} ({NONCODE} v2.0), the number of collected {ncRNAs} has reached 206 226, including a wide range of {microRNAs}, Piwi-interacting {RNAs} and {mRNA}-like {ncRNAs}. The improvements brought to the database include not only new and updated {ncRNA} data sets, but also an incorporation of {BLAST} alignment search service and access through our custom {UCSC} Genome Browser. {NONCODE} can be found under http://www.noncode.org or http://noncode.bioinfo.org.cn.},
	pages = {D170--2},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {He, S and Liu, C and Skogerbo, G and Zhao, H and Wang, J and Liu, T and Bai, B and Zhao, Y and Chen, R},
	date = {2008},
	pmid = {18000000},
	keywords = {Animals, Humans, {RNA}, Nucleic Acid, *Databases, Internet, Untranslated/*chemistry/classification/geneti, User-Computer Interface}
}

@article{xiao_regulation_2011,
	title = {Regulation of cyclin-dependent kinase 4 translation through {CUG}-binding protein 1 and {microRNA}-222 by polyamines},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21737690},
	doi = {10.1091/mbc.E11-01-0069},
	abstract = {The amino acid-derived polyamines are organic cations that are essential for growth in all mammalian cells, but their exact roles at the molecular level remain largely unknown. Here we provide evidence that polyamines promote the translation of cyclin-dependent kinase 4 ({CDK}4) by the action of {CUG}-binding protein 1 ({CUGBP}1) and {microRNA}-222 ({miR}-222) in intestinal epithelial cells. Both {CUGBP}1 and {miR}-222 were found to bind the {CDK}4 {mRNA} coding region and 3'-untranslated region and repressed {CDK}4 translation synergistically. Depletion of cellular polyamines increased cytoplasmic {CUGBP}1 abundance and {miR}-222 levels, induced their associations with the {CDK}4 {mRNA}, and inhibited {CDK}4 translation, whereas increasing the levels of cellular polyamines decreased {CDK}4 {mRNA} interaction with {CUGBP}1 and {miR}-222, in turn inducing {CDK}4 expression. Polyamine-deficient cells exhibited an increased colocalization of tagged {CDK}4 {mRNA} with processing bodies; this colocalization was abolished by silencing {CUGBP}1 and {miR}-222. Together, our findings indicate that polyamine-regulated {CUGBP}1 and {miR}-222 modulate {CDK}4 translation at least in part by altering the recruitment of {CDK}4 {mRNA} to processing bodies.},
	pages = {3055--3069},
	number = {17},
	journaltitle = {Mol Biol Cell},
	author = {Xiao, L and Cui, Y H and Rao, J N and Zou, T and Liu, L and Smith, A and Turner, D J and Gorospe, M and Wang, J Y},
	date = {2011},
	pmid = {21737690},
	keywords = {Animals, Genetic, {RNA}, Transcription, Gene Expression Regulation, Protein Binding, Cells, Cultured, Open Reading Frames, *Protein Biosynthesis, Cell Proliferation, Cyclin-Dependent Kinase 4/*biosynthesis, Eflornithine/pharmacology, Enzyme Assays, Epithelial Cells/metabolism/physiology, Firefly/biosynthesis/genetics, Gene Silencing, Genes, Intestinal Mucosa/cytology, Luciferases, Messenger/metabolism, {MicroRNAs}/*metabolism, Ornithine Decarboxylase/antagonists \& inhibitors/b, Putrescine/*metabolism, Rats, Recombinant Proteins/biosynthesis, Reporter, {RNA}-Binding Proteins/*metabolism, Spermidine/*metabolism, Spermine/*metabolism}
}

@article{welter_nhgri_2014,
	title = {The {NHGRI} {GWAS} Catalog, a curated resource of {SNP}-trait associations},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24316577},
	doi = {10.1093/nar/gkt1229},
	abstract = {The National Human Genome Research Institute ({NHGRI}) Catalog of Published Genome-Wide Association Studies ({GWAS}) Catalog provides a publicly available manually curated collection of published {GWAS} assaying at least 100,000 single-nucleotide polymorphisms ({SNPs}) and all {SNP}-trait associations with P {\textbackslash}textless1 x 10(-5). The Catalog includes 1751 curated publications of 11 912 {SNPs}. In addition to the {SNP}-trait association data, the Catalog also publishes a quarterly diagram of all {SNP}-trait associations mapped to the {SNPs}' chromosomal locations. The Catalog can be accessed via a tabular web interface, via a dynamic visualization on the human karyotype, as a downloadable tab-delimited file and as an {OWL} knowledge base. This article presents a number of recent improvements to the Catalog, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.},
	pages = {D1001--6},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Welter, D and {MacArthur}, J and Morales, J and Burdett, T and Hall, P and Junkins, H and Klemm, A and Flicek, P and Manolio, T and Hindorff, L and Parkinson, H},
	date = {2014},
	pmid = {24316577},
	keywords = {Human, Genome, Humans, Nucleic Acid, *Databases, *Genome-Wide Association Study, *Polymorphism, Gene Ontology, Internet, Karyotype, Single Nucleotide}
}

@article{routray_emphasizing_2013,
	title = {Emphasizing on heat shock protein 90's utility in head and neck squamous cell carcinoma treatment},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24518700},
	doi = {10.4103/0973-1482.126451},
	abstract = {Heat shock protein 90 (Hsp90) a member of the heat shock proteins ({HSPs}) family, is an adenosine triphosphate dependent molecular chaperone protein, which integrates multiple oncogenic pathways. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma using the first generation Hsp90 inhibitors. Hsp90 as the target of anticancer activity of geldanamycin sparked much interest in the inhibition of Hsp90 as a strategy for the treatment of cancer. Hsp90 inhibitors demonstrate rapid clearance from normal tissues and the blood compartment with prolonged retention in tumors making it a sought after modality for treating cancer. Our review emphasizes its role as anti-cancer therapy for head and neck squamous cell carcinoma.},
	pages = {583--586},
	number = {4},
	journaltitle = {J Cancer Res Ther},
	author = {Routray, S and Sunkavalli, A and Swain, N and Shankar, A A},
	date = {2013},
	pmid = {24518700}
}

@article{dunagin_visualization_2015,
	title = {Visualization of {lncRNA} by single-molecule fluorescence in situ hybridization},
	volume = {1262},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25555572},
	doi = {10.1007/978-1-4939-2253-6_1},
	abstract = {Single-molecule {RNA} fluorescence in situ hybridization is a technique that holds great potential for the study of long noncoding {RNA}. It enables quantification and spatial resolution of single {RNA} molecules within cells via hybridization of multiple, labeled nucleic acid probes to a target {RNA}. It has recently become apparent that single-molecule {RNA} {FISH} probes targeting noncoding {RNA} are more prone to off-target binding yielding spurious results than when targeting {mRNA}. Here we present a protocol for the application of single-molecule {RNA} {FISH} to the study of noncoding {RNA} as well as an experimental procedure for validating legitimate signals.},
	pages = {3--19},
	journaltitle = {Methods Mol Biol},
	author = {Dunagin, M and Cabili, M N and Rinn, J and Raj, A},
	date = {2015},
	pmid = {25555572}
}

@article{gorospe_hur_2003,
	title = {{HuR} in the mammalian genotoxic response: post-transcriptional multitasking},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12963828},
	pages = {412--414},
	number = {5},
	journaltitle = {Cell Cycle},
	author = {Gorospe, M},
	date = {2003},
	pmid = {12963828},
	keywords = {Animals, Humans, Antigens, Biological, {DNA} Damage/*physiology, {DNA} Repair/*physiology, Hu Paraneoplastic Encephalomyelitis Antigens, Ionizing, Models, Radiation, Ribonucleoproteins/genetics/metabolism, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism, Tumor Suppressor Protein p53/genetics/*metabolism, Ultraviolet Rays}
}

@article{gomolka_[tobacco_2008,
	title = {[Tobacco smoking by alcohol addicted patients–preliminary report]},
	volume = {65},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19189538},
	abstract = {The problem of alcohol and nicotine addiction is both social and medical. The substances are often used together and give complex addiction. The knowledge about mechanisms of complex addiction would be useful for creating effective ways of treatment the abused patients. The aim of the paper was to describe the complex ethanol and nicotine addiction phenomenon. The research was made using data from 30 ethanol and nicotine addicted patients treated in Clinic of Toxicology Jagiellonian University Collegium Medicum in Krakow. 90\% of them were nicotine addicted. Tobacco was the first abused substance in the group of patients. The mean period of addiction was 29.0 years for tobacco and 22.2 years for alcohol. The majority of the patients (51.9\%) smoked more than 20 cigarettes per day; 29.6\% smoked 11-20 cigarettes per day. Single patients were narcotics and drugs addicted. Continuation of the research and toxicological determination of the substances and their metabolites concentrations would be useful for the complex addiction problem explanation and description.},
	pages = {522--523},
	number = {10},
	journaltitle = {Przegl Lek},
	author = {Gomolka, E and Krol, A and Wilimowska, J and Kamenczak, A},
	date = {2008},
	pmid = {19189538},
	keywords = {Humans, Adult, Alcoholism/*epidemiology, Comorbidity, Female, Male, Middle Aged, Risk Factors, Smoking/*epidemiology, Substance-Related Disorders/epidemiology, Tobacco Use Disorder/*epidemiology}
}

@article{lee_mir-130_2011,
	title = {{miR}-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21135128},
	doi = {10.1128/MCB.00894-10},
	abstract = {Adipose tissue development is tightly regulated by altering gene expression. {MicroRNAs} are strong posttranscriptional regulators of mammalian differentiation. We hypothesized that {microRNAs} might influence human adipogenesis by targeting specific adipogenic factors. We identified {microRNAs} that showed varying abundance during the differentiation of human preadipocytes into adipocytes. Among them, {miR}-130 strongly affected adipocyte differentiation, as overexpressing {miR}-130 impaired adipogenesis and reducing {miR}-130 enhanced adipogenesis. A key effector of {miR}-130 actions was the protein peroxisome proliferator-activated receptor gamma ({PPARgamma}), a major regulator of adipogenesis. Interestingly, {miR}-130 potently repressed {PPARgamma} expression by targeting both the {PPARgamma} {mRNA} coding and 3' untranslated regions. Adipose tissue from obese women contained significantly lower {miR}-130 and higher {PPARgamma} {mRNA} levels than that from nonobese women. Our findings reveal that {miR}-130 reduces adipogenesis by repressing {PPARgamma} biosynthesis and suggest that perturbations in this regulation is linked to human obesity.},
	pages = {626--638},
	number = {4},
	journaltitle = {Mol Cell Biol},
	author = {Lee, E K and Lee, M J and Abdelmohsen, K and Kim, W and Kim, M M and Srikantan, S and Martindale, J L and Hutchison, E R and Kim, H H and Marasa, B S and Selimyan, R and Egan, J M and Smith, S R and Fried, S K and Gorospe, M},
	date = {2011},
	pmid = {21135128},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Gene Expression Regulation, 3T3-L1 Cells, Adipocytes/cytology/metabolism, Adipogenesis/*genetics/*physiology, Adult Stem Cells/cytology/metabolism, Cell Differentiation/genetics/physiology, Developmental, {DNA} Primers/genetics, Female, Messenger/genetics/metabolism, {MicroRNAs}/*genetics/*metabolism, Obesity/genetics/metabolism, {PPAR} gamma/*genetics/*metabolism, Species Specificity, Thinness/genetics/metabolism}
}

@article{mathelier_jaspar_2016,
	title = {{JASPAR} 2016: a major expansion and update of the open-access database of transcription factor binding profiles},
	volume = {44},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26531826},
	doi = {10.1093/nar/gkv1176},
	abstract = {{JASPAR} (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor ({TF}) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the {JASPAR} {CORE} collection with 494 new {TF} binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83\% expansion and 10\% update when compared to the previous release. We updated the structural annotation of the {TF} {DNA} binding domains ({DBDs}) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on {ChIP}-seq data for vertebrates, which capture dinucleotide dependencies within {TF} binding sites. This new {JASPAR} release is accompanied by a new web tool to infer {JASPAR} {TF} binding profiles recognized by a given {TF} protein sequence. Moreover, we provide the users with a Ruby module complementing the {JASPAR} {API} to ease programmatic access and use of the {JASPAR} collection of profiles. Finally, we provide the {JASPAR}2016 R/Bioconductor data package with the data of this release.},
	pages = {D110--5},
	issue = {D1},
	journaltitle = {Nucleic Acids Res},
	author = {Mathelier, A and Fornes, O and Arenillas, D J and Chen, C Y and Denay, G and Lee, J and Shi, W and Shyr, C and Tan, G and Worsley-Hunt, R and Zhang, A W and Parcy, F and Lenhard, B and Sandelin, A and Wasserman, W W},
	date = {2016},
	pmid = {26531826},
	keywords = {Animals, Genetic, Binding Sites, Software, *Databases, *Regulatory Elements, {DNA}-Binding Proteins/chemistry, Protein Structure, Tertiary, Transcription Factors/chemistry/*metabolism, Transcriptional}
}

@article{ulitsky_expander:_2010,
	title = {Expander: from expression microarrays to networks and functions},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20134430},
	doi = {10.1038/nprot.2009.230},
	abstract = {A major challenge in the analysis of gene expression microarray data is to extract meaningful biological knowledge out of the huge volume of raw data. Expander ({EXPression} {ANalyzer} and {DisplayER}) is an integrated software platform for the analysis of gene expression data, which is freely available for academic use. It is designed to support all the stages of microarray data analysis, from raw data normalization to inference of transcriptional regulatory networks. The microarray analysis described in this protocol starts with importing the data into Expander 5.0 and is followed by normalization and filtering. Then, clustering and network-based analyses are performed. The gene groups identified are tested for enrichment in function (based on Gene Ontology), co-regulation (using transcription factor and {microRNA} target predictions) or co-location. The results of each analysis step can be visualized in a number of ways. The complete protocol can be executed in approximately 1 h.},
	pages = {303--322},
	number = {2},
	journaltitle = {Nat Protoc},
	author = {Ulitsky, I and Maron-Katz, A and Shavit, S and Sagir, D and Linhart, C and Elkon, R and Tanay, A and Sharan, R and Shiloh, Y and Shamir, R},
	date = {2010},
	pmid = {20134430},
	keywords = {Animals, Genetic, Humans, Mice, Promoter Regions, Algorithms, Software, *Gene Expression Regulation, *Oligonucleotide Array Sequence Analysis, Chromosome Mapping, Escherichia coli/genetics, Gene Expression, Genetic Techniques, {MicroRNAs}/genetics, Multigene Family/genetics, Plants/genetics, Rats, Saccharomyces cerevisiae/genetics, Transcription Factors/genetics}
}

@article{zhang_model-based_2008,
	title = {Model-based analysis of {ChIP}-Seq ({MACS})},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18798982},
	doi = {10.1186/gb-2008-9-9-r137},
	abstract = {We present Model-based Analysis of {ChIP}-Seq data, {MACS}, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. {MACS} empirically models the shift size of {ChIP}-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. {MACS} also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. {MACS} compares favorably to existing {ChIP}-Seq peak-finding algorithms, and is freely available.},
	pages = {R137},
	number = {9},
	journaltitle = {Genome Biol},
	author = {Zhang, Y and Liu, T and Meyer, C A and Eeckhoute, J and Johnson, D S and Bernstein, B E and Nusbaum, C and Myers, R M and Brown, M and Li, W and Liu, X S},
	date = {2008},
	pmid = {18798982},
	keywords = {Genetic, Humans, *Algorithms, Cell Line, Chromatin Immunoprecipitation/*methods, Hepatocyte Nuclear Factor 3-alpha/analysis/*geneti, Models, Oligonucleotide Array Sequence Analysis/*methods, Tumor}
}

@article{kundrapu_easily_2013,
	title = {Easily modified factors contribute to delays in diagnosis of Clostridium difficile infection: a cohort study and intervention},
	volume = {51},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23678072},
	doi = {10.1128/JCM.03142-12},
	abstract = {Although rapid laboratory tests are available for diagnosis of Clostridium difficile infection ({CDI}), delays in completion of {CDI} testing are common in clinical practice. We conducted a cohort study of 242 inpatients tested for {CDI} to determine the timing of different steps involved in diagnostic testing and to identify modifiable factors contributing to delays in diagnosis. The average time from test order to test result was 1.8 days (range, 0.2 to 10.6), with time from order to stool collection accounting for most of the delay (mean, 1.0 day; range, 0 to 10). Several modifiable factors contributed to delays, including not providing stool collection supplies to patients in a timely fashion, rejection of specimens due to incorrect labeling or leaking from the container, and holding samples in the laboratory for batch processing. Delays in testing contributed to delays in initiation of treatment for patients diagnosed with {CDI} and to frequent prescription of empirical {CDI} therapy for patients with mild to moderate symptoms whose testing was ultimately negative. An intervention that addressed several easily modified factors contributing to delays resulted in a significant decrease in the time required to complete {CDI} testing. These findings suggest that health care facilities may benefit from a review of their processes for {CDI} testing to identify and address modifiable factors that contribute to delays in diagnosis and treatment of {CDI}.},
	pages = {2365--2370},
	number = {7},
	journaltitle = {J Clin Microbiol},
	author = {Kundrapu, S and Jury, L A and Sitzlar, B and Sunkesula, V C and Sethi, A K and Donskey, C J},
	date = {2013},
	pmid = {23678072},
	keywords = {Humans, *Delayed Diagnosis, Aged, Clostridium difficile/*isolation \& purification, Clostridium Infections/*diagnosis, Cohort Studies, Female, Intervention Studies, Male, Middle Aged, Specimen Handling/*methods}
}

@article{kuwano_mkp-1_2008,
	title = {{MKP}-1 {mRNA} stabilization and translational control by {RNA}-binding proteins {HuR} and {NF}90},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18490444},
	doi = {10.1128/MCB.00165-08},
	abstract = {The mitogen-activated protein ({MAP}) kinase phosphatase 1 ({MKP}-1) plays a major role in dephosphorylating and thereby inactivating the {MAP} kinases extracellular signal-regulated kinase ({ERK}), c-Jun N-terminal kinase ({JNK}), and p38. Here, we examine the posttranscriptional events underlying the robust {MKP}-1 induction by oxidants in {HeLa} cells. H(2)O(2) treatment potently stabilized the {MKP}-1 {mRNA} and increased the association of {MKP}-1 {mRNA} with the translation machinery. Four {RNA}-binding proteins ({RNA}-{BPs}) that influence {mRNA} turnover and/or translation ({HuR}, {NF}90, {TIAR}, and {TIA}-1) were found to bind to biotinylated transcripts spanning the {MKP}-1 {AU}-rich 3' untranslated region. By using ribonucleoprotein immunoprecipitation analysis, we showed that H(2)O(2) treatment increased the association of {MKP}-1 {mRNA} with {HuR} and {NF}90 and decreased its association with the translational repressors {TIAR} and {TIA}-1. {HuR} or {NF}90 silencing significantly diminished the H(2)O(2)-stimulated {MKP}-1 {mRNA} stability; {HuR} silencing also markedly decreased {MKP}-1 translation. In turn, lowering {MKP}-1 expression in {HuR}-silenced cultures resulted in substantially elevated phosphorylation of {JNK} and p38 after H(2)O(2) treatment. Collectively, {MKP}-1 upregulation by oxidative stress is potently influenced by increased {mRNA} stability and translation, mediated at least in part by the {RNA}-{BPs} {HuR} and {NF}90.},
	pages = {4562--4575},
	number = {14},
	journaltitle = {Mol Cell Biol},
	author = {Kuwano, Y and Kim, H H and Abdelmohsen, K and Pullmann Jr., R and Martindale, J L and Yang, X and Gorospe, M},
	date = {2008},
	pmid = {18490444},
	keywords = {Humans, {RNA}, *Protein Biosynthesis, *{RNA} Stability/drug effects, 3' Untranslated Regions/metabolism, Antigens, Cytoplasm/metabolism, Dual Specificity Phosphatase 1/*genetics, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Hydrogen Peroxide/pharmacology, Messenger/*metabolism, Mitogen-Activated Protein Kinases/metabolism, Nuclear Factor 90 Proteins/*metabolism, Oxidative Stress, Recombinant Proteins/genetics, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism, Up-Regulation}
}

@article{royce-tolland_x-inactivation:_2008,
	title = {X-inactivation: it takes two to count},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18364230},
	doi = {10.1016/j.cub.2008.01.039},
	abstract = {Mammals balance X-linked gene dosage by silencing one X chromosome in female cells, a process that begins with counting the number of X chromosomes. Recent reports suggest homologous X chromosome pairing may be a prerequisite for silencing, providing a basis for counting by ensuring that silencing only occurs in cells with two X chromosomes.},
	pages = {R255--6},
	number = {6},
	journaltitle = {Curr Biol},
	author = {Royce-Tolland, M and Panning, B},
	date = {2008},
	pmid = {18364230},
	keywords = {Animals, {RNA}, Female, Long Untranslated, Untranslated/genetics, X Chromosome Inactivation/*physiology, X Chromosome/genetics/*metabolism}
}

@article{yang_long_2011,
	title = {Long noncoding {RNA} high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans},
	volume = {54},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21769904},
	doi = {10.1002/hep.24563},
	abstract = {In recent years, long noncoding {RNAs} ({lncRNAs}) have been shown to have critical regulatory roles in cancer biology. However, the contributions of {lncRNAs} to hepatitis B virus ({HBV})-related hepatocellular carcinoma ({HCC}) remain largely unknown. Differentially expressed {lncRNAs} between {HBV}-related {HCC} and paired peritumoral tissues were identified by microarray and validated using quantitative real-time polymerase chain reaction. Liver samples from patients with {HBV}-related {HCC} were analyzed for levels of a specific differentially expressed {lncRNA} High Expression In {HCC} (termed {lncRNA}-{HEIH}); data were compared with survival data using the Kaplan-Meier method and compared between groups by the log-rank test. The effects of {lncRNA}-{HEIH} were assessed by silencing and overexpressing the {lncRNA} in vitro and in vivo. The expression level of {lncRNA}-{HEIH} in {HBV}-related {HCC} is significantly associated with recurrence and is an independent prognostic factor for survival. We also found that {lncRNA}-{HEIH} plays a key role in G(0) /G(1) arrest, and further demonstrated that {lncRNA}-{HEIH} was associated with enhancer of zeste homolog 2 ({EZH}2) and that this association was required for the repression of {EZH}2 target genes. {CONCLUSIONS}: Together, these results indicate that {lncRNA}-{HEIH} is an oncogenic {lncRNA} that promotes tumor progression and leads us to propose that {lncRNAs} may serve as key regulatory hubs in {HCC} progression.},
	pages = {1679--1689},
	number = {5},
	journaltitle = {Hepatology},
	author = {Yang, F and Zhang, L and Huo, X S and Yuan, J H and Xu, D and Yuan, S X and Zhu, N and Zhou, W P and Yang, G S and Wang, Y Z and Shang, J L and Gao, C F and Zhang, F R and Wang, F and Sun, S H},
	date = {2011},
	pmid = {21769904},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Untranslated/*genetics, Carcinoma, Cell Cycle/genetics, {DNA}-Binding Proteins/*genetics, Female, Gene Silencing, Hepatocellular/*genetics/mortality/path, Liver Neoplasms/*genetics/mortality/pathology, Male, Middle Aged, Neoplastic/physiology, Polycomb Repressive Complex 2, Polycomb-Group Proteins, Prognosis, Repressor Proteins/genetics, Transcription Factors/*genetics}
}

@article{zhang_stabilization_2014,
	title = {Stabilization of {XIAP} {mRNA} through the {RNA} binding protein {HuR} regulated by cellular polyamines},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24615811},
	doi = {10.1093/nar/gku196},
	journaltitle = {Nucleic Acids Res},
	author = {Zhang, X and Zou, T and Rao, J N and Liu, L and Xiao, L and Wang, P Y and Cui, Y H and Gorospe, M and Wang, J Y},
	date = {2014},
	pmid = {24615811}
}

@article{clarke_dopamine_2002,
	title = {Dopamine agonist monotherapy in Parkinson's disease},
	volume = {360},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12480442},
	abstract = {{CONTEXT}: Levodopa is the gold-standard therapy for Parkinson's disease. However, long-term treatment leads to involuntary movements and response fluctuations which add to the complexities of later disease-management. In addition, preclinical evidence suggests that levodopa is toxic to dopaminergic neurons. These problems have led to a move away from levodopa towards initial monotherapy with a dopamine agonist. {STARTING} {POINT}: Positron-emission tomography ({PET}) and single-photon emission computed tomography ({SPECT}) tracers have been developed which may be considered surrogate markers for remaining dopaminergic neurons. In a randomised controlled trial in patients with early Parkinson's disease, the Parkinson Study Group used 123I-beta-{CIT} {SPECT} ({JAMA} 2002; 287: 1653-61). Those patients given pramipexole had significantly reduced loss of striatal uptake at 46 months compared with those given levodopa (16.0\% vs 25.5\%). In a similar trial, Alan Whone and colleagues used 18F-{DOPA} {PET} (Neurology 2002; 58 [suppl 3]: A82-83). Patients given ropinirole had significantly reduced loss of striatal uptake at 24 months compared with those given levodopa (13\% vs 20\%). These studies suggest that agonist monotherapy may be neuroprotective and/or that levodopa is toxic. This work has been criticised as the {SPECT} results may have resulted from a differential effect of the agonist and levodopa on the regulation of the dopamine transporter, thereby influencing the imaging outcome measure. Other criticisms include insufficient data on the use of the potential neuroprotectant selegiline and patients on pramipexole in the {SPECT} study appear to have been clinically slow progressors. Single clinical trials with each of the four modern agonists compared with levodopa show that as monotherapy the agonists delay the onset of involuntary movements, although at the expense of poorer treatment of motor impairments and disability and more dopaminergic adverse events. The only health-related quality of life data show no difference between pramipexole and levodopa after 4 years. No information on health-economics measures is available but agonists cost two to three times as much as levodopa. {WHERE} {NEXT}? Young patients should be treated with agonist monotherapy since the trials included predominantly younger patients who have a higher incidence of motor complications. Those with significant co-morbidity, dementia, or a short life-expectancy should be treated with the lowest dose of levodopa required to maintain motor function. For the vast majority though, no clear guidance can be given. Further large-scale pragmatic trials in large numbers of patients over prolonged periods are urgently required.},
	pages = {1767--1769},
	number = {9347},
	journaltitle = {Lancet},
	author = {Clarke, C E and Guttman, M},
	date = {2002},
	pmid = {12480442},
	keywords = {Humans, Benzothiazoles, Dopamine Agonists/*therapeutic use, Emission-Computed, Ergolines/therapeutic use, Indoles/therapeutic use, Levodopa/*therapeutic use, Middle Aged, Parkinson Disease/*drug therapy, Pergolide/therapeutic use, Randomized Controlled Trials as Topic, Single-Photon, Thiazoles/therapeutic use, Tomography}
}

@article{tamborero_oncodriveclust:_2013,
	title = {{OncodriveCLUST}: exploiting the positional clustering of somatic mutations to identify cancer genes},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23884480},
	doi = {10.1093/bioinformatics/btt395},
	abstract = {{MOTIVATION}: Gain-of-function mutations often cluster in specific protein regions, a signal that those mutations provide an adaptive advantage to cancer cells and consequently are positively selected during clonal evolution of tumours. We sought to determine the overall extent of this feature in cancer and the possibility to use this feature to identify drivers. {RESULTS}: We have developed {OncodriveCLUST}, a method to identify genes with a significant bias towards mutation clustering within the protein sequence. This method constructs the background model by assessing coding-silent mutations, which are assumed not to be under positive selection and thus may reflect the baseline tendency of somatic mutations to be clustered. {OncodriveCLUST} analysis of the Catalogue of Somatic Mutations in Cancer retrieved a list of genes enriched by the Cancer Gene Census, prioritizing those with dominant phenotypes but also highlighting some recessive cancer genes, which showed wider but still delimited mutation clusters. Assessment of datasets from The Cancer Genome Atlas demonstrated that {OncodriveCLUST} selected cancer genes that were nevertheless missed by methods based on frequency and functional impact criteria. This stressed the benefit of combining approaches based on complementary principles to identify driver mutations. We propose {OncodriveCLUST} as an effective tool for that purpose. {AVAILABILITY}: {OncodriveCLUST} has been implemented as a Python script and is freely available from http://bg.upf.edu/oncodriveclust {CONTACT}: nuria.lopez@upf.edu or abel.gonzalez@upf.edu {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at Bioinformatics online.},
	pages = {2238--2244},
	number = {18},
	journaltitle = {Bioinformatics},
	author = {Tamborero, D and Gonzalez-Perez, A and Lopez-Bigas, N},
	date = {2013},
	pmid = {23884480},
	keywords = {Genomics, Sequence Analysis, Humans, Software, *Genes, *Mutation, Cluster Analysis, Neoplasm, Neoplasm Proteins/*genetics, Protein/*methods}
}

@article{cartault_mutation_2012,
	title = {Mutation in a primate-conserved retrotransposon reveals a noncoding {RNA} as a mediator of infantile encephalopathy},
	url = {http://www.pnas.org/content/early/2012/03/06/1111596109.abstractN2 - The human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recogni},
	journaltitle = {Proceedings of the National Academy of Sciences},
	author = {Cartault, François and Munier, Patrick and Benko, Edgar and Desguerre, Isabelle and Hanein, Sylvain and Boddaert, Nathalie and Bandiera, Simonetta and Vellayoudom, Jeanine and Krejbich-Trotot, Pascale and Bintner, Marc and Hoarau, Jean-Jacques and Girard, Muriel and Génin, Emmanuelle and de Lonlay, Pascale and Fourmaintraux, Alain and Naville, Magali and Rodriguez, Diana and Feingold, Josué and Renouil, Michel and Munnich, Arnold and Westhof, Eric and Fähling, Michael and Lyonnet, Stanislas and Henrion-Caude, Alexandra},
	date = {2012}
}

@article{fan_array-based_2012,
	title = {Array-based nuclear run-on analysis},
	volume = {809},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22113297},
	doi = {10.1007/978-1-61779-376-9_33},
	abstract = {There is extensive evidence that posttranscriptional mechanisms of gene regulation, such as {mRNA} turnover, critically affect the patterns of expressed {mRNAs}. Conventional microarray analysis measures steady-state messenger {RNA} ({mRNA}) levels, which represents the dynamic balance between new transcription and {mRNA} degradation. Accordingly, only de novo transcription can accurately reflect the temporal and spatial events of transcriptional regulation. In this chapter, we describe a recently reported method to study transcription systematically. It involves the genome-wide labeling of nascent transcripts using nonradioactive modified nucleotides, their isolation for amplification, and their hybridization and analysis using commercial microarrays.},
	pages = {505--517},
	journaltitle = {Methods Mol Biol},
	author = {Fan, J and Chen, Y C and Watkins, T and Dang, C V and Gorospe, M and Cheadle, C},
	date = {2012},
	pmid = {22113297},
	keywords = {Animals, Humans, Mice, {RNA}, Messenger/genetics, Biotin, Cell Line, Oligonucleotide Array Sequence Analysis/*methods, {RNA} Stability/genetics}
}

@article{lin_whole-genome_2007,
	title = {Whole-genome cartography of estrogen receptor alpha binding sites},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17542648},
	doi = {10.1371/journal.pgen.0030087},
	abstract = {Using a chromatin immunoprecipitation-paired end {diTag} cloning and sequencing strategy, we mapped estrogen receptor alpha ({ERalpha}) binding sites in {MCF}-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94\% are projected to be bona fide {ERalpha} binding regions. Only 5\% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations ({\textbackslash}textgreater5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71\% harbored putative full estrogen response elements ({EREs}), 25\% bore {ERE} half sites, and only 4\% had no recognizable {ERE} sequences. Genes in the vicinity of {ERalpha} binding sites were enriched for regulation by estradiol in {MCF}-7 cells, and their expression profiles in patient samples segregate {ERalpha}-positive from {ERalpha}-negative breast tumors. The expression dynamics of the genes adjacent to {ERalpha} binding sites suggest a direct induction of gene expression through binding to {ERE}-like sequences, whereas transcriptional repression by {ERalpha} appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied {EREs} at frequencies much greater than by chance, including the previously reported {FOXA}1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of {ERalpha} target genes. Unexpectedly, we found that only 22\%-24\% of the bona fide human {ERalpha} binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing {ERalpha} binding and gene regulation.},
	pages = {e87},
	number = {6},
	journaltitle = {{PLoS} Genet},
	author = {Lin, C Y and Vega, V B and Thomsen, J S and Zhang, T and Kong, S L and Xie, M and Chiu, K P and Lipovich, L and Barnett, D H and Stossi, F and Yeo, A and George, J and Kuznetsov, V A and Lee, Y K and Charn, T H and Palanisamy, N and Miller, L D and Cheung, E and Katzenellenbogen, B S and Ruan, Y and Bourque, G and Wei, C L and Liu, E T},
	date = {2007},
	pmid = {17542648},
	keywords = {Human, Animals, Humans, *Genome, Binding Sites/genetics, Cell Line, {DNA}/*metabolism, Estrogen Receptor alpha/genetics/*metabolism, Female, Gene Expression Regulation/physiology, Tumor}
}

@article{vance_long_2014,
	title = {The long non-coding {RNA} Paupar regulates the expression of both local and distal genes},
	volume = {33},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24488179},
	doi = {10.1002/embj.201386225},
	abstract = {Although some long noncoding {RNAs} ({lncRNAs}) have been shown to regulate gene expression in cis, it remains unclear whether {lncRNAs} can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed {lncRNA} transcribed from a locus upstream of the gene encoding the {PAX}6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neural differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with {PAX}6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a {lncRNA} can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes.},
	pages = {296--311},
	number = {4},
	journaltitle = {{EMBO} J},
	author = {Vance, K W and Sansom, S N and Lee, S and Chalei, V and Kong, L and Cooper, S E and Oliver, P L and Ponting, C P},
	date = {2014},
	pmid = {24488179},
	keywords = {Animals, Conserved Sequence, Genetic, Mice, {RNA}, Transcription, Binding Sites, Protein Binding, Gene Expression Profiling, *Gene Expression Regulation, cdc, Cell Line, Chromatin/metabolism, Developmental, Eye Proteins/biosynthesis/*genetics, Gene Knockdown Techniques, Genes, Genome-Wide Association Study, Homeodomain Proteins/biosynthesis/*genetics, Long Noncoding/antagonists \& inhibitors/genet, Nerve Tissue Proteins/genetics, Neuroblastoma/pathology, Neurogenesis, Neurons/metabolism, Paired Box Transcription Factors/biosynthesis/*gen, Regulatory Elements, Repressor Proteins/biosynthesis/*genetics, Small Interfering/pharmacology, Transcriptional, Transfection, Tumor}
}

@article{lipovich_macrorna_2010,
	title = {{MacroRNA} underdogs in a {microRNA} world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding {RNA}},
	volume = {1799},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20951849},
	doi = {10.1016/j.bbagrm.2010.10.001},
	abstract = {The central dogma of molecular biology relegates {RNAs} to the role of "messengers" of genetic information, with proteins as the end products that perform key roles as regulators and effectors of biological processes. Notable exceptions include non-protein-coding {RNAs}, which function as adaptors ({tRNAs}) and ribosomal components ({rRNAs}) during translation, as well as in splicing ({snRNAs}) and {RNA} maturation including editing ({snoRNAs}). Genome and transcriptome projects have revealed, however, a significant number, rivaling the protein-coding transcripts, of non-protein-coding {RNAs} not related to these previously characterized transcript classes. Non-protein-coding {RNA} research has primarily focused on {microRNAs}, a small subclass of non-protein-coding {RNAs}, and their regulatory roles in gene expression, and these findings have been reviewed extensively. Here, we turn our attention to the larger, in number and size, long non-coding {RNAs} ({lncRNAs}), and review their evolutionary complexity and the growing evidence for their diverse mechanisms of action and functional roles in basic molecular and cellular biology and in human disease. In contrast to the focus on in-silico and expression studies in existing {lncRNA} literature, we emphasize direct evidence for {lncRNA} function, presenting experimental approaches and strategies for systematic characterization of {lncRNA} activities, with applications to known gene regulatory networks and diseases.},
	pages = {597--615},
	number = {9},
	journaltitle = {Biochim Biophys Acta},
	author = {Lipovich, L and Johnson, R and Lin, C Y},
	date = {2010},
	pmid = {20951849},
	keywords = {Animals, Humans, {RNA}, *Evolution, Biological, Biomedical Research/*methods/trends, Gene Expression Regulation/physiology, Gene Regulatory Networks/physiology, {MicroRNAs}/*genetics/metabolism, Models, Molecular, {RNA}/genetics/*physiology, Untranslated/genetics/metabolism/*physiology}
}

@article{ulitsky_towards_2010,
	title = {Towards computational prediction of {microRNA} function and activity},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20576699},
	doi = {10.1093/nar/gkq570},
	abstract = {While it has been established that {microRNAs} ({miRNAs}) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual {miRNAs} are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human {miRNAs}. Our approach improves upon standard statistical tools by addressing specific characteristics of {miRNA} regulation. Our analysis is based on a novel compendium of experimentally verified {miRNA}-pathway and {miRNA}-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel {miRNA}-regulated pathways, refines the annotation of {miRNAs} for which only crude functions are known, and assigns differential functions to {miRNAs} with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify {miRNAs} and genomic {miRNA} clusters with functional importance in specific stages of early human development. A full list of the predicted {mRNA} functions is available at http://acgt.cs.tau.ac.il/fame/.},
	pages = {e160},
	number = {15},
	journaltitle = {Nucleic Acids Res},
	author = {Ulitsky, I and Laurent, L C and Shamir, R},
	date = {2010},
	pmid = {20576699},
	keywords = {Genomics, 3' Untranslated Regions, Humans, {RNA}, *Gene Silencing, Cell Line, Computational Biology/*methods, Data Interpretation, Messenger/metabolism, {MicroRNAs}/chemistry/*metabolism/physiology, Statistical, Stem Cells/metabolism}
}

@article{amit_unbiased_2009,
	title = {Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses},
	volume = {326},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19729616},
	doi = {10.1126/science.1179050},
	abstract = {Models of mammalian regulatory networks controlling gene expression have been inferred from genomic data but have largely not been validated. We present an unbiased strategy to systematically perturb candidate regulators and monitor cellular transcriptional responses. We applied this approach to derive regulatory networks that control the transcriptional response of mouse primary dendritic cells to pathogens. Our approach revealed the regulatory functions of 125 transcription factors, chromatin modifiers, and {RNA} binding proteins, which enabled the construction of a network model consisting of 24 core regulators and 76 fine-tuners that help to explain how pathogen-sensing pathways achieve specificity. This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.},
	pages = {257--263},
	number = {5950},
	journaltitle = {Science},
	author = {Amit, I and Garber, M and Chevrier, N and Leite, A P and Donner, Y and Eisenhaure, T and Guttman, M and Grenier, J K and Li, W and Zuk, O and Schubert, L A and Birditt, B and Shay, T and Goren, A and Zhang, X and Smith, Z and Deering, R and {McDonald}, R C and Cabili, M and Bernstein, B E and Rinn, J L and Meissner, A and Root, D E and Hacohen, N and Regev, A},
	date = {2009},
	pmid = {19729616},
	keywords = {{DNA}, Animals, Genetic, Mice, Transcription, Transcription Factors/metabolism, Gene Expression Profiling, *Gene Expression Regulation, *Gene Regulatory Networks, Bacteria/*immunology, Chromatin Assembly and Disassembly, Dendritic Cells/*immunology/*metabolism, Feedback, Inbred C57BL, Inflammation/immunology/*metabolism, Lipopeptides/immunology, Lipopolysaccharides/immunology, Physiological, Poly I-C/immunology, {RNA}-Binding Proteins/metabolism, Single-Stranded/immunology, Toll-Like Receptors/agonists, Viruses/*immunology}
}

@article{raj_thousands_2016,
	title = {Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27232982},
	doi = {10.7554/eLife.13328},
	abstract = {Accurate annotation of protein coding regions is essential for understanding how genetic information is translated into function. We describe {riboHMM}, a new method that uses ribosome footprint data to accurately infer translated sequences. Applying {riboHMM} to human lymphoblastoid cell lines, we identified 7273 novel coding sequences, including 2442 translated upstream open reading frames. We observed an enrichment of footprints at inferred initiation sites after drug-induced arrest of translation initiation, validating many of the novel coding sequences. The novel proteins exhibit significant selective constraint in the inferred reading frames, suggesting that many are functional. Moreover, ∼40\% of bicistronic transcripts showed negative correlation in the translation levels of their two coding sequences, suggesting a potential regulatory role for these novel regions. Despite known limitations of mass spectrometry to detect protein expressed at low level, we estimated a 14\% validation rate. Our work significantly expands the set of known coding regions in humans.},
	journaltitle = {Elife},
	author = {Raj, A and Wang, S H and Shim, H and Harpak, A and Li, Y I and Engelmann, B and Stephens, M and Gilad, Y and Pritchard, J K},
	date = {2016},
	pmid = {27232982}
}

@article{pineda_hurs_2012,
	title = {{HuR}'s post-transcriptional regulation of Death Receptor 5 in pancreatic cancer cells},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22785201},
	doi = {10.4161/cbt.20952},
	abstract = {Apoptosis is one of the core signaling pathways disrupted in pancreatic ductal adenocarcinoma ({PDA}). Death receptor 5 ({DR}5) is a member of the tumor necrosis factor ({TNF})-receptor superfamily that is expressed in cancer cells. Binding of {TNF}-related apoptosis-inducing ligand ({TRAIL}) to {DR}5 is a potent trigger of the extrinsic apoptotic pathway, and numerous clinical trials are based on {DR}5-targeted therapies for cancer, including {PDA}. Human antigen R ({HuR}), an {RNA}-binding protein, regulates a select number of transcripts under stress conditions. Here we report that {HuR} translocates from the nucleus to the cytoplasm of {PDA} cells upon treatment with a {DR}5 agonist. High doses of {DR}5 agonist induce cleavage of both {HuR} and caspase 8. {HuR} binds to {DR}5 {mRNA} at the 5'-untranslated region ({UTR}) in {PDA} cells in response to different cancer-associated stressors and subsequently represses {DR}5 protein expression; silencing {HuR} augments {DR}5 protein production by enabling its translation and thus enhances apoptosis. In {PDA} specimens (n = 53), negative {HuR} cytoplasmic expression correlated with elevated {DR}5 expression (odds ratio 16.1, p {\textbackslash}textless 0.0001). Together, these data demonstrate a feedback mechanism elicited by {HuR}-mediated repression of the key apoptotic membrane protein {DR}5.},
	pages = {946--955},
	number = {10},
	journaltitle = {Cancer Biol Ther},
	author = {Pineda, D M and Rittenhouse, D W and Valley, C C and Cozzitorto, J A and Burkhart, R A and Leiby, B and Winter, J M and Weber, M C and Londin, E R and Rigoutsos, I and Yeo, C J and Gorospe, M and Witkiewicz, A K and Sachs, J N and Brody, J R},
	date = {2012},
	pmid = {22785201},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Messenger, *{RNA} Processing, 5' Untranslated Regions, Antimetabolites, Antineoplastic/pharmacology, Cell Line, Cytoplasm/metabolism, Deoxycytidine/analogs \& derivatives/pharmacology, Gene Silencing, Hu Paraneoplastic Encephalomyelitis Antigens/genet, Neoplastic, Pancreatic Neoplasms/*genetics/*metabolism, Post-Transcriptional, Protein Transport/drug effects, Proteolysis/drug effects, Receptors, {TNF}-Related Apoptosis-Inducing Ligand/a, Tumor}
}

@article{santoro_rna-protein_1994,
	title = {{RNA}-protein interactions in the nuclei of Xenopus oocytes: complex formation and processing activity on the regulatory intron of ribosomal protein gene L1},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7935414},
	abstract = {The gene encoding ribosomal protein L1 in Xenopus laevis is known to be posttranscriptionally regulated; the third intron can be processed from the pre-{mRNA} in two alternative ways, resulting either in the production of L1 {mRNA} or in the release of a small nucleolar {RNA} (U16). The formation of splicing complexes was studied in vivo by oocyte microinjection. We show that spliceosome assembly is impaired on the L1 third intron and that the low efficiency of the process is due to the presence of suboptimal consensus sequences. An analysis of heterogeneous nuclear ribonucleoprotein ({hnRNP}) distribution was also performed, revealing a distinct site for {hnRNP} C binding proximal to the 5' end of the L1 third intron. Cleavage, leading to the production of the small nucleolar {RNA} U16, occurs in the same position, and we show that conditions under which {hnRNP} C binding is reduced result in an increase of the processing activity of the intron.},
	pages = {6975--6982},
	number = {10},
	journaltitle = {Mol Cell Biol},
	author = {Santoro, B and De Gregorio, E and Caffarelli, E and Bozzoni, I},
	date = {1994},
	pmid = {7935414},
	keywords = {Animals, Base Sequence, Protein Binding, *{RNA} Splicing, Binding, Cell Nucleus/*metabolism, Competitive, {DNA} Mutational Analysis, Heterogeneous-Nuclear Ribonucleoprotein Group C, Heterogeneous-Nuclear Ribonucleoproteins, Introns/*genetics, Molecular Sequence Data, Oocytes/metabolism, Ribonucleoproteins/metabolism, Ribosomal Proteins/*genetics, {RNA} Precursors/metabolism, Spliceosomes/*metabolism, Xenopus}
}

@article{legnini_feedforward_2014,
	title = {A Feedforward Regulatory Loop between {HuR} and the Long Noncoding {RNA} linc-{MD}1 Controls Early Phases of Myogenesis},
	volume = {53},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24440503},
	doi = {10.1016/j.molcel.2013.12.012},
	abstract = {The muscle-specific long noncoding {RNA} linc-{MD}1 was shown to be expressed during early phases of muscle differentiation and to trigger the switch to later stages by acting as a sponge for {miR}-133 and {miR}-135. Notably, linc-{MD}1 is also the host transcript of {miR}-133b, and their biogenesis is mutually exclusive. Here, we describe that this alternative synthesis is controlled by the {HuR} protein, which favors linc-{MD}1 accumulation through its ability to bind linc-{MD}1 and repress Drosha cleavage. We show that {HuR} is under the repressive control of {miR}-133 and that the sponging activity of linc-{MD}1 consolidates {HuR} expression in a feedforward positive loop. Finally, we show that {HuR} also acts in the cytoplasm, reinforcing linc-{MD}1 sponge activity by cooperating for {miRNA} recruitment. An increase in {miR}-133 synthesis, mainly from the two unrelated {miR}-133a coding genomic loci, is likely to trigger the exit from this circuitry and progression to later differentiation stages.},
	pages = {506--514},
	number = {3},
	journaltitle = {Mol Cell},
	author = {Legnini, I and Morlando, M and Mangiavacchi, A and Fatica, A and Bozzoni, I},
	date = {2014},
	pmid = {24440503}
}

@article{mlynarczyk-evans_x_2006,
	title = {X chromosomes alternate between two states prior to random X-inactivation},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16669701},
	doi = {10.1371/journal.pbio.0040159},
	abstract = {Early in the development of female mammals, one of the two X chromosomes is silenced in half of cells and the other X chromosome is silenced in the remaining half. The basis of this apparent randomness is not understood. We show that before X-inactivation, the two X chromosomes appear to exist in distinct states that correspond to their fates as the active and inactive X chromosomes. Xist and Tsix, noncoding {RNAs} that control X chromosome fates upon X-inactivation, also determine the states of the X chromosomes prior to X-inactivation. In wild-type {ES} cells, X chromosomes switch between states; among the progeny of a single cell, a given X chromosome exhibits each state with equal frequency. We propose a model in which the concerted switching of homologous X chromosomes between mutually exclusive future active and future inactive states provides the basis for the apparently random silencing of one X chromosome in female cells.},
	pages = {e159},
	number = {6},
	journaltitle = {{PLoS} Biol},
	author = {Mlynarczyk-Evans, S and Royce-Tolland, M and Alexander, M K and Andersen, A A and Kalantry, S and Gribnau, J and Panning, B},
	date = {2006},
	pmid = {16669701},
	keywords = {Animals, Genetic, Mice, {RNA}, Cells, Cultured, {DNA} Replication, Female, Fluorescence, In Situ Hybridization, Long Untranslated, Models, Stem Cells/cytology, Untranslated/physiology, X Chromosome Inactivation/*physiology, X Chromosome/*genetics/metabolism}
}

@article{muppirala_predicting_2011,
	title = {Predicting {RNA}-protein interactions using only sequence information},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22192482},
	doi = {10.1186/1471-2105-12-489},
	abstract = {{BACKGROUND}: {RNA}-protein interactions ({RPIs}) play important roles in a wide variety of cellular processes, ranging from transcriptional and post-transcriptional regulation of gene expression to host defense against pathogens. High throughput experiments to identify {RNA}-protein interactions are beginning to provide valuable information about the complexity of {RNA}-protein interaction networks, but are expensive and time consuming. Hence, there is a need for reliable computational methods for predicting {RNA}-protein interactions. {RESULTS}: We propose {RPISeq}, a family of classifiers for predicting {RNA}-protein interactions using only sequence information. Given the sequences of an {RNA} and a protein as input, {RPIseq} predicts whether or not the {RNA}-protein pair interact. The {RNA} sequence is encoded as a normalized vector of its ribonucleotide 4-mer composition, and the protein sequence is encoded as a normalized vector of its 3-mer composition, based on a 7-letter reduced alphabet representation. Two variants of {RPISeq} are presented: {RPISeq}-{SVM}, which uses a Support Vector Machine ({SVM}) classifier and {RPISeq}-{RF}, which uses a Random Forest classifier. On two non-redundant benchmark datasets extracted from the Protein-{RNA} Interface Database ({PRIDB}), {RPISeq} achieved an {AUC} (Area Under the Receiver Operating Characteristic ({ROC}) curve) of 0.96 and 0.92. On a third dataset containing only {mRNA}-protein interactions, the performance of {RPISeq} was competitive with that of a published method that requires information regarding many different features (e.g., {mRNA} half-life, {GO} annotations) of the putative {RNA} and protein partners. In addition, {RPISeq} classifiers trained using the {PRIDB} data correctly predicted the majority (57-99\%) of non-coding {RNA}-protein interactions in {NPInter}-derived networks from E. coli, S. cerevisiae, D. melanogaster, M. musculus, and H. sapiens. {CONCLUSIONS}: Our experiments with {RPISeq} demonstrate that {RNA}-protein interactions can be reliably predicted using only sequence-derived information. {RPISeq} offers an inexpensive method for computational construction of {RNA}-protein interaction networks, and should provide useful insights into the function of non-coding {RNAs}. {RPISeq} is freely available as a web-based server at http://pridb.gdcb.iastate.edu/{RPISeq}/.},
	pages = {489},
	journaltitle = {{BMC} Bioinformatics},
	author = {Muppirala, U K and Honavar, V G and Dobbs, D},
	date = {2011},
	pmid = {22192482},
	keywords = {Animals, Humans, Mice, {RNA}, Databases, Software, *Algorithms, *Protein Interaction Maps, *Sequence Analysis, Drosophila melanogaster/metabolism, Escherichia coli/metabolism, Protein, Proteins/*metabolism, {RNA} Stability, {RNA}-Binding Proteins/*metabolism, {RNA}/*chemistry/metabolism, Saccharomyces cerevisiae/metabolism, Support Vector Machines}
}

@article{kretz_control_2013,
	title = {Control of somatic tissue differentiation by the long non-coding {RNA} {TINCR}},
	volume = {493},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23201690},
	doi = {10.1038/nature11661},
	abstract = {Several of the thousands of human long non-coding {RNAs} ({lncRNAs}) have been functionally characterized; however, potential roles for {lncRNAs} in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase {lncRNA}, terminal differentiation-induced {ncRNA} ({TINCR}), controls human epidermal differentiation by a post-transcriptional mechanism. {TINCR} is required for high messenger {RNA} abundance of key differentiation genes, many of which are mutated in human skin diseases, including {FLG}, {LOR}, {ALOXE}3, {ALOX}12B, {ABCA}12, {CASP}14 and {ELOVL}3. {TINCR}-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale {RNA} interactome analysis revealed that {TINCR} interacts with a range of differentiation {mRNAs}. {TINCR}-{mRNA} interaction occurs through a 25-nucleotide '{TINCR} box' motif that is strongly enriched in interacting {mRNAs} and required for {TINCR} binding. A high-throughput screen to analyse {TINCR} binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of {TINCR} {RNA} to the staufen1 ({STAU}1) protein. {STAU}1-deficient tissue recapitulated the impaired differentiation seen with {TINCR} depletion. Loss of {UPF}1 and {UPF}2, both of which are required for {STAU}1-mediated {RNA} decay, however, did not have differentiation effects. Instead, the {TINCR}-{STAU}1 complex seems to mediate stabilization of differentiation {mRNAs}, such as {KRT}80. These data identify {TINCR} as a key {lncRNA} required for somatic tissue differentiation, which occurs through {lncRNA} binding to differentiation {mRNAs} to ensure their expression.},
	pages = {231--235},
	number = {7431},
	journaltitle = {Nature},
	author = {Kretz, M and Siprashvili, Z and Chu, C and Webster, D E and Zehnder, A and Qu, K and Lee, C S and Flockhart, R J and Groff, A F and Chow, J and Johnston, D and Kim, G E and Spitale, R C and Flynn, R A and Zheng, G X and Aiyer, S and Raj, A and Rinn, J L and Chang, H Y and Khavari, P A},
	date = {2013},
	pmid = {23201690},
	keywords = {Base Sequence, Humans, {RNA}, Gene Expression Regulation, Protein Binding, Cells, Cultured, Cell Differentiation/*genetics, Cytoskeletal Proteins/metabolism, Epidermis/*cytology/*metabolism, High-Throughput Screening Assays, Keratinocytes, Long Noncoding/*genetics/*metabolism, Messenger/genetics/metabolism, Mutation, Nucleotide Motifs/genetics, {RNA} Stability/genetics, {RNA}-Binding Proteins/metabolism, Skin Diseases/genetics}
}

@article{gonzalez-perez_functional_2012,
	title = {Functional impact bias reveals cancer drivers},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22904074},
	doi = {10.1093/nar/gks743},
	abstract = {Identifying cancer driver genes and pathways among all somatic mutations detected in a cohort of tumors is a key challenge in cancer genomics. Traditionally, this is done by prioritizing genes according to the recurrence of alterations that they bear. However, this approach has some known limitations, such as the difficulty to correctly estimate the background mutation rate, and the fact that it cannot identify lowly recurrently mutated driver genes. Here we present a novel approach, Oncodrive-fm, to detect candidate cancer drivers which does not rely on recurrence. First, we hypothesized that any bias toward the accumulation of variants with high functional impact observed in a gene or group of genes may be an indication of positive selection and can thus be used to detect candidate driver genes or gene modules. Next, we developed a method to measure this bias ({FM} bias) and applied it to three datasets of tumor somatic variants. As a proof of concept of our hypothesis we show that most of the highly recurrent and well-known cancer genes exhibit a clear {FM} bias. Moreover, this novel approach avoids some known limitations of recurrence-based approaches, and can successfully identify lowly recurrent candidate cancer drivers.},
	pages = {e169},
	number = {21},
	journaltitle = {Nucleic Acids Res},
	author = {Gonzalez-Perez, A and Lopez-Bigas, N},
	date = {2012},
	pmid = {22904074},
	keywords = {Genomics/*methods, Humans, *Genes, *Mutation, Genetic Variation, Neoplasm}
}

@article{kim_tophat2:_2013,
	title = {{TopHat}2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23618408},
	doi = {10.1186/gb-2013-14-4-r36},
	abstract = {{TopHat} is a popular spliced aligner for {RNA}-sequence ({RNA}-seq) experiments. In this paper, we describe {TopHat}2, which incorporates many significant enhancements to {TopHat}. {TopHat}2 can align reads of various lengths produced by the latest sequencing technologies, while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment, {TopHat}2 can align reads across fusion breaks, which can occur after genomic translocations. {TopHat}2 combines the ability to identify novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes. {TopHat}2 is available at http://ccb.jhu.edu/software/tophat.},
	pages = {R36},
	number = {4},
	journaltitle = {Genome Biol},
	author = {Kim, D and Pertea, G and Trapnell, C and Pimentel, H and Kelley, R and Salzberg, S L},
	date = {2013},
	pmid = {23618408},
	keywords = {Transcriptome, *Software, Sequence Analysis, Humans, *Gene Duplication, *Gene Fusion, *Mutagenesis, Insertional, {RNA}/methods, Sensitivity and Specificity, Sequence Alignment/*methods}
}

@article{lopez_de_silanes_rna-binding_2009,
	title = {The {RNA}-binding protein {HuR} regulates {DNA} methylation through stabilization of {DNMT}3b {mRNA}},
	volume = {37},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19270063},
	doi = {10.1093/nar/gkp123},
	abstract = {The molecular basis underlying the aberrant {DNA}-methylation patterns in human cancer is largely unknown. Altered {DNA} methyltransferase ({DNMT}) activity is believed to contribute, as {DNMT} expression levels increase during tumorigenesis. Here, we present evidence that the expression of {DNMT}3b is post-transcriptionally regulated by {HuR}, an {RNA}-binding protein that stabilizes and/or modulates the translation of target {mRNAs}. The presence of a putative {HuR}-recognition motif in the {DNMT}3b 3'{UTR} prompted studies to investigate if this transcript associated with {HuR}. The interaction between {HuR} and {DNMT}3b {mRNA} was studied by immunoprecipitation of endogenous {HuR} ribonucleoprotein complexes followed by {RT}-{qPCR} detection of {DNMT}3b {mRNA}, and by in vitro pulldown of biotinylated {DNMT}3b {RNAs} followed by western blotting detection of {HuR}. These studies revealed that binding of {HuR} stabilized the {DNMT}3b {mRNA} and increased {DNMT}3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [{HuR}-{DNMT}3b {mRNA}] complex, in turn promoting {DNMT}3b {mRNA} decay, decreasing {DNMT}3b abundance, and lowering the methylation of repeated sequences and global {DNA} methylation. In summary, our data identify {DNMT}3b {mRNA} as a novel {HuR} target, present evidence that {HuR} affects {DNMT}3b expression levels post-transcriptionally, and reveal the functional consequences of the {HuR}-regulated {DNMT}3b upon {DNA} methylation patterns.},
	pages = {2658--2671},
	number = {8},
	journaltitle = {Nucleic Acids Res},
	author = {Lopez de Silanes, I and Gorospe, M and Taniguchi, H and Abdelmohsen, K and Srikantan, S and Alaminos, M and Berdasco, M and Urdinguio, R G and Fraga, M F and Jacinto, F V and Esteller, M},
	date = {2009},
	pmid = {19270063},
	keywords = {Base Sequence, Humans, {RNA}, *{DNA} Methylation, *{RNA} Stability, Antigens, Antineoplastic Agents/pharmacology, Cell Line, Cisplatin/pharmacology, {DNA} (Cytosine-5-)-Methyltransferase/*genetics/meta, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/*metabolism, Molecular Sequence Data, {RNA}-Binding Proteins/analysis/*metabolism, Surface/analysis/*metabolism, Tumor}
}

@article{masuda_rna-binding_2009,
	title = {{RNA}-binding proteins implicated in the hypoxic response},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19583805},
	doi = {10.1111/j.1582-4934.2009.00842.x},
	abstract = {In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post-transcriptional processes. {RNA}-binding proteins ({RBPs}) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the {RBPs} that modulate {mRNA} turnover and translation in response to hypoxic challenge. The {RBPs} {HuR} (human antigen R) and {PTB} (polypyrimidine tract-binding protein) associate with {mRNAs} encoding hypoxia-response proteins such as {HIF}-1alpha and {VEGF} {mRNAs}, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional {RBPs} such as iron-response element-binding proteins ({IRPs}), cytoplasmic polyadenylation-element-binding proteins ({CPEBs}) and several heterogeneous nuclear ribonucleoproteins ({hnRNPs}) also bind to hypoxia-regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by {RBPs} and the mounting interest in targeting hypoxia-regulatory {RBPs} in diseases with aberrant hypoxic responses.},
	pages = {2759--2769},
	number = {9},
	journaltitle = {J Cell Mol Med},
	author = {Masuda, K and Abdelmohsen, K and Gorospe, M},
	date = {2009},
	pmid = {19583805},
	keywords = {Animals, Humans, Gene Expression Regulation, Antigens, Cell Hypoxia/physiology, Hu Paraneoplastic Encephalomyelitis Antigens, {RNA}-Binding Proteins/*metabolism, Surface/metabolism}
}

@article{haerty_mutations_2013,
	title = {Mutations within {lncRNAs} are effectively selected against in fruitfly but not in human},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23710818},
	doi = {10.1186/gb-2013-14-5-r49},
	abstract = {{BACKGROUND}: Previous studies in Drosophila and mammals have revealed levels of long non-coding {RNAs} ({lncRNAs}) sequence conservation that are intermediate between neutrally evolving and protein-coding sequence. These analyses compared conservation between species that diverged up to 75 million years ago. However, analysis of sequence polymorphisms within a species' population can provide an understanding of essentially contemporaneous selective constraints that are acting on {lncRNAs} and can quantify the deleterious effect of mutations occurring within these loci. {RESULTS}: We took advantage of polymorphisms derived from the genome sequences of 163 Drosophila melanogaster strains and 174 human individuals to calculate the distribution of fitness effects of single nucleotide polymorphisms occurring within intergenic {lncRNAs} and compared this to distributions for {SNPs} present within putatively neutral or protein-coding sequences. Our observations show that in D.melanogaster there is a significant excess of rare frequency variants within intergenic {lncRNAs} relative to neutrally evolving sequences, whereas selection on human intergenic {lncRNAs} appears to be effectively neutral. Approximately 30\% of mutations within these fruitfly {lncRNAs} are estimated as being weakly deleterious. {CONCLUSIONS}: These contrasting results can be attributed to the large difference in effective population sizes between the two species. Our results suggest that while the sequences of {lncRNAs} will be well conserved across insect species, such loci in mammals will accumulate greater proportions of deleterious changes through genetic drift.},
	pages = {R49},
	number = {5},
	journaltitle = {Genome Biol},
	author = {Haerty, W and Ponting, C P},
	date = {2013},
	pmid = {23710818}
}

@article{schultz_smart_1998,
	title = {{SMART}, a simple modular architecture research tool: identification of signaling domains},
	volume = {95},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9600884},
	abstract = {Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool ({SMART}: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25\% of our domain set could not be deduced from {SwissProt} and 41\% could not be annotated by Pfam. {SMART} is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7\% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing {SMART} predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains ({UBA}); (iv) cellular roles for proteins, such predicted {DEATH} domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as {SPRY} domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.},
	pages = {5857--5864},
	number = {11},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Schultz, J and Milpetz, F and Bork, P and Ponting, C P},
	date = {1998},
	pmid = {9600884},
	keywords = {*Software, Animals, Genome, Humans, *Sequence Analysis, Amino Acid Sequence, Molecular Sequence Data, Phylogeny, Proteins/*genetics}
}

@article{schwanhausser_global_2011,
	title = {Global quantification of mammalian gene expression control},
	volume = {473},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21593866},
	doi = {10.1038/nature10098},
	abstract = {Gene expression is a multistep process that involves the transcription, translation and turnover of messenger {RNAs} and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute {mRNA} and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas {mRNA} and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of {mRNAs} and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of {mRNA} and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.},
	pages = {337--342},
	number = {7347},
	journaltitle = {Nature},
	author = {Schwanhausser, B and Busse, D and Li, N and Dittmar, G and Schuchhardt, J and Wolf, J and Chen, W and Selbach, M},
	date = {2011},
	pmid = {21593866},
	keywords = {Gene Expression Profiling/*methods, Animals, Genetic, Mice, {RNA}, Reproducibility of Results, *Gene Expression Regulation, Half-Life, Mammals/genetics, Messenger/*analysis/biosynthesis/genetics/met, Models, {NIH} 3T3 Cells, Protein Biosynthesis/genetics, Proteins/*analysis/genetics/metabolism, Staining and Labeling}
}

@article{voorhoeve_tumor-suppressive_2003,
	title = {The tumor-suppressive functions of the human {INK}4A locus},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14585358},
	abstract = {The {INK}4A locus is often inactivated in human cancer. {INK}4A encodes for p14ARF and p16INK4A that inhibit growth through p53 and {pRb}, respectively. We used {RNA} interference vectors in transformation assays of human primary cells to analyze tumor-suppressive functions. We first show that a concerted inactivation of {pRb} and p53 is required for transformation. We then demonstrate that loss of p14ARF enhances growth in a p53-dependent manner but has little tumorigenic effect. In contrast, suppression of p16INK4A expression does not affect cellular proliferation but synergizes with p53 loss to accelerate growth and cause transformation. Our results delineate the functions of the human {INK}4A genes in normal and tumorigenic growth.},
	pages = {311--319},
	number = {4},
	journaltitle = {Cancer Cell},
	author = {Voorhoeve, P M and Agami, R},
	date = {2003},
	pmid = {14585358},
	keywords = {Humans, {RNA}, Cells, Cultured, Cell Division/*physiology, Cyclin-Dependent Kinase Inhibitor p16/genetics/*me, Fibroblasts/metabolism, Gene Deletion, Genes, {HeLa} Cells, Mutation, ras/genetics/physiology, Retinoblastoma Protein/metabolism, Skin/metabolism, Small Interfering/metabolism, Tumor Suppressor Protein p14ARF/genetics/*metaboli, Tumor Suppressor Protein p53/metabolism}
}

@article{liu_age-related_1996,
	title = {Age-related decline in mitogen-activated protein kinase activity in epidermal growth factor-stimulated rat hepatocytes},
	volume = {271},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8631968},
	abstract = {A number of studies have demonstrated that the proliferative capacity of cells declines with aging. In particular, epidermal growth factor ({EGF})-stimulated {DNA} synthesis is reduced in hepatocytes from aged rats relative to young rats. Growth factor stimulation activates a genetic program in large part regulated by a family of mitogen-activated protein kinases ({MAPK}) that phosphorylate and thereby activate transcription factors involved in controlling the expression of proliferation-associated genes. In the present study, we compared the activation of the extracellular signal-regulated kinase 2 ({ERK}2) and c-Jun N-terminal kinase 1 ({JNK}1) {MAPK} in {EGF}-stimulated hepatocytes derived from young (6-month) and aged (24-month) rats. {JNK} activity was not appreciably altered by {EGF} treatment of cells from either age group. In contrast, {ERK}2 was highly activated by {EGF} treatment, but the magnitude of activation was significantly lower in hepatocytes of aged animals compared to those of young animals (7-fold versus 20-fold, respectively). The reduced {ERK}2 activity in response to {EGF} was associated with decreased c-fos and c-jun {mRNA} expression and lower levels of {AP}-1 transcription factor {DNA} binding activity in the aged hepatocytes. Finally, the basal expression of {MAPK} phosphatase 1, a {MAPK}-regulated gene involved in regulating {MAPK} activity, was higher in aged hepatocytes. Taken together, these findings suggest that an alteration in the balance between {MAP} kinase-phosphatase activities could contribute to the age-related decline in proliferative capacity.},
	pages = {3604--3607},
	number = {7},
	journaltitle = {J Biol Chem},
	author = {Liu, Y and Guyton, K Z and Gorospe, M and Xu, Q and Kokkonen, G C and Mock, Y D and Roth, G S and Holbrook, N J},
	date = {1996},
	pmid = {8631968},
	keywords = {Animals, Base Sequence, Binding Sites, Cells, Cultured, *Cell Cycle Proteins, *Mitogen-Activated Protein Kinases, *Phosphoprotein Phosphatases, Aging/*metabolism, Blotting, Calcium-Calmodulin-Dependent Protein Kinases/biosy, Dual Specificity Phosphatase 1, Enzyme Activation, Epidermal Growth Factor/*pharmacology, Gene Expression, Immediate-Early Proteins/biosynthesis/metabolism, {JNK} Mitogen-Activated Protein Kinases, Kinetics, Liver/drug effects/*enzymology/growth \& developmen, Male, Mitogen-Activated Protein Kinase 1, Molecular Sequence Data, Northern, Oligodeoxyribonucleotides, Protein Phosphatase 1, Protein Tyrosine Phosphatases/biosynthesis/metabol, Rats, Transcription Factor {AP}-1/metabolism, Western, Wistar}
}

@article{robinson_mitogen-activated_2008,
	title = {Mitogen-activated protein kinase kinase 4/c-Jun {NH}2-terminal kinase kinase 1 protein expression is subject to translational regulation in prostate cancer cell lines},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18337456},
	doi = {10.1158/1541-7786.MCR-07-2075},
	abstract = {Mitogen-activated protein kinase kinase 4/c-Jun {NH}(2)-terminal kinase kinase 1 ({MKK}4/{JNKK}1; hereafter referred to as {MKK}4) is a dual-specificity kinase with a critical role in regulating the activity of c-Jun {NH}(2)-terminal kinase and p38 kinases. We identified a novel biological function for {MKK}4 in the regulation of growth of ovarian and prostate cancer metastases. Clinical correlative studies showed that {MKK}4 protein levels were reduced in high-grade prostate cancer and prostate and ovarian cancer metastases compared with normal tissue, which prompted investigation into the mechanism(s) responsible for down-regulation of {MKK}4 in a panel of cancer cell lines. Initial studies found that low levels of {MKK}4 protein did not correlate with either exon deletion or decreased levels of {MKK}4 {mRNA}, suggesting that {MKK}4 protein levels were regulated posttranscriptionally by either reduced translation or reduced protein stability. Endogenous {MKK}4 was highly stable and not subject to altered proteolysis. Instead, {MKK}4 biosynthesis seemed to be regulated by altered translation. In support of this assertion, we found that cytosolic {MKK}4 {mRNA} was shifted toward active polysomes in cells with higher levels of {MKK}4 protein, suggesting that {MKK}4 {mRNA} was translated more efficiently in these cells. This study supports a novel mechanism for the regulation of {MKK}4 protein levels. Further, these findings have potential therapeutic implications for modulating the expression of a signaling kinase involved in the regulation of metastatic growth.},
	pages = {501--508},
	number = {3},
	journaltitle = {Mol Cancer Res},
	author = {Robinson, V L and Shalhav, O and Otto, K and Kawai, T and Gorospe, M and Rinker-Schaeffer, C W},
	date = {2008},
	pmid = {18337456},
	keywords = {Humans, Gene Expression Regulation, *Gene Expression Regulation, *Protein Biosynthesis, Acetylcysteine/analogs \& derivatives/pharmacology, Blotting, Cell Line, Cycloheximide/pharmacology, Dactinomycin/pharmacology, Enzymologic/drug effec, Ethanol/pharmacology, Female, Male, {MAP} Kinase Kinase 4/*genetics, Neoplasm Metastasis, Neoplastic/drug effec, Northern, Ovarian Neoplasms/enzymology/genetics/pathology, Polymerase Chain Reaction, Prostatic Neoplasms/enzymology/*genetics, Tumor}
}

@article{sunkara_long_2014,
	title = {Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial},
	volume = {101},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24188873},
	doi = {10.1016/j.fertnstert.2013.09.035},
	abstract = {{OBJECTIVE}: To compare the efficacy of the long {GnRH} agonist vs. the short {GnRH} agonist vs. the {GnRH} antagonist regimens in poor responders undergoing {IVF}. {DESIGN}: Randomized controlled trial. {SETTING}: Tertiary referral fertility units. {PATIENT}(S): Women with previous poor ovarian response undergoing {IVF}. {INTERVENTION}(S): One hundred eleven women were randomized to the long {GnRH} agonist, short agonist, and antagonist regimens. {MAIN} {OUTCOME} {MEASURE}(S): The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching {ET}, and clinical and ongoing pregnancy rates. {RESULT}(S): Number of oocytes retrieved was significantly higher with long {GnRH} agonist compared with the short agonist regimen (4.42 +/- 3.06 vs. 2.71 +/- 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 +/- 3.06 vs. 3.30 +/- 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1\% with long and short agonist regimens and 16.2\% with the antagonist regimen. {CONCLUSION}(S): Long {GnRH} agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved.},
	pages = {147--153},
	number = {1},
	journaltitle = {Fertil Steril},
	author = {Sunkara, S K and Coomarasamy, A and Faris, R and Braude, P and Khalaf, Y},
	date = {2014},
	pmid = {24188873},
	keywords = {Humans, Adult, Female, Female/*administration \& dosage, Fertility Agents, Fertilization in Vitro/*methods, Gonadotropin-Releasing Hormone/*agonists/*antagoni, Gonadotropins/administration \& dosage, Nafarelin/administration \& dosage, Pregnancy, Pregnancy Rate/trends, Treatment Outcome}
}

@article{marin-bejar_rna_2015,
	title = {{RNA} pulldown protocol for in vitro detection and identification of {RNA}-associated proteins},
	volume = {1206},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25240889},
	doi = {10.1007/978-1-4939-1369-5_8},
	abstract = {Recent advances in genomics have revealed that cells encode thousands of noncoding {RNA} molecules that do not require translation to proteins to perform their biological roles. Although very little is known about the mechanisms of function of noncoding {RNAs}, these undoubtedly involve the interaction with multiple cellular proteins. Here we describe a detailed {RNA} pulldown protocol for the in vitro detection of proteins specifically interacting with a long {RNA} molecule.},
	pages = {87--95},
	journaltitle = {Methods Mol Biol},
	author = {Marin-Bejar, O and Huarte, M},
	date = {2015},
	pmid = {25240889},
	keywords = {Animals, Mice, {RNA}, Cells, Cultured, Biotin/chemistry, Fibroblasts, Molecular Biology/*methods, Proteins/analysis/*metabolism, Untranslated/*analysis/chemistry/*metabolism}
}

@article{ohta_slightly_1973,
	title = {Slightly deleterious mutant substitutions in evolution},
	volume = {246},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/4585855},
	pages = {96--98},
	number = {5428},
	journaltitle = {Nature},
	author = {Ohta, T},
	date = {1973},
	pmid = {4585855},
	keywords = {Genetic, *Biological Evolution, *Models, *Mutation, Alleles, Biological, Dominant, Gene Frequency, Genes, Homozygote, Polymorphism, Recessive}
}

@article{ikeyama_expression_2003,
	title = {Expression of the pro-apoptotic gene gadd153/chop is elevated in liver with aging and sensitizes cells to oxidant injury},
	volume = {278},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12609979},
	doi = {10.1074/jbc.M300677200},
	abstract = {Aging is generally accompanied by reduced tolerance to oxidative stress and altered responsiveness to proliferative signals. We have shown that hepatocytes derived from aged rats (24-26 months) exhibit greater sensitivity to H(2)O(2) treatment and reduced proliferation following epidermal growth factor ({EGF}) treatment than cells of young adult rats (5-6 months). Here we examined the effects of aging and calorie restriction ({CR}) on expression of the oxidative stress-inducible and pro-apoptotic gene gadd153 (chop) in these hepatocytes, and we investigated its influence on sensitivity to oxidants. We show that aging was associated with elevated expression of gadd153, both basally and in response to H(2)O(2) treatment. {CR}, which attenuates age-associated declines in stress tolerance, prevented the age-related increase in gadd153 expression. {EGF} treatment also resulted in gadd153 induction in old cells. This effect was absent in young cells and in old cells of {CR} rats. gadd153 induction by {EGF} was reactive oxygen species-dependent and correlated with heightened sensitivity to subsequent H(2)O(2) treatment, suggesting that elevated Gadd153 contributes to the greater sensitivity of {EGF}-pretreated old cells to oxidative stress. Additional support for this hypothesis was provided by experiments with Rat1 fibroblasts in which conditional expression of Gadd153 conferred increased sensitivity to H(2)O(2). We propose a model whereby the diminished ability of old hepatocytes to overcome an {EGF}-triggered reactive oxygen species load leads to induction of the proapoptotic gene gadd153, which, in turn, sensitizes the cells to oxidant injury. Our findings point to gadd153 expression levels as an important factor in liver aging.},
	pages = {16726--16731},
	number = {19},
	journaltitle = {J Biol Chem},
	author = {Ikeyama, S and Wang, X T and Li, J and Podlutsky, A and Martindale, J L and Kokkonen, G and van Huizen, R and Gorospe, M and Holbrook, N J},
	date = {2003},
	pmid = {12609979},
	keywords = {Animals, Gene Expression Regulation, Aging/*genetics/metabolism/pathology, Apoptosis/genetics, {CCAAT}-Enhancer-Binding Proteins/biosynthesis/*gene, Inbred F344, Liver/*metabolism/pathology, Male, Oxidative Stress/*genetics, Rats, Transcription Factor {CHOP}, Transcription Factors/biosynthesis/*genetics}
}

@article{sunkara_isolation_2013,
	title = {Isolation and Functional Characterization of a Novel Seed-Specific Promoter Region from Peanut},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24078220},
	doi = {10.1007/s12010-013-0482-x},
	abstract = {The importance of using tissue-specific promoters in the genetic transformation of plants has been emphasized increasingly. Here, we report the isolation of a novel seed-specific promoter region from peanut and its validation in Arabidopsis and tobacco seeds. The reported promoter region referred to as groundnut seed promoter ({GSP}) confers seed-specific expression in heterologous systems, which include putative promoter regions of the peanut (Arachis hypogaea L.) gene 8A4R19G1. This region was isolated, sequenced, and characterized using gel shift assays. Tobacco transgenics obtained using binary vectors carrying {uidA} reporter gene driven by {GSP} and/or cauliflower mosaic virus 35S promoters were confirmed through polymerase chain reaction ({PCR}), {RT}-{PCR}, and computational analysis of motifs which revealed the presence of {TATA}, {CAAT} boxes, and {ATG} signals. This seed-specific promoter region successfully targeted the reporter {uidA} gene to seed tissues in both Arabidopsis and tobacco model systems, where its expression was confirmed by histochemical analysis of the transgenic seeds. This promoter region is routinely being used in the genetic engineering studies in legumes aimed at targeting novel transgenes to the seeds, especially those involved in micronutrient enhancement, fungal resistance, and molecular pharming.},
	journaltitle = {Appl Biochem Biotechnol},
	author = {Sunkara, S and Bhatnagar-Mathur, P and Sharma, K K},
	date = {2013},
	pmid = {24078220}
}

@article{xu_exploring_2014,
	title = {Exploring the potential benefits of stratified false discovery rates for region-based testing of association with rare genetic variation},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24523729},
	doi = {10.3389/fgene.2014.00011},
	abstract = {When analyzing the data that arises from exome or whole-genome sequencing studies, window-based tests, (i.e., tests that jointly analyze all genetic data in a small genomic region), are very popular. However, power is known to be quite low for finding associations with phenotypes using these tests, and therefore a variety of analytic strategies may be employed to potentially improve power. Using sequencing data of all of chromosome 3 from an interim release of data on 2432 individuals from the {UK}10K project, we simulated phenotypes associated with rare genetic variation, and used the results to explore the window-based test power. We asked two specific questions: firstly, whether there could be substantial benefits associated with incorporating information from external annotation on the genetic variants, and secondly whether the false discovery rate ({FDRs}) would be a useful metric for assessing significance. Although, as expected, there are benefits to using additional information (such as annotation) when it is associated with causality, we confirmed the general pattern of low sensitivity and power for window-based tests. For our chosen example, even when power is high to detect some of the associations, many of the regions containing causal variants are not detectable, despite using lax significance thresholds and optimal analytic methods. Furthermore, our estimated {FDR} values tended to be much smaller than the true {FDRs}. Long-range correlations between variants-due to linkage disequilibrium-likely explain some of this bias. A more sophisticated approach to using the annotation information may improve power, however, many causal variants of realistic effect sizes may simply be undetectable, at least with this sample size. Perhaps annotation information could assist in distinguishing windows containing causal variants from windows that are merely correlated with causal variants.},
	pages = {11},
	journaltitle = {Front Genet},
	author = {Xu, C and Ciampi, A and Greenwood, C M},
	date = {2014},
	pmid = {24523729}
}

@article{haygood_promoter_2007,
	title = {Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17694055},
	doi = {10.1038/ng2104},
	abstract = {Surveys of protein-coding sequences for evidence of positive selection in humans or chimpanzees have flagged only a few genes known to function in neural or nutritional processes, despite pronounced differences between humans and chimpanzees in behavior, cognition and diet. It may be that most such differences are due to changes in gene regulation rather than protein structure. Here, we present the first survey of promoter (5'-flanking) regions, which are rich in cis-regulatory sequences, for evidence of positive selection in humans. Our results indicate that positive selection has targeted the regulation of many genes known to be involved in neural development and function, both in the brain and elsewhere in the nervous system, and in nutrition, particularly in glucose metabolism.},
	pages = {1140--1144},
	number = {9},
	journaltitle = {Nat Genet},
	author = {Haygood, R and Fedrigo, O and Hanson, B and Yokoyama, K D and Wray, G A},
	date = {2007},
	pmid = {17694055},
	keywords = {Human, Animals, Genetic, Genome, Humans, Promoter Regions, Gene Expression Regulation, *Evolution, *Nutrigenomics, *Selection, 5' Flanking Region, Computational Biology/methods, Developmental, Energy Metabolism/genetics, Genetic/*genetics, Models, Molecular, Nervous System/embryology/growth \& development/*me, Pan troglodytes}
}

@article{leucci_melanoma_2016,
	title = {Melanoma addiction to the long non-coding {RNA} {SAMMSON}},
	volume = {531},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27008969},
	doi = {10.1038/nature17161},
	abstract = {Focal amplifications of chromosome 3p13-3p14 occur in about 10\% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene {MITF} resides at the epicentre of this amplicon. However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding {RNA} ({lncRNA}) gene {SAMMSON} is consistently co-gained with {MITF}. In addition, {SAMMSON} is a target of the lineage-specific transcription factor {SOX}10 and its expression is detectable in more than 90\% of human melanomas. Whereas exogenous {SAMMSON} increases the clonogenic potential in trans, {SAMMSON} knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and {BRAF}, {NRAS} or {TP}53 mutational status. Moreover, {SAMMSON} targeting sensitizes melanoma to {MAPK}-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, {SAMMSON} interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene {SAMMSON} disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.},
	pages = {518--522},
	number = {7595},
	journaltitle = {Nature},
	author = {Leucci, E and Vendramin, R and Spinazzi, M and Laurette, P and Fiers, M and Wouters, J and Radaelli, E and Eyckerman, S and Leonelli, C and Vanderheyden, K and Rogiers, A and Hermans, E and Baatsen, P and Aerts, S and Amant, F and Van Aelst, S and van den Oord, J and de Strooper, B and Davidson, I and Lafontaine, D L and Gevaert, K and Vandesompele, J and Mestdagh, P and Marine, J C},
	date = {2016},
	pmid = {27008969},
	keywords = {Human, Animals, Humans, Mice, {RNA}, Carcinogenesis/genetics/pathology, Cell Lineage, Cell Proliferation, Cell Survival, Chromosomes, Clone Cells/metabolism/pathology, Female, Gene Amplification/genetics, Gene Knockdown Techniques, Long Noncoding/*genetics/therapeutic use, Melanoma/*genetics/*pathology/therapy, Microphthalmia-Associated Transcription Factor/gen, Mitochondria/genetics/metabolism/pathology, Mitochondrial Proteins/metabolism, Mitogen-Activated Protein Kinases/antagonists \& in, Molecular Targeted Therapy, Oncogenes/*genetics, Pair 3/genetics, {SOXE} Transcription Factors/metabolism, Xenograft Model Antitumor Assays}
}

@article{paulsen_preparing_2006,
	title = {Preparing for preventive clinical trials: the Predict-{HD} study},
	volume = {63},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16769871},
	doi = {10.1001/archneur.63.6.883},
	abstract = {{BACKGROUND}: The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown. {OBJECTIVE}: To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease ({HD}). {DESIGN}: The Predict-{HD} study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia. {SETTING}: Genetics and {HD} outpatient clinics. {PARTICIPANTS}: Five hundred five at-risk individuals who had previously undergone elective {DNA} analyses for the {CAG} expansion in the {HD} gene (predictive testing) and did not currently have a clinical diagnosis of {HD}. {MAIN} {OUTCOME} {MEASURES}: Basal ganglia volumes on magnetic resonance images, estimated probability of diagnosis (based on {CAG} repeat length), performances on 21 standardized cognitive tasks, total scores on 3 scales of psychiatric distress, and motor diagnosis based on the Unified Huntington's Disease Rating Scale. {RESULTS}: Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. Estimated probability of diagnosis was associated with Unified Huntington's Disease Rating Scale prediagnostic stages and varied from 15\% in persons with no motor abnormalities to nearly 40\% in those with abnormalities suggestive of probable disease. Striatal volumes, cognitive performances, and even psychiatric ratings declined significantly with motor manifestations of disease. {CONCLUSIONS}: The documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials. Longitudinal study is critical to further validate possible markers for prediagnosed {HD}.},
	pages = {883--890},
	number = {6},
	journaltitle = {Arch Neurol},
	author = {Paulsen, J S and Hayden, M and Stout, J C and Langbehn, D R and Aylward, E and Ross, C A and Guttman, M and Nance, M and Kieburtz, K and Oakes, D and Shoulson, I and Kayson, E and Johnson, S and Penziner, E},
	date = {2006},
	pmid = {16769871},
	keywords = {Humans, Adult, Age Factors, {DNA} Mutational Analysis, Female, Huntington Disease/diagnosis/*genetics/*physiopath, International Cooperation, Longitudinal Studies, Magnetic Resonance Imaging/methods, Male, Middle Aged, Neurologic Examination, Neuropsychological Tests/statistics \& numerical da, Probability, Trinucleotide Repeats/*genetics}
}

@article{grote_tissue-specific_2013,
	title = {The tissue-specific {lncRNA} Fendrr is an essential regulator of heart and body wall development in the mouse},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23369715},
	doi = {10.1016/j.devcel.2012.12.012},
	abstract = {The histone-modifying complexes {PRC}2 and {TrxG}/{MLL} play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long noncoding {RNAs} ({lncRNAs}) can bind to either complex, and some have been shown to act as modulators of {PRC}2 or {TrxG}/{MLL} activity. Here we show that the lateral mesoderm-specific {lncRNA} Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in {PRC}2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the {PRC}2 and {TrxG}/{MLL} complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, we identified an {lncRNA} that plays an essential role in the regulatory networks controlling the fate of lateral mesoderm derivatives.},
	pages = {206--214},
	number = {2},
	journaltitle = {Dev Cell},
	author = {Grote, P and Wittler, L and Hendrix, D and Koch, F and Wahrisch, S and Beisaw, A and Macura, K and Blass, G and Kellis, M and Werber, M and Herrmann, B G},
	date = {2013},
	pmid = {23369715},
	keywords = {Animals, Genetic, Mice, Promoter Regions, {RNA}, Transcription Factors/metabolism, *Embryonic Development, Cell Differentiation/genetics, {DNA} Methylation, Embryo, Forkhead Transcription Factors/metabolism, Heart/*embryology, Histones/metabolism, Homeodomain Proteins/metabolism, Long Untranslated/genetics/*metabolism, Mammalian/embryology/metabolism, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein/*metabolism, Polycomb Repressive Complex 2/*metabolism}
}

@article{bourque_evolution_2008,
	title = {Evolution of the mammalian transcription factor binding repertoire via transposable elements},
	volume = {18},
	url = {http://genome.cshlp.org/content/18/11/1752.abstractN2 - Identification of lineage-specific innovations in genomic control elements is critical for understanding transcriptional regulatory networks and phenotypic heterogeneity. We analyzed, from an evoluti},
	pages = {1752--1762},
	number = {11},
	journaltitle = {Genome Res},
	author = {Bourque, Guillaume and Leong, Bernard and Vega, Vinsensius B and Chen, Xi and Lee, Yen Ling and Srinivasan, Kandhadayar G and Chew, Joon-Lin and Ruan, Yijun and Wei, Chia-Lin and Ng, Huck Hui and Liu, Edison T},
	date = {2008},
	keywords = {{DNA}, Animals, Base Sequence, Conserved Sequence, Humans, Mice, Binding Sites, {DNA} Transposable Elements, Transcription Factors, Evolution, Molecular, Repetitive Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/DAPGUECX/Bourque et al. - 2008 - Evolution of the mammalian transcription factor bi.pdf:application/pdf}
}

@article{potapova_c-jun_2000,
	title = {c-Jun N-terminal kinase is essential for growth of human T98G glioblastoma cells},
	volume = {275},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10825181},
	doi = {10.1074/jbc.M904591199},
	abstract = {The c-Jun N-terminal kinase/stress-activated protein kinase ({JNK}/{SAPK}) pathway is activated by numerous cellular stresses. Although it has been implicated in mediating apoptosis and growth factor signaling, its role in regulating cell growth is not yet clear. Here, the influence of {JNK} on basal (unstimulated) growth of human tumor glioblastoma T98G cells was investigated using highly specific {JNK} antisense oligonucleotides to inhibit {JNK} expression. Transient depletion of either {JNK}1 or {JNK}2 suppressed cell growth associated with an inhibition of {DNA} synthesis and cell cycle arrest in S phase. The growth-inhibitory potency of {JNK}2 antisense (({JNK})2 {IC}(50) = 0.14 micrometer) was greater than that of {JNK}1 antisense (({JNK})1 {IC}(50) = 0.37 micrometer), suggesting that {JNK}2 plays a dominant role in regulating growth of T98G cells. Indeed, {JNK}2 antisense-treated populations exhibited greater inhibition of {DNA} synthesis and accumulation of S-phase cells than did the {JNK}1 antisense-treated cultures, with a significant proportion of these cells detaching from the tissue culture plate. {JNK}2 (but not {JNK}1) antisense-treated cultures exhibited marked elevation in the expression of the cyclin-dependent kinase inhibitor p21(cip1/waf1) accompanied by inhibition of Cdk2/Cdc2 kinase activities. Taken together, these results indicate that {JNK} is required for growth of T98G cells in nonstress conditions and that p21(cip1/waf1) may contribute to the sustained growth arrest of {JNK}2-depleted T98G cultures.},
	pages = {24767--24775},
	number = {32},
	journaltitle = {J Biol Chem},
	author = {Potapova, O and Gorospe, M and Bost, F and Dean, N M and Gaarde, W A and Mercola, D and Holbrook, N J},
	date = {2000},
	pmid = {10825181},
	keywords = {{DNA}, Humans, Transcription, Gene Expression Regulation, Cultured, Antisense/*pharmacology, Cell Cycle/*drug effects, Cell Division/drug effects/*physiology, Genetic/*drug effects, Glioblastoma, {JNK} Mitogen-Activated Protein Kinases, Kinetics, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinases/*genetics/metabo, Neoplasm/biosynthesis, Neoplastic/drug effect, Oligodeoxyribonucleotides, S Phase, Thionucleotides, Tumor Cells}
}

@article{davo-blanes_[public_2014,
	title = {[Public health competencies and contents in Spanish university degree programs of physical therapy, occupational therapy, environmental science, dentistry and veterinary science]},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24041446},
	doi = {10.1016/j.gaceta.2013.06.008},
	abstract = {{OBJECTIVE}: To identify the basic competencies and contents related to public health to be included in degree programs according to the perspective of lecturers from various Spanish universities. {METHOD}: In the context of the Second Workshop on Public Health Contents in Degree Programs (Mahon, 19 to 20 September 2012), 20 lecturers from different Spanish universities were distributed in five working groups. The lecturers had been selected from the instructional guides on public health and epidemiology published on the web sites of the Rectors' Conference of Spanish Universities. Each group worked on a degree program and the results were discussed in plenary sessions. {RESULTS}: The activities and competencies related to the three basic functions of public health were identified in all degree programs. Most of the professional competencies identified were related to the function of {\textbackslash}textless{\textbackslash}textlessassessment of population health needs{\textbackslash}textgreater{\textbackslash}textgreater. The contents proposed by the working groups related to epidemiology, basic concepts in public health, public health intervention, health management, and health policy. The main common topics among the degrees concerned the first three contents. {CONCLUSIONS}: Public health professional competencies and contents were identified in the degree programs examined. These results may serve as a starting point for a more detailed review of public health programs across degree levels and the search for a consensus on the common content that should be included in each of them.},
	pages = {123--128},
	number = {2},
	journaltitle = {Gac Sanit},
	author = {Davo-Blanes, M C and Vives-Cases, C and Alvarez-Dardet, C and Segura-Benedicto, A A and Bosch Llonch, F and F, G Benavides},
	date = {2014},
	pmid = {24041446}
}

@article{ratnayaka_interventional_2008,
	title = {Interventional cardiovascular magnetic resonance: still tantalizing},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19114017},
	doi = {10.1186/1532-429X-10-62},
	abstract = {The often touted advantages of {MR} guidance remain largely unrealized for cardiovascular interventional procedures in patients. Many procedures have been simulated in animal models. We argue these opportunities for clinical interventional {MR} will be met in the near future. This paper reviews technical and clinical considerations and offers advice on how to implement a clinical-grade interventional cardiovascular {MR} ({iCMR}) laboratory. We caution that this reflects our personal view of the "state of the art."},
	pages = {62},
	journaltitle = {J Cardiovasc Magn Reson},
	author = {Ratnayaka, K and Faranesh, A Z and Guttman, M A and Kocaturk, O and Saikus, C E and Lederman, R J},
	date = {2008},
	pmid = {19114017},
	keywords = {Animals, Humans, *Cardiac Catheterization/adverse effects/instrumen, *Magnetic Resonance Imaging, Angioplasty, Balloon, Cardiac, Cardiovascular Diseases/*pathology/physiopathology, Coronary, Electrophysiologic Techniques, Embolization, Equipment Design, Heart Valve Prosthesis Implantation, Hemodynamics, Interventional/advers, Monitoring, Operating Rooms/organization \& administration, Physiologic, Predictive Value of Tests, Stents, Therapeutic, Treatment Outcome}
}

@article{wutz_chromosomal_2002,
	title = {Chromosomal silencing and localization are mediated by different domains of Xist {RNA}},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11780141},
	doi = {10.1038/ng820},
	abstract = {The gene Xist initiates the chromosomal silencing process of X inactivation in mammals. Its product, a noncoding {RNA}, is expressed from and specifically associates with the inactive X chromosome in female cells. Here we use an inducible Xist expression system in mouse embryonic stem cells that recapitulates long-range chromosomal silencing to elucidate which Xist {RNA} sequences are necessary for chromosomal association and silencing. We show that chromosomal association and spreading of Xist {RNA} can be functionally separated from silencing by specific mutations. Silencing requires a conserved repeat sequence located at the 5' end of Xist. Deletion of this element results in Xist {RNA} that still associates with chromatin and spreads over the chromosome but does not effect transcriptional repression. Association of Xist {RNA} with chromatin is mediated by functionally redundant sequences that act cooperatively and are dispersed throughout the remainder of Xist but show little or no homology.},
	pages = {167--174},
	number = {2},
	journaltitle = {Nat Genet},
	author = {Wutz, A and Rasmussen, T P and Jaenisch, R},
	date = {2002},
	pmid = {11780141},
	keywords = {Animals, Base Sequence, Conserved Sequence, Genetic, Mice, {RNA}, Untranslated/*genetics, *Gene Silencing, Chromosome Mapping, Dosage Compensation, Female, Gene Transfer Techniques, Histones/metabolism, Hypoxanthine Phosphoribosyltransferase/genetics, Leukemia, Long Untranslated, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Plasma Cell, {RNA}/chemistry/*genetics, Stem Cells/metabolism, Transcription Factors/*genetics, X Chromosome/genetics/metabolism}
}

@article{chkhotua_transplanting_2013,
	title = {Transplanting kidneys with small renal masses: a new source of renal allografts},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24323957},
	abstract = {The number of publications on transplanting kidneys with small renal masses is steadily growing. There are several transplant centers worldwide with organized programs of transplanting such kidneys. Nevertheless, despite growing number of reports this practice remains controversial. The existing guidelines for kidney transplantation give controversial recommendations concerning transplantation of the kidneys with renal masses. There are arguments in favour as well as against this policy. Importance of the subject is emphasized by calculations showing that about 3000 kidneys with tumors could be transplanted in the United States annually. Based on the results reported in the literature the risk of occurrence of de novo graft tumor is extremely low and varies from 0.24\% to 0.46\%. A risk of getting a transmitted cancer is even lower and reported as 0.015-0.2\%. The patient and graft survival rates of these kidneys are comparable to that of the standard criteria deceased and living transplant. More studies with higher number of patients are needed to prove the functional and oncological safety of this practice.},
	pages = {11--14},
	number = {224},
	journaltitle = {Georgian Med News},
	author = {Chkhotua, A and Mshvildadze, Sh and Managadze, L},
	date = {2013},
	pmid = {24323957},
	keywords = {Humans, *Kidney Transplantation, *Tissue Donors, Allografts/*pathology/transplantation, Kidney Neoplasms/*pathology/surgery, Survival Rate}
}

@article{fragapane_identification_1992,
	title = {Identification of the sequences responsible for the splicing phenotype of the regulatory intron of the L1 ribosomal protein gene of Xenopus laevis},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1545793},
	abstract = {Splicing of the regulated third intron of the L1 ribosomal protein gene of Xenopus laevis has been studied in vivo by oocyte microinjection of wild-type and mutant {SP}6 precursor {RNAs} and in vitro in the heterologous {HeLa} nuclear extract. We show that two different phenomena combine to produce the peculiar splicing phenotype of this intron. One, which can be defined constitutive, shows the same features in the two systems and leads to the accumulation of spliced {mRNA}, but in very small amounts. The low efficiency of splicing is due to the presence of a noncanonical 5' splice site which acts in conjunction with sequences present in the 3' portion of the intron. The second leads to the massive conversion of the pre-{mRNA} into site specific truncated molecules. This has the effect of decreasing the concentration of the pre-{mRNA} available for splicing. We show that this aberrant cleavage activity occurs only in the in vivo oocyte system and depends on the presence of an intact U1 {RNA}.},
	pages = {1117--1125},
	number = {3},
	journaltitle = {Mol Cell Biol},
	author = {Fragapane, P and Caffarelli, E and Lener, M and Prislei, S and Santoro, B and Bozzoni, I},
	date = {1992},
	pmid = {1545793},
	keywords = {Animals, Base Sequence, Genetic, Humans, Transcription, Nucleic Acid, *Introns, *Regulatory Sequences, Dna, {HeLa} Cells, Kinetics, Molecular Sequence Data, Oocytes/metabolism, Phenotype, Ribosomal Proteins/*genetics, {RNA} Splicing/*genetics, Xenopus laevis}
}

@article{presutti_ribosomal_1991,
	title = {The ribosomal protein L2 in S. cerevisiae controls the level of accumulation of its own {mRNA}},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2065661},
	abstract = {The expression of the yeast L2 r-protein gene is controlled at the level of {mRNA} accumulation. The product of the gene appears to participate in this regulation by an autogenous feedback mechanism. This control does not operate at the level of transcription but instead affects L2 {mRNA} accumulation. This autogenous regulation of {mRNA} accumulation provides an interesting analogy to the autogenous translational regulation of r-proteins in Escherichia coli.},
	pages = {2215--2221},
	number = {8},
	journaltitle = {{EMBO} J},
	author = {Presutti, C and Ciafre, S A and Bozzoni, I},
	date = {1991},
	pmid = {2065661},
	keywords = {{DNA}, Genetic, {RNA}, Transcription, Gene Expression Regulation, Blotting, Fungal, Fungal/genetics, Fungal/genetics/*metabolism, Messenger/genetics/*metabolism, Northern, Plasmids, Post-Transcriptional, Ribosomal Proteins/genetics/*metabolism, {RNA} Processing, Saccharomyces cerevisiae/*metabolism, Southern}
}

@article{luo_systematic_2014,
	title = {Systematic prioritization and integrative analysis of copy number variations in schizophrenia reveal key schizophrenia susceptibility genes},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24664977},
	doi = {10.1093/schbul/sbu045},
	abstract = {Schizophrenia is a common mental disorder with high heritability and strong genetic heterogeneity. Common disease-common variants hypothesis predicts that schizophrenia is attributable in part to common genetic variants. However, recent studies have clearly demonstrated that copy number variations ({CNVs}) also play pivotal roles in schizophrenia susceptibility and explain a proportion of missing heritability. Though numerous {CNVs} have been identified, many of the regions affected by {CNVs} show poor overlapping among different studies, and it is not known whether the genes disrupted by {CNVs} contribute to the risk of schizophrenia. By using cumulative scoring, we systematically prioritized the genes affected by {CNVs} in schizophrenia. We identified 8 top genes that are frequently disrupted by {CNVs}, including {NRXN}1, {CHRNA}7, {BCL}9, {CYFIP}1, {GJA}8, {NDE}1, {SNAP}29, and {GJA}5. Integration of genes affected by {CNVs} with known schizophrenia susceptibility genes (from previous genetic linkage and association studies) reveals that many genes disrupted by {CNVs} are also associated with schizophrenia. Further protein-protein interaction ({PPI}) analysis indicates that protein products of genes affected by {CNVs} frequently interact with known schizophrenia-associated proteins. Finally, systematic integration of {CNVs} prioritization data with genetic association and {PPI} data identifies key schizophrenia candidate genes. Our results provide a global overview of genes impacted by {CNVs} in schizophrenia and reveal a densely interconnected molecular network of de novo {CNVs} in schizophrenia. Though the prioritized top genes represent promising schizophrenia risk genes, further work with different prioritization methods and independent samples is needed to confirm these findings. Nevertheless, the identified key candidate genes may have important roles in the pathogenesis of schizophrenia, and further functional characterization of these genes may provide pivotal targets for future therapeutics and diagnostics.},
	pages = {1285--1299},
	number = {6},
	journaltitle = {Schizophr Bull},
	author = {Luo, X and Huang, L and Han, L and Luo, Z and Hu, F and Tieu, R and Gan, L},
	date = {2014},
	pmid = {24664977}
}

@article{kim_different_2011,
	title = {Different modes of interaction by {TIAR} and {HuR} with target {RNA} and {DNA}},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21233170},
	doi = {10.1093/nar/gkq837},
	abstract = {{TIAR} and {HuR} are {mRNA}-binding proteins that play important roles in the regulation of translation. They both possess three {RNA} recognition motifs ({RRMs}) and bind to {AU}-rich elements ({AREs}), with seemingly overlapping specificity. Here we show using {SPR} that {TIAR} and {HuR} bind to both U-rich and {AU}-rich {RNA} in the nanomolar range, with higher overall affinity for U-rich {RNA}. However, the higher affinity for U-rich sequences is mainly due to faster association with U-rich {RNA}, which we propose is a reflection of the higher probability of association. Differences between {TIAR} and {HuR} are observed in their modes of binding to {RNA}. {TIAR} is able to bind deoxy-oligonucleotides with nanomolar affinity, whereas {HuR} affinity is reduced to a micromolar level. Studies with U-rich {DNA} reveal that {TIAR} binding depends less on the 2'-hydroxyl group of {RNA} than {HuR} binding. Finally we show that {SAXS} data, recorded for the first two domains of {TIAR} in complex with {RNA}, are more consistent with a flexible, elongated shape and not the compact shape that the first two domains of Hu proteins adopt upon binding to {RNA}. We thus propose that these triple-{RRM} proteins, which compete for the same binding sites in cells, interact with their targets in fundamentally different ways.},
	pages = {1117--1130},
	number = {3},
	journaltitle = {Nucleic Acids Res},
	author = {Kim, H S and Wilce, M C and Yoga, Y M and Pendini, N R and Gunzburg, M J and Cowieson, N P and Wilson, G M and Williams, B R and Gorospe, M and Wilce, J A},
	date = {2011},
	pmid = {21233170},
	keywords = {Protein Binding, Adenine/analysis, Antigens, {DNA}/*chemistry/metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Kinetics, Models, Molecular, Protein Conformation, {RNA}-Binding Proteins/*chemistry/metabolism, {RNA}/*chemistry/metabolism, Scattering, Small Angle, Surface/*chemistry/metabolism, Uracil/analysis, X-Ray Diffraction}
}

@article{chang_interaction_2012,
	title = {Interaction between {microRNAs} and actin-associated protein Arpc5 regulates translational suppression during male germ cell differentiation},
	volume = {109},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22447776},
	doi = {10.1073/pnas.1117837109},
	abstract = {Decoupling of transcription and translation during postmeiotic germ cell differentiation is critical for successful spermatogenesis. Here we establish that the interaction between {microRNAs} and actin-associated protein Arpc5 sets the stage for an elaborate translational control mechanism by facilitating the sequestration of germ cell {mRNAs} into translationally inert ribonucleoprotein particles until they are later translated. Our studies reveal that loss of {microRNA}-dependent regulation of Arpc5, which controls the distribution of germ cell {mRNAs} between translationally active and inactive pools, results in abnormal round spermatid differentiation and impaired fertility. Interestingly, Arpc5 functions as a broadly acting translational suppressor, as it inhibits translation initiation by blocking 80S formation and facilitates the transport of {mRNAs} to chromatoid/P bodies. These findings identify a unique role for actin-associated proteins in translational regulation, and suggest that {mRNA}-specific and general translational control mechanisms work in tandem to regulate critical germ cell differentiation events and diverse somatic cell functions.},
	pages = {5750--5755},
	number = {15},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Chang, Y F and Lee-Chang, J S and Imam, J S and Buddavarapu, K C and Subaran, S S and Sinha-Hikim, A P and Gorospe, M and Rao, M K},
	date = {2012},
	pmid = {22447776},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Gene Expression Regulation, Protein Binding, Actin-Related Protein 2-3 Complex/*metabolism, Cell Differentiation/*genetics, Chromatin/metabolism, Enzyme Activation, Haploidy, {HeLa} Cells, Male, Meiosis/genetics, Messenger/genetics/metabolism, {MicroRNAs}/genetics/*metabolism, Molecular Sequence Data, Protamines/metabolism, Protein Biosynthesis, Reproduction, Ribonuclease {III}/metabolism, Ribosomes/metabolism, Sperm Head/metabolism/pathology/ultrastructure, Spermatozoa/*metabolism/*pathology, Testis/abnormalities/pathology/ultrastructure}
}

@article{noren_hooten_microrna_2010,
	title = {{microRNA} expression patterns reveal differential expression of target genes with age},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20505758},
	doi = {10.1371/journal.pone.0010724},
	abstract = {Recent evidence supports a role for {microRNAs} ({miRNAs}) in regulating the life span of model organisms. However, little is known about how these small {RNAs} contribute to human aging. Here, we profiled the expression of over 800 {miRNAs} in peripheral blood mononuclear cells from young and old individuals by real-time {RT}-{PCR} analysis. This genome-wide assessment of {miRNA} expression revealed that the majority of {miRNAs} studied decreased in abundance with age. We identified nine {miRNAs} ({miR}-103, {miR}-107, {miR}-128, {miR}-130a, {miR}-155, {miR}-24, {miR}-221, {miR}-496, {miR}-1538) that were significantly lower in older individuals. Among them, five have been implicated in cancer pathogenesis. Predicted targets of several of these {miRNAs}, including {PI}3 kinase ({PI}3K), c-Kit and H2AX, were found to be elevated with advancing age, supporting a possible role for them in the aging process. Furthermore, we found that decreasing the levels of {miR}-221 was sufficient to cause a corresponding increase in the expression of the predicted target, {PI}3K. Taken together, these findings demonstrate that changes in {miRNA} expression occur with human aging and suggest that {miRNAs} and their predicted targets have the potential to be diagnostic indicators of age or age-related diseases.},
	pages = {e10724},
	number = {5},
	journaltitle = {{PLoS} One},
	author = {Noren Hooten, N and Abdelmohsen, K and Gorospe, M and Ejiogu, N and Zonderman, A B and Evans, M K},
	date = {2010},
	pmid = {20505758},
	keywords = {Animals, Base Sequence, Humans, Reproducibility of Results, *Gene Expression Profiling, *Gene Expression Regulation, Adult, Aging/*genetics, Caenorhabditis elegans/genetics/growth \& developme, Developmental, Down-Regulation/genetics, Female, {HeLa} Cells, Male, {MicroRNAs}/*genetics/metabolism, Middle Aged, Molecular Sequence Data, Phosphatidylinositol 3-Kinases/genetics/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/genetics, Up-Regulation/genetics}
}

@article{smith_classification_1998,
	title = {Classification of gas5 as a multi-small-nucleolar-{RNA} ({snoRNA}) host gene and a member of the 5'-terminal oligopyrimidine gene family reveals common features of {snoRNA} host genes},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9819378},
	abstract = {We have identified gas5 (growth arrest-specific transcript 5) as a non-protein-coding multiple small nucleolar {RNA} ({snoRNA}) host gene similar to {UHG} (U22 host gene). Encoded within the 11 introns of the mouse gas5 gene are nine (10 in human) box C/D {snoRNAs} predicted to function in the 2'-O-methylation of {rRNA}. The only regions of conservation between mouse and human gas5 genes are their {snoRNAs} and 5'-end sequences. Mapping the 5' end of the mouse gas5 transcript demonstrates that it possesses an oligopyrimidine tract characteristic of the 5'-terminal oligopyrimidine (5'{TOP}) class of genes. Arrest of cell growth or inhibition of translation by cycloheximide, pactamycin, or rapamycin-which specifically inhibits the translation of 5'{TOP} {mRNAs}-results in accumulation of the gas5 spliced {RNA}. Classification of gas5 as a 5'{TOP} gene provides an explanation for why it is a growth arrest specific transcript: while the spliced gas5 {RNA} is normally associated with ribosomes and rapidly degraded, during arrested cell growth it accumulates in {mRNP} particles, as has been reported for other 5'{TOP} messages. Strikingly, inspection of the 5'-end sequences of currently known {snoRNA} host gene transcripts reveals that they all exhibit features of the 5'{TOP} gene family.},
	pages = {6897--6909},
	number = {12},
	journaltitle = {Mol Cell Biol},
	author = {Smith, C M and Steitz, J A},
	date = {1998},
	pmid = {9819378},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Transcription, Messenger/genetics, Genetic/genetics, *{RNA}, 3T3 Cells, Antisense/genetics, Cell Division/genetics, Cell Nucleolus/*genetics, Cloning, Membrane Proteins/*genetics, Molecular, Molecular Sequence Data, Multigene Family/*genetics, Protein Biosynthesis/genetics, Ribonucleoproteins/genetics, Ribosomes/genetics, {RNA} Splicing/genetics, Small Nuclear/*genetics, Small Nucleolar}
}

@article{lai_ddx3_2010,
	title = {{DDX}3 regulates cell growth through translational control of cyclin E1},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20837705},
	doi = {10.1128/MCB.00560-10},
	abstract = {{DDX}3 belongs to the {DEAD} box family of {RNA} helicases, but the details of its biological function remain largely unclear. Here we show that knockdown of {DDX}3 expression impedes G(1)/S-phase transition of the cell cycle. To know how {DDX}3 may act in cell cycle control, we screened for cellular {mRNA} targets of {DDX}3. Many of the identified {DDX}3 targets encoded cell cycle regulators, including G(1)/S-specific cyclin E1. {DDX}3 depletion specifically downregulates translation of cyclin E1 {mRNA}. Moreover, our data suggest that {DDX}3 participates in translation initiation of targeted {mRNAs} as well as in cell growth control via its {RNA} helicase activity. Consistent with these findings, we show that in the temperature-sensitive {DDX}3 mutant hamster cell line {tsET}24, cyclin E1 expression is downregulated at a nonpermissive temperature that inactivates mutant {DDX}3. Taken together, our results indicate that {DDX}3 is critical for translation of cyclin E1 {mRNA}, which provides an alternative mechanism for regulating cyclin E1 expression during the cell cycle.},
	pages = {5444--5453},
	number = {22},
	journaltitle = {Mol Cell Biol},
	author = {Lai, M C and Chang, W C and Shieh, S Y and Tarn, W Y},
	date = {2010},
	pmid = {20837705},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation, *Protein Biosynthesis, 5' Untranslated Regions, Cell Cycle/physiology, Cell Growth Processes/*physiology, Cell Line, Cricetinae, Cricetulus, Cyclin E/genetics/*metabolism, {DEAD}-box {RNA} Helicases/genetics/*metabolism, Gene Knockdown Techniques, Messenger/genetics/metabolism, Mutation, Oncogene Proteins/genetics/*metabolism, Small Interfering/genetics/metabolism}
}

@article{crain_absence_1976,
	title = {Absence of short period interspersion of repetitive and non-repetitive sequences in the {DNA} of Drosophila melanogaster},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/820526},
	abstract = {A sensitive search has been made in Drosophila melanogaster {DNA} for short repetitive sequences interspersed with single copy sequences. Five kinds of measurements all yield the conclusion that there are few short repetitive sequences in this genome: () Comparison of the kinetics of reassociation of short (360 nucleotide) and long (1,830 nucleotide) fragments of {DNA}; 2) reassociation kinetics of long fragments (2,200 nucleotide) with an excess of short (390 short nucleotide) fragments; 3) measurement of the size of S1 nuclease resistant reassociated repeated sequences; 4) measurement of the hyperchromicity of reassociated repetive fragments as a function of length; 5) direct assay by kinetics of reassociation of the amount of single copy sequence present on 1,200 nucletodie long fragments which also contain repetitive sequences.},
	pages = {309--326},
	number = {4},
	journaltitle = {Chromosoma},
	author = {Crain, W R and Eden, F C and Pearson, W R and Davidson, E H and Britten, R J},
	date = {1976},
	pmid = {820526},
	keywords = {Animals, Base Sequence, {DNA}/*analysis, Drosophila melanogaster/*chemistry, Nucleic Acid Renaturation, Nucleotides}
}

@article{puetz_frequency_2009,
	title = {Frequency and clinical course of stroke and transient ischemic attack patients with intracranial nonocclusive thrombus on computed tomographic angiography},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18988908},
	doi = {10.1161/STROKEAHA.108.526277},
	abstract = {{BACKGROUND} {AND} {PURPOSE}: We sought to determine the frequency and clinical course of patients with acute ischemic stroke or transient ischemic attack ({TIA}) who had intracranial nonocclusive thrombus ({iNOT}) on {CT} angiography ({CTA}). {METHODS}: We retrospectively (June 2002-March 2007) reviewed consecutive patients with acute ischemic stroke or {TIA} who had {CTA} performed acutely for diagnostic work-up. A neuroradiologist reviewed all cases with potential {iNOT}. Criteria to diagnose {iNOT} rather than occlusive thrombus or atherosclerotic stenosis were: (1) residual lumen present and eccentric; (2) nontapering thrombus; (3) smooth and well-defined thrombus margins; and (4) absence of vessel wall calcification. We defined functional independence at discharge as modified Rankin scale score {\textbackslash}textless/=2. {RESULTS}: Of 865 patients, 23 (2.7\%) exhibited {iNOT} on {CTA} (43\% women, mean age 69+/-14 years, median National Institute of Health Stroke Scale score 3 [range, 0-23]; median onset-to-{CTA} time 3.5 hours [range, 0.9-75]). Four patients (17\%) deteriorated clinically during the hospital course and had persistent new focal neurological deficits. All of them were functionally dependent at discharge. All 19 patients (83\%) without persistent clinical deterioration (2 patients had recurrent {TIAs}) were functionally independent at discharge. {CONCLUSIONS}: Intracranial nonocclusive thrombus on {CTA} is relatively uncommon. The majority of patients have a good clinical outcome. However, some patients deteriorate clinically and are functionally dependent at discharge.},
	pages = {193--199},
	number = {1},
	journaltitle = {Stroke},
	author = {Puetz, V and Dzialowski, I and Coutts, S B and Hill, M D and Krol, A and O'Reilly, C and Goyal, M and Demchuk, A M},
	date = {2009},
	pmid = {18988908},
	keywords = {Humans, Aged, Cerebral Arteries/pathology/physiopathology/*radio, Comorbidity, Disability Evaluation, Disease Progression, Female, Incidence, Intracranial Thrombosis/*epidemiology/*radiography, Ischemic Attack, Male, Middle Aged, Outcome Assessment (Health Care), Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Factors, Severity of Illness Index, Stroke/*epidemiology, Tomography, Transient/*epidemiology, X-Ray Computed/methods/standards/*stat}
}

@article{bozzoni_xenopus_1981,
	title = {Xenopus laevis ribosomal protein genes: isolation of recombinant {cDNA} clones and study of the genomic organization},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6112733},
	abstract = {Poly-A+ {mRNA} from Xenopus laevis oocytes, partially enriched for r-protein coding capacity has been used as starting material for preparing a {cDNA} bank in plasmid {pBR}322. The clones containing sequences specific for r-proteins have been selected by translation of the complementary {mRNAs}. Clones for six different r-proteins have been identified and utilized as probes for studying their genomic organization. Two gene copies per haploid genome were found for r-proteins L1, L14, S19, and four-five for protein S1, S8 and L32. Moreover a population polymorphism has been observed for the genomic regions containing sequences for r-protein S1, S8 and L14.},
	pages = {1069--1086},
	number = {5},
	journaltitle = {Nucleic Acids Res},
	author = {Bozzoni, I and Beccari, E and Luo, Z X and Amaldi, F},
	date = {1981},
	pmid = {6112733},
	keywords = {{DNA}, Animals, {RNA}, Cloning, {DNA}/*genetics, Electrophoresis, Messenger/isolation \& purification, Molecular, Nucleic Acid Hybridization, Poly A/isolation \& purification, Polyacrylamide Gel, Recombinant/*isolation \& purification, Ribosomal Proteins/*genetics, Xenopus laevis/*genetics}
}

@article{britten_repetitive_1971,
	title = {Repetitive and non-repetitive {DNA} sequences and a speculation on the origins of evolutionary novelty},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/5160087},
	pages = {111--138},
	number = {2},
	journaltitle = {Q Rev Biol},
	author = {Britten, R J and Davidson, E H},
	date = {1971},
	pmid = {5160087},
	keywords = {Base Sequence, *Biological Evolution, *Dna, *Genetic Code, *Molecular Biology, Chemical, Models, Rna}
}

@article{fatica_cic1p/nsa3p_2003,
	title = {Cic1p/Nsa3p is required for synthesis and nuclear export of 60S ribosomal subunits},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14623999},
	abstract = {Cic1p/Nsa3p was previously reported to be associated with the 26S proteasome and required for the degradation of specific substrates, but was also shown to be associated with early pre-60S particles and to be localized to the nucleolus. Here we report that Cic1p/Nsa3p is required for the synthesis of 60S ribosome subunits. A temperature-sensitive lethal cic1-2 point mutation inhibits synthesis of the mature 5.8S and 25S {rRNAs}. Release of the pre-60S particles from the nucleolus to the nucleoplasm was also inhibited as judged by the nuclear accumulation of an Rpl11b-{GFP} reporter construct. We suggest that Cic1p/Nsa3p associates early with nascent preribosomal particles and is required for correct processing and nuclear release of large ribosomal subunit precursors.},
	pages = {1431--1436},
	number = {12},
	journaltitle = {{RNA}},
	author = {Fatica, A and Oeffinger, M and Tollervey, D and Bozzoni, I},
	date = {2003},
	pmid = {14623999},
	keywords = {Base Sequence, {RNA}, *Ribosomes, Biological Transport, Carrier Proteins/*physiology, Cell Nucleus/*metabolism, {DNA} Primers, Green Fluorescent Proteins, Luminescent Proteins/metabolism, Recombinant Fusion Proteins/metabolism, Ribosomal/*metabolism, Saccharomyces cerevisiae Proteins/*physiology}
}

@article{clop_mutation_2006,
	title = {A mutation creating a potential illegitimate {microRNA} target site in the myostatin gene affects muscularity in sheep},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16751773},
	doi = {10.1038/ng1810},
	abstract = {Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin ({GDF}8) gene. We herein demonstrate that the {GDF}8 allele of Texel sheep is characterized by a G to A transition in the 3' {UTR} that creates a target site for mir1 and mir206, {microRNAs} ({miRNAs}) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of {SNP} databases for humans and mice demonstrates that mutations creating or destroying putative {miRNA} target sites are abundant and might be important effectors of phenotypic variation.},
	pages = {813--818},
	number = {7},
	journaltitle = {Nat Genet},
	author = {Clop, A and Marcq, F and Takeda, H and Pirottin, D and Tordoir, X and Bibe, B and Bouix, J and Caiment, F and Elsen, J M and Eychenne, F and Larzul, C and Laville, E and Meish, F and Milenkovic, D and Tobin, J and Charlier, C and Georges, M},
	date = {2006},
	pmid = {16751773},
	keywords = {Animals, Humans, Mice, *Mutation, Binding Sites/genetics, Chromosome Mapping, Hypertrophy, {MicroRNAs}/*genetics, Muscle, Myostatin, Polymorphism, Quantitative Trait Loci, Sheep/anatomy \& histology/*genetics, Single Nucleotide, Skeletal/metabolism/pathology, Transforming Growth Factor beta/*genetics}
}

@article{brubaker_bicistronic_2014,
	title = {A Bicistronic {MAVS} Transcript Highlights a Class of Truncated Variants in Antiviral Immunity},
	volume = {156},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24529381},
	doi = {10.1016/j.cell.2014.01.021},
	abstract = {Bacterial and viral {mRNAs} are often polycistronic. Akin to alternative splicing, alternative translation of polycistronic messages is a mechanism to generate protein diversity and regulate gene function. Although a few examples exist, the use of polycistronic messages in mammalian cells is not widely appreciated. Here we report an example of alternative translation as a means of regulating innate immune signaling. {MAVS}, a regulator of antiviral innate immunity, is expressed from a bicistronic {mRNA} encoding a second protein, {miniMAVS}. This truncated variant interferes with interferon production induced by full-length {MAVS}, whereas both proteins positively regulate cell death. To identify other polycistronic messages, we carried out genome-wide ribosomal profiling and identified a class of antiviral truncated variants. This study therefore reveals the existence of a functionally important bicistronic antiviral {mRNA} and suggests a widespread role for polycistronic {mRNAs} in the innate immune system.},
	pages = {800--811},
	number = {4},
	journaltitle = {Cell},
	author = {Brubaker, S W and Gauthier, A E and Mills, E W and Ingolia, N T and Kagan, J C},
	date = {2014},
	pmid = {24529381}
}

@article{gorospe_post-transcriptional_2011,
	title = {Post-Transcriptional Control of the Hypoxic Response by {RNA}-Binding Proteins and {MicroRNAs}},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21747757},
	doi = {10.3389/fnmol.2011.00007},
	abstract = {Mammalian gene expression patterns change profoundly in response to low oxygen levels. These changes in gene expression programs are strongly influenced by post-transcriptional mechanisms mediated by {mRNA}-binding factors: {RNA}-binding proteins ({RBPs}) and {microRNAs} ({miRNAs}). Here, we review the {RBPs} and {miRNAs} that modulate {mRNA} turnover and translation in response to hypoxic challenge. {RBPs} such as {HuR} (human antigen R), {PTB} (polypyrimidine tract-binding protein), heterogeneous nuclear ribonucleoproteins ({hnRNPs}), tristetraprolin, nucleolin, iron-response element-binding proteins ({IRPs}), and cytoplasmic polyadenylation-element-binding proteins ({CPEBs}), selectively bind to numerous hypoxia-regulated transcripts and play a major role in establishing hypoxic gene expression patterns. {MiRNAs} including {miR}-210, {miR}-373, and {miR}-21 associate with hypoxia-regulated transcripts and further modulate the levels of the encoded proteins to implement the hypoxic gene expression profile. We discuss the potent regulation of hypoxic gene expression by {RBPs} and {miRNAs} and their integrated actions in the cellular hypoxic response.},
	pages = {7},
	journaltitle = {Front Mol Neurosci},
	author = {Gorospe, M and Tominaga, K and Wu, X and Fahling, M and Ivan, M},
	date = {2011},
	pmid = {21747757}
}

@article{brastianos_genomic_2013,
	title = {Genomic sequencing of meningiomas identifies oncogenic {SMO} and {AKT}1 mutations},
	volume = {45},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23334667},
	doi = {10.1038/ng.2526},
	abstract = {Meningiomas are the most common primary nervous system tumor. The tumor suppressor {NF}2 is disrupted in approximately half of all meningiomas, but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal {NF}2 inactivation in 43\% of tumors and found alterations in epigenetic modifiers in an additional 8\% of tumors. A subset of meningiomas lacking {NF}2 alterations harbored recurrent oncogenic mutations in {AKT}1 (p.Glu17Lys) and {SMO} (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets.},
	pages = {285--289},
	number = {3},
	journaltitle = {Nat Genet},
	author = {Brastianos, P K and Horowitz, P M and Santagata, S and Jones, R T and {McKenna}, A and Getz, G and Ligon, K L and Palescandolo, E and Van Hummelen, P and Ducar, M D and Raza, A and Sunkavalli, A and Macconaill, L E and Stemmer-Rachamimov, A O and Louis, D N and Hahn, W C and Dunn, I F and Beroukhim, R},
	date = {2013},
	pmid = {23334667},
	keywords = {Genomics, Base Sequence, Humans, Brain Neoplasms/*genetics/pathology, G-Protein-Coupled/*genetics, Meningioma/*genetics/pathology, Mutation, Neurofibromin 2/genetics/metabolism, Proto-Oncogene Proteins c-akt/*genetics, Receptors}
}

@article{borkin_what_2013,
	title = {What makes a visualization memorable?},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24051797},
	doi = {10.1109/TVCG.2013.234},
	abstract = {An ongoing debate in the Visualization community concerns the role that visualization types play in data understanding. In human cognition, understanding and memorability are intertwined. As a first step towards being able to ask questions about impact and effectiveness, here we ask: 'What makes a visualization memorable?' We ran the largest scale visualization study to date using 2,070 single-panel visualizations, categorized with visualization type (e.g., bar chart, line graph, etc.), collected from news media sites, government reports, scientific journals, and infographic sources. Each visualization was annotated with additional attributes, including ratings for data-ink ratios and visual densities. Using Amazon's Mechanical Turk, we collected memorability scores for hundreds of these visualizations, and discovered that observers are consistent in which visualizations they find memorable and forgettable. We find intuitive results (e.g., attributes like color and the inclusion of a human recognizable object enhance memorability) and less intuitive results (e.g., common graphs are less memorable than unique visualization types). Altogether our findings suggest that quantifying memorability is a general metric of the utility of information, an essential step towards determining how to design effective visualizations.},
	pages = {2306--2315},
	number = {12},
	journaltitle = {{IEEE} Trans Vis Comput Graph},
	author = {Borkin, M A and Vo, A A and Bylinskii, Z and Isola, P and Sunkavalli, S and Oliva, A and Pfister, H},
	date = {2013},
	pmid = {24051797}
}

@article{kraft_deletions_2015,
	title = {Deletions, Inversions, Duplications: Engineering of Structural Variants using {CRISPR}/Cas in Mice},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25660031},
	doi = {10.1016/j.celrep.2015.01.016},
	abstract = {Structural variations ({SVs}) contribute to the variability of our genome and are often associated with disease. Their study in model systems was hampered until now by labor-intensive genetic targeting procedures and multiple mouse crossing steps. Here we present the use of {CRISPR}/Cas for the fast (10 weeks) and efficient generation of {SVs} in mice. We specifically produced deletions, inversions, and also duplications at six different genomic loci ranging from 1.1 kb to 1.6 Mb with efficiencies up to 42\%. After {PCR}-based selection, clones were successfully used to create mice via aggregation. To test the practicability of the method, we reproduced a human 500 kb disease-associated deletion and were able to recapitulate the human phenotype in mice. Furthermore, we evaluated the regulatory potential of a large genomic interval by deleting a 1.5 Mb fragment. The method presented permits rapid in vivo modeling of genomic rearrangements.},
	journaltitle = {Cell Rep},
	author = {Kraft, K and Geuer, S and Will, A J and Chan, W L and Paliou, C and Borschiwer, M and Harabula, I and Wittler, L and Franke, M and Ibrahim, D M and Kragesteen, B K and Spielmann, M and Mundlos, S and Lupianez, D G and Andrey, G},
	date = {2015},
	pmid = {25660031}
}

@article{johnson_genome-wide_2012,
	title = {A genome-wide screen for genetic variants that modify the recruitment of {REST} to its target genes},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22496669},
	doi = {10.1371/journal.pgen.1002624},
	abstract = {Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from {DNA} sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that {SNPs} within the binding sites of the transcriptional repressor {REST} alter the degree of repression of target genes. Given that changes in the effective concentration of {REST} contribute to several pathologies-various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation-these {SNPs} should alter disease-susceptibility in carriers. We devised a strategy to identify {SNPs} that affect the recruitment of {REST} to target genes through the alteration of its {DNA} recognition element, the {RE}1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic {RE}1 sequences with robust and statistically significant differences of affinity between alleles. These {SNPs} have a considerable effect on the the functional recruitment of {REST} to {DNA} in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in {RE}1 affinity. Amongst the targets of polymorphic {RE}1 elements are important disease genes including {NPPA}, {PTPRT}, and {CDH}4. Thus, considerable genetic variation exists in the {DNA} motifs that connect gene regulatory networks. Recently available {ChIP}-seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism.},
	pages = {e1002624},
	number = {4},
	journaltitle = {{PLoS} Genet},
	author = {Johnson, R and Richter, N and Bogu, G K and Bhinge, A and Teng, S W and Choo, S H and Andrieux, L O and de Benedictis, C and Jauch, R and Stanton, L W},
	date = {2012},
	pmid = {22496669},
	keywords = {Human, Genome, Humans, Regulatory Sequences, Oligonucleotide Array Sequence Analysis, *Disease/genetics, *Repressor Proteins/genetics/metabolism, Binding Sites/*genetics, Cell Line, {DNA}-Binding Proteins/genetics, Gene Regulatory Networks, Nucleic Acid/*genetics, Nucleotide Motifs/*genetics, Phenotype, Polymorphism, Single Nucleotide/genetics, Transcription Factors/genetics}
}

@article{liu_lncrna_2013,
	title = {{LncRNA} loc285194 is a p53-regulated tumor suppressor},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23558749},
	doi = {10.1093/nar/gkt182},
	abstract = {Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding {RNAs} including long non-coding {RNAs} ({lncRNAs}). Accumulating evidence indicates that {lncRNAs} could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. {LncRNA} loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two {miR}-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of {miR}-211. We further demonstrate a reciprocal repression between loc285194 and {miR}-211; in contrast to loc285194, {miR}-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative {PCR} arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of {miR}-211.},
	pages = {4976--4987},
	number = {9},
	journaltitle = {Nucleic Acids Res},
	author = {Liu, Q and Huang, J and Zhou, N and Zhang, Z and Zhang, A and Lu, Z and Wu, F and Mo, Y Y},
	date = {2013},
	pmid = {23558749},
	keywords = {Animals, Humans, {RNA}, *Genes, Cell Line, Cell Proliferation, Colonic Neoplasms/genetics/metabolism, Down-Regulation, Long Noncoding/biosynthesis/genetics/*metabol, {MicroRNAs}/metabolism, Neoplasms/pathology, Response Elements, Tumor, Tumor Suppressor, Tumor Suppressor Protein p53/*metabolism}
}

@article{srikantan_uneclipsing_2011,
	title = {{UneCLIPsing} {HuR} nuclear function},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21816340},
	doi = {10.1016/j.molcel.2011.07.016},
	abstract = {The {RNA}-binding protein {HuR}, while known to stabilize cytoplasmic {mRNAs}, is largely nuclear. In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide {HuR}-{RNA} interactions using {PAR}-{CLIP}, unveiling {HuR}'s nuclear role in pre-{mRNA} processing.},
	pages = {319--321},
	number = {3},
	journaltitle = {Mol Cell},
	author = {Srikantan, S and Gorospe, M},
	date = {2011},
	pmid = {21816340}
}

@article{zhang_amd1_2012,
	title = {{AMD}1 is essential for {ESC} self-renewal and is translationally down-regulated on differentiation to neural precursor cells},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22391449},
	doi = {10.1101/gad.182998.111},
	abstract = {The gene expression networks governing embryonic stem cell ({ESC}) pluripotency are complex and finely regulated during differentiation toward specific lineages. We describe a new role for Amd1 (adenosyl methionine decarboxylase), a key enzyme in the polyamine synthesis pathway, in regulating both {ESC} self-renewal and differentiation to the neural lineage. Amd1 is highly expressed in {ESCs} and is translationally down-regulated by the neural precursor cell ({NPC})-enriched {microRNA} {miR}-762 during {NPC} differentiation. Overexpression of Amd1 or addition of the polyamine spermine blocks {ESC}-to-{NPC} conversion, suggesting Amd1 must be down-regulated to decrease the levels of inhibitory spermine during differentiation. In addition, we demonstrate that high levels of Amd1 are required for maintenance of the {ESC} state. We show that forced overexpression of Amd1 in {ESCs} results in maintenance of high Myc levels and a delay in differentiation on removal of {LIF}. We propose that Amd1 is a major regulator of {ESC} self-renewal and that its essential role lies in its regulation of Myc levels within the cell.},
	pages = {461--473},
	number = {5},
	journaltitle = {Genes Dev},
	author = {Zhang, D and Zhao, T and Ang, H S and Chong, P and Saiki, R and Igarashi, K and Yang, H and Vardy, L A},
	date = {2012},
	pmid = {22391449},
	keywords = {Animals, Mice, Gene Expression Regulation, *Down-Regulation, Adenosylmethionine Decarboxylase/*genetics/*metabo, Cell Differentiation/*genetics, Developmental, Embryonic Stem Cells/*cytology/*enzymology, {MicroRNAs}/metabolism, Neurons/cytology/enzymology, Proto-Oncogene Proteins c-myc/genetics/metabolism}
}

@article{slavoff_peptidomic_2013,
	title = {Peptidomic discovery of short open reading frame-encoded peptides in human cells},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23160002},
	doi = {10.1038/nchembio.1120},
	abstract = {The complete extent to which the human genome is translated into polypeptides is of fundamental importance. We report a peptidomic strategy to detect short open reading frame ({sORF})-encoded polypeptides ({SEPs}) in human cells. We identify 90 {SEPs}, 86 of which are previously uncharacterized, which is the largest number of human {SEPs} ever reported. {SEP} abundances range from 10-1,000 molecules per cell, identical to abundances of known proteins. {SEPs} arise from {sORFs} in noncoding {RNAs} as well as multicistronic {mRNAs}, and many {SEPs} initiate with non-{AUG} start codons, indicating that noncanonical translation may be more widespread in mammals than previously thought. In addition, coding {sORFs} are present in a small fraction (8 out of 1,866) of long intergenic noncoding {RNAs}. Together, these results provide strong evidence that the human proteome is more complex than previously appreciated.},
	pages = {59--64},
	number = {1},
	journaltitle = {Nat Chem Biol},
	author = {Slavoff, S A and Mitchell, A J and Schwaid, A G and Cabili, M N and Ma, J and Levin, J Z and Karger, A D and Budnik, B A and Rinn, J L and Saghatelian, A},
	date = {2013},
	pmid = {23160002},
	keywords = {Humans, {RNA}, Messenger/genetics, *Open Reading Frames, *Proteome, Codon, Peptides/*chemistry}
}

@article{castano_hypopigmented_2013,
	title = {Hypopigmented mycosis fungoides in childhood and adolescence: a long-term retrospective study},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24320808},
	doi = {10.1111/cup.12217},
	abstract = {Patients with hypopigmented mycosis fungoides ({HMF}) present at a younger age than those with classic {MF}. Our goal was to describe the clinical presentation, histopathologic features and long-term outcome in patients who developed {HMF} before the age of 21. It was observed that among 69 pediatric patients diagnosed with {MF} between 1992 and 2010, 50 had {HMF}. Thirty-five patients had clinical follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were {CD}8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. {HMF} patients were followed for {\textbackslash}textless1-12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow-up. We present a large cohort of children with {HMF} and report on the features of disease and progression. A major difference in histology of {HMF} was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing-and-waning course and relapse after discontinuation of therapy, requiring repetitive treatment.},
	pages = {924--934},
	number = {11},
	journaltitle = {J Cutan Pathol},
	author = {Castano, E and Glick, S and Wolgast, L and Naeem, R and Sunkara, J and Elston, D and Jacobson, M},
	date = {2013},
	pmid = {24320808}
}

@article{wan_identification_2016,
	title = {Identification of androgen-responsive {lncRNAs} as diagnostic and prognostic markers for prostate cancer},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27556357},
	doi = {10.18632/oncotarget.11391},
	abstract = {Prostate cancer ({PCa}) is a leading cause of mortality among males. Long non-coding {RNAs} ({lncRNAs}) are subclass of noncoding {RNAs} that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global {lncRNA} expression patterns by using our own cohort ({GSE}73397) and two public available gene expression datasets: The Cancer Genome Atlas ({TCGA}) and {GSE}55909. Next, we performed microarray to observe genome-wide {lncRNAs}' expressions under dihydrotestosterone ({DHT}) stimulation in {LNCaP} cells ({GSE}72866), and overlapped the result with {ChIPBase} data to predict androgen-responsive {lncRNAs} with {ARE}. Combined the two results, a total of 44 androgen-responsive {lncRNAs} with {ARE} were found to be over-expressed in {PCa} samples. Ten {lncRNAs} were selected for further validation by examining their expressions in {LNCaP} cells under {DHT} stimulation, and in {PCa} samples and cell lines. Among them, {RP}1-4514.2, {LINC}01138, {SUZ}12P1 and {KLKP}1 were validated as directly {AR}-targeted {lncRNAs} by {ChIP}-{PCR}. Then we conducted a bioinformatic analysis to identify {lncRNAs} as putative prognostic and therapeutic targets by using {TCGA} data. Three androgen-responsive {lncRNAs}, {LINC}01138, {SUZ}12P1 and {SNHG}1 showed association with gleason score and {pT}-stage. The biological functions of {LINC}01138 and {SUZ}12P1 were also evaluated, both {lncRNAs} promoted the proliferation and inhibited apoptosis of {PCa}. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant {PCa}.},
	journaltitle = {Oncotarget},
	author = {Wan, X and Huang, W and Yang, S and Zhang, Y and Pu, H and Fu, F and Huang, Y and Wu, H and Li, T and Li, Y},
	date = {2016},
	pmid = {27556357}
}

@article{filippini_p62_2000,
	title = {p62, a novel Xenopus laevis component of box C/D {snoRNPs}},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10744023},
	abstract = {U16 belongs to the family of box C/D small nucleolar {RNAs} ({snoRNAs}) whose members participate in ribosome biogenesis, mainly acting as guides for site-specific methylation of the pre-{rRNA}. Like all the other members of the family, U16 is associated with a set of protein factors forming a ribonucleoprotein particle, localized in the nucleolus. So far, only a few box C/D-specific proteins are known: in Xenopus laevis, fibrillarin and p68 have been identified by {UV} crosslinking and shown to require the conserved boxes C and D for {snoRNA} interaction. In this study, we have identified an additional protein factor (p62), common to box C/D {snoRNPs}, that crosslinks to the internal stem region, distinct from the conserved box C/D "core motif," of U16 {snoRNA}. We show here that, although the absence of the core motif and, as a consequence, of fibrillarin and p68 binding prevents processing and accumulation of the {snoRNA}, the lack of the internal stem does not interfere with the efficient release of U16 from its host intron and only slightly affects {snoRNA} stability. Because this region is likely to be the binding site for p62, we propose that this protein plays an accessory role in the formation of a mature and stable U16 {snoRNP} particle.},
	pages = {391--401},
	number = {3},
	journaltitle = {{RNA}},
	author = {Filippini, D and Bozzoni, I and Caffarelli, E},
	date = {2000},
	pmid = {10744023},
	keywords = {Animals, Conserved Sequence, {RNA}, Introns, *Xenopus laevis, Molecular Weight, Nucleic Acid Conformation, Oocytes, Post-Transcriptional, Ribonucleoproteins, {RNA} Processing, {RNA}-Binding Proteins/genetics, Small Nuclear/metabolism, Small Nucleolar/*biosynthesis/}
}

@article{rowe_dynamic_2011,
	title = {Dynamic control of endogenous retroviruses during development},
	volume = {411},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21251689},
	doi = {10.1016/j.virol.2010.12.007},
	abstract = {Close to half of the human genome encompasses mobile genetic elements, most of which are retrotransposons. These genetic invaders are formidable evolutionary forces that have shaped the architecture of the genomes of higher organisms, with some conserving the ability to induce new integrants within their hosts' genome. Expectedly, the control of endogenous retroviruses is tight and multi-pronged. It is most crucially established in the germ line and during the first steps of embryogenesis, primarily through transcriptional mechanisms that have likely evolved under their very pressure, but are now engaged in controlling gene expression at large, notably during early development.},
	pages = {273--287},
	number = {2},
	journaltitle = {Virology},
	author = {Rowe, H M and Trono, D},
	date = {2011},
	pmid = {21251689},
	keywords = {Humans, *Gene Expression Regulation, Embryonic Development, Endogenous Retroviruses/*genetics, Fetal Development, Fetus/*virology, Viral}
}

@article{yang_paml:_1997,
	title = {{PAML}: a program package for phylogenetic analysis by maximum likelihood},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9367129},
	pages = {555--556},
	number = {5},
	journaltitle = {Comput Appl Biosci},
	author = {Yang, Z},
	date = {1997},
	pmid = {9367129},
	keywords = {*Software, Base Sequence, *Likelihood Functions, *Mathematical Computing, *Phylogeny, Amino Acid Sequence, {DNA}/*analysis}
}

@article{lim_sall4_2008,
	title = {Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18804426},
	doi = {10.1016/j.stem.2008.08.004},
	abstract = {Stem cells self-renew or differentiate under the governance of a stem-cell-specific transcriptional program, with each transcription factor orchestrating the activities of a particular set of genes. Here we demonstrate that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem cells ({ESCs}) and extraembryonic endoderm ({XEN}) cells. The transcription factor Sall4 is required for early embryonic development and for {ESC} pluripotency. Sall4 is also expressed in {XEN} cells, and depletion of Sall4 disrupts self-renewal and induces differentiation. Genome-wide analysis reveals that Sall4 is regulating different gene sets in {ESCs} and {XEN} cells, and depletion of Sall4 targets in the respective cell types induces differentiation. With Oct4, Sox2, and Nanog, Sall4 forms a crucial interconnected autoregulatory network in {ESCs}. In {XEN} cells, Sall4 regulates the key {XEN} lineage-associated genes Gata4, Gata6, Sox7, and Sox17. Our findings demonstrate how Sall4 functions as an essential stemness factor for two different stem cell lines.},
	pages = {543--554},
	number = {5},
	journaltitle = {Cell Stem Cell},
	author = {Lim, C Y and Tam, W L and Zhang, J and Ang, H S and Jia, H and Lipovich, L and Ng, H H and Wei, C L and Sung, W K and Robson, P and Yang, H and Lim, B},
	date = {2008},
	pmid = {18804426},
	keywords = {Animals, Mice, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Blastocyst, Cell Differentiation, Cell Line, Cell Lineage/*genetics, Developmental, Embryonic Stem Cells/cytology/*metabolism, Endoderm/cytology/growth \& development/*metabolism, {GATA} Transcription Factors/genetics/metabolism, High Mobility Group Proteins/genetics/metabolism, Homeostasis, Small Interfering, Transcription Factors/genetics/*metabolism, Transcriptional Activation}
}

@article{atala_re:_2014,
	title = {Re: The long noncoding {RNA} {SChLAP}1 promotes aggressive prostate cancer and antagonizes the {SWI}/{SNF} complex},
	volume = {192},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25035039},
	doi = {10.1016/j.juro.2014.05.031},
	pages = {613},
	number = {2},
	journaltitle = {J Urol},
	author = {Atala, A},
	date = {2014},
	pmid = {25035039},
	keywords = {Animals, Humans, {RNA}, Long Noncoding/*genetics, Chromosomal Proteins, {DNA}-Binding Proteins/*genetics, Female, Male, Non-Histone/*genetics/*metab, Prostatic Neoplasms/*genetics, Transcription Factors/*genetics/*metabolism}
}

@article{miller_conserved_2013,
	title = {Conserved molecular signatures of neurogenesis in the hippocampal subgranular zone of rodents and primates},
	volume = {140},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24154525},
	doi = {10.1242/dev.097212},
	abstract = {The neurogenic potential of the subgranular zone ({SGZ}) of the hippocampal dentate gyrus is likely to be regulated by molecular cues arising from its complex heterogeneous cellular environment. Through transcriptome analysis using laser microdissection coupled with {DNA} microarrays, in combination with analysis of genome-wide in situ hybridization data, we identified 363 genes selectively enriched in adult mouse {SGZ}. These genes reflect expression in the different constituent cell types, including progenitor and dividing cells, immature granule cells, astrocytes, oligodendrocytes and {GABAergic} interneurons. Similar transcriptional profiling in the rhesus monkey dentate gyrus across postnatal development identified a highly overlapping set of {SGZ}-enriched genes, which can be divided based on temporal profiles to reflect maturation of glia versus granule neurons. Furthermore, we identified a neurogenesis-related gene network with decreasing postnatal expression that is highly correlated with the declining number of proliferating cells in dentate gyrus over postnatal development. Many of the genes in this network showed similar postnatal downregulation in mouse, suggesting a conservation of molecular mechanisms underlying developmental and adult neurogenesis in rodents and primates. Conditional deletion of Sox4 and Sox11, encoding two neurogenesis-related transcription factors central in this network, produces a mouse with no hippocampus, confirming the crucial role for these genes in regulating hippocampal neurogenesis.},
	pages = {4633--4644},
	number = {22},
	journaltitle = {Development},
	author = {Miller, J A and Nathanson, J and Franjic, D and Shim, S and Dalley, R A and Shapouri, S and Smith, K A and Sunkin, S M and Bernard, A and Bennett, J L and Lee, C K and Hawrylycz, M J and Jones, A R and Amaral, D G and Sestan, N and Gage, F H and Lein, E S},
	date = {2013},
	pmid = {24154525},
	keywords = {Animals, Genetic, Mice, Transcription, Gene Expression Regulation, *Gene Expression Profiling, Biological Markers/metabolism, Developmental, Gene Regulatory Networks, Genome/genetics, Hippocampus/cytology/*metabolism, Inbred C57BL, Interneurons/cytology/metabolism, Macaca mulatta/*genetics, Male, Multigene Family, Neurogenesis/*genetics, Newborn, Oligodendroglia/cytology/metabolism, {SOXC} Transcription Factors/genetics/metabolism, Spatio-Temporal Analysis}
}

@article{nakatsu_ptdins4p_2012,
	title = {{PtdIns}4P synthesis by {PI}4KIIIalpha at the plasma membrane and its impact on plasma membrane identity},
	volume = {199},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23229899},
	doi = {10.1083/jcb.201206095},
	abstract = {Plasma membrane phosphatidylinositol ({PI}) 4-phosphate ({PtdIns}4P) has critical functions via both direct interactions and metabolic conversion to {PI} 4,5-bisphosphate ({PtdIns}(4,5)P(2)) and other downstream metabolites. However, mechanisms that control this {PtdIns}4P pool in cells of higher eukaryotes remain elusive. {PI}4KIIIalpha, the enzyme thought to synthesize this {PtdIns}4P pool, is reported to localize in the {ER}, contrary to the plasma membrane localization of its yeast homologue, Stt4. In this paper, we show that {PI}4KIIIalpha was targeted to the plasma membrane as part of an evolutionarily conserved complex containing Efr3/rolling blackout, which we found was a palmitoylated peripheral membrane protein. {PI}4KIIIalpha knockout cells exhibited a profound reduction of plasma membrane {PtdIns}4P but surprisingly only a modest reduction of {PtdIns}(4,5)P(2) because of robust up-regulation of {PtdIns}4P 5-kinases. In these cells, however, much of the {PtdIns}(4,5)P(2) was localized intracellularly, rather than at the plasma membrane as in control cells, along with proteins typically restricted to this membrane, revealing a major contribution of {PI}4KIIIalpha to the definition of plasma membrane identity.},
	pages = {1003--1016},
	number = {6},
	journaltitle = {J Cell Biol},
	author = {Nakatsu, F and Baskin, J M and Chung, J and Tanner, L B and Shui, G and Lee, S Y and Pirruccello, M and Hao, M and Ingolia, N T and Wenk, M R and De Camilli, P},
	date = {2012},
	pmid = {23229899},
	keywords = {Animals, Humans, Mice, 129 Strain, Cell Membrane/*metabolism, Electroporation, Female, Fibroblasts/metabolism, Genetic Vectors, {HeLa} Cells, Inbred C57BL, Knockout, Male, Phosphatidylinositol Phosphates/*biosynthesis, Phosphotransferases (Alcohol Group Acceptor)/genet, Up-Regulation}
}

@article{caffarelli_accumulation_1987,
	title = {The accumulation of mature {RNA} for the Xenopus laevis ribosomal protein L1 is controlled at the level of splicing and turnover of the precursor {RNA}},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2448138},
	abstract = {A specific control regulates, at the level of {RNA} splicing, the expression of the L1 ribosomal protein gene in Xenopus laevis. Under particular conditions, which can be summarized as an excess of free L1 protein, a precursor {RNA} which still contains two of the nine introns of the L1 gene accumulates. In addition to the splicing block the two intron regions undergo specific endonucleolytic cleavages which produce abortive truncated molecules. The accumulation of mature L1 {RNA} therefore results from the regulation of the nuclear stability of its precursor {RNA}. We propose that a block to splicing can permit the attack of specific intron regions by nucleases which destabilize the pre-{mRNA} in the nucleus. Therefore the efficiency of splicing could indirectly control the stability of the pre-{mRNA}.},
	pages = {3493--3498},
	number = {11},
	journaltitle = {{EMBO} J},
	author = {Caffarelli, E and Fragapane, P and Gehring, C and Bozzoni, I},
	date = {1987},
	pmid = {2448138},
	keywords = {Animals, Base Sequence, Genetic, *Transcription, {RNA}/*genetics, *{RNA} Splicing, Bacterial Proteins/biosynthesis/*genetics, {DNA} Restriction Enzymes, Female, Oocytes/metabolism, Plasmids, Ribosomal Proteins/biosynthesis/*genetics, Xenopus laevis}
}

@article{ingolia_genome-wide_2013,
	title = {Genome-wide annotation and quantitation of translation by ribosome profiling},
	volume = {Chapter 4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23821443},
	doi = {10.1002/0471142727.mb0418s103},
	abstract = {Recent studies highlight the importance of translational control in determining protein abundance, underscoring the value of measuring gene expression at the level of translation. A protocol for genome-wide, quantitative analysis of in vivo translation by deep sequencing is presented here. This ribosome-profiling approach maps the exact positions of ribosomes on transcripts by nuclease footprinting. The nuclease-protected {mRNA} fragments are converted into a {DNA} library suitable for deep sequencing using a strategy that minimizes bias. The abundance of different footprint fragments in deep sequencing data reports on the amount of translation of a gene. Additionally, footprints reveal the exact regions of the transcriptome that are translated. To better define translated reading frames, an adaptation that reveals the sites of translation initiation by pre-treating cells with harringtonine to immobilize initiating ribosomes is described. The protocol described requires 5 to 7 days to generate a completed ribosome profiling sequencing library. Sequencing and data analysis requires an additional 4 to 5 days.},
	pages = {Unit 4 18},
	journaltitle = {Curr Protoc Mol Biol},
	author = {Ingolia, N T and Brar, G A and Rouskin, S and {McGeachy}, A M and Weissman, J S},
	date = {2013},
	pmid = {23821443},
	keywords = {Gene Expression Profiling/*methods, *Protein Biosynthesis, Computational Biology/methods, High-Throughput Nucleotide Sequencing/*methods, Ribosomes/*metabolism, Time Factors}
}

@article{lipovich_pharmaceutical_2003,
	title = {Pharmaceutical companies need to broaden research},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12546985},
	pages = {18},
	number = {1},
	journaltitle = {Drug Discov Today},
	author = {Lipovich, L},
	date = {2003},
	pmid = {12546985},
	keywords = {Animals, Humans, *Genomics, Drug Industry/*trends, Research/*trends}
}

@article{casolaro_posttranscriptional_2008,
	title = {Posttranscriptional regulation of {IL}-13 in T cells: role of the {RNA}-binding protein {HuR}},
	volume = {121},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18279945},
	doi = {10.1016/j.jaci.2007.12.1166},
	abstract = {{BACKGROUND}: {IL}-13, a critical cytokine in allergy, is regulated by as-yet-elusive mechanisms. {OBJECTIVE}: We investigated {IL}-13 posttranscriptional regulation by {HuR}, a protein associating with adenylate-uridylate-rich elements in the 3' untranslated regions ({UTRs}) of {mRNA}, promoting {mRNA} stability and translation. {METHODS}: {IL}-13 {mRNA} decay was monitored in human T(H)2-skewed cells by using the transcriptional inhibitor actinomycin D. The {IL}-13 3'{UTR} was subcloned into an inducible beta-globin reporter transiently expressed in H2 cells in the absence or presence of overexpressed {HuR}. Association of {HuR} with {IL}-13 {mRNA} was detected by means of immunoprecipitation of ribonucleoprotein complexes and a biotin pull-down assay. The effects of {HuR} transient overexpression and silencing on {IL}-13 expression were investigated. {RESULTS}: {IL}-13 {mRNA} half-life increased significantly in restimulated T(H)2-skewed cells compared with baseline values. Decay of beta-globin {mRNA} was significantly faster in H2 cells transfected with the {IL}-13 3'{UTR}-containing plasmid than in those carrying a control vector. {HuR} overexpression increased the beta-globin {IL}-13 3'{UTR} reporter half-life. Significant enrichment of {IL}-13 {mRNA} was produced by means of immunoprecipitation of Jurkat cell ribonucleoprotein complexes with anti-{HuR}. {HuR} binding to the {IL}-13 3'{UTR} was confirmed by means of pull-down assay of biotin-labeled {RNA} probes spanning the {IL}-13 3'{UTR}. Two-dimensional Western blot analysis showed stimulus-induced posttranslational modification of {HuR}. In Jurkat cells mitogen-induced {IL}-13 {mRNA} was significantly affected by {HuR} overexpression and silencing. {CONCLUSIONS}: Mitogen-induced {IL}-13 expression involves changes in transcript turnover and a change in phosphorylation of {HuR} and its association with the {mRNA} 3'{UTR}.},
	pages = {853--9 e4},
	number = {4},
	journaltitle = {J Allergy Clin Immunol},
	author = {Casolaro, V and Fang, X and Tancowny, B and Fan, J and Wu, F and Srikantan, S and Asaki, S Y and De Fanis, U and Huang, S K and Gorospe, M and Atasoy, U X and Stellato, C},
	date = {2008},
	pmid = {18279945},
	keywords = {Base Sequence, Humans, {RNA}, Cells, Cultured, 3' Untranslated Regions/genetics/immunology, Antigens, Cell Line, Hu Paraneoplastic Encephalomyelitis Antigens, Interleukin-13/biosynthesis/*genetics/*metabolism, Jurkat Cells, Lymphocyte Activation/genetics/immunology, Messenger/metabolism, Molecular Sequence Data, Monensin/pharmacology, Post-Transcriptional/*immunology, {RNA} Processing, {RNA}-Binding Proteins/*physiology, Surface/*physiology, Tetradecanoylphorbol Acetate/pharmacology, Th2 Cells/*immunology/*metabolism, Tumor}
}

@article{shack_caveolin-induced_2003,
	title = {Caveolin-induced activation of the phosphatidylinositol 3-kinase/Akt pathway increases arsenite cytotoxicity},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12640124},
	abstract = {The inhibitory effect of caveolin on the cellular response to growth factor stimulation is well established. Given the significant overlap in signaling pathways involved in regulating cell proliferation and stress responsiveness, we hypothesized that caveolin would also affect a cell's ability to respond to environmental stress. Here we investigated the ability of caveolin-1 to modulate the cellular response to sodium arsenite and thereby alter survival of the human cell lines 293 and {HeLa}. Cells stably transfected with caveolin-1 were found to be much more sensitive to the toxic effects of sodium arsenite than either untransfected parental cells or parental cells transfected with an empty vector. Unexpectedly, the caveolin-overexpressing cells also exhibited a significant activation of the phosphatidylinositol 3-kinase ({PI}3K)/Akt pathway, which additional studies suggested was likely due to decreased neutral sphingomyelinase activity and ceramide synthesis. In contrast to its extensively documented antiapoptotic influence, the elevated activity of Akt appears to be important in sensitizing caveolin-expressing cells to arsenite-induced toxicity, as both pretreatment of cells with the {PI}3K inhibitor wortmannin and overexpression of a dominant-negative Akt mutant markedly improved the survival of arsenite-treated cells. This death-promoting influence of the {PI}3K/Akt pathway in caveolin-overexpressing cells appeared not to be unique to sodium arsenite, as wortmannin pretreatment also resulted in increased survival in the presence of H(2)O(2). In summary, our results indicate that caveolin-induced upregulation of the {PI}3K/Akt signaling pathway, which appears to be a death signal in the presence of arsenite and H(2)O(2), sensitizes cells to environmental stress.},
	pages = {2407--2414},
	number = {7},
	journaltitle = {Mol Cell Biol},
	author = {Shack, S and Wang, X T and Kokkonen, G C and Gorospe, M and Longo, D L and Holbrook, N J},
	date = {2003},
	pmid = {12640124},
	keywords = {Humans, *Protein-Serine-Threonine Kinases, Androstadienes/pharmacology, Arsenites/*toxicity, Blotting, Caveolin 1, Caveolins/genetics/*metabolism, Cell Line, Cell Survival/drug effects/genetics, Ceramides/metabolism, Dominant, Enzyme Activation/drug effects/genetics, Enzyme Inhibitors/pharmacology, Fibroblasts/cytology/drug effects/metabolism, Genes, {HeLa} Cells, Oxidants/pharmacology, Phosphatidylinositol 3-Kinases/antagonists \& inhib, Phosphorylation, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins/genetics/*metabolism, Signal Transduction/drug effects/*physiology, Transfection, Western}
}

@article{makarova_noncoding_2005,
	title = {Noncoding {RNA} of U87 host gene is associated with ribosomes and is relatively resistant to nonsense-mediated decay},
	volume = {363},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16226852},
	doi = {10.1016/j.gene.2005.08.010},
	abstract = {Non-coding {RNAs} are involved in many cellular processes. In particular, most of C/D box small nucleolar {RNAs} ({snoRNAs}) function as guide {RNAs} in site-specific 2'-O-methylation of {rRNAs}. While most {snoRNA} genes reside in introns of protein-coding genes, here we demonstrated an unusual {snoRNA} gene occupying an intron of a previously unknown non-protein-coding gene U87HG. We characterized this host gene in human, mouse, rat, and dog. It is a member of 5'{TOP} gene family, which includes many translation apparatus genes. U87HG {RNA} carried multiple stop-codons and was associated with ribosomes, suggesting that it may be a target for nonsense-mediated {mRNA} decay ({NMD}), a process that eliminates transcripts bearing nonsense mutations. Surprisingly, we found that U87HG {RNA} was hardly susceptible to {NMD}. Possible mechanisms (translation reinitiation, ribosomal leaky scanning, and low efficiency of translation) of this phenomenon are discussed. Unlike transcripts of four other known non-protein-coding host genes, U87HG {RNA} shows a relatively high degree of conservation suggesting a selective pressure and a possible functional activity of U87HG apart from producing U87 {snoRNA}.},
	pages = {51--60},
	journaltitle = {Gene},
	author = {Makarova, J A and Kramerov, D A},
	date = {2005},
	pmid = {16226852},
	keywords = {Animals, Base Sequence, Humans, {RNA}, Nucleic Acid, Introns, Cycloheximide/pharmacology, {DNA} Primers, Dogs, Molecular Sequence Data, Protein Biosynthesis/drug effects, Protein Synthesis Inhibitors/pharmacology, Rats, Ribosomes/*genetics, Sequence Homology, Untranslated/chemistry/*genetics}
}

@article{feijao_stability_2013,
	title = {Stability of kinetochore-microtubule attachment and the role of different {KMN} network components in Drosophila},
	volume = {70},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23959943},
	doi = {10.1002/cm.21131},
	abstract = {Kinetochores bind spindle microtubules and also act as signaling centers that monitor this interaction. Defects in kinetochore assembly lead to chromosome missegregation and aneuploidy. The interaction between microtubules and chromosomes involves a conserved super-complex of proteins, known as the {KNL}1Mis12Ndc80 ({KMN}) network, composed by the {KNL}1 (Spc105), Mis12, and Ndc80 complexes. Previous studies indicate that all components of the network are required for kinetochore-microtubule attachment and all play relevant functions in chromosome congression, biorientation, and segregation. Here, we report a comparative study addressing the role of the different {KMN} components using {dsRNA} and in vivo fluorescence microscopy in Drosophila S2 cells allowing us to suggest that different {KMN} network components might perform different roles in chromosome segregation and the mitotic checkpoint signaling. Depletion of different components results in mostly lateral kinetochore-microtubule attachments that are relatively stable on depletion of Mis12 or Ndc80 but very unstable after Spc105 depletion. In vivo analysis on depletion of Mis12, Ndc80, and to some extent Spc105, shows that lateral kinetochore-microtubule interactions are still functional allowing poleward kinetochore movement. We also find that different {KMN} network components affect differently the localization of spindle assembly checkpoint ({SAC}) proteins at kinetochores. Depletion of Ndc80 and Spc105 abolishes the mitotic checkpoint, whereas depletion of Mis12 causes a delay in mitotic progression. Taken together, our results suggest that Mis12 and Ndc80 complexes help to properly orient microtubule attachment, whereas Spc105 plays a predominant role in the kinetochore-microtubule attachment as well as in the poleward movement of chromosomes, {SAC} response, and cell viability.},
	pages = {661--675},
	number = {10},
	journaltitle = {Cytoskeleton (Hoboken)},
	author = {Feijao, T and Afonso, O and Maia, A F and Sunkel, C E},
	date = {2013},
	pmid = {23959943}
}

@article{tessitore_preferential_2006,
	title = {Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16979943},
	doi = {10.1016/j.ymthe.2006.07.008},
	abstract = {Autosomal dominant retinitis pigmentosa caused by the frequent rhodopsin P23H mutation is characterized by progressive photoreceptor cell death eventually leading to blindness and for which no therapies are available. Considering the gain-of-function effect exerted by the P23H mutation, strategies aimed at silencing the expression of the mutated allele, like {RNA} interference, are desirable. We have designed small interfering {RNAs} ({siRNA}) to silence specifically the P23H rhodopsin allele expressed by a transgenic rat model of the disease. We have selected in vitro one {siRNA} and generated an adeno-associated viral ({AAV}) vector expressing the short hairpin {RNA} ({shRNA}) based on the selected {siRNA}. In vitro the {shRNA} significantly inhibits the expression of the P23H but not the wild-type rhodopsin allele. Subretinal administration of the {AAV}2/5 vector encoding the {shRNA} in P23H transgenic rats results in inhibition of rhodopsin P23H expression that is not able to prevent or block photoreceptor degeneration. Since rhodopsin is the most abundant rod photoreceptor protein, systems resulting in more robust {shRNA} expression in the retina may be required to achieve therapeutic efficacy in vivo.},
	pages = {692--699},
	number = {5},
	journaltitle = {Mol Ther},
	author = {Tessitore, A and Parisi, F and Denti, M A and Allocca, M and Di Vicino, U and Domenici, L and Bozzoni, I and Auricchio, A},
	date = {2006},
	pmid = {16979943},
	keywords = {Animals, Base Sequence, Mice, {RNA}, *Gene Silencing, Alleles, Animal, Dependovirus/genetics, Genetic Vectors/genetics, Genetically Modified, Models, Molecular Sequence Data, Mutation/*genetics, Proline/genetics/metabolism, Rats, Retinal Degeneration/*genetics/metabolism/*patholo, Rhodopsin/*genetics/metabolism, Small Interfering/genetics}
}

@article{peppard_cerebral_1992,
	title = {Cerebral glucose metabolism in Parkinson's disease with and without dementia},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1449406},
	abstract = {Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with {PD} with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early {PD} and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with {PD} showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with {PD} resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.},
	pages = {1262--1268},
	number = {12},
	journaltitle = {Arch Neurol},
	author = {Peppard, R F and Martin, W R and Carr, G D and Grochowski, E and Schulzer, M and Guttman, M and {McGeer}, P L and Phillips, A G and Tsui, J K and Calne, D B},
	date = {1992},
	pmid = {1449406},
	keywords = {Humans, Aged, Alzheimer Disease/metabolism, Brain/*metabolism/radionuclide imaging, Dementia/complications/*metabolism/radionuclide im, Emission-Computed, Glucose/*metabolism, Middle Aged, Parkinson Disease/complications/*metabolism/radion, Tomography}
}

@article{caffarelli_processing_1996,
	title = {Processing of the intron-encoded U16 and U18 {snoRNAs}: the conserved C and D boxes control both the processing reaction and the stability of the mature {snoRNA}},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8605882},
	abstract = {A novel class of small nucleolar {RNAs} ({snoRNAs}), encoded in introns of protein coding genes and originating from processing of their precursor molecules, has recently been described. The L1 ribosomal protein (r-protein) gene of Xenopus laevis and its human homologue contain two {snoRNAs}, U16 and U18. It has been shown that these {snoRNAs} are excised from their intron precursors by endonucleolytic cleavage and that their processing is alternative to splicing. Two sequences, internal to the {snoRNA} coding region, have been identified as indispensable for processing the conserved boxes C and D. Competition experiments have shown that these sequences interact with diffusible factors which can bind both the pre-{mRNA} and the mature U16 {snoRNA}. Fibrillarin, which is known to associate with complexes formed on C and D boxes of other {snoRNAs}, is found in association with mature U16 {RNA}, as well as with its precursor molecules. This fact suggests that the complex formed on the pre-{mRNA} remains bound to U16 throughout all the processing steps. We also show that the complex formed on the C and D boxes is necessary to stabilize mature {snoRNA}.},
	pages = {1121--1131},
	number = {5},
	journaltitle = {{EMBO} J},
	author = {Caffarelli, E and Fatica, A and Prislei, S and De Gregorio, E and Fragapane, P and Bozzoni, I},
	date = {1996},
	pmid = {8605882},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, {RNA}, Introns, *{RNA} Processing, Binding, Cell Nucleolus/metabolism, Chromosomal Proteins, Competitive, {DNA}/genetics, Female, Molecular Sequence Data, Mutation, Non-Histone/metabolism, Oocytes/metabolism, Post-Transcriptional, {RNA} Precursors/metabolism, {RNA} Splicing/genetics, Small Nuclear/*genetics/*metabolism, Xenopus, Xenopus laevis}
}

@article{keyes_deltanp63alpha_2011,
	title = {{DeltaNp}63alpha is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21295273},
	doi = {10.1016/j.stem.2010.12.009},
	abstract = {The p53 homolog p63 is essential for development, yet its role in cancer is not clear. We discovered that p63 deficiency evokes the tumor-suppressive mechanism of cellular senescence, causing a striking absence of stratified epithelia such as the skin. Here we identify the predominant p63 isoform, {DeltaNp}63alpha, as a protein that bypasses oncogene-induced senescence to drive tumorigenesis in vivo. Interestingly, bypass of senescence promotes stem-like proliferation and maintains survival of the keratin 15-positive stem cell population. Furthermore, we identify the chromatin-remodeling protein Lsh as a new target of {DeltaNp}63alpha that is an essential mediator of senescence bypass. These findings indicate that {DeltaNp}63alpha is an oncogene that cooperates with Ras to promote tumor-initiating stem-like proliferation and suggest that Lsh-mediated chromatin-remodeling events are critical to this process.},
	pages = {164--176},
	number = {2},
	journaltitle = {Cell Stem Cell},
	author = {Keyes, W M and Pecoraro, M and Aranda, V and Vernersson-Lindahl, E and Li, W and Vogel, H and Guo, X and Garcia, E L and Michurina, T V and Enikolopov, G and Muthuswamy, S K and Mills, A A},
	date = {2011},
	pmid = {21295273},
	keywords = {Animals, Humans, Mice, Protein Binding, Cells, Cultured, Cell Proliferation, Chromatin Immunoprecipitation, {DNA} Helicases/*metabolism, Flow Cytometry, Keratinocytes/metabolism, Nude, Phosphoproteins/genetics/*metabolism, Polymerase Chain Reaction, Skin/*cytology, Stem Cells/*cytology/*metabolism, Trans-Activators/genetics/*metabolism}
}

@article{raman_real-time_2005,
	title = {Real-time magnetic resonance-guided endovascular repair of experimental abdominal aortic aneurysm in swine},
	volume = {45},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15963411},
	doi = {10.1016/j.jacc.2005.03.029},
	abstract = {{OBJECTIVES}: This study tested the hypotheses that endografts can be visualized and navigated in vivo solely under real-time magnetic resonance imaging ({rtMRI}) guidance to repair experimental abdominal aortic aneurysms ({AAA}) in swine, and that {MRI} can provide immediate assessment of endograft apposition and aneurysm exclusion. {BACKGROUND}: Endovascular repair for {AAA} is limited by endoleak caused by inflow or outflow malapposition. The ability of {rtMRI} to image soft tissue and flow may improve on X-ray guidance of this procedure. {METHODS}: Infrarenal {AAA} was created in swine by balloon overstretch. We used one passive commercial endograft, imaged based on metal-induced {MRI} artifacts, and several types of homemade active endografts, incorporating {MRI} receiver coils (antennae). Custom interactive {rtMRI} features included color coding the catheter-antenna signals individually, simultaneous multislice imaging, and real-time three-dimensional rendering. {RESULTS}: Eleven repairs were performed solely using {rtMRI}, simultaneously depicting the device and soft-tissue pathology during endograft deployment. Active devices proved most useful. Intraprocedural {MRI} provided anatomic confirmation of stent strut apposition and functional corroboration of aneurysm exclusion and restoration of laminar flow in successful cases. In two cases, there was clear evidence of contrast accumulation in the aneurysm sac, denoting endoleak. {CONCLUSIONS}: Endovascular {AAA} repair is feasible under {rtMRI} guidance. Active endografts facilitate device visualization and complement the soft tissue contrast afforded by {MRI} for precise positioning and deployment. Magnetic resonance imaging also permits immediate post-procedural anatomic and functional evaluation of successful aneurysm exclusion.},
	pages = {2069--2077},
	number = {12},
	journaltitle = {J Am Coll Cardiol},
	author = {Raman, V K and Karmarkar, P V and Guttman, M A and Dick, A J and Peters, D C and Ozturk, C and Pessanha, B S and Thompson, R B and Raval, A N and {DeSilva}, R and Aviles, R J and Atalar, E and {McVeigh}, E R and Lederman, R J},
	date = {2005},
	pmid = {15963411},
	keywords = {Animals, *Magnetic Resonance Imaging, Abdominal/pathology/radiography/*, Angioplasty/*methods, Animal, Aortic Aneurysm, Blood Vessel Prosthesis Implantation/*methods, Computer-Assisted/*methods, Disease Models, Feasibility Studies, Prosthesis Design, Stents, Surgery, Swine}
}

@article{renzi_characterization_2002,
	title = {Characterization of the sequences encoding for Xenopus laevis box C/D {snoRNP} Nop56 protein},
	volume = {1575},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12020815},
	abstract = {Nop56p was initially identified in yeast as the third common component of the ribonucleoprotein particles ({snoRNPs}) assembled on box C/D small nucleolar {RNAs} ({snoRNAs}). Thereafter, the characterization of Nop56p homologs in Archaea and in several eukaryotes pointed to the highly conserved structure of this factor. Studies in yeast indicate that Nop56 is not required for the stability of box C/D {snoRNAs}. Through the isolation of a Xenopus laevis Nop56 {cDNA} clone, we have been able to characterize the X. laevis Nop56 protein ({XNop}56p). We showed that it is a common component of X. laevis box C/D {snoRNPs} and that it displays the same electrophoretic mobility of p62 protein that we previously characterized as a box C/D {snoRNP} component, not essential for {snoRNA} stability in X. laevis. Mapping the 5' end of X. laevis Nop56 transcript indicates that it starts with a pyrimidine tract and the analysis of genomic clones revealed a {snoRNA} encoded in one of {NOP}56 introns. Although these two characteristics could suggest that {XNOP}56 is a {TOP} gene, it is not translationally controlled in a growth-dependent manner.},
	pages = {26--30},
	number = {1},
	journaltitle = {Biochim Biophys Acta},
	author = {Renzi, F and Filippini, D and Loreni, F and Bozzoni, I and Caffarelli, E},
	date = {2002},
	pmid = {12020815},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation, *Saccharomyces cerevisiae Proteins, *Xenopus Proteins, Amino Acid Sequence, Antibodies/immunology, Molecular Sequence Data, Nuclear Proteins/*genetics/immunology/metabolism, Ribonucleoproteins, Saccharomyces cerevisiae, Sequence Alignment, Small Nucleolar/*genetics/immu, Small Nucleolar/immunology/metabolism, Xenopus laevis/*genetics}
}

@article{zou_polyamines_2010,
	title = {Polyamines regulate the stability of {JunD} {mRNA} by modulating the competitive binding of its 3' untranslated region to {HuR} and {AUF}1},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20805360},
	doi = {10.1128/MCB.00807-10},
	abstract = {Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including {JunD}. Decreasing the levels of cellular polyamines stabilizes {JunD} {mRNA} without affecting its transcription, but the exact mechanism whereby polyamines regulate {JunD} {mRNA} degradation has not been elucidated. {RNA}-binding proteins {HuR} and {AUF}1 associate with labile {mRNAs} bearing {AU}-rich elements located in the 3' untranslated regions (3'-{UTRs}) and modulate their stability. Here, we show that {JunD} {mRNA} is a target of {HuR} and {AUF}1 and that polyamines modulate {JunD} {mRNA} degradation by altering the competitive binding of {HuR} and {AUF}1 to the {JunD} 3'-{UTR}. The depletion of cellular polyamines enhanced {HuR} binding to {JunD} {mRNA} and decreased the levels of {JunD} transcript associated with {AUF}1, thus stabilizing {JunD} {mRNA}. The silencing of {HuR} increased {AUF}1 binding to the {JunD} {mRNA}, decreased the abundance of {HuR}-{JunD} {mRNA} complexes, rendered the {JunD} {mRNA} unstable, and prevented increases in {JunD} {mRNA} and protein in polyamine-deficient cells. Conversely, increasing the cellular polyamines repressed {JunD} {mRNA} interaction with {HuR} and enhanced its association with {AUF}1, resulting in an inhibition of {JunD} expression. These results indicate that polyamines modulate the stability of {JunD} {mRNA} in intestinal epithelial cells through {HuR} and {AUF}1 and provide new insight into the molecular functions of cellular polyamines.},
	pages = {5021--5032},
	number = {21},
	journaltitle = {Mol Cell Biol},
	author = {Zou, T and Rao, J N and Liu, L and Xiao, L and Yu, T X and Jiang, P and Gorospe, M and Wang, J Y},
	date = {2010},
	pmid = {20805360},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, Humans, {RNA}, *Genes, *{RNA} Stability, Antigens, Binding, Binding Sites/genetics, Caco-2 Cells, Cell Line, Competitive, {DNA} Primers/genetics, Heterogeneous-Nuclear Ribonucleoprotein D/antagoni, Hu Paraneoplastic Encephalomyelitis Antigens, inhibitors/genetics/*metabolism, jun, Messenger/genetics/metabolism, Molecular Sequence Data, Polyamines/*metabolism, Rats, {RNA} Interference, {RNA}-Binding Proteins/antagonists \& inhibitors/gene, Sequence Deletion, Small Interfering/genetics, Surface/genetics/*metabolism}
}

@article{lee_rna-binding_2012,
	title = {{RNA}-binding protein {HuD} controls insulin translation},
	volume = {45},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22387028},
	doi = {10.1016/j.molcel.2012.01.016},
	abstract = {Although expression of the mammalian {RNA}-binding protein {HuD} was considered to be restricted to neurons, we report that {HuD} is present in pancreatic beta cells, where its levels are controlled by the insulin receptor pathway. We found that {HuD} associated with a 22-nucleotide segment of the 5' untranslated region ({UTR}) of preproinsulin (Ins2) {mRNA}. Modulating {HuD} abundance did not alter Ins2 {mRNA} levels, but {HuD} overexpression decreased Ins2 {mRNA} translation and insulin production, and conversely, {HuD} silencing enhanced Ins2 {mRNA} translation and insulin production. Following treatment with glucose, {HuD} rapidly dissociated from Ins2 {mRNA} and enabled insulin biosynthesis. Importantly, {HuD}-knockout mice displayed higher insulin levels in pancreatic islets, while {HuD}-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify {HuD} as a pivotal regulator of insulin translation in pancreatic beta cells.},
	pages = {826--835},
	number = {6},
	journaltitle = {Mol Cell},
	author = {Lee, E K and Kim, W and Tominaga, K and Martindale, J L and Yang, X and Subaran, S S and Carlson, O D and Mercken, E M and Kulkarni, R N and Akamatsu, W and Okano, H and Perrone-Bizzozero, N I and de Cabo, R and Egan, J M and Gorospe, M},
	date = {2012},
	pmid = {22387028},
	keywords = {Animals, Humans, Mice, *Protein Biosynthesis, 5' Untranslated Regions, Glucose/metabolism, Hu Paraneoplastic Encephalomyelitis Antigens/genet, Inbred C57BL, Insulin-Secreting Cells/metabolism, Insulin/*genetics/*metabolism, Knockout, Protein Precursors/genetics, Transgenic}
}

@article{clark_genome-wide_2012,
	title = {Genome-wide analysis of long noncoding {RNA} stability},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22406755},
	doi = {10.1101/gr.131037.111},
	abstract = {Transcriptomic analyses have identified tens of thousands of intergenic, intronic, and cis-antisense long noncoding {RNAs} ({lncRNAs}) that are expressed from mammalian genomes. Despite progress in functional characterization, little is known about the post-transcriptional regulation of {lncRNAs} and their half-lives. Although many are easily detectable by a variety of techniques, it has been assumed that {lncRNAs} are generally unstable, but this has not been examined genome-wide. Utilizing a custom noncoding {RNA} array, we determined the half-lives of approximately 800 {lncRNAs} and approximately 12,000 {mRNAs} in the mouse Neuro-2a cell line. We find only a minority of {lncRNAs} are unstable. {LncRNA} half-lives vary over a wide range, comparable to, although on average less than, that of {mRNAs}, suggestive of complex metabolism and widespread functionality. Combining half-lives with comprehensive {lncRNA} annotations identified hundreds of unstable (half-life {\textbackslash}textless 2 h) intergenic, cis-antisense, and intronic {lncRNAs}, as well as {lncRNAs} showing extreme stability (half-life {\textbackslash}textgreater 16 h). Analysis of {lncRNA} features revealed that intergenic and cis-antisense {RNAs} are more stable than those derived from introns, as are spliced {lncRNAs} compared to unspliced (single exon) transcripts. Subcellular localization of {lncRNAs} indicated widespread trafficking to different cellular locations, with nuclear-localized {lncRNAs} more likely to be unstable. Surprisingly, one of the least stable {lncRNAs} is the well-characterized paraspeckle {RNA} Neat1, suggesting Neat1 instability contributes to the dynamic nature of this subnuclear domain. We have created an online interactive resource (http://stability.matticklab.com) that allows easy navigation of {lncRNA} and {mRNA} stability profiles and provides a comprehensive annotation of ∼7200 mouse {lncRNAs}.},
	pages = {885--898},
	number = {5},
	journaltitle = {Genome Res},
	author = {Clark, M B and Johnston, R L and Inostroza-Ponta, M and Fox, A H and Fortini, E and Moscato, P and Dinger, M E and Mattick, J S},
	date = {2012},
	pmid = {22406755},
	keywords = {Animals, Humans, {RNA}, *Genome, Oligonucleotide Array Sequence Analysis, *{RNA} Stability, Analysis of Variance, Cell Line, Cluster Analysis, Gene Expression, Half-Life, Messenger/genetics/metabolism, Mice/*genetics, Molecular Sequence Annotation, Tumor, Untranslated/genetics/*metabolism}
}

@article{thomas_2-amino-4-methyl-pyrimidinium_2013,
	title = {2-Amino-4-methyl-pyrimidinium dihydrogen phosphate},
	volume = {69},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23634070},
	doi = {10.1107/S160053681300648X},
	abstract = {A charge-assisted hydrogen-bonding network involving N-Hcdots, three dots, {centeredO} and O-Hcdots, three dots, {centeredO} hydrogen bonds stabilizes the crystal of the title salt, C5H8N3 (+).H2PO4 (-). The dihydrogen phosphate anions form one-dimensional chains along [100], via O-Hcdots, three dots, {centeredO} hydrogen bonds. The 2-amino-4-methyl-pyrimidinium cations are linked to these chains by means of two different kinds of N-Hcdots, three dots, {centeredO} hydrogen bonds. Neighbouring chains are linked via C-Hcdots, three dots, {centeredN} and C-Hcdots, three dots, {centeredO} hydrogen bonds forming two-dimensional slab-like networks lying parallel to (01-1).},
	pages = {o529},
	issue = {Pt 4},
	journaltitle = {Acta Crystallogr Sect E Struct Rep Online},
	author = {Thomas, S P and Sunkari, J},
	date = {2013},
	pmid = {23634070},
	file = {2-Amino-4-methyl-pyrimidinium dihydrogen phosphate:/home/jlagarde/Zotero/storage/AA7XQAYK/thomas2013.pdf:application/pdf}
}

@article{incitti_exon_2010,
	title = {Exon skipping and duchenne muscular dystrophy therapy: selection of the most active U1 {snRNA} antisense able to induce dystrophin exon 51 skipping},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20551908},
	doi = {10.1038/mt.2010.123},
	abstract = {One promising approach for the gene therapy of Duchenne muscular dystrophy ({DMD}) is exon skipping. When thinking of possible intervention on human, it is very crucial to identify the most appropriate antisense sequences able to provide the highest possible skipping efficiency. In this article, we compared the exon 51 skipping activity of 10 different antisense molecules, raised against splice junctions and/or exonic splicing enhancers ({ESEs}), expressed as part of the U1 small nuclear {RNA} ({snRNA}). The effectiveness of each construct was tested in human {DMD} myoblasts carrying the deletion of exons 48-50, which can be treated with skipping of exon 51. Our results show that the highest skipping activity and dystrophin rescue is achieved upon expression of a U1 {snRNA}-derived antisense molecule targeting exon 51 splice sites in combination with an internal exon sequence. The efficacy of this molecule was further proven on an exon 45-50 deletion background, utilizing patient's fibroblasts transdifferentiated into myoblasts. In this system, we showed that the selected antisense was able to produce 50\% skipping of exon 51.},
	pages = {1675--1682},
	number = {9},
	journaltitle = {Mol Ther},
	author = {Incitti, T and De Angelis, F G and Cazzella, V and Sthandier, O and Pinnaro, C and Legnini, I and Bozzoni, I},
	date = {2010},
	pmid = {20551908},
	keywords = {Animals, Humans, Mice, {RNA}, Cells, Cultured, Antisense/*genetics, Blotting, Cell Line, Duchenne/*genetics/*therapy, Dystrophin/*genetics/metabolism, Exons/*genetics, Muscular Dystrophy, Northern, Polymerase Chain Reaction, Small Nuclear/*genetics, Western}
}

@article{sun_iseerna:_2013,
	title = {{iSeeRNA}: identification of long intergenic non-coding {RNA} transcripts from transcriptome sequencing data},
	volume = {14 Suppl 2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23445546},
	doi = {10.1186/1471-2164-14-S2-S7},
	abstract = {{BACKGROUND}: Long intergenic non-coding {RNAs} ({lincRNAs}) are emerging as a novel class of non-coding {RNAs} and potent gene regulators. High-throughput {RNA}-sequencing combined with de novo assembly promises quantity discovery of novel transcripts. However, the identification of {lincRNAs} from thousands of assembled transcripts is still challenging due to the difficulties of separating them from protein coding transcripts ({PCTs}). {RESULTS}: We have implemented {iSeeRNA}, a support vector machine ({SVM})-based classifier for the identification of {lincRNAs}. {iSeeRNA} shows better performance compared to other software. A public available webserver for {iSeeRNA} is also provided for small size dataset. {CONCLUSIONS}: {iSeeRNA} demonstrates high prediction accuracy and runs several magnitudes faster than other similar programs. It can be integrated into the transcriptome data analysis pipelines or run as a web server, thus offering a valuable tool for {lincRNA} study.},
	pages = {S7},
	journaltitle = {{BMC} Genomics},
	author = {Sun, K and Chen, X and Jiang, P and Song, X and Wang, H and Sun, H},
	date = {2013},
	pmid = {23445546},
	keywords = {Gene Expression Profiling/*methods, Animals, Humans, Mice, {RNA}, Software, *Support Vector Machines, Internet, Long Noncoding/*classification, {ROC} Curve}
}

@article{bussmann_robust_2009,
	title = {A robust and highly efficient immune cell reprogramming system},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19896445},
	doi = {10.1016/j.stem.2009.10.004},
	abstract = {Here we describe a lineage reprogramming system consisting of a B cell line with an estradiol-inducible form of C/{EBPalpha} where cells can be converted into macrophage-like cells at 100\% efficiency within 2 to 3 days. The reprogrammed cells are larger, contain altered organelle and cytoskeletal structures, are phagocytic, and exhibit an inflammatory response. Time-lapse experiments showed that the cells acquire a macrophage morphology and increased migratory activity as early as 10 hr. During induction, thousands of genes become up- or downregulated, including several dozen transcription and chromatin-remodeling factors. Time-limited exposure of cells to the inducer showed that the reprogrammed cells become transgene independent within 1 to 2 days. The reprogramming can be inhibited, at least partially, by perturbation experiments with B cell and macrophage transcription factors. The tightness, robustness, and speed of the system described make it a versatile tool to study biochemical and biological aspects of lineage reprogramming.},
	pages = {554--566},
	number = {5},
	journaltitle = {Cell Stem Cell},
	author = {Bussmann, L H and Schubert, A and Vu Manh, T P and De Andres, L and Desbordes, S C and Parra, M and Zimmermann, T and Rapino, F and Rodriguez-Ubreva, J and Ballestar, E and Graf, T},
	date = {2009},
	pmid = {19896445},
	keywords = {Animals, Genetic, Mice, Gene Expression Regulation, Gene Expression Profiling, *Cell Transdifferentiation, Antigens, B-Lymphoid/cytology/immunology/*m, Basic-Leucine Zipper Transcription Factors/genetic, Cell Line, Cell Movement/genetics/immunology, Developmental/immunolo, Differentiation/metabolism, {DNA}-Binding Proteins/genetics/metabolism, Estradiol/metabolism, Estrogen Receptor alpha/genetics, Inflammation Mediators/metabolism, Macrophages/cytology/immunology/*metabolism, Precursor Cells, Recombinant Fusion Proteins/genetics/*metabolism, Transcription Factor {AP}-2, Transcriptional Activation, Transduction, Transformed}
}

@article{sandhir_curcumin_2014,
	title = {Curcumin Nanoparticles Attenuate Neurochemical and Neurobehavioral Deficits in Experimental Model of Huntington's Disease},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24008671},
	doi = {10.1007/s12017-013-8261-y},
	abstract = {Till date, an exact causative pathway responsible for neurodegeneration in Huntington's disease ({HD}) remains elusive; however, mitochondrial dysfunction appears to play an important role in {HD} pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-{SLNs}) to ameliorate 3-nitropropionic acid (3-{NP})-induced {HD} in rats. Results of {MTT} (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase ({SDH}) staining of striatum revealed a marked decrease in Complex {II} activity. However, C-{SLN}-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-{SLNs} also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-{SLNs}. Quantitative {PCR} and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-{SLNs} administration in 3-{NP}-treated animals. In addition, C-{SLN}-treated rats showed significant improvement in neuromotor coordination when compared with 3-{NP}-treated rats. Thus, the results of this study suggest that C-{SLNs} administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in {HD}.},
	pages = {106--118},
	number = {1},
	journaltitle = {Neuromolecular Med},
	author = {Sandhir, R and Yadav, A and Mehrotra, A and Sunkaria, A and Singh, A and Sharma, S},
	date = {2014},
	pmid = {24008671}
}

@article{pang_loss_2013,
	title = {Loss of {CARM}1 is linked to reduced {HuR} function in replicative senescence},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23837869},
	doi = {10.1186/1471-2199-14-15},
	abstract = {{BACKGROUND}: The co-activator-associated arginine methyltransferase 1 ({CARM}1) catalyzes the methylation of {HuR}. However, the functional impact of this modification is not fully understood. Here, we investigated the influence of {HuR} methylation by {CARM}1 upon the turnover of {HuR} target {mRNAs} encoding senescence-regulatory proteins. {RESULTS}: Changing the methylation status of {HuR} in {HeLa} cells by either silencing {CARM}1 or mutating the major methylation site (R217K) greatly diminished the effect of {HuR} in regulating the turnover of {mRNAs} encoding cyclin A, cyclin B1, c-fos, {SIRT}1, and p16. Although knockdown of {CARM}1 or {HuR} individually influenced the expression of cyclin A, cyclin B1, c-fos, {SIRT}1, and p16, joint knockdown of both {CARM}1 and {HuR} did not show further effect. Methylation by {CARM}1 enhanced the association of {HuR} with the 3'{UTR} of p16 {mRNA}, but not with the 3'{UTR} of cyclin A, cyclin B1, c-fos, or {SIRT}1 {mRNAs}. In senescent human diploid fibroblasts ({HDFs}), reduced {CARM}1 was accompanied by reduced {HuR} methylation. In addition, knockdown of {CARM}1 or mutation of the major methylation site of {HuR} in {HDF} markedly impaired the ability of {HuR} to regulate the expression of cyclin A, cyclin B1, c-fos, {SIRT}1, and p16 as well to maintain a proliferative phenotype. {CONCLUSION}: {CARM}1 represses replicative senescence by methylating {HuR} and thereby enhancing {HuR}'s ability to regulate the turnover of cyclin A, cyclin B1, c-fos, {SIRT}1, and p16 {mRNAs}.},
	pages = {15},
	journaltitle = {{BMC} Mol Biol},
	author = {Pang, L and Tian, H and Chang, N and Yi, J and Xue, L and Jiang, B and Gorospe, M and Zhang, X and Wang, W},
	date = {2013},
	pmid = {23837869},
	keywords = {3' Untranslated Regions, Humans, {RNA}, Gene Expression Regulation, *Cell Aging, Cell Cycle, Cells/*cytology/enzymology/metabolism, Cyclin A/genetics/metabolism, Cyclin B1/genetics/metabolism, Cyclin-Dependent Kinase Inhibitor p16/genetics/met, Hu Paraneoplastic Encephalomyelitis Antigens/genet, Messenger/genetics/metabolism, Methylation, Protein-Arginine N-Methyltransferases/genetics/*me, Proto-Oncogene Proteins c-fos/genetics/metabolism, Sirtuin 1/genetics/metabolism}
}

@article{morlando_functional_2002,
	title = {Functional analysis of yeast {snoRNA} and {snRNA} 3'-end formation mediated by uncoupling of cleavage and polyadenylation},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11839805},
	abstract = {Many nuclear and nucleolar small {RNAs} are accumulated as nonpolyadenylated species and require 3'-end processing for maturation. Here, we show that several genes coding for box C/D and H/{ACA} {snoRNAs} and for the U5 and U2 {snRNAs} contain sequences in their 3' portions which direct cleavage of primary transcripts without being polyadenylated. Genetic analysis of yeasts with mutations in different components of the pre-{mRNA} cleavage and polyadenylation machinery suggests that this mechanism of 3"-end formation requires cleavage factor {IA} ({CF} {IA}) but not cleavage and polyadenylation factor activity. However, in vitro results indicate that other factors participate in the reaction besides {CF} {IA}. Sequence analysis of {snoRNA} genes indicated that they contain conserved motifs in their 3" noncoding regions, and mutational studies demonstrated their essential role in 3"-end formation. We propose a model in which {CF} {IA} functions in cleavage and polyadenylation of pre-{mRNAs} and, in combination with a different set of factors, in 3"-end formation of nonpolyadenylated polymerase {II} transcripts.},
	pages = {1379--1389},
	number = {5},
	journaltitle = {Mol Cell Biol},
	author = {Morlando, M and Greco, P and Dichtl, B and Fatica, A and Keller, W and Bozzoni, I},
	date = {2002},
	pmid = {11839805},
	keywords = {Base Sequence, {RNA}, *{mRNA} Cleavage and Polyadenylation Factors, *Polyadenylation, *{RNA} 3' End Processing, *Saccharomyces cerevisiae Proteins, Chromosomes, Fungal, Fungal Proteins/metabolism, Fungal/genetics/*metabolism, Genes, Molecular Sequence Data, Mutation, Nuclear Proteins/metabolism, {RNA} Precursors/metabolism, Saccharomyces cerevisiae, Small Nuclear/genetics, Small Nucleolar/genetics/*metabolism}
}

@article{sakuma_multiplex_2014,
	title = {Multiplex genome engineering in human cells using all-in-one {CRISPR}/Cas9 vector system},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24954249},
	doi = {10.1038/srep05400},
	abstract = {{CRISPR}/Cas9-mediated genome editing is a next-generation strategy for genetic modifications, not only for single gene targeting, but also for multiple targeted mutagenesis. To make the most of the multiplexity of {CRISPR}/Cas9, we established a system for constructing all-in-one expression vectors containing multiple guide {RNA} expression cassettes and a Cas9 nuclease/nickase expression cassette. We further demonstrated successful examples of multiple targeting including chromosomal deletions in human cells using the all-in-one {CRISPR}/Cas9 vectors constructed with our novel system. Our system provides an efficient targeting strategy for multiplex genome/epigenome editing, simultaneous activation/repression of multiple genes, and beyond.},
	pages = {5400},
	journaltitle = {Sci Rep},
	author = {Sakuma, T and Nishikawa, A and Kume, S and Chayama, K and Yamamoto, T},
	date = {2014},
	pmid = {24954249}
}

@article{potapova_inhibition_2000,
	title = {Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10669748},
	abstract = {c-Jun N-terminal kinase ({JNK}) plays a critical role in coordinating the cellular response to stress and has been implicated in regulating cell growth and transformation. To investigate the growth-regulatory functions of {JNK}1 and {JNK}2, we used specific antisense oligonucleotides ({AS}) to inhibit their expression. A survey of several human tumor cell lines revealed that {JNKAS} treatment markedly inhibited the growth of cells with mutant p53 status but not that of cells with normal p53 function. To further examine the influence of p53 on cell sensitivity to {JNKAS} treatment, we compared the responsiveness of {RKO}, {MCF}-7, and {HCT}116 cells with normal p53 function to that of {RKO} E6, {MCF}-7 E6, and {HCT}116 p53(-/-), which were rendered p53 deficient by different methods. Inhibition of {JNK}2 (and to a lesser extent {JNK}1) expression dramatically reduced the growth of p53-deficient cells but not that of their normal counterparts. {JNK}2AS-induced growth inhibition was correlated with significant apoptosis. {JNK}2AS treatment induced the expression of the cyclin-dependent kinase inhibitor p21(Cip1/Waf1) in parental {MCF}-7, {RKO}, and {HCT}116 cells but not in the p53-deficient derivatives. That p21(Cip1/Waf1) expression contributes to the survival of {JNK}2AS-treated cells was supported by additional experiments demonstrating that p21(Cip1/Waf1) deficiency in {HCT}116 cells also results in heightened sensitivity to {JNKAS} treatment. Our results indicate that perturbation of {JNK}2 expression adversely affects the growth of otherwise nonstressed cells. p53 and its downstream effector p21(Cip1/Waf1) are important in counteracting these detrimental effects and promoting cell survival.},
	pages = {1713--1722},
	number = {5},
	journaltitle = {Mol Cell Biol},
	author = {Potapova, O and Gorospe, M and Dougherty, R H and Dean, N M and Gaarde, W A and Holbrook, N J},
	date = {2000},
	pmid = {10669748},
	keywords = {Humans, Gene Expression Regulation, Cultured, *Apoptosis/genetics, *Mitogen-Activated Protein Kinases, Cell Division/genetics, Cell Survival/genetics, Enzymologic, Female, Mitogen-Activated Protein Kinase 9, Neoplastic, Protein Kinases/biosynthesis/*genetics, Signal Transduction/genetics, Tumor Cells, Tumor Suppressor Protein p53/*genetics/metabolism}
}

@article{alioto_comprehensive_2015,
	title = {A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26647970},
	doi = {10.1038/ncomms10001},
	abstract = {As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using {PCR}-free methods and increasing sequencing depth to approximately 100 x shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.},
	pages = {10001},
	journaltitle = {Nat Commun},
	author = {Alioto, T S and Buchhalter, I and Derdak, S and Hutter, B and Eldridge, M D and Hovig, E and Heisler, L E and Beck, T A and Simpson, J T and Tonon, L and Sertier, A S and Patch, A M and Jager, N and Ginsbach, P and Drews, R and Paramasivam, N and Kabbe, R and Chotewutmontri, S and Diessl, N and Previti, C and Schmidt, S and Brors, B and Feuerbach, L and Heinold, M and Grobner, S and Korshunov, A and Tarpey, P S and Butler, A P and Hinton, J and Jones, D and Menzies, A and Raine, K and Shepherd, R and Stebbings, L and Teague, J W and Ribeca, P and Giner, F C and Beltran, S and Raineri, E and Dabad, M and Heath, S C and Gut, M and Denroche, R E and Harding, N J and Yamaguchi, T N and Fujimoto, A and Nakagawa, H and Quesada, V and Valdes-Mas, R and Nakken, S and Vodak, D and Bower, L and Lynch, A G and Anderson, C L and Waddell, N and Pearson, J V and Grimmond, S M and Peto, M and Spellman, P and He, M and Kandoth, C and Lee, S and Zhang, J and Letourneau, L and Ma, S and Seth, S and Torrents, D and Xi, L and Wheeler, D A and Lopez-Otin, C and Campo, E and Campbell, P J and Boutros, P C and Puente, X S and Gerhard, D S and Pfister, S M and {McPherson}, J D and Hudson, T J and Schlesner, M and Lichter, P and Eils, R and Jones, D T and Gut, I G},
	date = {2015},
	pmid = {26647970},
	keywords = {Human, Genome, Humans, *Mutation, High-Throughput Nucleotide Sequencing/*methods, Leukemia, Lymphoid/*genetics, Medulloblastoma/*genetics}
}

@article{letunic_recent_2002,
	title = {Recent improvements to the {SMART} domain-based sequence annotation resource},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11752305},
	abstract = {{SMART} (Simple Modular Architecture Research Tool, http://smart.embl-heidelberg.de) is a web-based resource used for the annotation of protein domains and the analysis of domain architectures, with particular emphasis on mobile eukaryotic domains. Extensive annotation for each domain family is available, providing information relating to function, subcellular localization, phyletic distribution and tertiary structure. The January 2002 release has added more than 200 hand-curated domain models. This brings the total to over 600 domain families that are widely represented among nuclear, signalling and extracellular proteins. Annotation now includes links to the Online Mendelian Inheritance in Man ({OMIM}) database in cases where a human disease is associated with one or more mutations in a particular domain. We have implemented new analysis methods and updated others. New advanced queries provide direct access to the {SMART} relational database using {SQL}. This database now contains information on intrinsic sequence features such as transmembrane regions, coiled-coils, signal peptides and internal repeats. {SMART} output can now be easily included in users' documents. A {SMART} mirror has been created at http://smart.ox.ac.uk.},
	pages = {242--244},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Letunic, I and Goodstadt, L and Dickens, N J and Doerks, T and Schultz, J and Mott, R and Ciccarelli, F and Copley, R R and Ponting, C P and Bork, P},
	date = {2002},
	pmid = {11752305},
	keywords = {Human, Animals, Genome, Humans, *Databases, *Protein Structure, Amino Acid, Information Storage and Retrieval, Internet, Protein, Protein Sorting Signals, Proteins/*chemistry/genetics/physiology, Quality Control, Repetitive Sequences, Sequence Alignment, Sequence Homology, Tertiary}
}

@article{knowles_recent_2009,
	title = {Recent de novo origin of human protein-coding genes},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19726446},
	doi = {10.1101/gr.095026.109},
	abstract = {The origin of new genes is extremely important to evolutionary innovation. Most new genes arise from existing genes through duplication or recombination. The origin of new genes from noncoding {DNA} is extremely rare, and very few eukaryotic examples are known. We present evidence for the de novo origin of at least three human protein-coding genes since the divergence with chimp. Each of these genes has no protein-coding homologs in any other genome, but is supported by evidence from expression and, importantly, proteomics data. The absence of these genes in chimp and macaque cannot be explained by sequencing gaps or annotation error. High-quality sequence data indicate that these loci are noncoding {DNA} in other primates. Furthermore, chimp, gorilla, gibbon, and macaque share the same disabling sequence difference, supporting the inference that the ancestral sequence was noncoding over the alternative possibility of parallel gene inactivation in multiple primate lineages. The genes are not well characterized, but interestingly, one of them was first identified as an up-regulated gene in chronic lymphocytic leukemia. This is the first evidence for entirely novel human-specific protein-coding genes originating from ancestrally noncoding sequences. We estimate that 0.075\% of human genes may have originated through this mechanism leading to a total expectation of 18 such cases in a genome of 24,000 protein-coding genes.},
	pages = {1752--1759},
	number = {10},
	journaltitle = {Genome Res},
	author = {Knowles, D G and {McLysaght}, A},
	date = {2009},
	pmid = {19726446},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Base Sequence, Genetic, Genome, Humans, Databases, Nucleic Acid, *Evolution, Biological, Genes/physiology, Intergenic/analysis/genetics, Models, Molecular, Molecular Sequence Data, Mutation/physiology, Pan troglodytes/genetics, Phylogeny, Proteins/*genetics, Sequence Homology}
}

@article{wilson_linkage_1986,
	title = {Linkage analysis of Dutch families at high risk for breast cancer},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3471674},
	pages = {87--92},
	journaltitle = {Genet Epidemiol Suppl},
	author = {Wilson, A F and Bailey-Wilson, J E and Cleton, F J and Elston, R C and King, M C},
	date = {1986},
	pmid = {3471674},
	keywords = {Humans, Breast Neoplasms/epidemiology/*genetics, Epidemiologic Methods, Female, Genetic Markers, Lod Score, Netherlands, Risk}
}

@article{yakovchuk_b2_2009,
	title = {B2 {RNA} and Alu {RNA} repress transcription by disrupting contacts between {RNA} polymerase {II} and promoter {DNA} within assembled complexes},
	volume = {106},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19307572},
	doi = {10.1073/pnas.0810738106},
	abstract = {Noncoding {RNAs} ({ncRNAs}) are now recognized as transregulators of eukaryotic transcription, a role once attributed exclusively to protein factors. Two {ncRNAs} in mammalian cells have been shown to repress general {mRNA} transcription by {RNA} polymerase {II} (Pol {II}) in response to heat shock: mouse B2 {RNA} and human Alu {RNA}. B2 and Alu {RNAs} bind directly and tightly to Pol {II} and co-occupy the promoters of repressed genes along with the polymerase. Here, we identified the molecular mechanism by which mouse B2 {RNA} and human Alu {RNA} repress Pol {II} transcription. Biochemical assays to probe the network of protein-{DNA} interactions at the promoter revealed that B2 and Alu {RNAs} prevent Pol {II} from establishing contacts with the promoter both upstream and downstream of the {TATA} box during closed complex formation. Disruption of these contacts correlates with transcriptional repression. We conclude that B2 and Alu {RNA} prevent Pol {II} from properly engaging the {DNA} during closed complex formation, resulting in complexes with an altered conformation that are transcriptionally inert. In the absence of its normal contacts with the promoter, Pol {II} is likely held in these inactive complexes on {DNA} through interactions with promoter-bound {TATA} box-binding protein and transcription factor {IIB}.},
	pages = {5569--5574},
	number = {14},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Yakovchuk, P and Goodrich, J A and Kugel, J F},
	date = {2009},
	pmid = {19307572},
	keywords = {Animals, Genetic, Humans, Mice, Promoter Regions, {RNA}, Protein Binding, *Transcription, Down-Regulation/genetics, Genetic/*genetics, Heat-Shock Response, {RNA} Polymerase {II}/*genetics/metabolism, {TATA}-Box Binding Protein, Transcription Factor {TFIIB}, Untranslated/*physiology}
}

@article{donskey_utility_2014,
	title = {Utility of a commercial {PCR} assay and a clinical prediction rule for detection of toxigenic Clostridium difficile in asymptomatic carriers},
	volume = {52},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24153132},
	doi = {10.1128/JCM.01852-13},
	abstract = {A commercial {PCR} assay of perirectal swab specimens detected 17 (68\%) of 25 asymptomatic carriers of toxigenic Clostridium difficile, including 93\% with skin and/or environmental contamination. A clinical prediction rule, followed by {PCR} screening, could be used to identify carriers at high risk of C. difficile shedding.},
	pages = {315--318},
	number = {1},
	journaltitle = {J Clin Microbiol},
	author = {Donskey, C J and Sunkesula, V C and Jencson, A L and Stone, N D and Gould, C V and {McDonald}, L C and Samore, M and Mayer, J and Pacheco, S and Sambol, S and Petrella, L and Terry, D and Gerding, D N},
	date = {2014},
	pmid = {24153132}
}

@article{chakraborty_pharmacokinetic_2013,
	title = {Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis},
	volume = {53},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24122883},
	doi = {10.1002/jcph.162},
	abstract = {Pharmacokinetics and pharmacodynamics of the anti-interleukin ({IL})-1beta monoclonal antibody, canakinumab, in gouty arthritis patients from three studies are reported. Canakinumab has low serum clearance (0.214 L/day), low steady-state volume of distribution (7.44 L), a 25.8-day half-life, and approximately 60\% subcutaneous absolute bioavailability in a typical 93-kg patient. Creatinine clearance had a small positive impact on serum canakinumab clearance that is not likely to be clinically relevant. Binding to circulating {IL}-1beta was demonstrated by increases in total serum {IL}-1beta following canakinumab dosing. Total {IL}-1beta kinetics and canakinumab pharmacokinetics were characterized by a population-based pharmacokinetic-binding model, where the estimated apparent in vivo dissociation constant (signifying binding affinity of canakinumab to circulating {IL}-1beta) was 0.99 nmol/L in gouty arthritis patients. Canakinumab treatment provided rapid, sustained decreases in C-reactive protein and serum amyloid A, provided superior pain relief to triamcinolone acetonide, and increased time to first recurrent attack (P {\textbackslash}textless/= 0.01 favoring all canakinumab doses vs. triamcinolone acetonide).},
	pages = {1240--1251},
	number = {12},
	journaltitle = {J Clin Pharmacol},
	author = {Chakraborty, A and Van, L M and Skerjanec, A and Floch, D and Klein, U R and Krammer, G and Sunkara, G and Howard, D},
	date = {2013},
	pmid = {24122883}
}

@article{church_lineage-specific_2009,
	title = {Lineage-specific biology revealed by a finished genome assembly of the mouse},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19468303},
	doi = {10.1371/journal.pbio.1000112},
	abstract = {The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier {MGSCv}3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non-protein-coding {RNAs} with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40\% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not.},
	pages = {e1000112},
	number = {5},
	journaltitle = {{PLoS} Biol},
	author = {Church, D M and Goodstadt, L and Hillier, L W and Zody, M C and Goldstein, S and She, X and Bult, C J and Agarwala, R and Cherry, J L and {DiCuccio}, M and Hlavina, W and Kapustin, Y and Meric, P and Maglott, D and Birtle, Z and Marques, A C and Graves, T and Zhou, S and Teague, B and Potamousis, K and Churas, C and Place, M and Herschleb, J and Runnheim, R and Forrest, D and Amos-Landgraf, J and Schwartz, D C and Cheng, Z and Lindblad-Toh, K and Eichler, E E and Ponting, C P},
	date = {2009},
	pmid = {19468303},
	keywords = {Animals, Genetic, Humans, Mice, Databases, Computational Biology/*methods, Gene Duplication, Genome/*genetics/physiology}
}

@article{guyton_activation_1996,
	title = {Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury},
	volume = {271},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8626753},
	abstract = {The mitogen-activated protein kinase ({MAPK}) family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. In this study we investigated the factors controlling {MAPK} activation by H2O2 and explored the impact of altering the pathways to kinase activation on cell survival following H2O2 exposure. Potent activation (10-20-fold) of extracellular signal-regulated protein kinase ({ERK}2) occurred within 10 min of H2O2 treatment, whereupon rapid inactivation ensued. H2O2 activated {ERK}2 in several cell types and also moderately activated (3-5-fold) both c-Jun N-terminal kinase and p38/{RK}/{CSBP}. Additionally, H2O2 increased the {mRNA} expression of {MAPK}-dependent genes c-jun, c-fos, and {MAPK} phosphatase-1. Suramin pretreatment completely inhibited H2O2 stimulation of {ERK}2, highlighting a role for growth factor receptors in this activation. Further, {ERK}2 activation by H2O2 was blocked by pretreatment with either N-acetyl-cysteine, o-phenanthroline, or mannitol, indicating that metal-catalyzed free radical formation mediates the initiation of signal transduction by H2O2. H2O2-stimulated activation of {ERK}2 was abolished in {PC}12 cells by inducible or constitutive expression of the dominant negative Ras-N-17 allele. Interestingly, {PC}12/Ras-N-17 cells were more sensitive than wild-type {PC}12 cells to H2O2 toxicity. Moreover, {NIH} 3T3 cells expressing constitutively active {MAPK} kinase ({MEK}, the immediate upstream regulator of {ERK}) were more resistant to H2O2 toxicity, while those expressing kinase-defective {MEK} were more sensitive, than cells expressing wild-type {MEK}. Taken together, these studies provide insight into mechanisms of {MAPK} regulation by H2O2 and suggest that {ERK} plays a critical role in cell survival following oxidant injury.},
	pages = {4138--4142},
	number = {8},
	journaltitle = {J Biol Chem},
	author = {Guyton, K Z and Liu, Y and Gorospe, M and Xu, Q and Holbrook, N J},
	date = {1996},
	pmid = {8626753},
	keywords = {Animals, Humans, Mice, Cells, Cultured, 3T3 Cells, Aorta/cytology/drug effects/physiology, Blotting, Calcium-Calmodulin-Dependent Protein Kinases/*meta, Cell Survival/*drug effects, Enzyme Activation, fos, Free Radicals/analysis/metabolism, Gene Expression/drug effects, Genes, {HeLa} Cells, Hydrogen Peroxide/*pharmacology, jun, Kinetics, Luciferases/analysis/biosynthesis, Muscle, {PC}12 Cells, Phosphoproteins/isolation \& purification/metabolis, Phosphotyrosine/analysis, Rats, Recombinant Proteins/analysis/biosynthesis, Smooth, Transfection, Vascular/cytology/*drug effects/ph, Western}
}

@article{uthaikhup_effects_2013,
	title = {The effects of head movement and walking speed on gait parameters in patients with chronic neck pain},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24144513},
	doi = {10.1016/j.math.2013.09.004},
	abstract = {It has been documented that neck pain can influence sensorimotor function. However, little is known about the effects of head movement and walking speed on gait characteristics in patients with neck pain. The aim of this study was to determine gait characteristics of patients with neck pain during walking with different head movements and gait speeds as compared to a control group without neck pain. Twenty women aged between 18 and 59 years with chronic neck pain ({\textbackslash}textgreater3 months) and 20 healthy controls of similar age, weight and height were recruited into the study. Participants with neck pain completed the Neck Disability Index and Visual Analogue Pain Scale. The experiment consisted of two walking sessions. The first session included walking with head straight, head up-down, and head turns from side to side. The second session included walking at comfortable and maximum speeds. Each trial was performed twice. Gait parameters measured using {GAITRite} walkway system were step length, stride length, step time, stride time, step width, cadence and gait speed. Patients with chronic neck pain demonstrated a narrower step width, a shorter step length and a slower gait speed during walking with the head movements and at maximum speed compared to the control group (all p {\textbackslash}textless 0.05). Maximum gait speed was moderately correlated with pain intensity and disability (p {\textbackslash}textless 0.01). The results suggest that patients with chronic neck pain have gait disturbances. This supports the notion that assessment of gait should be addressed in patients with persistent neck pain.},
	journaltitle = {Man Ther},
	author = {Uthaikhup, S and Sunkarat, S and Khamsaen, K and Meeyan, K and Treleaven, J},
	date = {2013},
	pmid = {24144513}
}

@article{seminario_pten_2003,
	title = {{PTEN} expression in {PTEN}-null leukaemic T cell lines leads to reduced proliferation via slowed cell cycle progression},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14603260},
	doi = {10.1038/sj.onc.1206872},
	abstract = {The balance of activities between the proto-oncogene phosphoinositide 3-kinase ({PI}3K) and the tumour suppressor gene {PTEN} has been shown to affect cellular growth and proliferation, as well as tumorigenesis. Previously, {PTEN} expression in the {PTEN}-null Jurkat T cell leukaemia line was shown to cause reduced proliferation without cell cycle arrest. Here, we further these investigations by determining the basis for this phenomenon. By {BrdU} pulse-chase and cell cycle arrest and release assays, we find that {PTEN} expression reduced proliferation by slowing progression through all phases of the cell cycle. This was associated with reduced levels of cyclins A, B1 and B2, cdk4, and cdc25A and increased p27KIP1 expression. Apoptosis played no role in the antiproliferative effect of {PTEN}, since only marginal increases in the rate of apoptosis were detected upon {PTEN} expression, and inhibitors of effector caspases did not restore proliferative capacity. Active Akt blocked the antiproliferative effects of {PTEN}, indicating that {PTEN} mediates its effects through conventional {PI}3K-linked signalling pathways. Similar results were obtained from a different {PTEN}-null leukaemia T cell line, {CEM}. Together, these results show that {PTEN} expression in leukaemic T cells leads to reduced proliferation via an apoptosis-independent mechanism involving slower passage through the cell cycle.},
	pages = {8195--8204},
	number = {50},
	journaltitle = {Oncogene},
	author = {Seminario, M C and Precht, P and Wersto, R P and Gorospe, M and Wange, R L},
	date = {2003},
	pmid = {14603260},
	keywords = {Humans, Apoptosis/genetics/physiology, Cell Cycle/*physiology, Cell Division/*physiology, Jurkat Cells, Leukemia, Phosphoric Monoester Hydrolases/*genetics/metaboli, {PTEN} Phosphohydrolase, T-Cell/*metabolism, T-Lymphocytes/*physiology, Tumor Suppressor Proteins/*genetics/metabolism}
}

@article{pulido-quetglas_scalable_2016,
	title = {Scalable Design of Paired {CRISPR} Guide {RNAs} for Genomic Deletion},
	doi = {http://dx.doi.org/10.1101/052795},
	journaltitle = {Biorxiv},
	author = {Pulido-Quetglas, Carlos and Arnan, Carme and Polidori, Taisia and Hermoso, Toni and Palumbo, Emilio and Johnson, Rory},
	date = {2016}
}

@article{chen_impact_2010,
	title = {Impact of replication timing on non-{CpG} and {CpG} substitution rates in mammalian genomes},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20103589},
	doi = {10.1101/gr.098947.109},
	abstract = {Neutral nucleotide substitutions occur at varying rates along genomes, and it remains a major issue to unravel the mechanisms that cause these variations and to analyze their evolutionary consequences. Here, we study the role of replication in the neutral substitution pattern. We obtained a high-resolution replication timing profile of the whole human genome by massively parallel sequencing of nascent {BrdU}-labeled replicating {DNA}. These data were compared to the neutral substitution rates along the human genome, obtained by aligning human and chimpanzee genomes using macaque and orangutan as outgroups. All substitution rates increase monotonously with replication timing even after controlling for local or regional nucleotide composition, crossover rate, distance to telomeres, and chromatin compaction. The increase in non-{CpG} substitution rates might result from several mechanisms including the increase in mutation-prone activities or the decrease in efficiency of {DNA} repair during the S phase. In contrast, the rate of C –{\textbackslash}textgreater T transitions in {CpG} dinucleotides increases in later-replicating regions due to increasing {DNA} methylation level that reflects a negative correlation between timing and gene expression. Similar results are observed in the mouse, which indicates that replication timing is a main factor affecting nucleotide substitution dynamics at non-{CpG} sites and constitutes a major neutral process driving mammalian genome evolution.},
	pages = {447--457},
	number = {4},
	journaltitle = {Genome Res},
	author = {Chen, C L and Rappailles, A and Duquenne, L and Huvet, M and Guilbaud, G and Farinelli, L and Audit, B and D'Aubenton-Carafa, Y and Arneodo, A and Hyrien, O and Thermes, C},
	date = {2010},
	pmid = {20103589},
	keywords = {Human, Animals, Genome, Humans, Mice, *Genome/genetics, *Mutation, {CpG} Islands/*genetics, {DNA} Replication Timing/*physiology, {DNA} Replication/genetics/physiology, Drosophila, Evolution, {HeLa} Cells, Macaca/genetics, Mammals/genetics, Missense/physiology, Molecular, Pan troglodytes/genetics, Pongo pygmaeus/genetics, Rats}
}

@article{guyton_age-related_1998,
	title = {Age-related changes in activation of mitogen-activated protein kinase cascades by oxidative stress},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9732053},
	abstract = {Oxidative stress is thought to play a critical role in aging and the pathogenesis of human disease. Molecular studies of both the physiologic function of oxidants and the deleterious consequences of exposure to oxidative stress have suggested that signal transduction cascades may be targeted by oxidants. Here, we review recent studies from this laboratory examining the molecular basis for the activation of mitogen-activated protein kinases by oxidative stress and the influence of these pathways on cellular fate. We examine the association between constitutive activation of extracellular signal-regulated kinase ({ERK}) and cancer, and discuss how such mechanisms may contribute to oxidant-induced skin carcinogenesis. We also address the relationship between a decline in activation of this same pathway and the aged phenotype. In this regard, we review evidence that a decrease in activation of {ERK} by growth factor correlates with a reduced proliferative capacity in the isolated rat hepatocyte model, and we provide new data indicating that the activation of the {ERK} pathway in response to oxidant stimuli is also decreased with age. Further evidence demonstrates that this alteration is associated with both a reduced mitogenic response and a decline in hepatocyte cell survival in response to oxidative stress. Finally, we provide perspective on how modulations in {ERK} signaling may interplay with other changes in signal transduction cascades in the aging process.},
	pages = {23--27},
	number = {1},
	journaltitle = {J Investig Dermatol Symp Proc},
	author = {Guyton, K Z and Gorospe, M and Wang, X and Mock, Y D and Kokkonen, G C and Liu, Y and Roth, G S and Holbrook, N J},
	date = {1998},
	pmid = {9732053},
	keywords = {Animals, Humans, *Oxidative Stress, Aging/*metabolism, Calcium-Calmodulin-Dependent Protein Kinases/*meta, Enzyme Activation, Rats, Signal Transduction}
}

@article{minor_srt1720_2011,
	title = {{SRT}1720 improves survival and healthspan of obese mice},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22355589},
	doi = {10.1038/srep00070},
	abstract = {Sirt1 is an {NAD}(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that {SRT}1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional {SIRT}1 knockout mouse and specific gene knockdowns we show {SRT}1720 affects mitochondrial respiration in a Sirt1- and {PGC}-1alpha-dependent manner. These findings indicate that {SRT}1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.},
	pages = {70},
	journaltitle = {Sci Rep},
	author = {Minor, R K and Baur, J A and Gomes, A P and Ward, T M and Csiszar, A and Mercken, E M and Abdelmohsen, K and Shin, Y K and Canto, C and Scheibye-Knudsen, M and Krawczyk, M and Irusta, P M and Martin-Montalvo, A and Hubbard, B P and Zhang, Y and Lehrmann, E and White, A A and Price, N L and Swindell, W R and Pearson, K J and Becker, K G and Bohr, V A and Gorospe, M and Egan, J M and Talan, M I and Auwerx, J and Westphal, C H and Ellis, J L and Ungvari, Z and Vlasuk, G P and Elliott, P J and Sinclair, D A and de Cabo, R},
	date = {2011},
	pmid = {22355589},
	keywords = {Animals, Mice, Apoptosis/drug effects, Body Composition/drug effects, Dietary Fats/administration \& dosage, Gene Expression/drug effects, Glucose/metabolism, Heterocyclic Compounds with 4 or More Rings/*pharm, Homeostasis/drug effects, Inbred C57BL, Liver/drug effects/pathology, Longevity/*drug effects, Male, Obesity/*physiopathology, Pancreas/drug effects}
}

@article{lopez_de_silanes_acquisition_2004,
	title = {Acquisition of resistance to butyrate enhances survival after stress and induces malignancy of human colon carcinoma cells},
	volume = {64},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15231671},
	doi = {10.1158/0008-5472.CAN-04-0711},
	abstract = {Acquired resistance to apoptosis by tumor cells remains a major obstacle for cancer treatment, and hence the analysis of resistance to apoptosis constitutes a major goal in the development of antitumoral drugs. We have established a butyrate-resistant human colon adenocarcinoma cell line ({BCS}-{TC}2.{BR}2) from nontumorigenic {BCS}-{TC}2 cells to analyze whether the acquisition of such phenotype confers resistance to apoptosis and stress. Although {BCS}-{TC}2.{BR}2 cells exhibited a more differentiated phenotype than the parental {BCS}-{TC}2 cells, higher butyrate concentrations remained capable of additionally enhancing their differentiation without inducing apoptosis. Survival rates of {BCS}-{TC}2.{BR}2 cells after glucose deprivation and heat shock were higher than those of parental cells, revealing a stress-resistant phenotype. These findings were accompanied by key differences between parental and butyrate-resistant cells in gene expression profiles and the acquisition of in vivo tumorigenicity. In conclusion, cells gaining resistance to an endogenous physiological modulator of growth, differentiation, and apoptosis concurrently acquired resistance to other agents that influence cell survival.},
	pages = {4593--4600},
	number = {13},
	journaltitle = {Cancer Res},
	author = {Lopez de Silanes, I and Olmo, N and Turnay, J and Gonzalez de Buitrago, G and Perez-Ramos, P and Guzman-Aranguez, A and Garcia-Diez, M and Lecona, E and Gorospe, M and Lizarbe, M A},
	date = {2004},
	pmid = {15231671},
	keywords = {Animals, Humans, Mice, Gene Expression Profiling, Adenocarcinoma/*drug therapy/genetics/metabolism/*, Apoptosis/drug effects/physiology, Butyrates/*pharmacology, Cell Differentiation/drug effects/physiology, Cell Line, Cell Survival/drug effects/physiology, Cellular, Colonic Neoplasms/*drug therapy/genetics/metabolis, Drug Resistance, Glucose/deficiency, Heat Stress Disorders/metabolism, Male, Neoplasm, Nude, Spheroids, Tumor}
}

@article{wang_long_2011,
	title = {A long noncoding {RNA} maintains active chromatin to coordinate homeotic gene expression},
	volume = {472},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21423168},
	doi = {10.1038/nature09819},
	abstract = {The genome is extensively transcribed into long intergenic noncoding {RNAs} ({lincRNAs}), many of which are implicated in gene silencing. Potential roles of {lincRNAs} in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control. Some locus control elements and enhancers transcribe {lincRNAs}, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5'of the cluster. Here we identify {HOTTIP}, a {lincRNA} transcribed from the 5' tip of the {HOXA} locus that coordinates the activation of several 5' {HOXA} genes in vivo. Chromosomal looping brings {HOTTIP} into close proximity to its target genes. {HOTTIP} {RNA} binds the adaptor protein {WDR}5 directly and targets {WDR}5/{MLL} complexes across {HOXA}, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for {HOTTIP} {RNA} activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, {lincRNAs} may organize chromatin domains to coordinate long-range gene activation.},
	pages = {120--124},
	number = {7341},
	journaltitle = {Nature},
	author = {Wang, K C and Yang, Y W and Liu, B and Sanyal, A and Corces-Zimmerman, R and Chen, Y and Lajoie, B R and Protacio, A and Flynn, R A and Gupta, R A and Wysocka, J and Lei, M and Dekker, J and Helms, J A and Chang, H Y},
	date = {2011},
	pmid = {21423168},
	keywords = {{DNA}, Animals, Genetic, Humans, Mice, {RNA}, Transcription, Gene Expression Regulation, Organ Specificity, Cells, Cultured, Untranslated/*genetics, Cell Line, Chromatin/*genetics/metabolism, Developmental/*genetic, Embryo, Fibroblasts/metabolism, Gene Knockdown Techniques, Genes, Histone-Lysine N-Methyltransferase/metabolism, Histones/chemistry/metabolism, Homeobox/*genetics, Intergenic/genetics, Lysine/metabolism, Mammalian/metabolism, Methylation, Molecular Sequence Data, Multigene Family/genetics}
}

@article{nikiforov_functional_2002,
	title = {A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12138190},
	abstract = {A {cDNA} library enriched with Myc-responsive {cDNAs} but depleted of myc {cDNAs} was used in a functional screen for growth enhancement in c-myc-null cells. A {cDNA} clone for mitochondrial serine hydroxymethyltransferase ({mSHMT}) that was capable of partial complementation of the growth defects of c-myc-null cells was identified. Expression analysis and chromatin immunoprecipitation demonstrated that {mSHMT} is a direct Myc target gene. Furthermore, a separate gene encoding the cytoplasmic isoform of the same enzyme is also a direct target of Myc regulation. {SHMT} enzymes are the major source of the one-carbon unit required for folate metabolism and for the biosynthesis of nucleotides and amino acids. Our data establish a novel functional link between Myc and the regulation of cellular metabolism.},
	pages = {5793--5800},
	number = {16},
	journaltitle = {Mol Cell Biol},
	author = {Nikiforov, M A and Chandriani, S and O'Connell, B and Petrenko, O and Kotenko, I and Beavis, A and Sedivy, J M and Cole, M D},
	date = {2002},
	pmid = {12138190},
	keywords = {Animals, Genetic, Humans, Promoter Regions, Cells, Cultured, *Cell Physiological Phenomena, Carbon/*metabolism, Cell Separation, Fibroblasts/physiology, Flow Cytometry, Gene Library, Genes, Glycine Hydroxymethyltransferase/genetics/*metabol, Mitochondria/enzymology, Mutant Strains, myc, Proto-Oncogene Proteins c-myc/genetics/*metabolism, Rats}
}

@article{mazan-mamczarz_post-transcriptional_2008,
	title = {Post-transcriptional gene regulation by {HuR} promotes a more tumorigenic phenotype},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18641687},
	doi = {10.1038/onc.2008.215},
	abstract = {In a breast tumor xenograft model, the {MCT}-1 oncogene increases the in vivo tumorgenicity of {MCF}7 cells by promoting angiogenesis and inhibiting apoptosis. Increases in the tumor microvascular density are accompanied by a strong reduction in the levels of the angiogenesis inhibitor thrombospondin-1 ({TSP}1), but the mechanisms underlying this process are unknown. We show that {TSP}1 expression is controlled, at least in part, by post-transcriptional events. Using {RNA} interference to knock down the expression of the {RNA}-binding protein {HuR} in {MCF}7 cells as well as {HuR} overexpression, we demonstrate that {HuR} plays an important role in translation of the {TSP}1 {mRNA}. Furthermore, employing the {RIP}-Chip assay yielded 595 transcripts with significantly altered binding to {HuR} in the more tumorigenic breast cancer clones compared with the weakly tumorigenic clones. These {mRNAs} clustered in several pathways implicated in the transformed phenotype, such as the {RAS} pathway (involved in mitogenesis), the {PI}3K pathway (evasion of apoptosis) and pathways mediating angiogenesis and the cellular response to hypoxia. These findings demonstrate for the first time that global changes in {HuR}-bound {mRNAs} are implicated in the evolution to a more tumorigenic phenotype in an in vivo tumor model and underscore the role of global {mRNA}-protein interactions toward tumor progression.},
	pages = {6151--6163},
	number = {47},
	journaltitle = {Oncogene},
	author = {Mazan-Mamczarz, K and Hagner, P R and Corl, S and Srikantan, S and Wood, W H and Becker, K G and Gorospe, M and Keene, J D and Levenson, A S and Gartenhaus, R B},
	date = {2008},
	pmid = {18641687},
	keywords = {Genetic, Humans, {RNA}, Transcription, *Gene Expression Regulation, Antigens, Breast Neoplasms/*metabolism/pathology, Cell Cycle Proteins/physiology, Cell Line, Female, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/analysis/metabolism, Neoplastic, Oncogene Proteins/physiology, Phenotype, Phosphatidylinositol 3-Kinases/physiology, Protein Biosynthesis, {RNA}-Binding Proteins/antagonists \& inhibitors/*phy, Signal Transduction, Surface/*physiology, Thrombospondin 1/*genetics, Tumor}
}

@article{ulitsky_metareg:_2008,
	title = {{MetaReg}: a platform for modeling, analysis and visualization of biological systems using large-scale experimental data},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18171474},
	doi = {10.1186/gb-2008-9-1-r1},
	abstract = {{MetaReg} http://acgt.cs.tau.ac.il/metareg/application.html is a computational tool that models cellular networks and integrates experimental results with such models. {MetaReg} represents established knowledge about a biological system, available today mostly in informal form in the literature, as probabilistic network models with underlying combinatorial regulatory logic. {MetaReg} enables contrasting predictions with measurements, model improvements and studying what-if scenarios. By summarizing prior knowledge and providing visual and computational aids, it helps the expert explore and understand her system better.},
	pages = {R1},
	number = {1},
	journaltitle = {Genome Biol},
	author = {Ulitsky, I and Gat-Viks, I and Shamir, R},
	date = {2008},
	pmid = {18171474},
	keywords = {*Software, Algorithms, *Models, Biological, Computational Biology/*methods, Computer Simulation, Leucine/*biosynthesis, Saccharomyces cerevisiae/*metabolism}
}

@article{schmidt_role_1999,
	title = {The role of c-myc in cellular growth control},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10378694},
	doi = {10.1038/sj.onc.1202751},
	abstract = {Cell division is coupled to cell growth. Since some c-myc target genes are regulators of cell growth while others function in cell division pathways, c-myc is apparently poised at the interface of these processes. Cell culture systems have shown specific myc-associated growth phenotypes. Increased cell growth precedes {DNA} synthesis after myc activation in cells expressing myc-estrogen receptor fuson constructs and cells lacking c-myc exhibit a marked loss of protein synthesis. A number of candidate c-myc target genes regulate processes required for cell growth including {rRNA} transcription and processing, ribosomal protein transcription and translation, and translation initiation. These interactions all have the potential to account for the growth phenotypes in c-myc mutant cells. The ability of translation initiation factors, including {eIF}4E, to transform cells makes them particularly interesting targets of c-myc. Further evaluation of these target genes will provide important insights into growth control and c-myc's functions in cellular proliferation.},
	pages = {2988--2996},
	number = {19},
	journaltitle = {Oncogene},
	author = {Schmidt, E V},
	date = {1999},
	pmid = {10378694},
	keywords = {Animals, Humans, Gene Expression Regulation, Cell Division/genetics/*physiology, Proto-Oncogene Proteins c-myc/*physiology}
}

@article{gill_value_2003,
	title = {The value of positron emission tomography in the clinical evaluation of dementia},
	volume = {51},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12558725},
	abstract = {Positron emission tomography ({PET}) has been promoted as a means of improving the diagnosis of Alzheimer's disease ({AD}), but the evidence to support its incremental value is unclear. To assess the evidence regarding the use of {PET} in the clinical evaluation of {AD}, a systematic review of the English-language literature indexed in {MEDLINE} (1975-January 2001), the Cochrane Library (issue 4, 2000), and health technology assessment ({HTA}) reports was conducted. Articles identified by this review process were graded for methodological and reporting quality using a standardized grading scheme. Sixteen original articles and seven {HTA} reports were identified. In general, the articles addressed: using {PET} to differentiate {AD} from normal aging or non-Alzheimer's dementias, {PET} imaging compared with single positron emission computed tomography imaging, using {PET} to predict the progression of dementia, and agreement and reliability in the interpretation of {PET} images. Serious problems with study design and methodology in all articles were identified. Previous {HTA} reports have generally recommended that {PET} not be used in the clinical evaluation of dementia. In conclusion, there is little evidence to support the addition of {PET} to the routine clinical evaluation of patients with suspected or established dementia. Suggestions for future research in this area are offered.},
	pages = {258--264},
	number = {2},
	journaltitle = {J Am Geriatr Soc},
	author = {Gill, S S and Rochon, P A and Guttman, M and Laupacis, A},
	date = {2003},
	pmid = {12558725},
	keywords = {Humans, *Tomography, Aged, Alzheimer Disease/*radionuclide imaging, Dementia/radionuclide imaging, Diagnosis, Differential, Emission-Computed/statistics \& numeri, Observer Variation}
}

@article{duszczyk_xist_2011,
	title = {The Xist {RNA} A-repeat comprises a novel {AUCG} tetraloop fold and a platform for multimerization},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21947263},
	doi = {10.1261/rna.2747411},
	abstract = {X-chromosome inactivation ({XCI}) in female mammals depends on the noncoding {RNA} X inactivation specific transcript (Xist). The mechanism of chromosome-wide silencing by Xist is poorly understood. While it is established that the 5' region of Xist {RNA}, comprising the A-repeats and holding 7.5-8.5 copies of a conserved 26-mer sequence, is essential for Xist-mediated silencing, high-resolution structural information for the A-repeats is not available. Here, we report the three-dimensional solution structure of a 14-mer hairpin in the 5' region of a human A-repeat. This hairpin is remarkably stable and adopts a novel {AUCG} tetraloop fold, the integrity of which is required for silencing. We show that, contrary to previous predictions, the 3' region of single or tandem A-repeats mediates duplex formation in vitro. Significantly, mutations in this region disrupt the inter-repeat duplex formation in vitro and abrogate the silencing function of Xist A-repeats in vivo. Our data suggest that the complete A-repeat region may be stabilized by inter-repeat duplex formation and, as such, may provide a platform for multimerization and specific recognition of the {AUCG} tetraloops by trans-acting factors.},
	pages = {1973--1982},
	number = {11},
	journaltitle = {{RNA}},
	author = {Duszczyk, M M and Wutz, A and Rybin, V and Sattler, M},
	date = {2011},
	pmid = {21947263},
	keywords = {Animals, Humans, {RNA}, Nucleic Acid, *Repetitive Sequences, *{RNA} Folding, Dimerization, Long Untranslated, Models, Molecular, Nucleic Acid Conformation, Untranslated/*chemistry/metabolism}
}

@article{coyle_economic_2003,
	title = {The economic evaluation of pharmacotherapies for Parkinson's disease},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12781598},
	abstract = {As well as the significant clinical effects of Parkinson's disease ({PD}), the disease places a high economic burden on society. Given the scarcity of health care resources, it is becoming increasingly necessary to demonstrate that new therapies for {PD} provide value for money in comparison with other potential interventions. This paper outlines the basic techniques of cost-effectiveness analysis and its application to {PD}. These techniques are illustrated by a recent economic evaluation of entacapone for use in Canada.},
	pages = {301--307},
	number = {5},
	journaltitle = {Parkinsonism Relat Disord},
	author = {Coyle, D and Barbeau, M and Guttman, M and Baladi, J F},
	date = {2003},
	pmid = {12781598},
	keywords = {Humans, Antiparkinson Agents/*economics/therapeutic use, Canada, Catechols/economics/therapeutic use, Cost-Benefit Analysis/methods, Drug Costs, Nitriles, Parkinson Disease/*drug therapy/economics}
}

@article{okun_piloting_2010,
	title = {Piloting the {NPF} data-driven quality improvement initiative},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20609611},
	doi = {10.1016/j.parkreldis.2010.06.005},
	abstract = {{OBJECTIVE}: To pilot a data-driven quality care program in National Parkinson Foundation ({NPF}) Centers of Excellence. {BACKGROUND}: Evidence from comparative effectiveness research ({CER}) can be used to guide decisions regarding health care and to improve quality and efficiency of care. We propose to develop the infrastructure required to conduct {CER} across an extensive network of {NPF} Centers of Excellence. {METHODS}: We present the staged planning for a pilot study which will demonstrate the development and implementation of the infrastructure that will be needed for a large standardized patient-centered, clinical practice database for {PD}. This database will support {CER} and drive quality improvement studies. {RESULTS}: We describe the infrastructure for the ongoing pilot feasibility testing in a subset of six {NPF} Centers of Excellence, and we discuss the impact that the data (available in 2010) could have in guiding {PD} management. {CONCLUSION}: This preliminary experience will facilitate the longitudinal tracking of therapies and of outcomes in {PD} clinical practice. Further, we are hopeful that the information will provide insight into {PD} that will extend beyond the clinical trials population (the population included in most available {PD} databases). This prospective standardized real-world multi-center clinical practice database will aim to identify positive health outcomes associated with treatment approaches, and to identify variations in clinical outcomes that may suggest improvements in best clinical practice patterns.},
	pages = {517--521},
	number = {8},
	journaltitle = {Parkinsonism Relat Disord},
	author = {Okun, M S and Siderowf, A and Nutt, J G and O'Conner, G T and Bloem, B R and Olmstead, E M and Guttman, M and Simuni, T and Cheng, E and Cohen, E V and Parashos, S and Marsh, L and Malaty, I A and Giladi, N and Schmidt, P and Oberdorf, J},
	date = {2010},
	pmid = {20609611},
	keywords = {Humans, Databases, *Parkinson Disease, Comparative Effectiveness Research/*methods/*organ, Database Management Systems/*organization \& admini, Databases as Topic/*organization \& administration, Factual, Pilot Projects, Registries, Research Design}
}

@article{srinivasan_prospective_2013,
	title = {Prospective detection of respiratory pathogens in symptomatic children with cancer},
	volume = {32},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23190778},
	doi = {10.1097/INF.0b013e31827bd619},
	abstract = {{BACKGROUND}: : The data on human rhinovirus, coronavirus, bocavirus, metapneumovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis infections in children with cancer is limited. {METHODS}: : We sought to determine prospectively the prevalence of respiratory pathogens in these children, using multiplexed-polymerase chain reaction. {RESULTS}: : We enrolled 253 children with upper or lower respiratory tract infection ({LRTI}) during a 1-year period. A respiratory virus was detected in 193 (76\%) patients; 156 (81\%) patients had upper respiratory tract infection. Human rhinovirus was the most common virus detected in 97 (62\%) and 24 (65\%) patients with upper respiratory tract infection and {LRTI}, respectively. Leukemia or lymphoma was the most common underlying diagnosis in 95 (49\%) patients followed by solid tumor 47 (24\%), posthematopoietic stem cell transplant 28 (15\%) and brain tumor in 23 (12\%) patients. By multiple logistic regression analysis, human bocavirus was the most commonly detected respiratory virus in patients with {LRTI} (P = 0.008; odds ratio, 4.52; 95\% confidence interval: 1.48-13.79). Coinfection with {\textbackslash}textgreater1 virus was present in 47 (24\%) patients, and did not increase the risk for {LRTI}. Two (0.7\%) patients succumbed to {LRTI} from parainfluenza virus-3 and respiratory syncytial virus/human rhinovirus infection, respectively. C. pneumoniae and M. pneumoniae were detected in 4 and 3 patients, respectively. {CONCLUSIONS}: : Human rhinovirus was the most common virus detected in children with cancer and posthematopoietic stem cell transplant hospitalized with an acute respiratory illness, and was not associated with increased morbidity. Prospective studies with viral load determination and asymptomatic controls are needed to study the association of these emerging respiratory viruses with {LRTI} in children with cancer and posthematopoietic stem cell transplant.},
	pages = {e99--e104},
	number = {3},
	journaltitle = {Pediatr Infect Dis J},
	author = {Srinivasan, A and Gu, Z and Smith, T and Morgenstern, M and Sunkara, A and Kang, G and Srivastava, D K and Gaur, A H and Leung, W and Hayden, R T},
	date = {2013},
	pmid = {23190778},
	keywords = {Humans, Adolescent, Bacteria/classification/genetics/*isolation \& puri, Child, Female, Infant, Male, Multiplex Polymerase Chain Reaction/methods, Neoplasms/*complications, Preschool, Prevalence, Prospective Studies, Respiratory Tract Infections/epidemiology/*microbi, Viruses/classification/genetics/*isolation \& purif}
}

@article{kim_gu-rich_2008,
	title = {{GU}-rich {RNA}: expanding {CUGBP}1 function, broadening {mRNA} turnover},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18243108},
	doi = {10.1016/j.molcel.2008.01.005},
	abstract = {In this issue of Molecular Cell, Vlasova et al. (2008) identify the {GU}-rich element ({GRE}) as a novel, widespread, degradation-promoting sequence through which the {RNA}-binding protein {CUGBP}1 elicits {mRNA} decay.},
	pages = {151--152},
	number = {2},
	journaltitle = {Mol Cell},
	author = {Kim, H H and Gorospe, M},
	date = {2008},
	pmid = {18243108},
	keywords = {Humans, {RNA}, 3' Untranslated Regions/genetics/*metabolism, Cytoplasm/genetics/metabolism, Globins/genetics/metabolism, {HeLa} Cells, Protein Binding/physiology, Proto-Oncogene Proteins c-jun/genetics/metabolism, Receptors, {RNA} Stability/*physiology, {RNA}-Binding Proteins/antagonists \& inhibitors/gene, Small Interfering/genetics, T-Lymphocytes/cytology/*metabolism, Tumor Necrosis Factor/genetics/metaboli}
}

@article{guyton_mitogen-activated_1996,
	title = {Mitogen-activated protein kinase ({MAPK}) activation by butylated hydroxytoluene hydroperoxide: implications for cellular survival and tumor promotion},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8758915},
	abstract = {The mitogen-activated protein kinase ({MAPK}) cascade plays an important role in carcinogenic development. Herein, we show that the skin tumor promoter butylated hydroxytoluene hydroperoxide ({BHTOOH}) stimulates a rapid and potent (14- to 20-fold) activation of extracellular signal-regulated kinase ({ERK}) in vivo and in cultured mouse keratinocytes. {BHTOOH} also moderately (5-fold) activated c-jun-N-terminal kinase, and 38-{kDa} {MAPK}-related protein in these same cells. N-acetylcysteine and o-phenanthroline abolished {ERK} activation by {BHTOOH}, consistent with a requirement for metal-dependent formation of reactive intermediates. Indeed, 4-{CD}3-{BHTOOH}, an analogue that generates less of the metabolite {BHT}-quinone methide (2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone) and fewer tumors in vivo, accordingly exhibited diminished potency for activating {ERK}. {ERK} activation by {BHTOOH} was inhibited by suramin, and by expression of dominant-negative Ras-N-17 in {PC}12 cells, suggesting overlap between the pathways for {BHTOOH} and growth factor signaling. Induction of {MAPK}-dependent genes c-fos and {MAPK} phosphatase-1 by {BHTOOH} was also blocked by Ras-N-17 expression. Moreover, expression of Ras-N-17 or kinase-defective {MAPK} kinase ({MEK}) diminished cell survival following {BHTOOH} exposure. Similarly, pretreatment with suramin or the {MEK} inhibitor {PD}098059 also potentiated the toxicity of {BHTOOH}. On the other hand, expression of constitutively active {MEK} enhanced cell survival. Thus, we demonstrate that the {MAPK} cascade is critical to the cellular response to {BHTOOH}. This study suggests a functional role for {MAPK} activation in tumor promotion stimulated by oxidants and other agents.},
	pages = {3480--3485},
	number = {15},
	journaltitle = {Cancer Res},
	author = {Guyton, K Z and Gorospe, M and Kensler, T W and Holbrook, N J},
	date = {1996},
	pmid = {8758915},
	keywords = {Animals, Base Sequence, Mice, Cells, Cultured, Calcium-Calmodulin-Dependent Protein Kinases/*meta, Carcinogens/*toxicity, Cell Survival/drug effects/physiology, Chemical, Enzyme Activation/drug effects, Female, Gene Expression/drug effects, Growth Factor/physiology, Inbred Strains, Keratinocytes/drug effects, Molecular Sequence Data, Oxidants/toxicity, Quinones/*toxicity, ras Proteins/physiology, Receptors, Signal Transduction/drug effects/physiology, Skin Neoplasms/*chemically induced/*enzymology, Skin/drug effects/enzymology, Stimulation}
}

@article{andersen_ribosomal_2009,
	title = {Ribosomal protein {mRNAs} are primary targets of regulation in {RNase}-L-induced senescence},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19411840},
	abstract = {The endoribonuclease {RNase}-L requires 2',5'-linked oligoadenylates for activation, and mediates antiviral and antiproliferative activities. We previously determined that {RNase}-L activation induces senescence; to determine potential mechanisms underlying this activity, we used microarrays to identify {RNase}-L-regulated {mRNAs}. {RNase}-L activation affected affected a finite number of transcripts, and thus does not lead to a global change in {mRNA} turnover. The largest classes of downregulated transcripts, that represent candidate {RNase}-L substrates, function in protein biosynthesis, metabolism and proliferation. Among these, {mRNAs} encoding ribosomal proteins ({RPs}) were particularly enriched. The reduced levels of four {RP} {mRNAs} corresponded with a decrease in their half lives and a physical association with an {RNase}-L-ribonucleoprotein ({RNP}) complex in cells, suggesting that they represent authentic {RNase}-L substrates. Sequence and structural analysis of the downregulated {mRNAs} identified a putative {RNase}-L target motif that was used for the in silico identification of a novel {RNase}-L-{RNP}-interacting transcript. The downregulation of {RP} {mRNAs} corresponded with a marked reduction in protein translation, consistent with the roles of {RP} proteins in ribosome function. Our data support a model in which the {RNase}-L-mediated degradation of {RP} {mRNAs} inhibits translation, and may contribute to its antiproliferative, senescence inducing and tumor suppressor activities.},
	pages = {305--315},
	number = {3},
	journaltitle = {{RNA} Biol},
	author = {Andersen, J B and Mazan-Mamczarz, K and Zhan, M and Gorospe, M and Hassel, B A},
	date = {2009},
	pmid = {19411840},
	keywords = {Animals, Base Sequence, Mice, {RNA}, Protein Binding, Gene Expression Profiling, *Cell Aging, *Down-Regulation, Cell Line, Endoribonucleases/deficiency/*metabolism, Enzyme Activation, Knockout, Messenger/chemistry/genetics/*metabolism, Nucleic Acid Conformation, Ribosomal Proteins/genetics/*metabolism}
}

@article{elkon_spikedatabase_2008,
	title = {{SPIKE}–a database, visualization and analysis tool of cellular signaling pathways},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18289391},
	doi = {10.1186/1471-2105-9-110},
	abstract = {{BACKGROUND}: Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level. {RESULTS}: To cope with this challenge, we are developing the {SPIKE} knowledge-base of signaling pathways. {SPIKE} contains three main software components: 1) A database ({DB}) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the {DB}. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the {DB} and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.{SPIKE} is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to {SPIKE} {DB}. Our vision is that the {DB} will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise. {CONCLUSION}: The integrated capabilities of {SPIKE} make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks with omics data.},
	pages = {110},
	journaltitle = {{BMC} Bioinformatics},
	author = {Elkon, R and Vesterman, R and Amit, N and Ulitsky, I and Zohar, I and Weisz, M and Mass, G and Orlev, N and Sternberg, G and Blekhman, R and Assa, J and Shiloh, Y and Shamir, R},
	date = {2008},
	pmid = {18289391},
	keywords = {*Cell Physiological Phenomena, *Database Management Systems/trends, *Databases, Genetic/trends, Metabolic Networks and Pathways/physiology, Signal Transduction/*physiology, Software/trends}
}

@article{laneve_purification_2003,
	title = {Purification, cloning, and characterization of {XendoU}, a novel endoribonuclease involved in processing of intron-encoded small nucleolar {RNAs} in Xenopus laevis},
	volume = {278},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12571235},
	doi = {10.1074/jbc.M211937200},
	abstract = {Here we report the purification, from Xenopus laevis oocyte nuclear extracts, of a new endoribonuclease, {XendoU}, that is involved in the processing of the intron-encoded box C/D U16 small nucleolar {RNA} ({snoRNA}) from its host pre-{mRNA}. Such an activity has never been reported before and has several uncommon features that make it quite a novel enzyme: it is poly(U)-specific, it requires Mn(2+) ions, and it produces molecules with 2'-3'-cyclic phosphate termini. Even if {XendoU} cleaves U-stretches, it displays some preferential cleavage on {snoRNA} precursor molecules. {XendoU} also participates in the biosynthesis of another intron-encoded {snoRNA}, U86, which is contained in the {NOP}56 gene of Xenopus laevis. A common feature of these {snoRNAs} is that their production is alternative to that of the {mRNA}, suggesting an important regulatory role for all the factors involved in the processing reaction.},
	pages = {13026--13032},
	number = {15},
	journaltitle = {J Biol Chem},
	author = {Laneve, P and Altieri, F and Fiori, M E and Scaloni, A and Bozzoni, I and Caffarelli, E},
	date = {2003},
	pmid = {12571235},
	keywords = {{DNA}, Animals, Base Sequence, {RNA}, *Introns, Amino Acid Sequence, Cell Nucleolus/genetics, Cell Nucleus/enzymology, Chromatography, Cloning, Complementary/genetics, Durapatite, Embryo, Endoribonucleases/chemistry/*genetics/isolation \&, Female, Gel, Ion Exchange, Molecular, Molecular Sequence Data, Nonmammalian, Oocytes/enzymology, Peptide Fragments/chemistry, Small Nuclear/*genetics, Xenopus laevis, Xenopus Proteins/chemistry/*genetics/metabolism}
}

@article{yu_coassembly_2011,
	title = {Coassembly of {REST} and its cofactors at sites of gene repression in embryonic stem cells},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21632747},
	doi = {10.1101/gr.114488.110},
	abstract = {The differentiation of pluripotent embryonic stem cells is regulated by networks of activating and repressing transcription factors that orchestrate determinate patterns of gene expression. With the recent mapping of target sites for many transcription factors, it has been a conundrum that so few of the genes directly targeted by these factors are transcriptionally responsive to the binding of that factor. To address this, we generated genome-wide maps of the transcriptional repressor {REST} and five of its corepressors in mouse embryonic stem cells. Combining these binding-site maps with comprehensive gene-expression profiling, we show that {REST} is functionally heterogeneous. Approximately half of its binding sites apparently are nonfunctional, having weaker binding of {REST} and low recruitment of corepressors. In contrast, the other sites strongly recruit {REST} and corepressor complexes with varying numbers of components. Strikingly, the latter sites account for almost all observed gene regulation. These data support a model where productive gene repression by {REST} requires assembly of a multimeric "repressosome" complex, whereas weak recruitment of {REST} and its cofactors is insufficient to repress gene expression.},
	pages = {1284--1293},
	number = {8},
	journaltitle = {Genome Res},
	author = {Yu, H B and Johnson, R and Kunarso, G and Stanton, L W},
	date = {2011},
	pmid = {21632747},
	keywords = {Animals, Genome, Mice, Binding Sites, Gene Expression Regulation, Cell Differentiation, Embryonic Stem Cells/*cytology/metabolism, Gene Regulatory Networks, Repressor Proteins/*genetics/metabolism, Transcription Factors/genetics/metabolism}
}

@article{ferretti_concerted_2008,
	title = {Concerted {microRNA} control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18756266},
	doi = {10.1038/emboj.2008.172},
	abstract = {{MicroRNAs} ({miRNA}) are crucial post-transcriptional regulators of gene expression and control cell differentiation and proliferation. However, little is known about their targeting of specific developmental pathways. Hedgehog (Hh) signalling controls cerebellar granule cell progenitor development and a subversion of this pathway leads to neoplastic transformation into medulloblastoma ({MB}). Using a {miRNA} high-throughput profile screening, we identify here a downregulated {miRNA} signature in human {MBs} with high Hh signalling. Specifically, we identify {miR}-125b and {miR}-326 as suppressors of the pathway activator Smoothened together with {miR}-324-5p, which also targets the downstream transcription factor Gli1. Downregulation of these {miRNAs} allows high levels of Hh-dependent gene expression leading to tumour cell proliferation. Interestingly, the downregulation of {miR}-324-5p is genetically determined by {MB}-associated deletion of chromosome 17p. We also report that whereas {miRNA} expression is downregulated in cerebellar neuronal progenitors, it increases alongside differentiation, thereby allowing cell maturation and growth inhibition. These findings identify a novel regulatory circuitry of the Hh signalling and suggest that misregulation of specific {miRNAs}, leading to its aberrant activation, sustain cancer development.},
	pages = {2616--2627},
	number = {19},
	journaltitle = {{EMBO} J},
	author = {Ferretti, E and De Smaele, E and Miele, E and Laneve, P and Po, A and Pelloni, M and Paganelli, A and Di Marcotullio, L and Caffarelli, E and Screpanti, I and Bozzoni, I and Gulino, A},
	date = {2008},
	pmid = {18756266},
	keywords = {Human, Animals, Base Sequence, Humans, Mice, Gene Expression Profiling, Adult, Aged, Cell Differentiation, Cell Proliferation, Cerebellum/*cytology, Chromosomes, G-Protein-Coupled/genetics/metabolism, Hedgehog Proteins/genetics/*metabolism, Medulloblastoma/genetics/*metabolism/pathology, Microarray Analysis, {MicroRNAs}/genetics/*metabolism, Middle Aged, Molecular Sequence Data, Neurons/cytology/*physiology, Pair 17/genetics, Receptors, Signal Transduction/*physiology, Stem Cells/cytology/*physiology, Transcription Factors/genetics/metabolism}
}

@article{fan_en_2006,
	title = {En masse nascent transcription analysis to elucidate regulatory transcription factors},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16540593},
	doi = {10.1093/nar/gkj510},
	abstract = {Despite exhaustively informing about steady-state {mRNA} abundance, {DNA} microarrays have been used with limited success to identify regulatory transcription factors ({TFs}). The main limitation of this approach is that altered {mRNA} stability also strongly governs the patterns of expressed genes. Here, we used nuclear run-on assays and microarrays to systematically interrogate changes in nascent transcription in cells treated with the topoisomerase inhibitor camptothecin ({CPT}). Analysis of the promoters of coordinately transcribed genes after {CPT} treatment suggested the involvement of {TFs} c-Myb and Rfx1. The predicted {CPT}-dependent associations were subsequently confirmed by chromatin immunoprecipitation assays. Importantly, after {RNAi}-mediated knockdown of each {TF}, the {CPT}-elicited induction of c-Myb- and/or Rfx1-regulated {mRNAs} was diminished and the overall cellular response was impaired. The strategies described here permit the successful identification of the {TFs} responsible for implementing adaptive gene expression programs in response to cellular stimulation.},
	pages = {1492--1500},
	number = {5},
	journaltitle = {Nucleic Acids Res},
	author = {Fan, J and Zhan, M and Shen, J and Martindale, J L and Yang, X and Kawai, T and Gorospe, M},
	date = {2006},
	pmid = {16540593},
	keywords = {Genetic, Humans, Promoter Regions, {RNA}, Binding Sites, Oligonucleotide Array Sequence Analysis, *Transcriptional Activation, Camptothecin/pharmacology, {DNA}-Binding Proteins/*physiology, {HeLa} Cells, Messenger/metabolism, Proto-Oncogene Proteins c-myb/*physiology, Transcription Factors/*physiology}
}

@article{gilbert_crispr-mediated_2013,
	title = {{CRISPR}-mediated modular {RNA}-guided regulation of transcription in eukaryotes},
	volume = {154},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23849981},
	doi = {10.1016/j.cell.2013.06.044},
	abstract = {The genetic interrogation and reprogramming of cells requires methods for robust and precise targeting of genes for expression or repression. The {CRISPR}-associated catalytically inactive {dCas}9 protein offers a general platform for {RNA}-guided {DNA} targeting. Here, we show that fusion of {dCas}9 to effector domains with distinct regulatory functions enables stable and efficient transcriptional repression or activation in human and yeast cells, with the site of delivery determined solely by a coexpressed short guide (sg){RNA}. Coupling of {dCas}9 to a transcriptional repressor domain can robustly silence expression of multiple endogenous genes. {RNA}-seq analysis indicates that {CRISPR} interference ({CRISPRi})-mediated transcriptional repression is highly specific. Our results establish that the {CRISPR} system can be used as a modular and flexible {DNA}-binding platform for the recruitment of proteins to a target {DNA} sequence, revealing the potential of {CRISPRi} as a general tool for the precise regulation of gene expression in eukaryotic cells.},
	pages = {442--451},
	number = {2},
	journaltitle = {Cell},
	author = {Gilbert, L A and Larson, M H and Morsut, L and Liu, Z and Brar, G A and Torres, S E and Stern-Ginossar, N and Brandman, O and Whitehead, E H and Doudna, J A and Lim, W A and Weissman, J S and Qi, L S},
	date = {2013},
	pmid = {23849981},
	keywords = {Humans, {RNA}, *Streptococcus pyogenes, Bacterial Proteins/*genetics, Gene Targeting/*methods, Guide/*genetics, {HEK}293 Cells, {HeLa} Cells, Saccharomyces cerevisiae/genetics}
}

@article{duran_unravelling_2013,
	title = {Unravelling the hidden {DNA} structural/physical code provides novel insights on promoter location},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23761436},
	doi = {10.1093/nar/gkt511},
	abstract = {Although protein recognition of {DNA} motifs in promoter regions has been traditionally considered as a critical regulatory element in transcription, the location of promoters, and in particular transcription start sites ({TSSs}), still remains a challenge. Here we perform a comprehensive analysis of putative core promoter sequences relative to non-annotated predicted {TSSs} along the human genome, which were defined by distinct {DNA} physical properties implemented in our {ProStar} computational algorithm. A representative sampling of predicted regions was subjected to extensive experimental validation and analyses. Interestingly, the vast majority proved to be transcriptionally active despite the lack of specific sequence motifs, indicating that physical signaling is indeed able to detect promoter activity beyond conventional {TSS} prediction methods. Furthermore, highly active regions displayed typical chromatin features associated to promoters of housekeeping genes. Our results enable to redefine the promoter signatures and analyze the diversity, evolutionary conservation and dynamic regulation of human core promoters at large-scale. Moreover, the present study strongly supports the hypothesis of an ancient regulatory mechanism encoded by the intrinsic physical properties of the {DNA} that may contribute to the complexity of transcription regulation in the human genome.},
	pages = {7220--7230},
	number = {15},
	journaltitle = {Nucleic Acids Res},
	author = {Duran, E and Djebali, S and Gonzalez, S and Flores, O and Mercader, J M and Guigo, R and Torrents, D and Soler-Lopez, M and Orozco, M},
	date = {2013},
	pmid = {23761436}
}

@article{goff_poly-combing_2013,
	title = {Poly-combing the genome for {RNA}},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24304912},
	doi = {10.1038/nsmb.2728},
	abstract = {An unresolved question in mammalian epigenetic regulation is how ubiquitously expressed chromatin-modifying complexes such as Polycomb group complex 2 ({PRC}2) find their specific target sites across an intricate choreography of localization events in time and space. Two recent studies now provide critical new insights into an intriguing genome-wide role for {RNA} in {PRC}2 regulation.},
	pages = {1344--1346},
	number = {12},
	journaltitle = {Nat Struct Mol Biol},
	author = {Goff, L A and Rinn, J L},
	date = {2013},
	pmid = {24304912},
	keywords = {Animals, Genetic, Humans, {RNA}, *Promoter Regions, Embryonic Stem Cells/*metabolism, Messenger/*metabolism, Polycomb Repressive Complex 2/*metabolism, {RNA}-Binding Proteins/*metabolism}
}

@article{black_tapas_2010,
	title = {Tapas and {RNA} in Renaissance Spain},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20534974},
	pages = {130--132},
	number = {2},
	journaltitle = {{RNA} Biol},
	author = {Black, D L and Gorospe, M},
	date = {2010},
	pmid = {20534974},
	keywords = {Animals, Humans, Mice, Drosophila melanogaster/embryology/genetics, Gene Regulatory Networks/genetics, Protein Biosynthesis/genetics, {RNA} Splicing/genetics, {RNA} Stability/genetics, {RNA} Transport/genetics, {RNA}-Binding Proteins/*metabolism, Spain}
}

@article{robinson_novel_2012,
	title = {Novel mutations target distinct subgroups of medulloblastoma},
	volume = {488},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22722829},
	doi = {10.1038/nature11213},
	abstract = {Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, {KDM}6A and {ZMYM}3), and {CTNNB}1-associated chromatin re-modellers in {WNT}-subgroup tumours (for example, {SMARCA}4 and {CREBBP}). Modelling of mutations in mouse lower rhombic lip progenitors that generate {WNT}-subgroup tumours identified genes that maintain this cell lineage ({DDX}3X), as well as mutated genes that initiate ({CDH}1) or cooperate ({PIK}3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.},
	pages = {43--48},
	number = {7409},
	journaltitle = {Nature},
	author = {Robinson, G and Parker, M and Kranenburg, T A and Lu, C and Chen, X and Ding, L and Phoenix, T N and Hedlund, E and Wei, L and Zhu, X and Chalhoub, N and Baker, S J and Huether, R and Kriwacki, R and Curley, N and Thiruvenkatam, R and Wang, J and Wu, G and Rusch, M and Hong, X and Becksfort, J and Gupta, P and Ma, J and Easton, J and Vadodaria, B and Onar-Thomas, A and Lin, T and Li, S and Pounds, S and Paugh, S and Zhao, D and Kawauchi, D and Roussel, M F and Finkelstein, D and Ellison, D W and Lau, C C and Bouffet, E and Hassall, T and Gururangan, S and Cohn, R and Fulton, R S and Fulton, L L and Dooling, D J and Ochoa, K and Gajjar, A and Mardis, E R and Wilson, R K and Downing, J R and Zhang, J and Gilbertson, R J},
	date = {2012},
	pmid = {22722829},
	keywords = {Genomics, Animals, Genome, Humans, Mice, Animal, beta Catenin/genetics, Cadherins/genetics, Cdh1 Proteins, Cell Cycle Proteins/deficiency/genetics, Cell Lineage, Cerebellar Neoplasms/*classification/*genetics/pat, Child, {CREB}-Binding Protein/genetics, {DEAD}-box {RNA} Helicases/genetics, Disease Models, {DNA} Copy Number Variations, {DNA} Helicases/genetics, {DNA} Mutational Analysis, Hedgehog Proteins/metabolism, Histone Demethylases/genetics, Histones/metabolism, Human/genetics, Medulloblastoma/*classification/*genetics/patholog, Methylation, Mutation/*genetics, Nuclear Proteins/genetics, Phosphatidylinositol 3-Kinases/genetics, Transcription Factors/genetics, Wnt Proteins/metabolism}
}

@article{ingolia_genome-wide_2010,
	title = {Genome-wide translational profiling by ribosome footprinting},
	volume = {470},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20946809},
	doi = {10.1016/S0076-6879(10)70006-9},
	abstract = {We present a detailed protocol for ribosome profiling, an approach that we developed to make comprehensive and quantitative measurements of translation in yeast. In this technique, ribosome positions are determined from their nuclease footprint on their {mRNA} template and the footprints are quantified by deep sequencing. Ribosome profiling has already enabled highly reproducible measurements of translational control. Because this technique reports on the exact position of ribosomes, it also revealed the presence of ribosomes on upstream open reading frames and demonstrated that ribosome density was higher near the beginning of protein-coding genes. Here, we describe nuclease digestion conditions that produce uniform ∼28 nucleotide (nt) protected fragments of {mRNA} templates that indicate the exact position of translating ribosomes. We also give a protocol for converting these {RNA} fragments into a {DNA} library that can be sequenced using the Illumina Genome Analyzer. Unbiased conversion of anonymous, small {RNAs} into a sequencing library is challenging, and we discuss standards that played a key role in optimizing library generation. Finally, we discuss how deep sequencing data can be used to quantify gene expression at the level of translation.},
	pages = {119--142},
	journaltitle = {Methods Enzymol},
	author = {Ingolia, N T},
	date = {2010},
	pmid = {20946809},
	keywords = {{RNA}, Messenger/genetics, Protein Biosynthesis/*genetics, Reverse Transcriptase Polymerase Chain Reaction, Ribosomes/*metabolism}
}

@article{cordaux_impact_2009,
	title = {The impact of retrotransposons on human genome evolution},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19763152},
	doi = {10.1038/nrg2640},
	abstract = {Their ability to move within genomes gives transposable elements an intrinsic propensity to affect genome evolution. Non-long terminal repeat ({LTR}) retrotransposons–including {LINE}-1, Alu and {SVA} elements–have proliferated over the past 80 million years of primate evolution and now account for approximately one-third of the human genome. In this Review, we focus on this major class of elements and discuss the many ways that they affect the human genome: from generating insertion mutations and genomic instability to altering gene expression and contributing to genetic innovation. Increasingly detailed analyses of human and other primate genomes are revealing the scale and complexity of the past and current contributions of non-{LTR} retrotransposons to genomic change in the human lineage.},
	pages = {691--703},
	number = {10},
	journaltitle = {Nat Rev Genet},
	author = {Cordaux, R and Batzer, M A},
	date = {2009},
	pmid = {19763152},
	keywords = {Genome, Humans, *Evolution, Genome-Wide Association Study, Human/*genetics, Molecular, Polymorphism, Retroelements/*genetics, Single Nucleotide/genetics}
}

@article{katayama_antisense_2005,
	title = {Antisense transcription in the mammalian transcriptome},
	volume = {309},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16141073},
	doi = {10.1126/science.1112009},
	abstract = {Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts ({RNA} interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense {RNA} can alter the expression of sense messenger {RNAs}, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.},
	pages = {1564--1566},
	number = {5740},
	journaltitle = {Science},
	author = {Katayama, S and Tomaru, Y and Kasukawa, T and Waki, K and Nakanishi, M and Nakamura, M and Nishida, H and Yap, C C and Suzuki, M and Kawai, J and Suzuki, H and Carninci, P and Hayashizaki, Y and Wells, C and Frith, M and Ravasi, T and Pang, K C and Hallinan, J and Mattick, J and Hume, D A and Lipovich, L and Batalov, S and Engstrom, P G and Mizuno, Y and Faghihi, M A and Sandelin, A and Chalk, A M and Mottagui-Tabar, S and Liang, Z and Lenhard, B and Wahlestedt, C},
	date = {2005},
	pmid = {16141073},
	keywords = {Animals, Genetic, Genome, Humans, Mice, {RNA}, Gene Expression Regulation, *Genome, *Transcription, Antisense/*biosynthesis, Messenger/biosynthesis, Mice/*genetics, {RNA} Interference, {RNA}, Messenger, Transcription, Genetic, {RNA}, Antisense}
}

@article{toyama_identification_2013,
	title = {Identification of long-lived proteins reveals exceptional stability of essential cellular structures},
	volume = {154},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23993091},
	doi = {10.1016/j.cell.2013.07.037},
	abstract = {Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes ({NPCs}) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of {NPC} function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. {PAPERCLIP}:},
	pages = {971--982},
	number = {5},
	journaltitle = {Cell},
	author = {Toyama, B H and Savas, J N and Park, S K and Harris, M S and Ingolia, N T and Yates 3rd, J R and Hetzer, M W},
	date = {2013},
	pmid = {23993091},
	keywords = {Animals, *Cell Aging, Brain/*cytology/metabolism, Neuroglia/metabolism, Neurons/metabolism, Nuclear Pore Complex Proteins/*metabolism, Nuclear Pore/metabolism, Protein Biosynthesis, Proteome/*metabolism, Rats}
}

@article{lanzos_detection_2015,
	title = {Detection of long non-coding {RNA} driver genes across 1104 tumour genomes with {ExInAtor}.},
	journaltitle = {Under Review},
	author = {Lanzos, A and Carlevaro-Fita, J and Mularoni, L and Reverter, F and Palumbo, E and Guigo, R and Lopez-Bigas, N and Johnson, R},
	date = {2015}
}

@article{sun_decreased_2014,
	title = {Decreased expression of long noncoding {RNA} {GAS}5 indicates a poor prognosis and promotes cell proliferation in gastric cancer},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24884417},
	doi = {10.1186/1471-2407-14-319},
	abstract = {{BACKGROUND}: Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding {RNAs} ({lncRNAs}) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of {lncRNA} {GAS}5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of {GAS}5 in gastric cancer. {METHODS}: Expression of {GAS}5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction ({qRT}-{PCR}). Over-expression and {RNA} interference ({RNAi}) approaches were used to investigate the biological functions of {GAS}5. The effect of {GAS}5 on proliferation was evaluated by {MTT} and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with {pCDNA}3.1 -{GAS}5 were injected into nude mice to study the effect of {GAS}5 on tumorigenesis in vivo. Protein levels of {GAS}5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). {RESULTS}: We found that {GAS}5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low {GAS}5 expression level had poorer disease-free survival ({DFS}; P = 0.001) and overall survival ({OS}; P {\textbackslash}textless 0.001) than those with high {GAS}5 expression. Further multivariable Cox regression analysis suggested that decreased {GAS}5 was an independent prognostic indicator for this disease (P = 0.006, {HR} = 0.412; 95\%{CI} = 2.218-0.766). Moreover, ectopic expression of {GAS}5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous {GAS}5 could promote cell proliferation. Finally, we found that {GAS}5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. {CONCLUSION}: Our study presents that {GAS}5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.},
	pages = {319},
	journaltitle = {{BMC} Cancer},
	author = {Sun, M and Jin, F Y and Xia, R and Kong, R and Li, J H and Xu, T P and Liu, Y W and Zhang, E B and Liu, X H and De, W},
	date = {2014},
	pmid = {24884417},
	keywords = {Animals, Humans, Mice, {RNA}, *Cell Proliferation, Apoptosis, Biological/genetics/*metabolism, Cell Line, Chi-Square Distribution, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Disease-Free Survival, Down-Regulation, E2F1 Transcription Factor/metabolism, Female, Inbred {BALB} C, Kaplan-Meier Estimate, Long Noncoding/genetics/*metabolism, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Nude, Proportional Hazards Models, {RNA} Interference, Stomach Neoplasms/genetics/*metabolism/mortality/p, Time Factors, Transfection, Tumor, Tumor Burden, Tumor Markers}
}

@article{ingolia_ribosome_2012,
	title = {The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected {mRNA} fragments},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22836135},
	doi = {10.1038/nprot.2012.086},
	abstract = {Recent studies highlight the importance of translational control in determining protein abundance, underscoring the value of measuring gene expression at the level of translation. We present a protocol for genome-wide, quantitative analysis of in vivo translation by deep sequencing. This ribosome profiling approach maps the exact positions of ribosomes on transcripts by nuclease footprinting. The nuclease-protected {mRNA} fragments are converted into a {DNA} library suitable for deep sequencing using a strategy that minimizes bias. The abundance of different footprint fragments in deep sequencing data reports on the amount of translation of a gene. In addition, footprints reveal the exact regions of the transcriptome that are translated. To better define translated reading frames, we describe an adaptation that reveals the sites of translation initiation by pretreating cells with harringtonine to immobilize initiating ribosomes. The protocol we describe requires 5-7 days to generate a completed ribosome profiling sequencing library. Sequencing and data analysis require a further 4-5 days.},
	pages = {1534--1550},
	number = {8},
	journaltitle = {Nat Protoc},
	author = {Ingolia, N T and Brar, G A and Rouskin, S and {McGeachy}, A M and Weissman, J S},
	date = {2012},
	pmid = {22836135},
	keywords = {Transcriptome, Sequence Analysis, Animals, Base Sequence, Humans, {RNA}, Gene Library, Harringtonines/pharmacology, Messenger/*genetics/metabolism, Molecular Sequence Data, Peptide Chain Initiation, Protein Biosynthesis/*genetics, Ribonucleases/metabolism, Ribosomal, Ribosomes/drug effects/*genetics/metabolism, {RNA}/*methods, Saccharomyces cerevisiae/cytology, Translational}
}

@article{bailey_meme_2009,
	title = {{MEME} {SUITE}: tools for motif discovery and searching},
	volume = {37},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19458158},
	doi = {10.1093/nar/gkp335},
	abstract = {The {MEME} Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as {DNA} binding sites and protein interaction domains. The popular {MEME} motif discovery algorithm is now complemented by the {GLAM}2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms–{MAST}, {FIMO} and {GLAM}2SCAN–allow scanning numerous {DNA} and protein sequence databases for motifs discovered by {MEME} and {GLAM}2. Transcription factor motifs (including those discovered using {MEME}) can be compared with motifs in many popular motif databases using the motif database scanning algorithm {TOMTOM}. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology ({GO}) terms using the motif-{GO} term association tool {GOMO}. {MEME} output now contains sequence {LOGOS} for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms ({MAST}, {FIMO} and {TOMTOM}), or to {GOMO}, for further analysis. {GLAM}2 output similarly contains buttons for further analysis using {GLAM}2SCAN and for rerunning {GLAM}2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net.},
	pages = {W202--8},
	issue = {Web Server issue},
	journaltitle = {Nucleic Acids Res},
	author = {Bailey, T L and Boden, M and Buske, F A and Frith, M and Grant, C E and Clementi, L and Ren, J and Li, W W and Noble, W S},
	date = {2009},
	pmid = {19458158},
	keywords = {*Software, {DNA}, Genetic, Binding Sites, Transcription Factors/metabolism, Databases, Algorithms, *Sequence Analysis, Internet, Protein, Regulatory Elements, Transcriptional}
}

@article{varki_comparing_2005,
	title = {Comparing the human and chimpanzee genomes: searching for needles in a haystack},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16339373},
	doi = {10.1101/gr.3737405},
	abstract = {The chimpanzee genome sequence is a long-awaited milestone, providing opportunities to explore primate evolution and genetic contributions to human physiology and disease. Humans and chimpanzees shared a common ancestor approximately 5-7 million years ago (Mya). The difference between the two genomes is actually not approximately 1\%, but approximately 4\%–comprising approximately 35 million single nucleotide differences and approximately 90 Mb of insertions and deletions. The challenge is to identify the many evolutionarily, physiologically, and biomedically important differences scattered throughout these genomes while integrating these data with emerging knowledge about the corresponding "phenomes" and the relevant environmental influences. It is logical to tackle the genetic aspects via both genome-wide analyses and candidate gene studies. Genome-wide surveys could eliminate the majority of genomic sequence differences from consideration, while simultaneously identifying potential targets of opportunity. Meanwhile, candidate gene approaches can be based on such genomic surveys, on genes that may contribute to known differences in phenotypes or disease incidence/severity, or on mutations in the human population that impact unique aspects of the human condition. These two approaches will intersect at many levels and should be considered complementary. We also cite some known genetic differences between humans and great apes, realizing that these likely represent only the tip of the iceberg.},
	pages = {1746--1758},
	number = {12},
	journaltitle = {Genome Res},
	author = {Varki, A and Altheide, T K},
	date = {2005},
	pmid = {16339373},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Humans, *Genome, Evolution, Genomics/methods, Molecular, Pan troglodytes/*genetics}
}

@article{wei_human_2001,
	title = {Human L1 retrotransposition: cis preference versus trans complementation},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11158327},
	doi = {10.1128/MCB.21.4.1429-1439.2001},
	abstract = {Long interspersed nuclear elements ({LINEs} or L1s) comprise approximately 17\% of human {DNA}; however, only about 60 of the approximately 400,000 L1s are mobile. Using a retrotransposition assay in cultured human cells, we demonstrate that L1-encoded proteins predominantly mobilize the {RNA} that encodes them. At much lower levels, L1-encoded proteins can act in trans to promote retrotransposition of mutant L1s and other cellular {mRNAs}, creating processed pseudogenes. Mutant L1 {RNAs} are mobilized at 0.2 to 0.9\% of the retrotransposition frequency of wild-type L1s, whereas cellular {RNAs} are mobilized at much lower frequencies (ca. 0.01 to 0.05\% of wild-type levels). Thus, we conclude that L1-encoded proteins demonstrate a profound cis preference for their encoding {RNA}. This mechanism could enable L1 to remain retrotransposition competent in the presence of the overwhelming number of nonfunctional L1s present in human {DNA}.},
	pages = {1429--1439},
	number = {4},
	journaltitle = {Mol Cell Biol},
	author = {Wei, W and Gilbert, N and Ooi, S L and Lawler, J F and Ostertag, E M and Kazazian, H H and Boeke, J D and Moran, J V},
	date = {2001},
	pmid = {11158327},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, Open Reading Frames, *Long Interspersed Nucleotide Elements, {DNA} Primers/genetics, Evolution, Genetic Complementation Test, {HeLa} Cells, Messenger/genetics/metabolism, Models, Molecular, Mutation, Post-Transcriptional, Pseudogenes, Recombination, {RNA} Processing}
}

@article{aguilar_plasma-membrane_2010,
	title = {A plasma-membrane E-{MAP} reveals links of the eisosome with sphingolipid metabolism and endosomal trafficking},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20526336},
	doi = {10.1038/nsmb.1829},
	abstract = {The plasma membrane delimits the cell and controls material and information exchange between itself and the environment. How different plasma-membrane processes are coordinated and how the relative abundance of plasma-membrane lipids and proteins is homeostatically maintained are not yet understood. Here, we used a quantitative genetic interaction map, or E-{MAP}, to functionally interrogate a set of approximately 400 genes involved in various aspects of plasma-membrane biology, including endocytosis, signaling, lipid metabolism and eisosome function. From this E-{MAP}, we derived a set of 57,799 individual interactions between genes functioning in these various processes. Using triplet genetic motif analysis, we identified a new component of the eisosome, Eis1, and linked the poorly characterized gene {EMP}70 to endocytic and eisosome function. Finally, we implicated Rom2, a {GDP}/{GTP} exchange factor for Rho1 and Rho2, in the regulation of sphingolipid metabolism.},
	pages = {901--908},
	number = {7},
	journaltitle = {Nat Struct Mol Biol},
	author = {Aguilar, P S and Frohlich, F and Rehman, M and Shales, M and Ulitsky, I and Olivera-Couto, A and Braberg, H and Shamir, R and Walter, P and Mann, M and Ejsing, C S and Krogan, N J and Walther, T C},
	date = {2010},
	pmid = {20526336},
	keywords = {*Genes, Cell Membrane/genetics/*metabolism, Endocytosis, Endosomes/genetics/*metabolism, Fungal, Membrane Proteins/genetics/metabolism, Saccharomyces cerevisiae Proteins/genetics/*metabo, Saccharomyces cerevisiae/*genetics/metabolism, Sphingolipids/genetics/*metabolism}
}

@article{michienzi_nucleolar_2006,
	title = {A nucleolar localizing Rev binding element inhibits {HIV} replication},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16712721},
	doi = {10.1186/1742-6405-3-13},
	abstract = {The Rev protein of the human immunodeficiency virus ({HIV}) facilitates the nuclear export of intron containing viral {mRNAs} allowing formation of infectious virions. Rev traffics through the nucleolus and shuttles between the nucleus and cytoplasm. Rev multimerization and interaction with the export protein {CRM}1 takes place in the nucleolus. To test the importance of Rev nucleolar trafficking in the {HIV}-1 replication cycle, we created a nucleolar localizing Rev Response Element ({RRE}) decoy and tested this for its anti-{HIV} activity. The {RRE} decoy provided marked inhibition of {HIV}-1 replication in both the {CEM} T-cell line and in primary {CD}34+ derived monocytes. These results demonstrate that titration of Rev in the nucleolus impairs {HIV}-1 replication and supports a functional role for Rev trafficking in this sub-cellular compartment.},
	pages = {13},
	journaltitle = {{AIDS} Res Ther},
	author = {Michienzi, A and De Angelis, F G and Bozzoni, I and Rossi, J J},
	date = {2006},
	pmid = {16712721}
}

@article{ballarino_cotranscriptional_2005,
	title = {The cotranscriptional assembly of {snoRNPs} controls the biosynthesis of H/{ACA} {snoRNAs} in Saccharomyces cerevisiae},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15964797},
	doi = {10.1128/MCB.25.13.5396-5403.2005},
	abstract = {The carboxy-terminal domain ({CTD}) of {RNA} polymerase {II} large subunit acts as a platform to assemble the {RNA} processing machinery in a controlled way throughout the transcription cycle. In yeast, recent findings revealed a physical connection between phospho-{CTD}, generated by the Ctk1p kinase, and protein factors having a function in small nucleolar {RNA} ({snoRNA}) biogenesis. The {snoRNAs} represent a large family of polymerase {II} noncoding transcripts that are associated with highly conserved polypeptides to form stable ribonucleoprotein particles ({snoRNPs}). In this work, we have studied the biogenesis of the {snoRNPs} belonging to the box H/{ACA} class. We report that the assembly factor Naf1p and the core components Cbf5p and Nhp2p are recruited on H/{ACA} {snoRNA} genes very early during transcription. We also show that the cotranscriptional recruitment of Naf1p and Cbf5p is Ctk1p dependent and that Ctk1p and Cbf5p are required for preventing the readthrough into the {snoRNA} downstream genes. All these data suggest that proper cotranscriptional {snoRNP} assembly controls 3'-end formation of {snoRNAs} and, consequently, the release of a functional particle.},
	pages = {5396--5403},
	number = {13},
	journaltitle = {Mol Cell Biol},
	author = {Ballarino, M and Morlando, M and Pagano, F and Fatica, A and Bozzoni, I},
	date = {2005},
	pmid = {15964797},
	keywords = {Genetic, {RNA}, *Transcription, Chromatin Immunoprecipitation, Cyclins/metabolism, Fungal Proteins/metabolism, Hydro-Lyases/metabolism, Microtubule-Associated Proteins/metabolism, Models, Molecular, Nuclear Proteins/metabolism, Protein Kinases/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleoproteins, Saccharomyces cerevisiae Proteins/metabolism, Saccharomyces cerevisiae/genetics/*metabolism, Small Nuclear/metabolism, Small Nucleolar/*biosynthesis, Small Nucleolar/genetics/*meta}
}

@article{lin_evolutionarily_2014,
	title = {An evolutionarily conserved long noncoding {RNA} {TUNA} controls pluripotency and neural lineage commitment},
	volume = {53},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24530304},
	doi = {10.1016/j.molcel.2014.01.021},
	abstract = {Here, we generated a genome-scale {shRNA} library targeting long intergenic noncoding {RNAs} ({lincRNAs}) in the mouse. We performed an unbiased loss-of-function study in mouse embryonic stem cells ({mESCs}) and identified 20 {lincRNAs} involved in the maintenance of pluripotency. Among these, {TUNA} (Tcl1 Upstream Neuron-Associated {lincRNA}, or megamind) was required for pluripotency and formed a complex with three {RNA}-binding proteins ({RBPs}). The {TUNA}-{RBP} complex was detected at the promoters of Nanog, Sox2, and Fgf4, and knockdown of {TUNA} or the individual {RBPs} inhibited neural differentiation of {mESCs}. {TUNA} showed striking evolutionary conservation of both sequence- and {CNS}-restricted expression in vertebrates. Accordingly, knockdown of tuna in zebrafish caused impaired locomotor function, and {TUNA} expression in the brains of Huntington's disease patients was significantly associated with disease grade. Our results suggest that the {lincRNA} {TUNA} plays a vital role in pluripotency and neural differentiation of {ESCs} and is associated with neurological function of adult vertebrates.},
	pages = {1005--1019},
	number = {6},
	journaltitle = {Mol Cell},
	author = {Lin, N and Chang, K Y and Li, Z and Gates, K and Rana, Z A and Dang, J and Zhang, D and Han, T and Yang, C S and Cunningham, T J and Head, S R and Duester, G and Dong, P D and Rana, T M},
	date = {2014},
	pmid = {24530304},
	keywords = {Animals, Conserved Sequence, Genetic, Humans, Mice, Promoter Regions, {RNA}, *Gene Expression Regulation, Amino Acid, Amino Acid Sequence, Biological Evolution, Cell Differentiation, Developmental, Embryonic Stem Cells/cytology/metabolism, Fibroblast Growth Factor 4/genetics/metabolism, Homeodomain Proteins/genetics/metabolism, Huntington Disease/*genetics/metabolism/pathology, Long Noncoding/*genetics/metabolism, Molecular Sequence Data, Motor Activity, Neurons/cytology/*metabolism, Pluripotent Stem Cells/cytology/*metabolism, {RNA}-Binding Proteins/genetics/metabolism, Sequence Homology, Severity of Illness Index, Signal Transduction, {SOXB}1 Transcription Factors/genetics/metabolism, Zebrafish/*genetics/growth \& development/metabolis}
}

@article{galupa_x-chromosome_2015,
	title = {X-chromosome inactivation: new insights into cis and trans regulation},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26004255},
	doi = {10.1016/j.gde.2015.04.002},
	abstract = {X-chromosome inactivation ({XCI}) is a developmentally associated process that evolved in mammals to enable gene dosage compensation between {XX} and {XY} individuals. In placental mammals, it is triggered by the long noncoding {RNA} Xist, which is produced from a complex regulatory locus, the X-inactivation centre (Xic). Recent insights into the regulatory landscape of the Xic, including its partitioning into topological associating domains ({TADs}) and its genetic dissection, have important implications for the monoallelic regulation of Xist. Here, we present some of the latest studies on X inactivation with a special focus on the regulation of Xist, its various functions and the putative role of chromosome conformation in regulating the dynamics of this locus during development and differentiation.},
	pages = {57--66},
	journaltitle = {Curr Opin Genet Dev},
	author = {Galupa, R and Heard, E},
	date = {2015},
	pmid = {26004255}
}

@article{ji_malat-1_2003,
	title = {{MALAT}-1, a novel noncoding {RNA}, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12970751},
	doi = {10.1038/sj.onc.1206928},
	abstract = {Early-stage non-small cell lung cancer ({NSCLC}) can be cured by surgical resection, but a substantial fraction of patients ultimately dies due to distant metastasis. In this study, we used subtractive hybridization to identify gene expression differences in stage I {NSCLC} tumors that either did or did not metastasize in the course of disease. Individual clones (n=225) were sequenced and quantitative {RT}-{PCR} verified overexpression in metastasizing samples. Several of the identified genes ({eIF}4A1, thymosin beta4 and a novel transcript named {MALAT}-1) were demonstrated to be significantly associated with metastasis in {NSCLC} patients (n=70). The genes' association with metastasis was stage- and histology specific. The Kaplan-Meier analyses identified {MALAT}-1 and thymosin beta4 as prognostic parameters for patient survival in stage I {NSCLC}. The novel {MALAT}-1 transcript is a noncoding {RNA} of more than 8000 nt expressed from chromosome 11q13. It is highly expressed in lung, pancreas and other healthy organs as well as in {NSCLC}. {MALAT}-1 expressed sequences are conserved across several species indicating its potentially important function. Taken together, these data contribute to the identification of early-stage {NSCLC} patients that are at high risk to develop metastasis. The identification of {MALAT}-1 emphasizes the potential role of noncoding {RNAs} in human cancer.},
	pages = {8031--8041},
	number = {39},
	journaltitle = {Oncogene},
	author = {Ji, P and Diederichs, S and Wang, W and Boing, S and Metzger, R and Schneider, P M and Tidow, N and Brandt, B and Buerger, H and Bulk, E and Thomas, M and Berdel, W E and Serve, H and Muller-Tidow, C},
	date = {2003},
	pmid = {12970751},
	keywords = {Humans, Untranslated, Gene Expression Regulation, Gene Expression Profiling, *{RNA}, Carcinoma, Gene Expression Profiling/methods, In Situ Hybridization, In Situ Hybridization/methods, Lung Neoplasms, Lung Neoplasms/*genetics/mortality/*pathology/surg, Molecular Sequence Data, Neoplasm Metastasis, Neoplasm Metastasis/genetics, Neoplasm Staging, Neoplastic, Non-Small-Cell Lung/*genetics/mortality, Predictive Value of Tests, Reference Values, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Thymosin/*genetics, {RNA}, Untranslated, Gene Expression Regulation, Neoplastic, Carcinoma, Non-Small-Cell Lung, Thymosin},
	file = {Full Text:/home/jlagarde/Zotero/storage/UGK2U7AC/Ji et al. - 2003 - MALAT-1, a novel noncoding RNA, and thymosin beta4.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/CRMERKXJ/Ji et al. - 2003 - MALAT-1, a novel noncoding RNA, and thymosin beta4.pdf:application/pdf}
}

@article{lykke-andersen_human_2014,
	title = {Human nonsense-mediated {RNA} decay initiates widely by endonucleolysis and targets {snoRNA} host genes},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25403180},
	doi = {10.1101/gad.246538.114},
	abstract = {Eukaryotic {RNAs} with premature termination codons ({PTCs}) are eliminated by nonsense-mediated decay ({NMD}). While human nonsense {RNA} degradation can be initiated either by an endonucleolytic cleavage event near the {PTC} or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of {NMD} substrates and their 5'-3' decay intermediates to establish that {SMG}6-catalyzed endonucleolysis widely initiates the degradation of human nonsense {RNAs}, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting {snoRNAs} in their introns produce considerable amounts of {NMD}-sensitive splice variants, indicating that these {RNAs} are merely by-products of a primary {snoRNA} production process. Additionally, transcripts from genes encoding multiple {snoRNAs} often yield alternative transcript isoforms that allow for differential expression of individual coencoded {snoRNAs}. Based on our findings, we hypothesize that {snoRNA} host genes need to be highly transcribed to accommodate high levels of {snoRNA} production and that the expression of individual {snoRNAs} and their cognate spliced {RNA} can be uncoupled via alternative splicing and {NMD}.},
	pages = {2498--2517},
	number = {22},
	journaltitle = {Genes Dev},
	author = {Lykke-Andersen, S and Chen, Y and Ardal, B R and Lilje, B and Waage, J and Sandelin, A and Jensen, T H},
	date = {2014},
	pmid = {25403180},
	keywords = {Humans, {RNA}, {RNA} Splicing, Endonucleases/metabolism, {HEK}293 Cells, Nonsense Mediated {mRNA} Decay/genetics/*physiology, Protein Isoforms, Small Nucleolar/*metabolism, Telomerase/genetics/metabolism}
}

@article{kondo_small_2010,
	title = {Small peptides switch the transcriptional activity of Shavenbaby during Drosophila embryogenesis},
	volume = {329},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20647469},
	doi = {10.1126/science.1188158},
	abstract = {A substantial proportion of eukaryotic transcripts are considered to be noncoding {RNAs} because they contain only short open reading frames ({sORFs}). Recent findings suggest, however, that some {sORFs} encode small bioactive peptides. Here, we show that peptides of 11 to 32 amino acids encoded by the polished rice (pri) {sORF} gene control epidermal differentiation in Drosophila by modifying the transcription factor Shavenbaby (Svb). Pri peptides trigger the amino-terminal truncation of the Svb protein, which converts Svb from a repressor to an activator. Our results demonstrate that during Drosophila embryogenesis, Pri {sORF} peptides provide a strict temporal control to the transcriptional program of epidermal morphogenesis.},
	pages = {336--339},
	number = {5989},
	journaltitle = {Science},
	author = {Kondo, T and Plaza, S and Zanet, J and Benrabah, E and Valenti, P and Hashimoto, Y and Kobayashi, S and Payre, F and Kageyama, Y},
	date = {2010},
	pmid = {20647469},
	keywords = {Animals, Genetic, {RNA}, *Transcription, Open Reading Frames, Cell Nucleus, Drosophila melanogaster, *Gene Expression Regulation, Cell Differentiation, Cell Nucleus/metabolism, Developmental, {DNA}-Binding Proteins, {DNA}-Binding Proteins/chemistry/genetics/*metabolis, Drosophila melanogaster/embryology/*genetics/metab, Drosophila Proteins/chemistry/genetics/*metabolism, Embryo, Embryonic Development, Epidermis/cytology/metabolism, Genes, Insect, Mutation, Nonmammalian/cytology/*metabolism, Peptides/genetics/*metabolism, Post-Translational, Protein Isoforms, Protein Isoforms/chemistry/genetics/metabolism, Protein Processing, Protein Structure, Recombinant Fusion Proteins/metabolism, Tertiary, Transcription Factors, Transcription Factors/chemistry/genetics/*metaboli, Untranslated/genetics, Transcription, Genetic, {RNA}, Untranslated, Genes, Insect, Protein Processing, Post-Translational, Protein Structure, Tertiary, Gene Expression Regulation, Developmental, Drosophila Proteins, Peptides, Embryo, Nonmammalian, Epidermal Cells, Epidermis, Recombinant Fusion Proteins}
}

@article{gioia_functional_2005,
	title = {Functional characterization of {XendoU}, the endoribonuclease involved in small nucleolar {RNA} biosynthesis},
	volume = {280},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15755742},
	doi = {10.1074/jbc.M501160200},
	abstract = {{XendoU} is the endoribonuclease involved in the biosynthesis of a specific subclass of Xenopus laevis intron-encoded small nucleolar {RNAs}. {XendoU} has no homology to any known cellular {RNase}, although it has sequence similarity with proteins tentatively annotated as serine proteases. It has been recently shown that {XendoU} represents the cellular counterpart of a nidovirus replicative endoribonuclease ({NendoU}), which plays a critical role in viral replication and transcription. In this paper, we combined prediction and experimental data to define the amino acid residues directly involved in {XendoU} catalysis. Specifically, we find that {XendoU} residues Glu-161, Glu-167, His-162, His-178, and Lys-224 are essential for {RNA} cleavage, which occurs in the presence of manganese ions. Furthermore, we identified the {RNA} sequence required for {XendoU} binding and showed that the formation of {XendoU}-{RNA} complex is Mn2+-independent.},
	pages = {18996--19002},
	number = {19},
	journaltitle = {J Biol Chem},
	author = {Gioia, U and Laneve, P and Dlakic, M and Arceci, M and Bozzoni, I and Caffarelli, E},
	date = {2005},
	pmid = {15755742},
	keywords = {Animals, Genetic, {RNA}, Transcription, Protein Binding, Introns, Amino Acid, Amino Acid Sequence, Catalysis, Catalytic Domain, Cloning, {DNA} Primers/chemistry, Endoribonucleases/chemistry/*physiology, Glutamic Acid/chemistry, Histidine/chemistry, Lysine/chemistry, Manganese/chemistry, Molecular, Molecular Sequence Data, Mutation, Oligopeptides/chemistry, Phylogeny, Plasmids/metabolism, Protein Structure, Recombinant Proteins/chemistry, Sequence Homology, Small Nuclear/*metabolism, Substrate Specificity, Tertiary, Xenopus, Xenopus laevis, Xenopus Proteins/chemistry/*physiology}
}

@article{yu_competitive_2013,
	title = {Competitive binding of {CUGBP}1 and {HuR} to occludin {mRNA} controls its translation and modulates epithelial barrier function},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23155001},
	doi = {10.1091/mbc.E12-07-0531},
	abstract = {{RNA}-binding proteins {CUG}-binding protein 1 ({CUGBP}1) and {HuR} are highly expressed in epithelial tissues and modulate the stability and translation of target {mRNAs}. Here we present evidence that {CUGBP}1 and {HuR} jointly regulate the translation of occludin and play a crucial role in the maintenance of tight junction ({TJ}) integrity in the intestinal epithelial cell monolayer. {CUGBP}1 and {HuR} competed for association with the same occludin 3'-untranslated region element and regulated occludin translation competitively and in opposite directions. {CUGBP}1 overexpression decreased {HuR} binding to occludin {mRNA}, repressed occludin translation, and compromised the {TJ} barrier function, whereas {HuR} overexpression inhibited {CUGBP}1 association with occludin {mRNA} and promoted occludin translation, thereby enhancing the barrier integrity. Repression of occludin translation by {CUGBP}1 was due to the colocalization of {CUGBP}1 and tagged occludin {RNA} in processing bodies (P-bodies), and this colocalization was prevented by {HuR} overexpression. These findings indicate that {CUGBP}1 represses occludin translation by increasing occludin {mRNA} recruitment to P-bodies, whereas {HuR} promotes occludin translation by blocking occludin {mRNA} translocation to P-bodies via the displacement of {CUGBP}1.},
	pages = {85--99},
	number = {2},
	journaltitle = {Mol Biol Cell},
	author = {Yu, T X and Rao, J N and Zou, T and Liu, L and Xiao, L and Ouyang, M and Cao, S and Gorospe, M and Wang, J Y},
	date = {2013},
	pmid = {23155001},
	keywords = {3' Untranslated Regions, Base Sequence, Humans, {RNA}, Binding Sites, Gene Expression Regulation, Protein Binding, Binding, Caco-2 Cells, Competitive, Electric Impedance, Epithelial Cells/*physiology, Gene Knockdown Techniques, Genes, Hu Paraneoplastic Encephalomyelitis Antigens/*meta, Intestines/cytology/physiology, Luciferases, Messenger/*metabolism, Occludin/*genetics/metabolism, Protein Biosynthesis, Renilla/biosynthesis/genetics, Reporter, {RNA}-Binding Proteins/genetics/*metabolism, Small Interfering/genetics, Tight Junctions/physiology}
}

@article{ablikim_observation_2014,
	title = {Observation of a charged ({DD}*)+/- mass peak in e+ e- –{\textbackslash}textgreater {piDD}* at sqrt[s] = 4.26 {GeV}},
	volume = {112},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24484002},
	abstract = {We report on a study of the process e+ e- –{\textbackslash}textgreater pi+/- ({DD}*)-/+ at sqrt[s] = 4.26 {GeV} using a 525 pb(-1) data sample collected with the {BESIII} detector at the {BEPCII} storage ring. A distinct charged structure is observed in the ({DD}*)-/+ invariant mass distribution. When fitted to a mass-dependent-width Breit-Wigner line shape, the pole mass and width are determined to be Mpole = (3883.9+/-1.5(stat)+/-4.2(syst)) {MeV}/c2 and Gammapole = (24.8+/-3.3(stat)+/-11.0(syst)) {MeV}. The mass and width of the structure, which we refer to as Zc(3885), are 2sigma and 1sigma, respectively, below those of the Zc(3900) –{\textbackslash}textgreater pi+/- J/psi peak observed by {BESIII} and Belle in pi+ pi- J/psi final states produced at the same center-of-mass energy. The angular distribution of the {piZc}(3885) system favors a {JP} = 1+ quantum number assignment for the structure and disfavors 1- or 0-. The Born cross section times the {DD}* branching fraction of the Zc(3885) is measured to be sigma(e+ e- –{\textbackslash}textgreater pi+/- Zc(3885)-/+){xB}(Zc(3885)-/+ –{\textbackslash}textgreater ({DD}*)-/+) = (83.5+/-6.6(stat)+/-22.0(syst)) pb. Assuming the Zc(3885) –{\textbackslash}textgreater {DD}* signal reported here and the Zc(3900) –{\textbackslash}textgreater {piJ}/psi signal are from the same source, the partial width ratio (Gamma(Zc(3885) –{\textbackslash}textgreater {DD}*)/Gamma(Zc(3900) –{\textbackslash}textgreater {piJ}/psi)) = 6.2+/-1.1(stat)+/-2.7(syst) is determined.},
	pages = {22001},
	number = {2},
	journaltitle = {Phys Rev Lett},
	author = {Ablikim, M and Achasov, M N and Albayrak, O and Ambrose, D J and An, F F and An, Q and Bai, J Z and Baldini Ferroli, R and Ban, Y and Becker, J and Bennett, J V and Bertani, M and Bian, J M and Boger, E and Bondarenko, O and Boyko, I and Braun, S and Briere, R A and Bytev, V and Cai, H and Cai, X and Cakir, O and Calcaterra, A and Cao, G F and Cetin, S A and Chang, J F and Chelkov, G and Chen, G and Chen, H S and Chen, J C and Chen, M L and Chen, S J and Chen, X R and Chen, Y B and Cheng, H P and Chu, X K and Chu, Y P and Cronin-Hennessy, D and Dai, H L and Dai, J P and Dedovich, D and Deng, Z Y and Denig, A and Denysenko, I and Destefanis, M and Ding, W M and Ding, Y and Dong, L Y and Dong, M Y and Du, S X and Fang, J and Fang, S S and Fava, L and Feng, C Q and Friedel, P and Fu, C D and Fu, J L and Fuks, O and Gao, Y and Geng, C and Goetzen, K and Gong, W X and Gradl, W and Greco, M and Gu, M H and Gu, Y T and Guan, Y H and Guo, A Q and Guo, L B and Guo, T and Guo, Y P and Han, Y L and Harris, F A and He, K L and He, M and He, Z Y and Held, T and Heng, Y K and Hou, Z L and Hu, C and Hu, H M and Hu, J F and Hu, T and Huang, G M and Huang, G S and Huang, J S and Huang, L and Huang, X T and Huang, Y and Hussain, T and Ji, C S and Ji, Q and Ji, Q P and Ji, X B and Ji, X L and Jiang, L L and Jiang, X S and Jiao, J B and Jiao, Z and Jin, D P and Jin, S and Jing, F F and Kalantar-Nayestanaki, N and Kavatsyuk, M and Kloss, B and Kopf, B and Kornicer, M and Kuehn, W and Lai, W and Lange, J S and Lara, M and Larin, P and Leyhe, M and Li, C H and Li, C and Li, D L and Li, D M and Li, F and Li, G and Li, H B and Li, J C and Li, K and Li, L and Li, N and Li, P R and Li, Q J and Li, W D and Li, W G and Li, X L and Li, X N and Li, X Q and Li, X R and Li, Z B and Liang, H and Liang, Y F and Liang, Y T and Liao, G R and Lin, D X and Liu, B J and Liu, C L and Liu, C X and Liu, F H and Liu, F and Liu, H B and Liu, H H and Liu, H M and Liu, J P and Liu, K and Liu, K Y and Liu, P L and Liu, Q and Liu, S B and Liu, X and Liu, Y B and Liu, Z A and Liu, Z and Loehner, H and Lou, X C and Lu, G R and Lu, H J and Lu, J G and Lu, X R and Lu, Y P and Luo, C L and Luo, M X and Luo, T and Luo, X L and Lv, M and Ma, F C and Ma, H L and Ma, Q M and Ma, S and Ma, T and Ma, X Y and Maas, F E and Maggiora, M and Malik, Q A and Mao, Y J and Mao, Z P and Messchendorp, J G and Min, J and Min, T J and Mitchell, R E and Mo, X H and Moeini, H and {MoralesMorales}, C and Moriya, K and Muchnoi, N Y and Muramatsu, H and Nefedov, Y and Nikolaev, I B and Ning, Z and Nisar, S and Olsen, S L and Ouyang, Q and Pacetti, S and Park, J W and Pelizaeus, M and Peng, H P and Peters, K and Ping, J L and Ping, R G and Poling, R and Prencipe, E and Qi, M and Qian, S and Qiao, C F and Qin, L Q and Qin, X S and Qin, Y and Qin, Z H and Qiu, J F and Rashid, K H and Redmer, C F and Ripka, M and Rong, G and Ruan, X D and Sarantsev, A and Schumann, S and Shan, W and Shao, M and Shen, C P and Shen, X Y and Sheng, H Y and Shepherd, M R and Song, W M and Song, X Y and Spataro, S and Spruck, B and Sun, G X and Sun, J F and Sun, S S and Sun, Y J and Sun, Y Z and Sun, Z J and Sun, Z T and Tang, C J and Tang, X and Tapan, I and Thorndike, E H and Toth, D and Ullrich, M and Uman, I and Varner, G S and Wang, B and Wang, D and Wang, D Y and Wang, K and Wang, L L and Wang, L S and Wang, M and Wang, P and Wang, P L and Wang, Q J and Wang, S G and Wang, X F and Wang, X L and Wang, Y D and Wang, Y F and Wang, Y Q and Wang, Z and Wang, Z G and Wang, Z H and Wang, Z Y and Wei, D H and Wei, J B and Weidenkaff, P and Wen, Q G and Wen, S P and Werner, M and Wiedner, U and Wu, L H and Wu, N and Wu, S X and Wu, W and Wu, Z and Xia, L G and Xia, Y X and Xiao, Z J and Xie, Y G and Xiu, Q L and Xu, G F and Xu, Q J and Xu, Q N and Xu, X P and Xue, Z and Yan, L and Yan, W B and Yan, W C and Yan, Y H and Yang, H X and Yang, Y and Yang, Y X and Yang, Y Z and Ye, H and Ye, M and Ye, M H and Yu, B X and Yu, C X and Yu, H W and Yu, J S and Yu, S P and Yuan, C Z and Yuan, W L and Yuan, Y and Zafar, A A and Zallo, A and Zang, S L and Zeng, Y and Zhang, B X and Zhang, B Y and Zhang, C and Zhang, C B and Zhang, C C and Zhang, D H and Zhang, H H and Zhang, H Y and Zhang, J L and Zhang, J Q and Zhang, J W and Zhang, J Y and Zhang, J Z and Zhang, L and Zhang, S H and Zhang, X J and Zhang, X Y and Zhang, Y and Zhang, Y H and Zhang, Z P and Zhang, Z Y and Zhang, Z and Zhao, G and Zhao, J W and Zhao, L and Zhao, M G and Zhao, Q and Zhao, S J and Zhao, T C and Zhao, X H and Zhao, Y B and Zhao, Z G and Zhemchugov, A and Zheng, B and Zheng, J P and Zheng, Y H and Zhong, B and Zhou, L and Zhou, X and Zhou, X K and Zhou, X R and Zhu, K and Zhu, K J and Zhu, X L and Zhu, Y C and Zhu, Y S and Zhu, Z A and Zhuang, J and Zou, B S and Zou, J H},
	date = {2014},
	pmid = {24484002}
}

@article{lee_hnrnp_2010,
	title = {{hnRNP} C promotes {APP} translation by competing with {FMRP} for {APP} {mRNA} recruitment to P bodies},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20473314},
	doi = {10.1038/nsmb.1815},
	abstract = {Amyloid precursor protein ({APP}) regulates neuronal synapse function, and its cleavage product Abeta is linked to Alzheimer's disease. Here, we present evidence that the {RNA}-binding proteins ({RBPs}) heterogeneous nuclear ribonucleoprotein ({hnRNP}) C and fragile X mental retardation protein ({FMRP}) associate with the same {APP} {mRNA} coding region element, and they influence {APP} translation competitively and in opposite directions. Silencing {hnRNP} C increased {FMRP} binding to {APP} {mRNA} and repressed {APP} translation, whereas silencing {FMRP} enhanced {hnRNP} C binding and promoted translation. Repression of {APP} translation was linked to colocalization of {FMRP} and tagged {APP} {RNA} within processing bodies; this colocalization was abrogated by {hnRNP} C overexpression or {FMRP} silencing. Our findings indicate that {FMRP} represses translation by recruiting {APP} {mRNA} to processing bodies, whereas {hnRNP} C promotes {APP} translation by displacing {FMRP}, thereby relieving the translational block.},
	pages = {732--739},
	number = {6},
	journaltitle = {Nat Struct Mol Biol},
	author = {Lee, E K and Kim, H H and Kuwano, Y and Abdelmohsen, K and Srikantan, S and Subaran, S S and Gleichmann, M and Mughal, M R and Martindale, J L and Yang, X and Worley, P F and Mattson, M P and Gorospe, M},
	date = {2010},
	pmid = {20473314},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, Humans, Mice, {RNA}, Alzheimer Disease/genetics/metabolism, Amyloid beta-Protein Precursor/*biosynthesis/*gene, Binding, Biological, Cell Line, Competitive, Cytoplasmic Structures/metabolism, Fragile X Mental Retardation Protein/genetics/*met, Genes, Green Fluorescent Proteins/genetics, Heterogeneous-Nuclear Ribonucleoprotein Group C/*m, Knockout, Messenger/*genetics/*metabolism, Models, Molecular Sequence Data, Neurons/*metabolism, Protein Biosynthesis, Recombinant Proteins/genetics, Reporter, Small Interfering/genetics}
}

@article{holdt_anril_2010,
	title = {{ANRIL} expression is associated with atherosclerosis risk at chromosome 9p21},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20056914},
	doi = {10.1161/ATVBAHA.109.196832},
	abstract = {{OBJECTIVE}: We tested the hypothesis that expression of transcripts adjacent to the chromosome 9p21 (Chr9p21) locus of coronary artery disease was affected by the genotype at this locus and associated with atherosclerosis risk. {METHODS} {AND} {RESULTS}: We replicated the locus for coronary artery disease (P=0.007; {OR}=1.28) and other manifestations of atherosclerosis such as carotid plaque (P=0.003; {OR}=1.31) in the Leipzig Heart Study, a cohort of 1134 patients with varying degree of angiographically assessed coronary artery disease. Expression analysis in peripheral blood mononuclear cells (n=1098) revealed that transcripts {EU}741058 and {NR}\_003529 of antisense noncoding {RNA} in the {INK}4 locus ({ANRIL}) were significantly increased in carriers of the risk haplotype (P=2.1x10(-12) and P=1.6x10(-5), respectively). In contrast, transcript {DQ}485454 remained unaffected, suggesting differential expression of {ANRIL} transcripts at Chr9p21. Results were replicated in whole blood (n=769) and atherosclerotic plaque tissue (n=41). Moreover, expression of {ANRIL} transcripts was directly correlated with severity of atherosclerosis ({EU}741058 and {NR}\_003529; P=0.02 and P=0.001, respectively). No consistent association of Chr9p21 or atherosclerosis was found with expression of other genes such as {CDKN}2A, {CDKN}2B, C9orf53, and {MTAP}. {CONCLUSIONS}: Our data provide robust evidence for an association of {ANRIL} but not {CDKN}2A, {CDKN}2B, C9orf53, and {MTAP}, with atherosclerosis and Chr9p21 genotype in a large cohort.},
	pages = {620--627},
	number = {3},
	journaltitle = {Arterioscler Thromb Vasc Biol},
	author = {Holdt, L M and Beutner, F and Scholz, M and Gielen, S and Gabel, G and Bergert, H and Schuler, G and Thiery, J and Teupser, D},
	date = {2010},
	pmid = {20056914},
	keywords = {Human, Humans, 80 and over, Adult, Aged, Atherosclerosis/*epidemiology/genetics, Biomarkers/metabolism, Chromosomes, Cohort Studies, Cross-Sectional Studies, Cyclin-Dependent Kinase Inhibitor p15/genetics, Cyclin-Dependent Kinase Inhibitor p16/genetics, Cyclin-Dependent Kinase Inhibitor Proteins/*geneti, Female, Genetic Predisposition to Disease/genetics, Genotype, Leukocytes, Male, Middle Aged, Mononuclear/metabolism, Pair 9/*genetics, Risk Factors}
}

@article{brown_gene_1991,
	title = {A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome},
	volume = {349},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1985261},
	doi = {10.1038/349038a0},
	abstract = {X-chromosome inactivation results in the cis-limited dosage compensation of genes on one of the pair of X chromosomes in mammalian females. Although most X-linked genes are believed to be subject to inactivation, several are known to be expressed from both active and inactive X chromosomes. Here we describe an X-linked gene with a novel expression pattern–transcripts are detected only from the inactive X chromosome (Xi) and not from the active X chromosome (Xa). This gene, called {XIST} (for Xi-specific transcripts), is a candidate for a gene either involved in or uniquely influenced by the process of X inactivation.},
	pages = {38--44},
	number = {6304},
	journaltitle = {Nature},
	author = {Brown, C J and Ballabio, A and Rupert, J L and Lafreniere, R G and Grompe, M and Tonlorenzi, R and Willard, H F},
	date = {1991},
	pmid = {1985261},
	keywords = {Base Sequence, Genetic, Humans, Transcription, *Chromosome Mapping, *Dosage Compensation, *Gene Expression, *X Chromosome, Chromosome Mapping, Gene Expression, Karyotyping, Molecular Sequence Data, X Chromosome, Transcription, Genetic, Dosage Compensation, Genetic}
}

@article{marom_point_2011,
	title = {A point mutation in translation initiation factor {eIF}2B leads to function–and time-specific changes in brain gene expression},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22073122},
	doi = {10.1371/journal.pone.0026992},
	abstract = {{BACKGROUND}: Mutations in eukaryotic translation initiation factor 2B ({eIF}2B) cause Childhood Ataxia with {CNS} Hypomyelination ({CACH}), also known as Vanishing White Matter disease ({VWM}), which is associated with a clinical pathology of brain myelin loss upon physiological stress. {eIF}2B is the guanine nucleotide exchange factor ({GEF}) of {eIF}2, which delivers the initiator {tRNA}(Met) to the ribosome. We recently reported that a R132H mutation in the catalytic subunit of this {GEF}, causing a 20\% reduction in its activity, leads under normal conditions to delayed brain development in a mouse model for {CACH}/{VWM}. To further explore the effect of the mutation on global gene expression in the brain, we conducted a wide-scale transcriptome analysis of the first three critical postnatal weeks. {METHODOLOGY}/{PRINCIPAL} {FINDINGS}: Genome-wide {mRNA} expression of wild-type and mutant mice was profiled at postnatal (P) days 1, 18 and 21 to reflect the early proliferative stage prior to white matter establishment (P1) and the peak of oligodendrocye differentiation and myelin synthesis (P18 and P21). At each developmental stage, between 441 and 818 genes were differentially expressed in the mutant brain with minimal overlap, generating unique time point-specific gene expression signatures. {CONCLUSIONS}: The current study demonstrates that a point mutation in {eIF}2B, a key translation initiation factor, has a massive effect on global gene expression in the brain. The overall changes in expression patterns reflect multiple layers of indirect effects that accumulate as the brain develops and matures. The differentially expressed genes seem to reflect delayed waves of gene expression as well as an adaptation process to cope with hypersensitivity to cellular stress.},
	pages = {e26992},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Marom, L and Ulitsky, I and Cabilly, Y and Shamir, R and Elroy-Stein, O},
	date = {2011},
	pmid = {22073122},
	keywords = {Animals, Mice, {RNA}, Messenger/genetics, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Cells, Cultured, *Gene Expression Regulation, Animal, Astrocytes/cytology/metabolism, Biological Markers/*metabolism, Brain/cytology/*metabolism, Cell Cycle, Developmental, Disease Models, Eukaryotic Initiation Factor-2B/*physiology, Inbred C57BL, Leukoencephalopathies/*genetics, Male, Myelin Sheath/metabolism, Point Mutation/*genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Time Factors}
}

@article{yoon_scaffold_2013,
	title = {Scaffold function of long non-coding {RNA} {HOTAIR} in protein ubiquitination},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24326307},
	doi = {10.1038/ncomms3939},
	abstract = {Although mammalian long non-coding (lnc){RNAs} are best known for modulating transcription, their post-transcriptional influence on {mRNA} splicing, stability and translation is emerging. Here we report a post-translational function for the {lncRNA} {HOTAIR} as an inducer of ubiquitin-mediated proteolysis. {HOTAIR} associates with E3 ubiquitin ligases bearing {RNA}-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, {HOTAIR} facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation. {HOTAIR} levels are highly upregulated in senescent cells, causing rapid decay of targets Ataxin-1 and Snurportin-1, and preventing premature senescence. These results uncover a role for a {lncRNA}, {HOTAIR}, as a platform for protein ubiquitination.},
	pages = {2939},
	journaltitle = {Nat Commun},
	author = {Yoon, J H and Abdelmohsen, K and Kim, J and Yang, X and Martindale, J L and Tominaga-Yamanaka, K and White, E J and Orjalo, A V and Rinn, J L and Kreft, S G and Wilson, G M and Gorospe, M},
	date = {2013},
	pmid = {24326307}
}

@article{zhang_trna_2012,
	title = {The {tRNA} methyltransferase {NSun}2 stabilizes p16INK(4) {mRNA} by methylating the 3'-untranslated region of p16},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22395603},
	doi = {10.1038/ncomms1692},
	abstract = {The impact of methylation of the 3'-untranslated region ({UTR}) of a messenger {RNA} ({mRNA}) remains largely unknown. Here we show that {NSun}2, a transfer {RNA} methyltransferase, inhibits the turnover of p16({INK}4) {mRNA}. Knockdown of {NSun}2 reduces p16 expression by shortening the half-life of the p16 {mRNA}, while overexpression of {NSun}2 stabilizes the p16 {mRNA}. In vitro methylation assays show that {NSun}2 methylates the p16 3'{UTR} at A988. Knockdown of {NSun}2 reduces the stability of the {EGFP}-p16 chimeric reporter transcripts bearing wild-type p16 3'{UTR}, but not p16 3'{UTR} with a mutant methylation site. Methylation by {NSun}2 prevents the association of p16 3'{UTR} with {HuR}, {AUF}1 and Ago2/{RISC}, and prevents the recruitment of {EGFP}-p16 3'{UTR} chimeric transcripts to processing bodies. In response to oxidative stress, {NSun}2 is essential for elevating p16 expression levels. We conclude that {NSun}2-mediated methylation of the p16 3'{UTR} is a novel mechanism to stabilize p16 {mRNA}.},
	pages = {712},
	journaltitle = {Nat Commun},
	author = {Zhang, X and Liu, Z and Yi, J and Tang, H and Xing, J and Yu, M and Tong, T and Shang, Y and Gorospe, M and Wang, W},
	date = {2012},
	pmid = {22395603},
	keywords = {Humans, {RNA}, *3' Untranslated Regions, Argonaute Proteins/metabolism, Cell Line, Cyclin-Dependent Kinase Inhibitor p16/*genetics/me, Green Fluorescent Proteins/metabolism, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoprotein D/metaboli, Hu Paraneoplastic Encephalomyelitis Antigens/metab, Messenger/genetics/metabolism, Methylation, Methyltransferases/genetics/*metabolism, Oxidative Stress, {RNA} Interference, Small Interfering, {tRNA} Methyltransferases/metabolism, Tumor}
}

@article{fan_chemokine_2011,
	title = {Chemokine transcripts as targets of the {RNA}-binding protein {HuR} in human airway epithelium},
	volume = {186},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21220697},
	doi = {10.4049/jimmunol.0903634},
	abstract = {{HuR} is a regulator of {mRNA} turnover or translation of inflammatory genes through binding to adenylate-uridylate-rich elements and related motifs present in the 3'untranslated region ({UTR}) of {mRNAs}. We postulate that {HuR} critically regulates the epithelial response by associating with multiple {ARE}-bearing, functionally related inflammatory transcripts. We aimed to identify {HuR} targets in the human airway epithelial cell line {BEAS}-2B challenged with {TNF}-alpha plus {IFN}-gamma, a strong stimulus for inflammatory epithelial responses. Ribonucleoprotein complexes from resting and cytokine-treated cells were immunoprecipitated using anti-{HuR} and isotype-control Ab, and eluted {mRNAs} were reverse-transcribed and hybridized to an inflammatory-focused gene array. The chemokines {CCL}2, {CCL}8, {CXCL}1, and {CXCL}2 ranked highest among 27 signaling and inflammatory genes significantly enriched in the {HuR} {RNP}-{IP} from stimulated cells over the control immunoprecipitation. Among these, 20 displayed published {HuR} binding motifs. Association of {HuR} with the four endogenous chemokine {mRNAs} was validated by single-gene ribonucleoprotein-immunoprecipitation and shown to be 3'{UTR}-dependent by biotin pull-down assay. Cytokine treatment increased {mRNA} stability only for {CCL}2 and {CCL}8, and transient silencing and overexpression of {HuR} affected only {CCL}2 and {CCL}8 expression in primary and transformed epithelial cells. Cytokine-induced {CCL}2 {mRNA} was predominantly cytoplasmic. Conversely, {CXCL}1 {mRNA} remained mostly nuclear and unaffected, as {CXCL}2, by changes in {HuR} levels. Increase in cytoplasmic {HuR} and {HuR} target expression partially relied on the inhibition of {AMP}-dependent kinase, a negative regulator of {HuR} nucleocytoplasmic shuttling. {HuR}-mediated regulation in airway epithelium appears broader than previously appreciated, coordinating numerous inflammatory genes through multiple posttranscriptional mechanisms.},
	pages = {2482--2494},
	number = {4},
	journaltitle = {J Immunol},
	author = {Fan, J and Ishmael, F T and Fang, X and Myers, A and Cheadle, C and Huang, S K and Atasoy, U and Gorospe, M and Stellato, C},
	date = {2011},
	pmid = {21220697},
	keywords = {Humans, Transcription, Reproducibility of Results, {AMP}-Activated Protein Kinases/physiology, Antigens, Biotinylation, Bronchi/immunology/metabolism/pathology, Cell Line, Chemokine {CCL}2/genetics/metabolism, Chemokine {CCL}8/genetics/metabolism, Chemokine {CXCL}1/genetics/metabolism, Chemokine {CXCL}2/genetics/metabolism, Chemokines/genetics/*metabolism, Genetic/immunology, Hu Paraneoplastic Encephalomyelitis Antigens, Inflammation Mediators/physiology, Protein Binding/genetics/immunology, Respiratory Mucosa/*immunology/metabolism/patholog, {RNA} Stability/genetics/immunology, {RNA}-Binding Proteins/*genetics/*metabolism, Signal Transduction/genetics/immunology, Surface/*genetics/*metabolism, Trachea/immunology/metabolism/pathology, Transformed}
}

@article{ozsolak_digital_2010,
	title = {Digital transcriptome profiling from attomole-level {RNA} samples},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20133332},
	doi = {10.1101/gr.102129.109},
	abstract = {Accurate profiling of minute quantities of {RNA} in a global manner can enable key advances in many scientific and clinical disciplines. Here, we present low-quantity {RNA} sequencing ({LQ}-{RNAseq}), a high-throughput sequencing-based technique allowing whole transcriptome surveys from subnanogram {RNA} quantities in an amplification/ligation-free manner. {LQ}-{RNAseq} involves first-strand {cDNA} synthesis from {RNA} templates, followed by 3' {polyA} tailing of the single-stranded {cDNA} products and direct single molecule sequencing. We applied {LQ}-{RNAseq} to profile S. cerevisiae {polyA}+ transcripts, demonstrate the reproducibility of the approach across different sample preparations and independent instrument runs, and establish the absolute quantitative power of this method through comparisons with other reported transcript profiling techniques and through utilization of {RNA} spike-in experiments. We demonstrate the practical application of this approach to define the transcriptional landscape of mouse embryonic and induced pluripotent stem cells, observing transcriptional differences, including over 100 genes exhibiting differential expression between these otherwise very similar stem cell populations. This amplification-independent technology, which utilizes small quantities of nucleic acid and provides quantitative measurements of cellular transcripts, enables global gene expression measurements from minute amounts of materials and offers broad utility in both basic research and translational biology for characterization of rare cells.},
	pages = {519--525},
	number = {4},
	journaltitle = {Genome Res},
	author = {Ozsolak, F and Goren, A and Gymrek, M and Guttman, M and Regev, A and Bernstein, B E and Milos, P M},
	date = {2010},
	pmid = {20133332},
	keywords = {Sequence Analysis, Animals, Mice, {RNA}, Gene Expression Regulation, Cells, Cultured, Reproducibility of Results, *Signal Processing, Biological, Computer-Assisted, Developmental, Embryonic Stem Cells/chemistry/metabolism, Fungal, Fungal/analysis/chemistry/metabolism, Gene Expression Profiling/instrumentation/*methods, High-Throughput Screening Assays/instrumentation/m, Induced Pluripotent Stem Cells/chemistry/metabolis, Messenger/analysis/chemistry/metabolism, Models, Osmolar Concentration, {RNA}/*analysis/chemistry/metabolism, {RNA}/instrumentation/methods, Saccharomyces cerevisiae/genetics/metabolism, Sensitivity and Specificity}
}

@article{renzi_structure_2006,
	title = {The structure of the endoribonuclease {XendoU}: From small nucleolar {RNA} processing to severe acute respiratory syndrome coronavirus replication},
	volume = {103},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16895992},
	doi = {10.1073/pnas.0602426103},
	abstract = {Small nucleolar {RNAs} ({snoRNAs}) play a key role in eukaryotic ribosome biogenesis. In most cases, {snoRNAs} are encoded in introns and are released through the splicing reaction. Some {snoRNAs} are, instead, produced by an alternative pathway consisting of endonucleolytic processing of pre-{mRNA}. {XendoU}, the endoribonuclease responsible for this activity, is a U-specific, metal-dependent enzyme that releases products with 2'-3' cyclic phosphate termini. {XendoU} is broadly conserved among eukaryotes, and it is a genetic marker of nidoviruses, including the severe acute respiratory syndrome coronavirus, where it is essential for replication and transcription. We have determined by crystallography the structure of {XendoU} that, by refined search methodologies, appears to display a unique fold. Based on sequence conservation, mutagenesis, and docking simulations, we have identified the active site. The conserved structural determinants of this site may provide a framework for attempting to design antiviral drugs to interfere with the infectious nidovirus life cycle.},
	pages = {12365--12370},
	number = {33},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Renzi, F and Caffarelli, E and Laneve, P and Bozzoni, I and Brunori, M and Vallone, B},
	date = {2006},
	pmid = {16895992},
	keywords = {Animals, Humans, {RNA}, Binding Sites, *Protein Structure, *{RNA} Processing, Amino Acid Sequence, Crystallography, Endoribonucleases/*chemistry/genetics/metabolism, Models, Molecular, Molecular Sequence Data, Post-Transcriptional, Protein Folding, {SARS} Virus/genetics/*physiology, Sequence Alignment, Small Nuclear/*metabolism, Tertiary, Uridine Monophosphate/metabolism, Virus Replication/*physiology, X-Ray, Xenopus laevis/*metabolism, Xenopus Proteins/*chemistry/genetics/metabolism}
}

@article{masuda_tissue-_2009,
	title = {Tissue- and age-dependent expression of {RNA}-binding proteins that influence {mRNA} turnover and translation},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20157551},
	abstract = {Gene expression patterns vary dramatically in a tissue-specific and age-dependent manner. {RNA}-binding proteins that regulate {mRNA} turnover and/or translation ({TTR}-{RBPs}) critically affect the subsets of expressed proteins. However, very little is known regarding the tissue- and age-dependent expression of {TTR}-{RBPs} in humans. Here, we use human tissue arrays containing a panel of organ biopsies from donors of different ages, to study the distribution and abundance of four {TTR}-{RBPs}: {HuR}, {AUF}1, {TIA}-1, and {TTP}. {HuR} and {AUF}1 were expressed with remarkably similar patterns. Both {TTR}-{RBPs} were present in high percentages of cells and displayed elevated intensities in many age groups and tissues, most notably in the gastrointestinal and reproductive systems; they were moderately expressed in the urinary and immune systems, and were almost undetectable in muscle and brain. {TIA}-1 was also abundant in many tissues and age groups; {TIA}-1 was expressed at high levels in the gastrointestinal, immune, urinary, and reproductive systems, and at low levels in brain and muscle. By contrast, {TTP}-expressing cells, as well as {TTP} signal intensities declined with advancing age, particularly in the immune, nervous, and muscular systems; however, {TTP} levels remained elevated in the gastrointestinal tract. The widespread abundance of {HuR}, {AUF}1, and {TIA}-1 throughout the body and in all age groups was in stark contrast with their declining levels in human diploid fibroblasts ({HDFs}) undergoing replicative senescence, a cultured-cell model of aging. Conversely, {TTP} levels increased in senescent {HDFs}, while {TTP} levels decreased with advancing age. Our studies provide a framework for the study of human {TTR}-{RBP} function in different tissues, throughout the human life span.},
	pages = {681--698},
	number = {8},
	journaltitle = {Aging (Albany {NY})},
	author = {Masuda, K and Marasa, B and Martindale, J L and Halushka, M K and Gorospe, M},
	date = {2009},
	pmid = {20157551},
	keywords = {Humans, {RNA}, Gene Expression Profiling, *Protein Biosynthesis, 80 and over, Adolescent, Adult, Aged, Aging/*metabolism, Brain/metabolism, Child, Female, Gastrointestinal Tract/metabolism, Genitalia/metabolism, Immune System/metabolism, Infant, Male, Messenger/*metabolism, Middle Aged, Muscles/metabolism, Newborn, Preschool, {RNA}-Binding Proteins/*metabolism, Tissue Distribution, Urinary Tract/metabolism, Young Adult}
}

@article{bryne_jaspar_2008,
	title = {{JASPAR}, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18006571},
	doi = {10.1093/nar/gkm955},
	abstract = {{JASPAR} is a popular open-access database for matrix models describing {DNA}-binding preferences for transcription factors and other {DNA} patterns. With its third major release, {JASPAR} has been expanded and equipped with additional functions aimed at both casual and power users. The heart of the {JASPAR} database-the {JASPAR} {CORE} sub-database-has increased by 12\% in size, and three new specialized sub-databases have been added. New functions include clustering of matrix models by similarity, generation of random matrices by sampling from selected sets of existing models and a language-independent Web Service applications programming interface for matrix retrieval. {JASPAR} is available at http://jaspar.genereg.net.},
	pages = {D102--6},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Bryne, J C and Valen, E and Tang, M H and Marstrand, T and Winther, O and da Piedade, I and Krogh, A and Lenhard, B and Sandelin, A},
	date = {2008},
	pmid = {18006571},
	keywords = {Animals, Genetic, Humans, Promoter Regions, Binding Sites, Computational Biology, Nucleic Acid, {RNA} Splice Sites, Software, *Databases, *Regulatory Elements, Access to Information, Data Interpretation, Internet, Models, Statistical, Transcription Factors/*metabolism, Transcriptional, User-Computer Interface}
}

@article{adepu_facile_2013,
	title = {Facile assembly of two 6-membered fused N-heterocyclic rings: a rapid access to novel small molecules via Cu-mediated reaction},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23169060},
	doi = {10.1039/c2cc37070k},
	abstract = {A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of {PDE}4.},
	pages = {190--192},
	number = {2},
	journaltitle = {Chem Commun (Camb)},
	author = {Adepu, R and Sunke, R and Meda, C L and Rambabu, D and Krishna, G R and Reddy, C M and Deora, G S and Parsa, K V and Pal, M},
	date = {2013},
	pmid = {23169060}
}

@article{kino_noncoding_2010,
	title = {Noncoding {RNA} gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20124551},
	doi = {10.1126/scisignal.2000568},
	abstract = {The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest-specific 5 (Gas5) noncoding {RNA}, which is abundant in cells whose growth has been arrested because of lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the {DNA}-binding domain of the glucocorticoid receptor ({GR}) by acting as a decoy glucocorticoid response element ({GRE}), thus competing with {DNA} {GREs} for binding to the {GR}. We conclude that Gas5 is a "riborepressor" of the {GR}, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the {GR}.},
	pages = {ra8},
	number = {107},
	journaltitle = {Sci Signal},
	author = {Kino, T and Hurt, D E and Ichijo, T and Nader, N and Chrousos, G P},
	date = {2010},
	pmid = {20124551},
	keywords = {Humans, {RNA}, *Cell Proliferation, *Gene Expression Regulation, Binding, Blotting, Cell Line, Competitive/drug effects, Culture Media/chemistry/pharmacology, Dexamethasone/metabolism/pharmacology, {DNA}/chemistry/genetics/metabolism, Fluorescence, Glucocorticoid/*genetics/metabolism, Glucocorticoids/metabolism/pharmacology, {HCT}116 Cells, {HeLa} Cells, In Situ Hybridization, Inhibitor of Apoptosis Proteins/genetics/metabolis, Jurkat Cells, Nucleic Acid Conformation, Receptors, Response Elements/genetics, Reverse Transcriptase Polymerase Chain Reaction, Small Nucleolar/*genetics/metabolism, Tumor, Two-Hybrid System Techniques, Untranslated/*genetics/metabolism, Western}
}

@article{ambrosino_negative_2003,
	title = {Negative feedback regulation of {MKK}6 {mRNA} stability by p38alpha mitogen-activated protein kinase},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12482988},
	abstract = {p38 mitogen-activated protein ({MAP}) kinases play an important role in the regulation of cellular responses to all kinds of stresses. The most abundant and broadly expressed p38 {MAP} kinase is p38alpha, which can also control the proliferation, differentiation, and survival of several cell types. Here we show that the absence of p38alpha correlates with the up-regulation of one of its upstream activators, the {MAP} kinase kinase {MKK}6, in p38alpha(-/-) knockout mice and in cultured cells derived from them. In contrast, the expression levels of the p38 activators {MKK}3 and {MKK}4 are not affected in p38alpha-deficient cells. The increase in {MKK}6 protein concentration correlates with increased amounts of {MKK}6 {mRNA} in the p38alpha(-/-) cells. Pharmacological inhibition of p38alpha also up-regulates {MKK}6 {mRNA} levels in {HEK}293 cells. Conversely, reintroduction of p38alpha into p38alpha(-/-) cells reduces the levels of {MKK}6 protein and {mRNA} to the normal levels found in wild-type cells. Moreover, we show that the {MKK}6 {mRNA} is more stable in p38alpha(-/-) cells and that the 3'untranslated region of this {mRNA} can differentially regulate the stability of the {lacZ} reporter gene in a p38alpha-dependent manner. Our data indicate that p38alpha can negatively regulate the stability of the {MKK}6 {mRNA} and thus control the steady-state concentration of one of its upstream activators.},
	pages = {370--381},
	number = {1},
	journaltitle = {Mol Cell Biol},
	author = {Ambrosino, C and Mace, G and Galban, S and Fritsch, C and Vintersten, K and Black, E and Gorospe, M and Nebreda, A R},
	date = {2003},
	pmid = {12482988},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, Mice, {RNA}, Gene Expression Regulation, Cells, Cultured, *Feedback, *{MAP} Kinase Kinase 4, *{RNA} Stability, Calcium-Calmodulin-Dependent Protein Kinases/*gene, Cardiac/metabolism, Cycloheximide/pharmacology, Enzyme Inhibitors/pharmacology, Imidazoles/pharmacology, Knockout, {MAP} Kinase Kinase 3, {MAP} Kinase Kinase 6, Messenger/metabolism, Mitogen-Activated Protein Kinase Kinases/genetics/, Mitogen-Activated Protein Kinases/drug effects/gen, Molecular Sequence Data, Myocytes, p38 Mitogen-Activated Protein Kinases, Physiological, Protein-Tyrosine Kinases/genetics/metabolism, Pyridines/pharmacology, Up-Regulation}
}

@article{potapova_targets_2002,
	title = {Targets of c-Jun {NH}(2)-terminal kinase 2-mediated tumor growth regulation revealed by serial analysis of gene expression},
	volume = {62},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12036942},
	abstract = {Although the c-Jun {NH}(2)-terminal kinase ({JNK}) pathway has been implicated in mediating cell growth and transformation, its downstream effectors remain to be identified. Using {JNK}2 antisense oligonucleotides ({JNK}2AS), we uncovered previously a role for {JNK}2 in regulating cell cycle progression and survival of human {PC}3 prostate carcinoma cells. Here, to identify genes involved in implementing {JNK}2-mediated effects, we have analyzed global gene expression changes in {JNK}2-deprived {PC}3 cells using Serial Analysis of Gene Expression. More than 40,000 tags each were generated from control and {PC}3-{JNK}2AS libraries, corresponding to 15,999 and 20,698 unique transcripts, respectively. Transcripts corresponding to transcription factors, stress-induced genes, and apoptosis-related genes were up-regulated in the {PC}3-{JNK}2AS library, revealing a significant stress response after the inhibition of {JNK}2 expression. Genes involved in {DNA} repair, {mRNA} turnover, and drug resistance were found to be down-regulated by inhibition of {JNK}2 expression, further highlighting the importance of {JNK}2 signaling in regulating cell homeostasis and tumor cell growth.},
	pages = {3257--3263},
	number = {11},
	journaltitle = {Cancer Res},
	author = {Potapova, O and Anisimov, S V and Gorospe, M and Dougherty, R H and Gaarde, W A and Boheler, K R and Holbrook, N J},
	date = {2002},
	pmid = {12036942},
	keywords = {Humans, Gene Expression Profiling, Antisense/genetics/pharmacology, Apoptosis/drug effects/physiology, Blotting, Cell Cycle/drug effects/physiology, Cell Division/physiology, Gene Expression/drug effects, {JNK} Mitogen-Activated Protein Kinases, Male, Mitogen-Activated Protein Kinases/antagonists \& in, Northern, Oligonucleotides, Prostatic Neoplasms/*enzymology/*genetics/patholog, Signal Transduction/physiology}
}

@article{mbitikon-kobo_characterization_2009,
	title = {Characterization of a {CD}44/{CD}122int memory {CD}8 T cell subset generated under sterile inflammatory conditions},
	volume = {182},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19265164},
	doi = {10.4049/jimmunol.0802438},
	abstract = {Most memory {CD}8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the {CD}8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a {TCR}-transgenic model and a model of contact hypersensitivity, we show that the priming of naive {CD}8 T cells under sterile inflammatory conditions generates memory. The corresponding memory {CD}8 T cells can be identified by their intermediate expression levels of {CD}44 and {CD}122. We also show that {CD}44/122(int) memory {CD}8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional ({IFN}-gamma secretion capacity, {CCL}5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in {CD}44/122(high) memory T cells. Altogether, our results identify a new memory {CD}8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.},
	pages = {3846--3854},
	number = {6},
	journaltitle = {J Immunol},
	author = {Mbitikon-Kobo, F M and Vocanson, M and Michallet, M C and Tomkowiak, M and Cottalorda, A and Angelov, G S and Coupet, C A and Djebali, S and Marcais, A and Dubois, B and Bonnefoy-Berard, N and Nicolas, J F and Arpin, C and Marvel, J},
	date = {2009},
	pmid = {19265164},
	keywords = {Animals, Mice, Antigens, Biological Markers/metabolism, {CD}44/biosynthesis/*physiology, {CD}8-Positive T-Lymphocytes/*immunology/*metabolism, Cell Differentiation/genetics/*immunology, Contact/genetics/immunology, Dermatitis, Immunologic Memory/*genetics, Inbred C57BL, Inflammation Mediators/metabolism/*physiology, Interleukin-2 Receptor beta Subunit/biosynthesis/*, Knockout, Lymphocyte Activation/genetics/*immunology, T-Lymphocyte Subsets/cytology/immunology/metabolis, Transgenic}
}

@article{faghihi_expression_2008,
	title = {Expression of a noncoding {RNA} is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18587408},
	doi = {10.1038/nm1784},
	abstract = {Recent efforts have revealed that numerous protein-coding messenger {RNAs} have natural antisense transcript partners, most of which seem to be noncoding {RNAs}. Here we identify a conserved noncoding antisense transcript for beta-secretase-1 ({BACE}1), a crucial enzyme in Alzheimer's disease pathophysiology. The {BACE}1-antisense transcript ({BACE}1-{AS}) regulates {BACE}1 {mRNA} and subsequently {BACE}1 protein expression in vitro and in vivo. Upon exposure to various cell stressors including amyloid-beta 1-42 (Abeta 1-42), expression of {BACE}1-{AS} becomes elevated, increasing {BACE}1 {mRNA} stability and generating additional Abeta 1-42 through a post-transcriptional feed-forward mechanism. {BACE}1-{AS} concentrations were elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. These data show that {BACE}1 {mRNA} expression is under the control of a regulatory noncoding {RNA} that may drive Alzheimer's disease-associated pathophysiology. In summary, we report that a long noncoding {RNA} is directly implicated in the increased abundance of Abeta 1-42 in Alzheimer's disease.},
	pages = {723--730},
	number = {7},
	journaltitle = {Nat Med},
	author = {Faghihi, M A and Modarresi, F and Khalil, A M and Wood, D E and Sahagan, B G and Morgan, T E and Finch, C E and St Laurent 3rd, G and Kenny, P J and Wahlestedt, C},
	date = {2008},
	pmid = {18587408},
	keywords = {Animals, Genetic, Humans, Mice, {RNA}, Transcription, Gene Expression Regulation, 80 and over, Aged, Alzheimer Disease/enzymology/*etiology/*metabolism, Amyloid beta-Peptides/metabolism, Amyloid Precursor Protein Secretases/genetics/*met, Aspartic Acid Endopeptidases/genetics/*metabolism, Cell Line, Feedback, Male, Messenger/metabolism, Middle Aged, Models, Neuroblastoma/pathology, Peptide Fragments/metabolism, Physiological, Post-Translational, Protein Processing, Small Interfering/pharmacology, Transfection, Transgenic, Tumor, Untranslated/analysis/*metabolism}
}

@article{bozzoni_clustered_1978,
	title = {Clustered and interspersed repetitive {DNA} sequences in four amphibian species with different genome size},
	volume = {520},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/101246},
	abstract = {We have compared the amount of clustered and interspersed repetitive sequences in the genome of four Amphibia with different {DNA} contents per haploid nucleus: two Anura (Xenopus laevis, 3 pg and Bufo bufo, 7 pg) and two Urodela (Triturus cristatus, 23 pg and Necturus maculosus, 52 pg). High molecular weight {DNA} of the four species was denatured and reassociated to the same Cot in order to obtain duplex sequences with a similar reiteration frequency. Single-stranded {DNA} was digested off with the Aspergillus S1 nuclease. {DNA} was then fractionated according to the molecular weight through an agarose A-50 column. We found that the amount of long repetitive sequences is roughly proportional to the genome size in the four species, while the number of short (about 300 base pairs) repetitive sequences is increased many-fold in the species with the larger {DNA} content, both in Anura and in Urodela.},
	pages = {245--252},
	number = {2},
	journaltitle = {Biochim Biophys Acta},
	author = {Bozzoni, I and Beccari, E},
	date = {1978},
	pmid = {101246},
	keywords = {Animals, Base Sequence, *{DNA}/blood, Amphibians, Bufo bufo, Electron, Erythrocytes/*analysis, Genes, Macromolecular Substances, Microscopy, Molecular Weight, Species Specificity, Triturus, Xenopus}
}

@article{halvorsen_combined_2003,
	title = {Combined loss of {PTEN} and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12684422},
	abstract = {{PURPOSE}: Recent experimental work indicates a major role for {PTEN} and p27 in prostate cancer. The combined loss of {PTEN} and p27 was found to strongly increase the development of prostatic carcinomas in an animal model, and a prognostic value in human tumors was postulated. The purpose of our study was to examine the impact of {PTEN} and p27 on prognosis in a series of prostate cancer patients, using high-density tissue microarray technology for expression profile analysis of {PTEN}, p27, and tumor cell proliferation. {EXPERIMENTAL} {DESIGN}: The expression of {PTEN} and p27 was examined in primary prostatic carcinomas from 104 patients treated with radical prostatectomy and with complete follow-up available. Using high-throughput tissue microarrays, the expression of {PTEN} and p27 was examined by immunohistochemistry, and the results were related to clinicopathological variables, tumor cell proliferation (Ki-67), and time to disease progression. {RESULTS}: {PTEN} was negative in 28 of 103 tumors (27.2\%), and median p27 expression was 64\%. Combined loss of {PTEN} and p27 expression defined a group of 18 tumors (17.5\%) associated with increased tumor diameter, seminal vesicle invasion, increased pathological stage, and elevated tumor cell proliferation by Ki-67. Cox regression analysis revealed that loss of {PTEN}/p27 expression and histological grade were both independent predictors of time to biochemical failure and clinical recurrence. {CONCLUSIONS}: Our findings strongly support the importance of {PTEN} and p27 for the progression of human prostate cancer because loss of {PTEN}/p27 expression was associated with adverse pathological parameters, tumor cell proliferation, and increased risk of recurrence.},
	pages = {1474--1479},
	number = {4},
	journaltitle = {Clin Cancer Res},
	author = {Halvorsen, O J and Haukaas, S A and Akslen, L A},
	date = {2003},
	pmid = {12684422},
	keywords = {Humans, Oligonucleotide Array Sequence Analysis, Cell Cycle Proteins/*biosynthesis, Cell Division, Cyclin-Dependent Kinase Inhibitor p27, Disease Progression, Immunohistochemistry, Ki-67 Antigen/*biosynthesis, Male, Multivariate Analysis, Phosphoric Monoester Hydrolases/*biosynthesis, Prognosis, Proportional Hazards Models, Prostatic Neoplasms/*metabolism/*pathology, {PTEN} Phosphohydrolase, Recurrence, Risk, Time Factors, Tumor Suppressor Proteins/*biosynthesis}
}

@article{khaitovich_parallel_2005,
	title = {Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees},
	volume = {309},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16141373},
	doi = {10.1126/science.1108296},
	abstract = {The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.},
	pages = {1850--1854},
	number = {5742},
	journaltitle = {Science},
	author = {Khaitovich, P and Hellmann, I and Enard, W and Nowick, K and Leinweber, M and Franz, H and Weiss, G and Lachmann, M and Paabo, S},
	date = {2005},
	pmid = {16141373},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Base Sequence, Genetic, Humans, Promoter Regions, Gene Expression Regulation, Proteins/genetics, *Genome, *Transcription, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Organ Specificity, *Evolution, *Gene Expression, Adult, Aged, Amino Acid Sequence, Child, Chromosomes, Female, Heart/physiology, Kidney/physiology, Liver/physiology, Male, Mammalian/genetics, Middle Aged, Models, Molecular, Pan troglodytes/*genetics, Prefrontal Cortex/physiology, Selection, Species Specificity, Testis/physiology, X Chromosome/genetics, X/genetics}
}

@article{galardi_purified_2002,
	title = {Purified box C/D {snoRNPs} are able to reproduce site-specific 2'-O-methylation of target {RNA} in vitro},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12215523},
	abstract = {Small nucleolar {RNAs} ({snoRNAs}) are associated in ribonucleoprotein particles localized to the nucleolus ({snoRNPs}). Most of the members of the box C/D family function in directing site-specific 2'-O-methylation of substrate {RNAs}. Although the selection of the target nucleotide requires the antisense element and the conserved box D or D' of the {snoRNA}, the methyltransferase activity is supposed to reside in one of the protein components. Through protein tagging of a {snoRNP}-specific factor, we purified to homogeneity box C/D {snoRNPs} from the yeast Saccharomyces cerevisiae. Mass spectrometric analysis demonstrated the presence of Nop1p, Nop58p, Nop56p, and Snu13p as integral components of the particle. We show that purified {snoRNPs} are able to reproduce the site-specific methylation pattern on target {RNA} and that the predicted S-adenosyl-L-methionine-binding region of Nop1p is responsible for the catalytic activity.},
	pages = {6663--6668},
	number = {19},
	journaltitle = {Mol Cell Biol},
	author = {Galardi, S and Fatica, A and Bachi, A and Scaloni, A and Presutti, C and Bozzoni, I},
	date = {2002},
	pmid = {12215523},
	keywords = {Conserved Sequence, {RNA}, Binding Sites, Fungal Proteins/chemistry, Fungal/*chemistry, Macromolecular Substances, Mass Spectrometry, Methylation, Methyltransferases/*chemistry/isolation \& purifica, Nuclear Proteins/chemistry, Oligoribonucleotides/chemistry, Ribonucleoproteins, Ribosomal/chemistry, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins/chemistry, Small Nuclear/chemistry, Small Nucleolar/*chemistry/iso, Substrate Specificity}
}

@article{peters_undersampled_2003,
	title = {Undersampled projection reconstruction for active catheter imaging with adaptable temporal resolution and catheter-only views},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12541240},
	doi = {10.1002/mrm.10390},
	abstract = {In this study undersampled projection reconstruction ({PR}) was used for rapid catheter imaging in the heart, employing steady-state free precession ({SSFP}) contrast. Active catheters and phased-array coils were used for combined imaging of anatomy and catheter position in swine. Real-time imaging of catheter position was performed with relatively high spatial and temporal resolution, providing 2 x 2 x 8 mm spatial resolution and four to eight frames per second. Two interactive features were introduced. The number of projections (Np) was adjusted interactively to trade off imaging speed and artifact reduction, allowing acquisition of high-quality or high-frame-rate images. Thin-slice imaging was performed, with interactive requests for thick-slab projection images of the signal received solely from the active catheter. Briefly toggling on catheter-only projection images was valuable for verifying that the catheter tip was contained within the selected slice, or for locating the catheter when part of it was outside the selected slice.},
	pages = {216--222},
	number = {2},
	journaltitle = {Magn Reson Med},
	author = {Peters, D C and Lederman, R J and Dick, A J and Raman, V K and Guttman, M A and Derbyshire, J A and {McVeigh}, E R},
	date = {2003},
	pmid = {12541240},
	keywords = {Animals, *Cardiac Catheterization, Aorta/anatomy \& histology, Computer-Assisted/*methods, Contrast Media/administration \& dosage, Gadolinium/diagnostic use, Heart Ventricles/anatomy \& histology, Image Processing, Injections, Magnetic Resonance Imaging/*methods, Myocardium, Swine}
}

@article{moskwa_mir-182-mediated_2011,
	title = {{miR}-182-mediated downregulation of {BRCA}1 impacts {DNA} repair and sensitivity to {PARP} inhibitors},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21195000},
	doi = {10.1016/j.molcel.2010.12.005},
	abstract = {Expression of {BRCA}1 is commonly decreased in sporadic breast tumors, and this correlates with poor prognosis of breast cancer patients. Here we show that {BRCA}1 transcripts are selectively enriched in the Argonaute/{miR}-182 complex and {miR}-182 downregulates {BRCA}1 expression. Antagonizing {miR}-182 enhances {BRCA}1 protein levels and protects them from {IR}-induced cell death, while overexpressing {miR}-182 reduces {BRCA}1 protein, impairs homologous recombination-mediated repair, and render cells hypersensitive to {IR}. The impaired {DNA} repair phenotype induced by {miR}-182 overexpression can be fully rescued by overexpressing {miR}-182-insensitive {BRCA}1. Consistent with a {BRCA}1-deficiency phenotype, {miR}-182-overexpressing breast tumor cells are hypersensitive to inhibitors of poly ({ADP}-ribose) polymerase 1 ({PARP}1). Conversely, antagonizing {miR}-182 enhances {BRCA}1 levels and induces resistance to {PARP}1 inhibitor. Finally, a clinical-grade {PARP}1 inhibitor impacts outgrowth of {miR}-182-expressing tumors in animal models. Together these results suggest that {miR}-182-mediated downregulation of {BRCA}1 impedes {DNA} repair and may impact breast cancer therapy.},
	pages = {210--220},
	number = {2},
	journaltitle = {Mol Cell},
	author = {Moskwa, P and Buffa, F M and Pan, Y and Panchakshari, R and Gottipati, P and Muschel, R J and Beech, J and Kulshrestha, R and Abdelmohsen, K and Weinstock, D M and Gorospe, M and Harris, A L and Helleday, T and Chowdhury, D},
	date = {2011},
	pmid = {21195000},
	keywords = {Animals, Humans, Mice, Antineoplastic Agents/*pharmacology, {BRCA}1 Protein/*genetics, Cell Differentiation, Cell Line, {DNA} Breaks, {DNA} Repair/*drug effects, Double-Stranded/radiation effects, Down-Regulation, K562 Cells, {MicroRNAs}/genetics/metabolism/*physiology, Phthalazines/*pharmacology, Piperazines/*pharmacology, Poly({ADP}-ribose) Polymerases/*antagonists \& inhibi, Tumor}
}

@article{bazzini_identification_2014,
	title = {Identification of small {ORFs} in vertebrates using ribosome footprinting and evolutionary conservation},
	volume = {33},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24705786},
	doi = {10.1002/embj.201488411},
	abstract = {Identification of the coding elements in the genome is a fundamental step to understanding the building blocks of living systems. Short peptides ({\textbackslash}textless 100 aa) have emerged as important regulators of development and physiology, but their identification has been limited by their size. We have leveraged the periodicity of ribosome movement on the {mRNA} to define actively translated {ORFs} by ribosome footprinting. This approach identifies several hundred translated small {ORFs} in zebrafish and human. Computational prediction of small {ORFs} from codon conservation patterns corroborates and extends these findings and identifies conserved sequences in zebrafish and human, suggesting functional peptide products (micropeptides). These results identify micropeptide-encoding genes in vertebrates, providing an entry point to define their function in vivo.},
	pages = {981--993},
	number = {9},
	journaltitle = {{EMBO} J},
	author = {Bazzini, A A and Johnstone, T G and Christiano, R and Mackowiak, S D and Obermayer, B and Fleming, E S and Vejnar, C E and Lee, M T and Rajewsky, N and Walther, T C and Giraldez, A J},
	date = {2014},
	pmid = {24705786},
	keywords = {Sequence Analysis, Animals, Base Sequence, Humans, {RNA}, Computational Biology, Gene Expression Profiling, *Conserved Sequence, *Evolution, Messenger/*genetics/metabolism, Molecular, Molecular Sequence Data, Nuclease Protection Assays, Oligopeptides/genetics, Open Reading Frames/*genetics, Ribosomes/*metabolism, {RNA}/methods, Zebrafish/embryology/*genetics}
}

@article{wang_molecular_2011,
	title = {Molecular mechanisms of long noncoding {RNAs}},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21925379},
	doi = {10.1016/j.molcel.2011.08.018},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that {lncRNAs} execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of {lncRNA} function may be a useful framework to consider how {lncRNAs} acquire properties as biological signal transducers and hint at their possible origins in evolution. As new {lncRNAs} are being discovered at a rapid pace, the molecular mechanisms of {lncRNAs} are likely to be enriched and diversified.},
	pages = {904--914},
	number = {6},
	journaltitle = {Mol Cell},
	author = {Wang, K C and Chang, H Y},
	date = {2011},
	pmid = {21925379},
	keywords = {Animals, Genetic, Humans, {RNA}, Transcription, Chromatin/metabolism, Models, Pseudogenes/physiology, {RNA} Polymerase {II}/physiology, {RNA} Stability, Telomerase/metabolism, Telomere/chemistry/genetics, Untranslated/chemistry/metabolism/*physiology}
}

@article{zhou_post-transcriptional_2010,
	title = {Post-transcriptional regulation of androgen receptor {mRNA} by an {ErbB}3 binding protein 1 in prostate cancer},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20159994},
	doi = {10.1093/nar/gkq084},
	abstract = {Androgen receptor ({AR})-mediated pathways play a critical role in the development and progression of prostate cancer. However, little is known about the regulation of {AR} {mRNA} stability and translation, two central processes that control {AR} expression. The {ErbB}3 binding protein 1 ({EBP}1), an {AR} corepressor, negatively regulates crosstalk between {ErbB}3 ligand heregulin ({HRG})-triggered signaling and the {AR} axis, affecting biological properties of prostate cancer cells. {EBP}1 protein expression is also decreased in clinical prostate cancer. We previously demonstrated that {EBP}1 overexpression results in decreased {AR} protein levels by affecting {AR} promoter activity. However, {EBP}1 has recently been demonstrated to be an {RNA} binding protein. We therefore examined the ability of {EBP}1 to regulate {AR} post-transcriptionally. Here we show that {EBP}1 promoted {AR} {mRNA} decay through physical interaction with a conserved {UC}-rich motif within the 3'-{UTR} of {AR}. The ability of {EBP}1 to accelerate {AR} {mRNA} decay was further enhanced by {HRG} treatment. {EBP}1 also bound to a {CAG}-formed stem-loop in the 5' coding region of {AR} {mRNA} and was able to inhibit {AR} translation. Thus, decreases of {EBP}1 in prostate cancer could be important for the post-transcriptional up-regulation of {AR} contributing to aberrant {AR} expression and disease progression.},
	pages = {3619--3631},
	number = {11},
	journaltitle = {Nucleic Acids Res},
	author = {Zhou, H and Mazan-Mamczarz, K and Martindale, J L and Barker, A and Liu, Z and Gorospe, M and Leedman, P J and Gartenhaus, R B and Hamburger, A W and Zhang, Y},
	date = {2010},
	pmid = {20159994},
	keywords = {3' Untranslated Regions, Base Sequence, Humans, {RNA}, *Gene Expression Regulation, *{RNA} Stability, Androgen/*genetics/metabolism, Cell Line, Male, Messenger/*metabolism, Molecular Sequence Data, Neoplastic, Polyribosomes/metabolism, Prostatic Neoplasms/*genetics/metabolism, Receptors, {RNA}-Binding Proteins/*metabolism, Tumor}
}

@article{chalei_long_2014,
	title = {The long non-coding {RNA} Dali is an epigenetic regulator of neural differentiation},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25415054},
	doi = {10.7554/eLife.04530},
	abstract = {Many intergenic long noncoding {RNA} ({lncRNA}) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic {lncRNAs} commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal {RNA}-dependent roles of Dali, a conserved central nervous system expressed intergenic {lncRNA}. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the {POU}3F3 protein. Dali interacts with the {DNMT}1 {DNA} methyltransferase in mouse and human and regulates {DNA} methylation status of {CpG} island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic {lncRNA} controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.},
	pages = {e04530},
	journaltitle = {Elife},
	author = {Chalei, V and Sansom, S N and Kong, L and Lee, S and Montiel, J F and Vance, K W and Ponting, C P},
	date = {2014},
	pmid = {25415054}
}

@article{huda_prediction_2011,
	title = {Prediction of transposable element derived enhancers using chromatin modification profiles},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22087331},
	doi = {10.1371/journal.pone.0027513},
	abstract = {Experimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element ({TE}) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the {ENCODE} project in two human hematopoietic cell types, {GM}12878 and K562. We predicted the locations of 2,107 and 1,448 {TE}-derived enhancers in the {GM}12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5\% of the {TE}-derived enhancers are shared between the two. We evaluated the functional effect of {TE}-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of {TE}-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of {TE}-derived enhancers in their vicinity. As such, genes that are up-regulated in the {GM}12878 cell line and down-regulated in K562 have significantly more {TE}-derived enhancers in their vicinity in the {GM}12878 cell line and vice versa. These data indicate that human {TE}-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of {TE}-derived sequences is mediated by epigenetic regulatory mechanisms.},
	pages = {e27513},
	number = {11},
	journaltitle = {{PLoS} One},
	author = {Huda, A and Tyagi, E and Marino-Ramirez, L and Bowen, N J and Jjingo, D and Jordan, I K},
	date = {2011},
	pmid = {22087331},
	keywords = {Human, Genetic, Humans, *Genome, *{DNA} Transposable Elements, *Gene Expression, *Transcription Factors, Cell Line, Chromatin/*metabolism, Epigenesis, Erythroid Precursor Cells, Histones, K562 Cells, Methods}
}

@article{zaragoza_repression_2010,
	title = {Repression of transcriptional activity of C/{EBPalpha} by E2F-dimerization partner complexes},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20176812},
	doi = {10.1128/MCB.01619-09},
	abstract = {The transcription factor {CCAAT}/enhancer-binding protein alpha (C/{EBPalpha}) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/{EBPalpha} transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/{EBPalpha} {BRM}2 mutant serves as a paradigm for recurrent human C-terminal {bZIP} C/{EBPalpha} mutations that are involved in acute myeloid leukemogenesis. {BRM}2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/{EBPalpha} interacts with the dimerization partner ({DP}) of E2F and that C/{EBPalpha}-E2F/{DP} interaction prevents both binding of C/{EBPalpha} to its cognate sites on {DNA} and transactivation of C/{EBP} target genes. The {BRM}2 mutant, in addition, exhibits enhanced interaction with E2F-{DP} and reduced affinity toward {DNA} and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/{DP} levels are low. Our data suggest a tripartite balance between C/{EBPalpha}, E2F/{DP}, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.},
	pages = {2293--2304},
	number = {9},
	journaltitle = {Mol Cell Biol},
	author = {Zaragoza, K and Begay, V and Schuetz, A and Heinemann, U and Leutz, A},
	date = {2010},
	pmid = {20176812},
	keywords = {Animals, Genetic, Humans, Mice, Promoter Regions, Binding Sites, Protein Binding, *Transcription, Genetic/genetics, *Protein Multimerization, Amino Acid Sequence, Biological, {CCAAT}-Enhancer-Binding Protein-alpha/*genetics/met, Cell Differentiation, Cell Line, Consensus Sequence, {DNA}/metabolism, E2F Transcription Factors/chemistry/*metabolism, Gene Knockdown Techniques, Models, Molecular Sequence Data, Mutant Proteins/chemistry/metabolism, Mutation/genetics, Repressor Proteins/*metabolism, Retinoblastoma Protein/metabolism}
}

@article{di_ruscio_dnmt1-interacting_2013,
	title = {{DNMT}1-interacting {RNAs} block gene-specific {DNA} methylation},
	volume = {503},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24107992},
	doi = {10.1038/nature12598},
	abstract = {{DNA} methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel {RNA} arising from the {CEBPA} gene locus that is critical in regulating the local {DNA} methylation profile. This {RNA} binds to {DNMT}1 and prevents {CEBPA} gene locus methylation. Deep sequencing of transcripts associated with {DNMT}1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of {DNMT}1-{RNA} interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.},
	pages = {371--376},
	number = {7476},
	journaltitle = {Nature},
	author = {Di Ruscio, A and Ebralidze, A K and Benoukraf, T and Amabile, G and Goff, L A and Terragni, J and Figueroa, M E and De Figueiredo Pontes, L L and Alberich-Jorda, M and Zhang, P and Wu, M and D'Alo, F and Melnick, A and Leone, G and Ebralidze, K K and Pradhan, S and Rinn, J L and Tenen, D G},
	date = {2013},
	pmid = {24107992},
	keywords = {Base Sequence, Genome, Humans, {RNA}, Transcription, Gene Expression Profiling, Genetic/genetics, {CCAAT}-Enhancer-Binding Proteins/*genetics, Cell Line, {DNA} (Cytosine-5-)-Methyltransferase/*metabolism, {DNA} Methylation/*genetics, {DNA}/genetics/metabolism, Gene Expression Regulation/*genetics, Human/genetics, Messenger/genetics/metabolism, {RNA}-Binding Proteins/metabolism, Substrate Specificity, Untranslated/genetics/*metabolism}
}

@article{presutti_primary_1993,
	title = {The primary sequence of the Schizosaccharomyces pombe protein homologous to S.cerevisiae ribosomal protein L2},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8367312},
	pages = {3900},
	number = {16},
	journaltitle = {Nucleic Acids Res},
	author = {Presutti, C and Villa, T and Bozzoni, I},
	date = {1993},
	pmid = {8367312},
	keywords = {Amino Acid, Amino Acid Sequence, Fungal Proteins/genetics, Molecular Sequence Data, Ribosomal Proteins/*genetics, Saccharomyces cerevisiae/*genetics, Schizosaccharomyces/*genetics, Sequence Homology}
}

@article{santos-rosa_active_2002,
	title = {Active genes are tri-methylated at K4 of histone H3},
	volume = {419},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12353038},
	doi = {10.1038/nature01080},
	abstract = {Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.},
	pages = {407--411},
	number = {6905},
	journaltitle = {Nature},
	author = {Santos-Rosa, H and Schneider, R and Bannister, A J and Sherriff, J and Bernstein, B E and Emre, N C and Schreiber, S L and Mellor, J and Kouzarides, T},
	date = {2002},
	pmid = {12353038},
	keywords = {Transcription, Gene Expression Profiling, *Gene Expression Regulation, Antibodies, {DNA}-Binding Proteins/genetics/*metabolism, Fungal/*genetics, Fungal/drug effects, Genes, Genetic/drug effects, Histone-Lysine N-Methyltransferase, Histones/chemistry/immunology/*metabolism, Inositol/pharmacology, Lysine/*metabolism, Methionine/pharmacology, Methylation/drug effects, Saccharomyces cerevisiae Proteins/genetics/metabol, Saccharomyces cerevisiae/drug effects/*genetics/*m, Transcription Factors/genetics/*metabolism}
}

@article{cacchiarelli_mirnas_2011,
	title = {{miRNAs} as serum biomarkers for Duchenne muscular dystrophy},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21425469},
	doi = {10.1002/emmm.201100133},
	abstract = {Dystrophin absence in Duchenne muscular dystrophy ({DMD}) causes severe muscle degeneration. We describe that, as consequence of fibre damage, specific muscle-{miRNAs} are released in to the bloodstream of {DMD} patients and their levels correlate with the severity of the disease. The same {miRNAs} are abundant also in the blood of mdx mice and recover to wild-type levels in animals 'cured' through exon skipping. Even though creatine kinase ({CK}) blood levels have been utilized as diagnostic markers of several neuromuscular diseases, including {DMD}, we demonstrate that they correlate less well with the disease severity. Although the analysis of a larger number of patients should allow to obtain more refined correlations with the different stages of disease progression, we propose that {miR}-1, {miR}-133, and {miR}-206 are new and valuable biomarkers for the diagnosis of {DMD} and possibly also for monitoring the outcomes of therapeutic interventions in humans. Despite many different {DMD} therapeutic approaches are now entering clinical trials, a unifying method for assessing the benefit of different treatments is still lacking.},
	pages = {258--265},
	number = {5},
	journaltitle = {{EMBO} Mol Med},
	author = {Cacchiarelli, D and Legnini, I and Martone, J and Cazzella, V and D'Amico, A and Bertini, E and Bozzoni, I},
	date = {2011},
	pmid = {21425469},
	keywords = {Animals, Humans, Mice, Biological Markers/*blood, Creatine Kinase/blood, Duchenne/*diagnosis/*pathology, {MicroRNAs}/*blood, Muscular Dystrophy, Serum/chemistry, Severity of Illness Index}
}

@article{arrington_enhanced_2000,
	title = {Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to {DNA} repair defects},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11121725},
	abstract = {While the Ku complex, comprised of Ku70 and Ku80, is primarily involved in the repair of {DNA} double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts ({MEFs}) derived from either wild-type or Ku80-null (Ku80(-/-)) mice with various stress agents revealed that hydrogen peroxide (H(2)O(2)) was markedly more cytotoxic for Ku80(-/-) {MEFs} and led to their long-term accumulation in the G2 phase. This differential response was not due to differences in {DNA} repair, since H(2)O(2)-triggered {DNA} damage was repaired with comparable efficiency in both Wt and Ku80(-/-) {MEFs}, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and G2-progression are not only dependent on the cell's {DNA} repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.},
	pages = {1166--1176},
	number = {11},
	journaltitle = {Free Radic Biol Med},
	author = {Arrington, E D and Caldwell, M C and Kumaravel, T S and Lohani, A and Joshi, A and Evans, M K and Chen, H T and Nussenzweig, A and Holbrook, N J and Gorospe, M},
	date = {2000},
	pmid = {11121725},
	keywords = {Animals, Mice, *Antigens, *{DNA} Helicases, *{DNA} Repair, Cell Line, Cell Survival/drug effects, Colony-Forming Units Assay, Cyclins/genetics, {DNA} Damage, {DNA}-Binding Proteins/*deficiency/physiology, Embryo, Fibroblasts/cytology/drug effects/metabolism, Flow Cytometry, Free Radicals, G2 Phase/*drug effects, Gamma Rays, Hydrogen Peroxide/*pharmacology, Immunosorbent Techniques, Knockout, Mammalian, Nuclear, Nuclear Proteins/*deficiency/physiology}
}

@article{smith_translation_2014,
	title = {Translation of small open reading frames within unannotated {RNA} transcripts in Saccharomyces cerevisiae},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24931603},
	doi = {10.1016/j.celrep.2014.05.023},
	abstract = {High-throughput gene expression analysis has revealed a plethora of previously undetected transcripts in eukaryotic cells. In this study, we investigate {\textbackslash}textgreater1,100 unannotated transcripts in yeast predicted to lack protein-coding capacity. We show that a majority of these {RNAs} are enriched on polyribosomes akin to {mRNAs}. Ribosome profiling demonstrates that many bind translocating ribosomes within predicted open reading frames 10-96 codons in size. We validate expression of peptides encoded within a subset of these {RNAs} and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent nonsense-mediated {RNA} decay ({NMD}) pathway. We identify {lncRNAs} that are also sensitive to {NMD}, indicating that translation of noncoding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein coding and expand the proteome of yeast and possibly other eukaryotes.},
	pages = {1858--1866},
	number = {6},
	journaltitle = {Cell Rep},
	author = {Smith, J E and Alvarez-Dominguez, J R and Kline, N and Huynh, N J and Geisler, S and Hu, W and Coller, J and Baker, K E},
	date = {2014},
	pmid = {24931603},
	keywords = {Animals, {RNA}, Gene Expression Regulation, *Open Reading Frames, Fungal, Fungal/*genetics, Messenger/*genetics, Polyribosomes/*metabolism, Protein Biosynthesis, {RNA} Stability, Saccharomyces cerevisiae Proteins/genetics/metabol, Saccharomyces cerevisiae/*genetics/metabolism}
}

@article{ray_compendium_2013,
	title = {A compendium of {RNA}-binding motifs for decoding gene regulation},
	volume = {499},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23846655},
	doi = {10.1038/nature12311},
	abstract = {{RNA}-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the {RNA} motifs recognized by {RNA}-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of {RNA}-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan {RNA}-binding proteins can thus be inferred from their {RNA}-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo {RNA}-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of {RNA}-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of {RNA}-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.},
	pages = {172--177},
	number = {7457},
	journaltitle = {Nature},
	author = {Ray, D and Kazan, H and Cook, K B and Weirauch, M T and Najafabadi, H S and Li, X and Gueroussov, S and Albu, M and Zheng, H and Yang, A and Na, H and Irimia, M and Matzat, L H and Dale, R K and Smith, S A and Yarosh, C A and Kelly, S M and Nabet, B and Mecenas, D and Li, W and Laishram, R S and Qiao, M and Lipshitz, H D and Piano, F and Corbett, A H and Carstens, R P and Frey, B J and Anderson, R A and Lynch, K W and Penalva, L O and Lei, E P and Fraser, A G and Blencowe, B J and Morris, Q D and Hughes, T R},
	date = {2013},
	pmid = {23846655},
	keywords = {Base Sequence, Humans, Autistic Disorder/genetics, Binding Sites/genetics, Conserved Sequence/genetics, Eukaryotic Cells/metabolism, Gene Expression Regulation/*genetics, Molecular Sequence Data, Nucleotide Motifs/*genetics, Protein Structure, {RNA} Stability/genetics, {RNA}-Binding Proteins/chemistry/genetics/*metabolis, Tertiary/genetics},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/HTS9R6BW/Ray et al. - 2013 - A compendium of RNA-binding motifs for decoding ge.pdf:application/pdf}
}

@article{halperin_allegro:_2009,
	title = {Allegro: analyzing expression and sequence in concert to discover regulatory programs},
	volume = {37},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19151090},
	doi = {10.1093/nar/gkn1064},
	abstract = {A major goal of system biology is the characterization of transcription factors and {microRNAs} ({miRNAs}) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' {UTR} sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes. We show that Allegro is more accurate and sensitive than existing techniques, and can simultaneously analyze multiple expression datasets with more than 100 conditions. We apply Allegro on datasets from several species and report on the transcriptional modules it uncovers. Our analysis reveals a novel motif over-represented in the promoters of genes highly expressed in murine oocytes, and several new motifs related to fly development. Finally, using stem-cell expression profiles, we identify three {miRNA} families with pivotal roles in human embryogenesis.},
	pages = {1566--1579},
	number = {5},
	journaltitle = {Nucleic Acids Res},
	author = {Halperin, Y and Linhart, C and Ulitsky, I and Shamir, R},
	date = {2009},
	pmid = {19151090},
	keywords = {{DNA}, Sequence Analysis, Animals, Genetic, Humans, Mice, {RNA}, *Promoter Regions, Transcription Factors/metabolism, Software, *Algorithms, *Gene Expression Profiling, *Gene Expression Regulation, 3' Untranslated Regions/*chemistry, Cell Cycle/genetics, {MicroRNAs}/metabolism, Mitogen-Activated Protein Kinases/metabolism, Saccharomyces cerevisiae Proteins/metabolism, Saccharomyces cerevisiae/genetics/metabolism, Stem Cells/metabolism}
}

@article{li_transposable_2012,
	title = {Transposable elements in {TDP}-43-mediated neurodegenerative disorders},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22957047},
	doi = {10.1371/journal.pone.0044099},
	abstract = {Elevated expression of specific transposable elements ({TEs}) has been observed in several neurodegenerative disorders. {TEs} also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-{RNA} interactions and of gene expression profiles, we uncovered extensive binding of {TE} transcripts to {TDP}-43, an {RNA}-binding protein central to amyotrophic lateral sclerosis ({ALS}) and frontotemporal lobar degeneration ({FTLD}). Second, we find that association between {TDP}-43 and many of its {TE} targets is reduced in {FTLD} patients. Third, we discovered that a large fraction of the {TEs} to which {TDP}-43 binds become de-repressed in mouse {TDP}-43 disease models. We propose the hypothesis that {TE} mis-regulation contributes to {TDP}-43 related neurodegenerative diseases.},
	pages = {e44099},
	number = {9},
	journaltitle = {{PLoS} One},
	author = {Li, W and Jin, Y and Prazak, L and Hammell, M and Dubnau, J},
	date = {2012},
	pmid = {22957047},
	keywords = {Animals, Genome, Humans, Mice, Protein Binding, Gene Expression Profiling, *{DNA} Transposable Elements, Case-Control Studies, {DNA}-Binding Proteins/*genetics, Frontal Lobe/pathology, Models, Molecular Sequence Data, Neurodegenerative Diseases/*genetics, Neurons/metabolism, Rats, {RNA}/metabolism, Statistical}
}

@article{peaston_retrotransposons_2004,
	title = {Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15469847},
	doi = {10.1016/j.devcel.2004.09.004},
	abstract = {A comprehensive analysis of transposable element ({TE}) expression in mammalian full-grown oocytes reveals that {LTR} class {III} retrotransposons make an unexpectedly high contribution to the maternal {mRNA} pool, which persists in cleavage stage embryos. The most abundant transcripts in the mouse oocyte are from the mouse transcript ({MT}) retrotransposon family, and expression of this and other {TE} families is developmentally regulated. Furthermore, {TEs} act as alternative promoters and first exons for a subset of host genes, regulating their expression in full-grown oocytes and cleavage stage embryos. To our knowledge, this is the first example of {TEs} initiating synchronous, developmentally regulated expression of multiple genes in mammals. We propose that differential {TE} expression triggers sequential reprogramming of the embryonic genome during the oocyte to embryo transition and in preimplantation embryos.},
	pages = {597--606},
	number = {4},
	journaltitle = {Dev Cell},
	author = {Peaston, A E and Evsikov, A V and Graber, J H and de Vries, W N and Holbrook, A E and Solter, D and Knowles, B B},
	date = {2004},
	pmid = {15469847},
	keywords = {Animals, Base Sequence, Genetic, Mice, Transcription, Exons, Introns, *Embryonic Development, *Gene Expression Regulation, Blastocyst/*physiology, Consensus Sequence, Developmental, Female, Inbred Strains, Molecular Sequence Data, Oocytes/*physiology, Phylogeny, Pregnancy, Retroelements/*physiology, Terminal Repeat Sequences}
}

@article{hanahan_hallmarks_2000,
	title = {The hallmarks of cancer},
	volume = {100},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10647931},
	pages = {57--70},
	number = {1},
	journaltitle = {Cell},
	author = {Hanahan, D and Weinberg, R A},
	date = {2000},
	pmid = {10647931},
	keywords = {Animals, Humans, Gene Expression Regulation, *Neoplasms, *Neoplasms/blood supply/etiology/genetics/patholog, Apoptosis, Cell Transformation, Experimental/blood supply/genetics/pat, Neoplastic, Neovascularization, Pathologic}
}

@article{przedborski_brain_1996,
	title = {Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8967746},
	doi = {10.1002/ana.410390204},
	abstract = {Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.},
	pages = {158--165},
	number = {2},
	journaltitle = {Ann Neurol},
	author = {Przedborski, S and Donaldson, D and Jakowec, M and Kish, S J and Guttman, M and Rosoklija, G and Hays, A P},
	date = {1996},
	pmid = {8967746},
	keywords = {Humans, Amyotrophic Lateral Sclerosis/*enzymology, Brain/*enzymology, Cadaver, Catalase/*metabolism, Cerebellar Cortex/enzymology, Cerebral Cortex/enzymology, Female, Glutathione Peroxidase/*metabolism, Male, Middle Aged, Reference Values, Superoxide Dismutase/*metabolism}
}

@article{lecona_kinetic_2008,
	title = {Kinetic analysis of butyrate transport in human colon adenocarcinoma cells reveals two different carrier-mediated mechanisms},
	volume = {409},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17760565},
	doi = {10.1042/BJ20070374},
	abstract = {Butyrate has antitumorigenic effects on colon cancer cells, inhibits cell growth and promotes differentiation and apoptosis. These effects depend on its intracellular concentration, which is regulated by its transport. We have analysed butyrate uptake kinetics in human colon adenocarcinoma cells sensitive to the apoptotic effects of butyrate ({BCS}-{TC}2, Caco-2 and {HT}-29), in butyrate-resistant cells ({BCS}-{TC}2.{BR}2) and in normal colonic cells ({FHC}). The properties of transport were analysed with structural analogues, specific inhibitors and different bicarbonate and sodium concentrations. Two carrier-mediated mechanisms were detected: a low-affinity/high-capacity (K(m)=109+/-16 {mM} in {BCS}-{TC}2 cells) anion exchanger and a high-affinity/low-capacity (K(m)=17.9+/-4.0 {microM} in {BCS}-{TC}2 cells) proton-monocarboxylate co-transporter that was energy-dependent and activated via {PKCdelta} (protein kinase Cdelta). All adenocarcinoma cells analysed express {MCT} (monocarboxylate transporter) 1, {MCT}4, ancillary protein {CD}147 and {AE}2 (anion exchanger 2). Silencing experiments show that {MCT}1, whose expression increases with butyrate treatment in butyrate-sensitive cells, plays a key role in high-affinity transport. Low-affinity uptake was mediated by a butyrate/bicarbonate antiporter along with a possible contribution of {AE}2 and {MCT}4. Butyrate treatment increased uptake in a time- and dose-dependent manner in butyrate-sensitive but not in butyrate-resistant cells. The two butyrate-uptake activities in human colon adenocarcinoma cells enable butyrate transport at different physiological conditions to maintain cell functionality. The high-affinity/low-capacity transport functions under low butyrate concentrations and may be relevant for the survival of carcinoma cells in tumour regions with low glucose and butyrate availability as well as for the normal physiology of colonocytes.},
	pages = {311--320},
	number = {1},
	journaltitle = {Biochem J},
	author = {Lecona, E and Olmo, N and Turnay, J and Santiago-Gomez, A and Lopez de Silanes, I and Gorospe, M and Lizarbe, M A},
	date = {2008},
	pmid = {17760565},
	keywords = {Humans, {RNA}, Adenocarcinoma/*metabolism, Anion Transport Proteins/biosynthesis, Anions, Antigens, Antiporters/biosynthesis, Biological Transport, Butyrates/*metabolism/pharmacokinetics, {CD}147/biosynthesis, Cell Cycle Proteins/biosynthesis, Cell Line, Colonic Neoplasms/*metabolism, {DNA} Primers/chemistry, Glucose/metabolism, Kinetics, Oncogene Proteins/biosynthesis, Protein Kinase C/metabolism, {SLC}4A Proteins, Small Interfering/metabolism, Tumor}
}

@article{montgomery_transcriptome_2010,
	title = {Transcriptome genetics using second generation sequencing in a Caucasian population},
	volume = {464},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20220756},
	doi = {10.1038/nature08903},
	abstract = {Gene expression is an important phenotype that informs about genetic and environmental effects on cellular state. Many studies have previously identified genetic variants for gene expression phenotypes using custom and commercially available microarrays. Second generation sequencing technologies are now providing unprecedented access to the fine structure of the transcriptome. We have sequenced the {mRNA} fraction of the transcriptome in 60 extended {HapMap} individuals of European descent and have combined these data with genetic variants from the {HapMap}3 project. We have quantified exon abundance based on read depth and have also developed methods to quantify whole transcript abundance. We have found that approximately 10 million reads of sequencing can provide access to the same dynamic range as arrays with better quantification of alternative and highly abundant transcripts. Correlation with {SNPs} (small nucleotide polymorphisms) leads to a larger discovery of {eQTLs} (expression quantitative trait loci) than with arrays. We also detect a substantial number of variants that influence the structure of mature transcripts indicating variants responsible for alternative splicing. Finally, measures of allele-specific expression allowed the identification of rare {eQTLs} and allelic differences in transcript structure. This analysis shows that high throughput sequencing technologies reveal new properties of genetic effects on the transcriptome and allow the exploration of genetic effects in cellular processes.},
	pages = {773--777},
	number = {7289},
	journaltitle = {Nature},
	author = {Montgomery, S B and Sammeth, M and Gutierrez-Arcelus, M and Lach, R P and Ingle, C and Nisbett, J and Guigo, R and Dermitzakis, E T},
	date = {2010},
	pmid = {20220756},
	keywords = {{DNA}/*methods, Gene Expression Profiling/*methods, Sequence Analysis, Humans, {RNA}, Exons/genetics, Alleles, Alternative Splicing/genetics, European Continental Ancestry Group/*genetics, Haplotypes/genetics, Homozygote, Messenger/*analysis/*genetics, Polymorphism, Quantitative Trait Loci/genetics, Single Nucleotide/genetics}
}

@article{sunkum_clinical_2013,
	title = {A clinical study of audiological profile in diabetes mellitus patients},
	volume = {270},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22695875},
	doi = {10.1007/s00405-012-2063-y},
	abstract = {The aim of this study is to compare the hearing thresholds of the diabetic patients with the age- and sex-matched normal control group regarding age, glucose level, duration and complications of diabetes with the degree of hearing impairment. Pure tone audiometry was performed in 58 patients with type 1 and 2 diabetes mellitus and compared with 58 age- and sex-matched controls. The patients were categorized into groups according to age, duration of diabetes, complications and control of diabetes. These observations were compared with those from the control subjects. 15-50 years age group with diabetes showed a significant high frequency hearing loss, as compared to the controls. Complicated and poorly controlled diabetics have significant degree of hearing loss in high frequencies as compared to those who were well controlled and uncomplicated. There was also a correlation between the level of hearing loss and duration of diabetes.},
	pages = {875--879},
	number = {3},
	journaltitle = {Eur Arch Otorhinolaryngol},
	author = {Sunkum, A J and Pingile, S},
	date = {2013},
	pmid = {22695875},
	keywords = {Humans, Adolescent, Adult, Audiometry, Auditory Threshold/*physiology, Case-Control Studies, Child, Diabetes Mellitus, Female, Hearing Loss, High-Frequency/*etiology, Hyperglycemia/complications, Male, Middle Aged, Preschool, Pure-Tone, Sensorineural/*etiology, Severity of Illness Index, Type 1/*complications, Type 2/*complications, Young Adult}
}

@article{garber_computational_2011,
	title = {Computational methods for transcriptome annotation and quantification using {RNA}-seq},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21623353},
	doi = {10.1038/nmeth.1613},
	abstract = {High-throughput {RNA} sequencing ({RNA}-seq) promises a comprehensive picture of the transcriptome, allowing for the complete annotation and quantification of all genes and their isoforms across samples. Realizing this promise requires increasingly complex computational methods. These computational challenges fall into three main categories: (i) read mapping, (ii) transcriptome reconstruction and (iii) expression quantification. Here we explain the major conceptual and practical challenges, and the general classes of solutions for each category. Finally, we highlight the interdependence between these categories and discuss the benefits for different biological applications.},
	pages = {469--477},
	number = {6},
	journaltitle = {Nat Methods},
	author = {Garber, M and Grabherr, M G and Guttman, M and Trapnell, C},
	date = {2011},
	pmid = {21623353},
	keywords = {Sequence Analysis, Animals, Humans, Computational Biology/methods, Gene Expression Profiling/*statistics \& numerical, Genomics/statistics \& numerical data, High-Throughput Nucleotide Sequencing/*statistics, {RNA}/*statistics \& numerical dat, Sequence Alignment/statistics \& numerical data}
}

@article{sunkara_aminosilane_2013,
	title = {Aminosilane layers on the plasma activated thermoplastics: influence of solvent on its structure and morphology},
	volume = {411},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24050640},
	doi = {10.1016/j.jcis.2013.08.038},
	abstract = {The chemistry and the structure of aminosilane layer on the plasma activated thermoplastic substrates, e.g., polycarbonate ({PC}), polystyrene ({PS}), poly(methyl methacrylate) ({PMMA}), and cyclic olefin co-polymer ({COC}) were investigated at the molecular level. The nature of the surface functional groups of the silane layers prepared by solution phase deposition in aqueous and anhydrous solvents were studied using various techniques including ellipsometry, goniometry, atomic force microscopy ({AFM}), X-ray photoelectron spectroscopy ({XPS}), and attenuated total reflectance infrared spectroscopy ({ATR}-{IR}). The {XPS} analyses revealed the presence of various oxygen functionalities on the plasma activated thermoplastics. Considerable differences were observed for the structure of aminosilane depending on the solvent used for the reaction. Deposition from aqueous solution resulted in relatively flat and smooth surfaces with consistent thickness compared to the anhydrous solution deposition. In the former case, 33\% of the total nitrogen accounted for protonated amine and 16\% for the free amino groups. In the latter, only 6\% accounted for the protonated amine. The point of zero charge (pzc), on the aminosilane modified {PC} was found to be around 7, indicated that the surface is positively charged below {pH} 7 and negatively charged above {pH} 7. The surface analysis data suggested that various interactions are possible between the plasma activated thermoplastic surface and the aminosilane. In general, they are bound to the surface through covalent bond formation between the oxygen functionalities on the thermoplastic surface and the amino or the silanol groups of the aminosilane.},
	pages = {122--128},
	journaltitle = {J Colloid Interface Sci},
	author = {Sunkara, V and Cho, Y K},
	date = {2013},
	pmid = {24050640}
}

@article{laneve_tumor_2008,
	title = {The tumor marker human placental protein 11 is an endoribonuclease},
	volume = {283},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18936097},
	doi = {10.1074/jbc.M805759200},
	abstract = {Human {PP}11 (placental protein 11) was previously described as a serine protease specifically expressed in the syncytiotrophoblast and in numerous tumor tissues. Several {PP}11-like proteins were annotated in distantly related organisms, such as worms and mammals, suggesting their involvement in evolutionarily conserved processes. Based on sequence similarity, human {PP}11 was included in a protein family whose characterized members are {XendoU}, a Xenopus laevis endoribonuclease involved in small nucleolar {RNA} processing, and Nsp15, an endoribonuclease essential for coronavirus replication. Here we show that the bacterially expressed human {PP}11 displays {RNA} binding capability and cleaves single stranded {RNA} in a Mn(2+)-dependent manner at uridylates, to produce molecules with 2',3'-cyclic phosphate ends. These features, together with structural and mutagenesis analyses, which identified the potential active site residues, reveal striking parallels to the amphibian {XendoU} and assign a ribonuclease function to {PP}11. This newly discovered enzymatic activity places {PP}11-like proteins in a completely new perspective.},
	pages = {34712--34719},
	number = {50},
	journaltitle = {J Biol Chem},
	author = {Laneve, P and Gioia, U and Ragno, R and Altieri, F and Di Franco, C and Santini, T and Arceci, M and Bozzoni, I and Caffarelli, E},
	date = {2008},
	pmid = {18936097},
	keywords = {Animals, Base Sequence, Humans, {RNA}, Protein Binding, Amino Acid Motifs, Biological/*metabolism, Catalysis, Catalytic Domain, Double-Stranded/chemistry, Endoribonucleases/*metabolism, Molecular Sequence Data, Mutagenesis, Pregnancy Proteins/metabolism/*physiology, {RNA}/metabolism, Tumor Markers, Xenopus laevis}
}

@article{ye_computational_2014,
	title = {Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24369421},
	doi = {10.1093/nar/gkt1338},
	abstract = {Alternative splicing ({AS}), in higher eukaryotes, is one of the mechanisms of post-transcriptional regulation that generate multiple transcripts from the same gene. One particular mode of {AS} is the skipping event where an exon may be alternatively excluded or constitutively included in the resulting mature {mRNA}. Both transcript isoforms from this skipping event site, i.e. in which the exon is either included (inclusion isoform) or excluded (skipping isoform), are typically present in one cell, and maintain a subtle balance that is vital to cellular function and dynamics. However, how the prevailing conditions dictate which isoform is expressed and what biological factors might influence the regulation of this process remain areas requiring further exploration. In this study, we have developed a novel computational method, graph-based exon-skipping scanner ({GESS}), for de novo detection of skipping event sites from raw {RNA}-seq reads without prior knowledge of gene annotations, as well as for determining the dominant isoform generated from such sites. We have applied our method to publicly available {RNA}-seq data in {GM}12878 and K562 cells from the {ENCODE} consortium and experimentally validated several skipping site predictions by {RT}-{PCR}. Furthermore, we integrated other sequencing-based genomic data to investigate the impact of splicing activities, transcription factors ({TFs}) and epigenetic histone modifications on splicing outcomes. Our computational analysis found that splice sites within the skipping-isoform-dominated group ({SIDG}) tended to exhibit weaker {MaxEntScan}-calculated splice site strength around middle, 'skipping', exons compared to those in the inclusion-isoform-dominated group ({IIDG}). We further showed the positional preference pattern of splicing factors, characterized by enrichment in the intronic splice sites immediately bordering middle exons. Finally, our analysis suggested that different epigenetic factors may introduce a variable obstacle in the process of exon-intron boundary establishment leading to skipping events.},
	pages = {2856--2869},
	number = {5},
	journaltitle = {Nucleic Acids Res},
	author = {Ye, Z and Chen, Z and Lan, X and Hara, S and Sunkel, B and Huang, T H and Elnitski, L and Wang, Q and Jin, V X},
	date = {2014},
	pmid = {24369421}
}

@article{maurano_systematic_2012,
	title = {Systematic localization of common disease-associated variation in regulatory {DNA}},
	volume = {337},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22955828},
	doi = {10.1126/science.1222794},
	abstract = {Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory {DNA} marked by deoxyribonuclease I ({DNase} I) hypersensitive sites ({DHSs}). Eighty-eight percent of such {DHSs} are active during fetal development and are enriched in variants associated with gestational exposure-related phenotypes. We identified distant gene targets for hundreds of variant-containing {DHSs} that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within {DHSs} and the de novo identification of pathogenic cell types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory {DNA} variation in common human disease and provide pathogenic insights into diverse disorders.},
	pages = {1190--1195},
	number = {6099},
	journaltitle = {Science},
	author = {Maurano, M T and Humbert, R and Rynes, E and Thurman, R E and Haugen, E and Wang, H and Reynolds, A P and Sandstrom, R and Qu, H and Brody, J and Shafer, A and Neri, F and Lee, K and Kutyavin, T and Stehling-Sun, S and Johnson, A K and Canfield, T K and Giste, E and Diegel, M and Bates, D and Hansen, R S and Neph, S and Sabo, P J and Heimfeld, S and Raubitschek, A and Ziegler, S and Cotsapas, C and Sotoodehnia, N and Glass, I and Sunyaev, S R and Kaul, R and Stamatoyannopoulos, J A},
	date = {2012},
	pmid = {22955828},
	keywords = {Human, {DNA}, Genetic, Genome, Humans, Promoter Regions, Nucleic Acid, Disease, Disease/*genetics, *Genetic Variation, *Polymorphism, *Regulatory Elements, *Regulatory Sequences, Alleles, Chromatin, Chromatin/metabolism/ultrastructure, Crohn Disease/genetics, Deoxyribonuclease I, Deoxyribonuclease I/metabolism, {DNA}/*genetics, Electrocardiography, Fetal Development, Fetus/metabolism, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Multiple Sclerosis/genetics, Phenotype, Single Nucleotide, Transcription Factors, Transcription Factors/chemistry/genetics/*metaboli, Transcriptional, Promoter Regions, Genetic, Genome, Human, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Regulatory Elements, Transcriptional, Multiple Sclerosis, Crohn Disease, Fetus},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/LCZGN2CZ/Maurano et al. - 2012 - Systematic localization of common disease-associat.pdf:application/pdf}
}

@article{aita_visualization_2011,
	title = {A visualization of 3D proteome universe: mapping of a proteome ensemble into 3D space based on the protein-structure composition},
	volume = {61},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21762784},
	doi = {10.1016/j.ympev.2011.06.020},
	abstract = {To visualize a bird's-eye view of an ensemble of proteomes for various species, we recently developed a novel method of mapping a proteome ensemble into Three-Dimensional (3D) vector space. In this study, the "proteome" is defined as the entire set of all proteins encoded in a genome sequence, and these proteins were dealt with at the level of the {SCOP} Fold. First, we represented the proteome of a species s by a 1053-dimensional vector x(s), where its length mid R:x(s)mid R: represents the overall amount of all the {SCOP} Folds in the proteome, and its unit vector x(s)/mid R:x(s)mid R: represents the relative composition of the {SCOP} Folds in the proteome and the size of the dimension, 1053, is the number of all possible Folds in the proteome ensemble given. Second, we mapped the vector x(s) to the 3D vector y(s), based on the two simple principles: (1) mid R:y(s)mid R:=mid R:x(s)mid R:, and (2) the angle between y(s) and y(t) maximally correlates with the angle between x(s) and x(t). We applied to the mapping of a proteome ensemble for 456 species, which were retrieved from the Genomes {TO} Protein structures and functions ({GTOP}) database. As a result, we succeeded in the mapping in that the properties of the 1053-dimensional vectors were quantitatively conserved in the 3D vectors. Particularly, the angles between vectors before and after the mapping highly correlated with each other (correlation coefficients were 0.95-0.96). This new mapping method will allow researchers to intuitively interpret the visual information presented in the maps in a highly effective manner.},
	pages = {484--494},
	number = {2},
	journaltitle = {Mol Phylogenet Evol},
	author = {Aita, T and Nishigaki, K},
	date = {2011},
	pmid = {21762784},
	keywords = {*Models, Molecular, Principal Component Analysis, Protein Conformation, Proteome/*analysis, Proteomics/*methods}
}

@article{cutruzzola_complementarity_1986,
	title = {Complementarity of conserved sequence elements present in 28S ribosomal {RNA} and in ribosomal protein genes of Xenopus laevis and Xenopus tropicalis},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3569921},
	abstract = {The sequence analysis of the L1 ribosomal protein (r-protein) gene of Xenopus laevis has revealed a strong homology in four out of the nine introns of the gene; this homology region spans 60 nucleotides (nt) with 80\% homology [Loreni et al., {EMBO} J. 4 (1985) 3483-3488]. We have extended our analysis to X. tropicalis, a species which is closely related to X. laevis. Partial sequencing of the isolated L1 gene has revealed that these 60-nt homology regions are also present in at least two introns of the X. tropicalis L1 gene. Computer analysis has revealed that perfect nt sequence complementarity exists between 13 nt of this intron region and the 28S ribosomal {RNA} in a region which is conserved in all eukaryotes, suggesting a possible base-pairing interaction between these two sequences.},
	pages = {371--376},
	number = {3},
	journaltitle = {Gene},
	author = {Cutruzzola, F and Loreni, F and Bozzoni, I},
	date = {1986},
	pmid = {3569921},
	keywords = {Animals, Base Sequence, {RNA}, Nucleic Acid, Introns, Biological Evolution, Genes, Nucleic Acid Conformation, Ribosomal Proteins/*genetics, Ribosomal/*genetics, Sequence Homology, Xenopus laevis/*genetics, Xenopus/*genetics}
}

@article{moreno-estrada_african_2010,
	title = {African signatures of recent positive selection in human {FOXI}1},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20809947},
	doi = {10.1186/1471-2148-10-267},
	abstract = {{BACKGROUND}: The human {FOXI}1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene under human-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences. Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans, 20 East Asians and 20 Yorubas and by analysing {SNP} variation in a 2 Mb region centered on {FOXI}1 in 39 worldwide human populations from the {HGDP}-{CEPH} diversity panel. {RESULTS}: The genome sequences recently available from other primate and non-primate species showed that {FOXI}1 divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant in Europeans, East Asians or Yorubas. However, the Long Range Haplotype ({LRH}) test, as well as the {iHS} and {XP}-Rsb statistics revealed significantly extended tracks of homozygosity around {FOXI}1 in Africa, suggesting a recent episode of positive selection acting on this gene. A functionally relevant {SNP}, as well as several {SNPs} either on the putatively selected core haplotypes or with significant {iHS} or {XP}-Rsb values, displayed allele frequencies strongly correlated with the absolute geographical latitude of the populations sampled. {CONCLUSIONS}: We present evidence for recent positive selection in the {FOXI}1 gene region in Africa. Climate might be related to this recent adaptive event in humans. Of the multiple functions of {FOXI}1, its role in kidney-mediated water-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.},
	pages = {267},
	journaltitle = {{BMC} Evol Biol},
	author = {Moreno-Estrada, A and Aparicio-Prat, E and Sikora, M and Engelken, J and Ramirez-Soriano, A and Calafell, F and Bosch, E},
	date = {2010},
	pmid = {20809947},
	keywords = {Humans, Africa, African Continental Ancestry Group/*genetics, Climate Change, Evolution, Forkhead Transcription Factors/*genetics, Gene Frequency/genetics, Genetic/*genetics, Haplotypes, Molecular, Polymorphism, Selection, Single Nucleotide/genetics}
}

@article{buske_triplexator:_2012,
	title = {Triplexator: detecting nucleic acid triple helices in genomic and transcriptomic data},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22550012},
	doi = {10.1101/gr.130237.111},
	abstract = {Double-stranded {DNA} is able to form triple-helical structures by accommodating a third nucleotide strand in its major groove. This sequence-specific process offers a potent mechanism for targeting genomic loci of interest that is of great value for biotechnological and gene-therapeutic applications. It is likely that nature has leveraged this addressing system for gene regulation, because computational studies have uncovered an abundance of putative triplex target sites in various genomes, with enrichment particularly in gene promoters. However, to draw a more complete picture of the in vivo role of triplexes, not only the putative targets but also the sequences acting as the third strand and their capability to pair with the predicted target sites need to be studied. Here we present Triplexator, the first computational framework that integrates all aspects of triplex formation, and showcase its potential by discussing research examples for which the different aspects of triplex formation are important. We find that chromatin-associated {RNAs} have a significantly higher fraction of sequence features able to form triplexes than expected at random, suggesting their involvement in gene regulation. We furthermore identify hundreds of human genes that contain sequence features in their promoter predicted to be able to form a triplex with a target within the same promoter, suggesting the involvement of triplexes in feedback-based gene regulation. With focus on biotechnological applications, we screen mammalian genomes for high-affinity triplex target sites that can be used to target genomic loci specifically and find that triplex formation offers a resolution of ∼1300 nt.},
	pages = {1372--1381},
	number = {7},
	journaltitle = {Genome Res},
	author = {Buske, F A and Bauer, D C and Mattick, J S and Bailey, T L},
	date = {2012},
	pmid = {22550012},
	keywords = {Human, Gene Expression Profiling/*methods, Genomics/*methods, Animals, Genetic, Genome, Humans, Promoter Regions, *Algorithms, Chromatin/chemistry/genetics, Circular Dichroism, Computational Biology/methods, {DNA}/chemistry/genetics, Genetic Loci, Hydrogen Bonding, Nucleic Acid Conformation, Oligonucleotides/*chemistry/genetics, {RNA} Stability, {RNA}-Binding Proteins/*chemistry/genetics, Time Factors}
}

@article{ismail_s6_2013,
	title = {S6 Kinase 2 is bound to chromatin-nuclear matrix cellular fractions and is able to phosphorylate histone H3 at threonine 45 in vitro and in vivo},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23564320},
	doi = {10.1002/jcb.24566},
	abstract = {The activity of S6 kinasesis highly induced in cancer cells highlighting an essential role in carcinogenesis. The S6K family has two members: S6K1 and S6K2 which bear common as well as distinct features. In an attempt to identify S6K2 unique sequence features compared to S6K1, we applied extensive bioinformatic analysis and motif search approaches. Interestingly, we identified a number of protein signatures which are present in proteins directly connected to chromatin and/or involved in transcription regulation including three high mobility group proteins signatures. Using chromatin binding assay, we biochemically showed that S6K2 is bound to chromatin as well as nuclear matrix cellular fractions in {HEK}293 cells. The presence of S6K2 in chromatin fractions raised the possibility that it may be in close proximity to a number of chromatin substrates. For that, we then searched for S6K phosphorylation consensus sites {RXRXXT}/S in mammalian proteins using the {SWISS}-{PROT} database. Interestingly, we identified some potential phosphorylation sites in Histone H3 (Thr45). Using in vitro kinase assays and {siRNA} based knockdown strategy; we confirmed that S6K2 but not S6K1 or {AKT} is essential for histone H3 Thr45 phosphorylation in {HEK}293 cells. Furthermore, we show that the nuclear localisation sequence in the S6K2 c-terminus is essential for this modification. We have found that, H3-Thr45 phosphorylation correlates to S6K activation in response to mitogens and {TPA} induced cell differentiation of leukemic cell lines U937, {HL}60 and {THP}1. Overall, we demonstrate that S6K2 is a novel kinase that can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation. (c) 2013 Wiley Periodicals, Inc.},
	journaltitle = {J Cell Biochem},
	author = {Ismail, H M and Khalil, M and Dawoud, M},
	date = {2013},
	pmid = {23564320}
}

@article{bolstad_probe_2001,
	title = {Probe Level Quantile Normalization of High Density Oligonucleotide Array Data},
	author = {Bolstad, Ben},
	date = {2001}
}

@article{kim_cannabinoids_2012,
	title = {Cannabinoids induce pancreatic beta-cell death by directly inhibiting insulin receptor activation},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22434934},
	doi = {10.1126/scisignal.2002519},
	abstract = {Cannabinoid 1 ({CB}1) receptors have been previously detected in pancreatic beta cells, where they attenuate insulin action. We now report that {CB}1 receptors form a heteromeric complex with insulin receptors and the heterotrimeric guanosine triphosphate-binding protein alpha subunit Galpha(i). Galpha(i) inhibited the kinase activity of the insulin receptor in beta cells by directly binding to the activation loop in the tyrosine kinase domain of the receptor. Consequently, phosphorylation of proapoptotic protein Bad was reduced and its apoptotic activity was stimulated, leading to beta-cell death. Pharmacological blockade or genetic deficiency of {CB}1 receptors enhanced insulin receptor signaling after injury, leading to reduced blood glucose concentrations and activation of Bad, which increased beta-cell survival. These findings provide direct evidence of physical and functional interactions between {CB}1 and insulin receptors and suggest a mechanism whereby peripherally acting {CB}1 receptor antagonists improve insulin action in insulin-sensitive tissues independent of the other metabolic effects of {CB}1 receptors.},
	pages = {ra23},
	number = {216},
	journaltitle = {Sci Signal},
	author = {Kim, W and Lao, Q and Shin, Y K and Carlson, O D and Lee, E K and Gorospe, M and Kulkarni, R N and Egan, J M},
	date = {2012},
	pmid = {22434934},
	keywords = {{DNA}, Animals, Humans, Mice, Cells, Cultured, Analysis of Variance, bcl-Associated Death Protein/metabolism, Blotting, Cannabinoid, Cannabinoids/*pharmacology, Caspase Inhibitors, {CB}1/genetics/*metabolism, Cell Death/*drug effects, Complementary/genetics, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Immunoprecipitation, Inbred C57BL, Insulin-Secreting Cells/*drug effects, Insulin/antagonists \& inhibitors/metabol, Knockout, Real-Time Polymerase Chain Reaction, Receptor, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Western}
}

@article{lipovich_activity-dependent_2012,
	title = {Activity-dependent human brain coding/noncoding gene regulatory networks},
	volume = {192},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22960213},
	doi = {10.1534/genetics.112.145128},
	abstract = {While most gene transcription yields {RNA} transcripts that code for proteins, a sizable proportion of the genome generates {RNA} transcripts that do not code for proteins, but may have important regulatory functions. The brain-derived neurotrophic factor ({BDNF}) gene, a key regulator of neuronal activity, is overlapped by a primate-specific, antisense long noncoding {RNA} ({lncRNA}) called {BDNFOS}. We demonstrate reciprocal patterns of {BDNF} and {BDNFOS} transcription in highly active regions of human neocortex removed as a treatment for intractable seizures. A genome-wide analysis of activity-dependent coding and noncoding human transcription using a custom {lncRNA} microarray identified 1288 differentially expressed {lncRNAs}, of which 26 had expression profiles that matched activity-dependent coding genes and an additional 8 were adjacent to or overlapping with differentially expressed protein-coding genes. The functions of most of these protein-coding partner genes, such as {ARC}, include long-term potentiation, synaptic activity, and memory. The nuclear {lncRNAs} {NEAT}1, {MALAT}1, and {RPPH}1, composing an {RNAse} P-dependent {lncRNA}-maturation pathway, were also upregulated. As a means to replicate human neuronal activity, repeated depolarization of {SY}5Y cells resulted in sustained {CREB} activation and produced an inverse pattern of {BDNF}-{BDNFOS} co-expression that was not achieved with a single depolarization. {RNAi}-mediated knockdown of {BDNFOS} in human {SY}5Y cells increased {BDNF} expression, suggesting that {BDNFOS} directly downregulates {BDNF}. Temporal expression patterns of other {lncRNA}-messenger {RNA} pairs validated the effect of chronic neuronal activity on the transcriptome and implied various {lncRNA} regulatory mechanisms. {lncRNAs}, some of which are unique to primates, thus appear to have potentially important regulatory roles in activity-dependent human brain plasticity.},
	pages = {1133--1148},
	number = {3},
	journaltitle = {Genetics},
	author = {Lipovich, L and Dachet, F and Cai, J and Bagla, S and Balan, K and Jia, H and Loeb, J A},
	date = {2012},
	pmid = {22960213},
	keywords = {Genetic, Humans, {RNA}, Transcription, Untranslated, Gene Expression Regulation, Messenger/genetics, Gene Expression Profiling, *Gene Regulatory Networks, *{RNA}, *Transcriptome, Brain-Derived Neurotrophic Factor/genetics, Brain/*metabolism, Cell Line, Long Untranslated/genetics}
}

@article{johnson_draft_2015,
	title = {A draft map of tranposon-derived domains of long non-coding {RNA}: evidence for roles in protein binding and subcellular localisation.},
	journaltitle = {In Preparation},
	author = {Johnson, R and Guigo, R},
	date = {2015}
}

@article{nesterets_soft_2008,
	title = {Soft tissue small avascular tumor imaging with x-ray phase-contrast micro-{CT} in-line holography},
	volume = {6913},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20052303},
	doi = {10.1117/12.772761},
	abstract = {To assess the feasibility of small soft tissue avascular tumor micro-{CT} imaging with x-ray phase-contrast in-line holography, we have studied micro-{CT} imaging with in-line geometry of small spheroidal avascular tumor models with quiescent cell core ({\textbackslash}textless 250 mum) and various distributions of the proliferating cell density ({PCD}) forming the outer shell. We have simulated imaging with an ultrafast laser-based x-ray source with a Mo target. We observe phase-contrast enhancement of the tumor boundaries in the reconstructed transaxial images, resulting in improved detection of small soft tissue tumors, providing that the {PCD} density gradient is sufficiently large.},
	pages = {69133z},
	journaltitle = {Proc Soc Photo Opt Instrum Eng},
	author = {Nesterets, Y and Gureyev, T and Stevenson, A and Pogany, A and Wilkins, S and Kincaid, R and Ye, H and Vogelsang, L and Lipson, E and Coman, I and Fourmaux, S and Kieffer, J C and Krol, A},
	date = {2008},
	pmid = {20052303}
}

@article{prislei_self-cleaving_1995,
	title = {Self-cleaving motifs are found in close proximity to the sites utilized for U16 {snoRNA} processing},
	volume = {163},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7590270},
	abstract = {A class of small nucleolar {RNAs} ({snoRNAs}) is encoded in introns of protein-coding genes. The U16 {snoRNA} belongs to this class; it is encoded in the third intron of the Xenopus laevis (Xl) L1 ribosomal protein encoding gene and is released from the pre-{mRNA} by processing both in vivo and in vitro systems. In this paper, we show that in close proximity to the U16 {snoRNA} processing sites, sequences displaying self-cleaving activity are present. These elements are conserved in the two copies of the Xl L1 and in the single copy of the X. tropicalis L1. The catalytic activity corresponds to that already described for the minimal hairpin ribozyme [Dange et al., Science 242 (1990) 585-588]; it is Mn(2+)-dependent, produces 2'-3' cyclic phosphate and 5'-{OH} termini and comprises an essential {GAAA} element. Here we show that the 2'-{OH} group of the G residue is essential for catalysis.},
	pages = {221--226},
	number = {2},
	journaltitle = {Gene},
	author = {Prislei, S and Fatica, A and De Gregorio, E and Arese, M and Fragapane, P and Caffarelli, E and Presutti, C and Bozzoni, I},
	date = {1995},
	pmid = {7590270},
	keywords = {Animals, Base Sequence, {RNA}, Catalytic/*genetics, Chromosome Mapping, {DNA} Transposable Elements/genetics, Gene Deletion, Molecular Sequence Data, Xenopus/*genetics}
}

@article{dong_modeling_2012,
	title = {Modeling gene expression using chromatin features in various cellular contexts},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22950368},
	doi = {10.1186/gb-2012-13-9-r53},
	abstract = {{BACKGROUND}: Previous work has demonstrated that chromatin feature levels correlate with gene expression. The {ENCODE} project enables us to further explore this relationship using an unprecedented volume of data. Expression levels from more than 100,000 promoters were measured using a variety of high-throughput techniques applied to {RNA} extracted by different protocols from different cellular compartments of several human cell lines. {ENCODE} also generated the genome-wide mapping of eleven histone marks, one histone variant, and {DNase} I hypersensitivity sites in seven cell lines. {RESULTS}: We built a novel quantitative model to study the relationship between chromatin features and expression levels. Our study not only confirms that the general relationships found in previous studies hold across various cell lines, but also makes new suggestions about the relationship between chromatin features and gene expression levels. We found that expression status and expression levels can be predicted by different groups of chromatin features, both with high accuracy. We also found that expression levels measured by {CAGE} are better predicted than by {RNA}-{PET} or {RNA}-Seq, and different categories of chromatin features are the most predictive of expression for different {RNA} measurement methods. Additionally, {PolyA}+ {RNA} is overall more predictable than {PolyA}- {RNA} among different cell compartments, and {PolyA}+ cytosolic {RNA} measured with {RNA}-Seq is more predictable than {PolyA}+ nuclear {RNA}, while the opposite is true for {PolyA}- {RNA}. {CONCLUSIONS}: Our study provides new insights into transcriptional regulation by analyzing chromatin features in different cellular contexts.},
	pages = {R53},
	number = {9},
	journaltitle = {Genome Biol},
	author = {Dong, X and Greven, M C and Kundaje, A and Djebali, S and Brown, J B and Cheng, C and Gingeras, T R and Gerstein, M and Guigo, R and Birney, E and Weng, Z},
	date = {2012},
	pmid = {22950368},
	keywords = {Human, Genetic, Humans, {RNA}, *Genome, *Transcription, Organ Specificity, *Models, Chromatin/*chemistry/metabolism, Histones/genetics/metabolism, Messenger/chemistry/metabolism, Poly A/metabolism, Statistical}
}

@article{cunningham_theoretical_2006,
	title = {Theoretical proposal: allele dosage of {MAP}2K4/{MKK}4 could rationalize frequent 17p loss in diverse human cancers},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16721048},
	abstract = {Although aneuploidy is a global genomic abnormality present in most human cancers, the clonal selection model best explains the action of select activating mutations in oncogenes and homozygous losses of tumor-suppressor genes. Simple gene dosage changes are difficult however, to incorporate into this model, in part due to negative feedback loops that govern major cancer mutational targets (e.g., {TP}53, {PTCH}, {SMAD}4) and essentially preclude a haploinsufficient phenotype. The 17p conundrum may offer a clue to reconciling this difficulty: In comparison to the moderate mutation rate of {TP}53, many tumors have a disproportionately high frequency of loss of 17p. This discrepancy, and similar discrepancies at other sites of {LOH}, has long been thought to be due to the presence of undiscovered yet frequently mutated tumor-suppressor genes. However, over 15 years of searching for this grail has distributed bountiful disappointment. It is perhaps time to seriously consider an alternative explanation. Located on 17p adjacent to the {TP}53 gene, {MKK}4 is one of the most consistently mutated genes across tumor types, and is located on one of the most frequently lost arms in the human genome. We theorized that a gene dosage-dependent phenotype of {MKK}4 could plausibly promote the emergence of 17p {LOH} and thereby the probability of evolving the biallelic inactivation of {TP}53. Using {MKK}4 somatic human knockout cancer cells, we observed the proof-of-principle in the downstream gene dosage-dependent phenotypes: heterozygous and homozygous knockouts were progressively deficient in Mkk4 protein, in stress-induced phosphorylation of Jnk, and the resultant upregulation of {JUN} {mRNA}. These observations highlight a lack of compensatory regulation when gene dosage changes perturb the Jnk-Jun relationship. Consideration of gene dosage changes specifically affecting members of positive feedback loops may permit integration of the aneuploidy process into a conventional model of clonal selection in tumorigenesis.},
	pages = {1090--1093},
	number = {10},
	journaltitle = {Cell Cycle},
	author = {Cunningham, S C and Gallmeier, E and Hucl, T and Dezentje, D A and Abdelmohsen, K and Gorospe, M and Kern, S E},
	date = {2006},
	pmid = {16721048},
	keywords = {Human, Genetic, Humans, *Chromosomes, *Gene Expression Regulation, *Models, Cell Line, Cell Transformation, Gene Dosage, Gene Silencing, Loss of Heterozygosity, {MAP} Kinase Kinase 4/*genetics/metabolism, Neoplasms/*genetics, Neoplastic, Neoplastic/genetics, Pair 17, Tumor, Tumor Suppressor Protein p53/genetics}
}

@article{lal_mir-24_2009,
	title = {{miR}-24 Inhibits cell proliferation by targeting E2F2, {MYC}, and other cell-cycle genes via binding to "seedless" 3'{UTR} {microRNA} recognition elements},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19748357},
	doi = {10.1016/j.molcel.2009.08.020},
	abstract = {{miR}-24, upregulated during terminal differentiation of multiple lineages, inhibits cell-cycle progression. Antagonizing {miR}-24 restores postmitotic cell proliferation and enhances fibroblast proliferation, whereas overexpressing {miR}-24 increases the G1 compartment. The 248 {mRNAs} downregulated upon {miR}-24 overexpression are highly enriched for {DNA} repair and cell-cycle regulatory genes that form a direct interaction network with prominent nodes at genes that enhance ({MYC}, E2F2, {CCNB}1, and {CDC}2) or inhibit (p27Kip1 and {VHL}) cell-cycle progression. {miR}-24 directly regulates {MYC} and E2F2 and some genes that they transactivate. Enhanced proliferation from antagonizing {miR}-24 is abrogated by knocking down E2F2, but not {MYC}, and cell proliferation, inhibited by {miR}-24 overexpression, is rescued by {miR}-24-insensitive E2F2. Therefore, E2F2 is a critical {miR}-24 target. The E2F2 3'{UTR} lacks a predicted {miR}-24 recognition element. In fact, {miR}-24 regulates expression of E2F2, {MYC}, {AURKB}, {CCNA}2, {CDC}2, {CDK}4, and {FEN}1 by recognizing seedless but highly complementary sequences.},
	pages = {610--625},
	number = {5},
	journaltitle = {Mol Cell},
	author = {Lal, A and Navarro, F and Maher, C A and Maliszewski, L E and Yan, N and O'Day, E and Chowdhury, D and Dykxhoorn, D M and Tsai, P and Hofmann, O and Becker, K G and Gorospe, M and Hide, W and Lieberman, J},
	date = {2009},
	pmid = {19748357},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, Binding Sites, Databases, Nucleic Acid, *3' Untranslated Regions, *Cell Proliferation, *Genes, *Regulatory Sequences, cdc, Cell Cycle/*genetics, Cell Differentiation/genetics, {DNA} Repair, Down-Regulation, E2F2 Transcription Factor/*genetics, Erythrocytes/metabolism, Fibroblasts/metabolism, Gene Regulatory Networks, {HL}-60 Cells, K562 Cells, Macrophages/metabolism, Megakaryocytes/metabolism, Messenger/metabolism, {MicroRNAs}/*metabolism, Molecular Sequence Data, Proto-Oncogene Proteins c-myc/*genetics, {RNA} Interference, Transcriptional Activation}
}

@article{subramanian_syntheses_2013,
	title = {Syntheses of deuterium labeled prenyldiphosphate and prenylcysteine analogues for in vivo mass spectrometric quantification},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24285475},
	doi = {10.1002/jlcr.3049},
	abstract = {A Wittig reaction employing Li({CD}3)2CP(C6H5)3 was used to prepare d6-farnesol and d6-geranylgeraniol. Reductive amination of aniline-2,3,4,5,6-d5 was used to prepare the unnatural isoprenoid analogues d5-anilinogeraniol and d5-anilinofarnesol. All of these deuterated isoprenols were elaborated into their diphosphate and cysteine thioether derivatives suitable for use as stable-isotope labeled standards for quantitative mass spectrometric analysis.},
	pages = {370--375},
	number = {8},
	journaltitle = {J Labelled Comp Radiopharm},
	author = {Subramanian, T and Subramanian, K L and Sunkara, M and Onono, F O and Morris, A J and Spielmann, H P},
	date = {2013},
	pmid = {24285475}
}

@article{ulitsky_conserved_2011,
	title = {Conserved function of {lincRNAs} in vertebrate embryonic development despite rapid sequence evolution},
	volume = {147},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22196729},
	doi = {10.1016/j.cell.2011.11.055},
	abstract = {Thousands of long intervening noncoding {RNAs} ({lincRNAs}) have been identified in mammals. To better understand the evolution and functions of these enigmatic {RNAs}, we used chromatin marks, poly(A)-site mapping and {RNA}-Seq data to identify more than 550 distinct {lincRNAs} in zebrafish. Although these shared many characteristics with mammalian {lincRNAs}, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other {lincRNAs} had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish {lincRNAs} caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature {lincRNA} or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of {lincRNAs} in model organisms and shows that {lincRNAs} play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.},
	pages = {1537--1550},
	number = {7},
	journaltitle = {Cell},
	author = {Ulitsky, I and Shkumatava, A and Jan, C H and Sive, H and Bartel, D P},
	date = {2011},
	pmid = {22196729},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Regulation, *Embryonic Development, *Evolution, Developmental, Embryonic Development, Molecular, Untranslated/*genetics/*metabolism, Vertebrates, Vertebrates/embryology/genetics, Zebrafish, Zebrafish/*embryology/*genetics, Evolution, Molecular, {RNA}, Untranslated, Gene Expression Regulation, Developmental},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/4GF6AYHJ/Ulitsky et al. - 2011 - Conserved function of lincRNAs in vertebrate embry.pdf:application/pdf}
}

@article{gutschner_noncoding_2013,
	title = {The noncoding {RNA} {MALAT}1 is a critical regulator of the metastasis phenotype of lung cancer cells},
	volume = {73},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23243023},
	doi = {10.1158/0008-5472.CAN-12-2850},
	abstract = {The long noncoding {RNA} {MALAT}1 (metastasis-associated lung adenocarcinoma transcript 1), also known as {MALAT}-1 or {NEAT}2 (nuclear-enriched abundant transcript 2), is a highly conserved nuclear noncoding {RNA} ({ncRNA}) and a predictive marker for metastasis development in lung cancer. To uncover its functional importance, we developed a {MALAT}1 knockout model in human lung tumor cells by genomically integrating {RNA} destabilizing elements using zinc finger nucleases. The achieved 1,000-fold {MALAT}1 silencing provides a unique loss-of-function model. Proposed mechanisms of action include regulation of splicing or gene expression. In lung cancer, {MALAT}1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes. Consequently, {MALAT}1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft. Antisense oligonucleotides ({ASO}) blocking {MALAT}1 prevent metastasis formation after tumor implantation. Thus, targeting {MALAT}1 with {ASOs} provides a potential therapeutic approach to prevent lung cancer metastasis with this {ncRNA} serving as both predictive marker and therapeutic target. Finally, regulating gene expression, but not alternative splicing, is the critical function of {MALAT}1 in lung cancer metastasis. In summary, 10 years after the discovery of the {lncRNA} {MALAT}1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of {MALAT}1 as a regulator of gene expression governing hallmarks of lung cancer metastasis.},
	pages = {1180--1189},
	number = {3},
	journaltitle = {Cancer Res},
	author = {Gutschner, T and Hammerle, M and Eissmann, M and Hsu, J and Kim, Y and Hung, G and Revenko, A and Arun, G and Stentrup, M and Gross, M and Zornig, M and {MacLeod}, A R and Spector, D L and Diederichs, S},
	date = {2013},
	pmid = {23243023},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Regulation, Alternative Splicing, Antisense/pharmacology, Cell Line, Cell Movement, Inbred {BALB} C, Long Noncoding/antagonists \& inhibitors/*phys, Lung Neoplasms, Lung Neoplasms/*secondary, Neoplasm Metastasis, Oligonucleotides, Phenotype, Tumor, {RNA}, Long Noncoding, Cell Line, Tumor, Oligonucleotides, Antisense, Mice, Inbred {BALB} C},
	file = {Full Text:/home/jlagarde/Zotero/storage/QS33JEPK/Gutschner et al. - 2013 - The noncoding RNA MALAT1 is a critical regulator o.pdf:application/pdf}
}

@article{abujamel_defining_2013,
	title = {Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24098459},
	doi = {10.1371/journal.pone.0076269},
	abstract = {{BACKGROUND}: Clostridium difficile is an anaerobic, spore-forming bacterium that is the most common cause of healthcare-associated diarrhea in developed countries. A significant proportion of patients receiving oral vancomycin or metronidazole for treatment of Clostridium difficile infection ({CDI}) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined. {PRINCIPAL} {FINDINGS}: In a prospective study of {CDI} patients, we demonstrated that most vancomycin-treated patients maintained inhibitory concentrations of vancomycin in stool for 4 to 5 days after therapy, whereas metronidazole was only detectable during therapy. From the time of elimination of the antibiotics to 14 to 21 days after therapy, a majority of stool suspensions supported growth of C. difficile and deep 16S {rRNA} sequencing demonstrated persistent marked alteration of the indigenous microbiota. By 21 to 28 days after completion of {CDI} treatment, a majority of stool suspensions inhibited growth of C. difficile and there was evidence of some recovery of the microbiota. {CONCLUSIONS}: These data demonstrate that there is a vulnerable period for re-establishment of C. difficile colonization after {CDI} treatment that begins within a few days after discontinuation of treatment and extends for about 3 weeks in most patients.},
	pages = {e76269},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Abujamel, T and Cadnum, J L and Jury, L A and Sunkesula, V C and Kundrapu, S and Jump, R L and Stintzi, A C and Donskey, C J},
	date = {2013},
	pmid = {24098459}
}

@article{ramirez_microrna_2013,
	title = {{MicroRNA} 33 regulates glucose metabolism},
	volume = {33},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23716591},
	doi = {10.1128/MCB.00016-13},
	abstract = {Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding {RNAs} ({microRNAs} [{miRNAs}]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that {miR}-33a and {miR}33b, intronic {miRNAs} located within the sterol regulatory element-binding protein ({SREBP}) genes, regulate lipid metabolism in concert with their host genes. Here, we show that {miR}-33b also cooperates with {SREBP}1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase ({PCK}1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of {miR}-33b in human hepatic cells inhibits {PCK}1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic {SREBP}1c/{miR}-33b levels correlate inversely with the expression of {PCK}1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that {miR}-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of {miR}-33a/b as novel therapeutic targets for a range of metabolic diseases.},
	pages = {2891--2902},
	number = {15},
	journaltitle = {Mol Cell Biol},
	author = {Ramirez, C M and Goedeke, L and Rotllan, N and Yoon, J H and Cirera-Salinas, D and Mattison, J A and Suarez, Y and de Cabo, R and Gorospe, M and Fernandez-Hernando, C},
	date = {2013},
	pmid = {23716591},
	keywords = {Animals, Humans, *Gene Expression Regulation, Gluconeogenesis, Glucose-6-Phosphatase/genetics/*metabolism, Glucose/genetics/*metabolism, Glycogen/metabolism, Hep G2 Cells, Hepatocytes/metabolism, Intracellular Signaling Peptides and Proteins/gene, Macaca mulatta, Male, {MicroRNAs}/genetics/*metabolism, Phosphoenolpyruvate Carboxykinase ({GTP})/genetics/*, Sterol Regulatory Element Binding Protein 1/geneti}
}

@article{figueroa_hacking_2009,
	title = {Hacking {RNA}: Hakai promotes tumorigenesis by enhancing the {RNA}-binding function of {PSF}},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19855157},
	abstract = {Hakai, an E3 ubiquitin ligase for the E-cadherin complex, plays a crucial role in lowering cell-cell contacts in epithelial cells, a hallmark feature of tumor progression. Recently, Hakai was also found to interact with {PSF} ({PTB}-associated splicing factor). While {PSF} can function as a {DNA}-binding protein with a tumor suppressive function, its association with Hakai promotes {PSF}'s {RNA}-binding ability and post-transcriptional influence on target {mRNAs}. Hakai overexpression enhanced the binding of {PSF} to {mRNAs} encoding cancer-related proteins, while knockdown of Hakai reduced the {RNA}-binding ability of {PSF}. Furthermore, the knockdown of {PSF} suppressed Hakai-induced cell proliferation. Thus, Hakai can affect the oncogenic phenotype both by altering E-cadherin-based intercellular adhesions and by increasing {PSF}'s ability to bind {RNAs} that promote cancer-related gene expression.},
	pages = {3648--3651},
	number = {22},
	journaltitle = {Cell Cycle},
	author = {Figueroa, A and Fujita, Y and Gorospe, M},
	date = {2009},
	pmid = {19855157},
	keywords = {Humans, {RNA}, Protein Binding, *Cell Proliferation, Biological, Cadherins/*metabolism, Messenger/metabolism/*physiology, Models, Neoplasms/*genetics, Oncogene Proteins/metabolism/*physiology, {RNA}-Binding Proteins/*metabolism, Ubiquitin-Protein Ligases/metabolism/*physiology}
}

@article{van_huizen_p58ipk_2003,
	title = {P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of {eIF}2alpha signaling},
	volume = {278},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12601012},
	doi = {10.1074/jbc.M212074200},
	abstract = {The unfolded protein response, which is activated in response to the loss of endoplasmic reticulum ({ER}) Ca(2+) homeostasis and/or the accumulation of misfolded, unassembled, or aggregated proteins in the {ER} lumen, involves both transcriptional and translational regulation. In the current studies we sought to identify novel {ER} stress-induced genes by conducting microarray analysis on tunicamycin-treated cells. We identified P58({IPK}), an inhibitor of the interferon-induced double-stranded {RNA}-activated protein kinase, as induced during {ER} stress. Additional studies suggested that p58({IPK}) induction was mediated via {ATF}6 and that P58({IPK}) played a role in down-regulating the activity of the pancreatic {eIF}2 kinase/eukaryotic initiation factor 2alpha ({eIF}2alpha)-like {ER} kinase/activation transcription factor ({ATF}) 4 pathway. Modulation of P58({IPK}) levels altered the phosphorylation status of {eIF}2alpha, and thereby affected expression of its downstream targets, {ATF}4 and Gadd153. Overexpression of P58({IPK}) inhibited {eIF}2alpha phosphorylation and reduced {ATF}4 and Gadd153 protein accumulation, whereas silencing of P58({IPK}) expression enhanced pancreatic {eIF}2alpha-like {ER} kinase and {eIF}2alpha phosphorylation and increased {ATF}4 and Gadd153 accumulation. These findings implicate P58({IPK}) as an important component of a negative feedback loop used by the cell to inhibit {eIF}2alpha signaling, and thus attenuate the unfolded protein response.},
	pages = {15558--15564},
	number = {18},
	journaltitle = {J Biol Chem},
	author = {van Huizen, R and Martindale, J L and Gorospe, M and Holbrook, N J},
	date = {2003},
	pmid = {12601012},
	keywords = {Humans, {RNA}, Oligonucleotide Array Sequence Analysis, Activating Transcription Factor 6, Apoptosis, {CCAAT}-Enhancer-Binding Proteins/biosynthesis, {DNA}-Binding Proteins/physiology, {eIF}-2 Kinase/metabolism, Endoplasmic Reticulum/metabolism, Eukaryotic Initiation Factor-2/*physiology, Gene Silencing, {HSP}40 Heat-Shock Proteins, Phosphorylation, Protein Folding, Repressor Proteins/genetics/*physiology, Small Interfering, Transcription Factor {CHOP}, Transcription Factors/biosynthesis/physiology}
}

@article{sharma_quercetin_2013,
	title = {Quercetin protects against chronic aluminum-induced oxidative stress and ensuing biochemical, cholinergic, and neurobehavioral impairments in rats},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22918785},
	doi = {10.1007/s12640-012-9351-6},
	abstract = {In this study, we investigated the protective effect of chronic quercetin (a natural flavanoid) administration against Al-induced cognitive impairments, oxidative damage, and cholinergic dysfunction in male Wistar rats. Al lactate (10 mg/kg b.wt./day) was administered intragastrically to rats which were pre-treated with quercetin (10 mg/kg b.wt./day, intragastrically) for 12 weeks. At the end of 6 or 12 weeks of the study, several behavioral parameters were carried out to evaluate cognitive functions. Further after 12 weeks of exposure, various biochemical tests and H\&E staining were performed to assess the extent of oxidative damage and neurodegeneration, respectively. Al levels were also estimated in {HC} and {CS} regions of rat brain. Chronic administration of quercetin caused significant improvement in the muscle coordination, cognition, anxiety, locomotion, and initial exploratory patterns in Al-treated rats. Quercetin supplementation to Al-treated animals also reduced oxidative stress, decreased {ROS} production, increased {MnSOD} activity and glutathione levels with decreased lipid peroxidation and protein oxidation. It increased {AChE} activity and {ATP} levels in {HC} and {CS} regions of rat brain compared to Al-treated rats. Quercetin administration ameliorates Al-induced neurodegenerative changes in Al-treated rats as seen by H\&E staining. Further with the help of atomic absorption spectrophotometer, we found that quercetin supplementation to Al-treated rats also decreases the accumulation of Al in the {HC} and {CS} regions of rat brain. Taken together the results of this study show that quercetin offers neuroprotection against Al-induced cognitive impairments, cholinergic dysfunction, and associated oxidative damage in rats.},
	pages = {336--357},
	number = {4},
	journaltitle = {Neurotox Res},
	author = {Sharma, D R and Wani, W Y and Sunkaria, A and Kandimalla, R J and Verma, D and Cameotra, S S and Gill, K D},
	date = {2013},
	pmid = {22918785},
	keywords = {Animals, Aluminum/*toxicity, Cholinergic Neurons/drug effects/*metabolism, Cognition Disorders/*metabolism/prevention \& contr, Male, Maze Learning/drug effects/physiology, Neuroprotective Agents/*pharmacology/therapeutic u, Oxidative Stress/drug effects/*physiology, Quercetin/*pharmacology/therapeutic use, Rats, Reactive Oxygen Species/metabolism, Wistar}
}

@article{chari_unraveling_2015,
	title = {Unraveling {CRISPR}-Cas9 genome engineering parameters via a library-on-library approach},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26167643},
	doi = {10.1038/nmeth.3473},
	abstract = {We developed an in vivo library-on-library methodology to simultaneously assess single guide {RNA} ({sgRNA}) activity across approximately 1,400 genomic loci. Assaying across multiple human cell types and end-processing enzymes as well as two Cas9 orthologs, we unraveled underlying nucleotide sequence and epigenetic parameters. Our results and software (http://crispr.med.harvard.edu/{sgRNAScorer}) enable improved design of reagents, shed light on mechanisms of genome targeting, and provide a generalizable framework to study nucleic acid-nucleic acid interactions and biochemistry in high throughput.},
	pages = {823--826},
	number = {9},
	journaltitle = {Nat Methods},
	author = {Chari, R and Mali, P and Moosburner, M and Church, G M},
	date = {2015},
	pmid = {26167643}
}

@article{khatun_whole_2013,
	title = {Whole human genome proteogenomic mapping for {ENCODE} cell line data: identifying protein-coding regions},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23448259},
	doi = {10.1186/1471-2164-14-141},
	abstract = {{BACKGROUND}: Proteogenomic mapping is an approach that uses mass spectrometry data from proteins to directly map protein-coding genes and could aid in locating translational regions in the human genome. In concert with the {ENcyclopedia} of {DNA} Elements ({ENCODE}) project, we applied proteogenomic mapping to produce proteogenomic tracks for the {UCSC} Genome Browser, to explore which putative translational regions may be missing from the human genome. {RESULTS}: We generated ∼1 million high-resolution tandem mass ({MS}/{MS}) spectra for Tier 1 {ENCODE} cell lines K562 and {GM}12878 and mapped them against the {UCSC} hg19 human genome, and the {GENCODE} V7 annotated protein and transcript sets. We then compared the results from the three searches to identify the best-matching peptide for each {MS}/{MS} spectrum, thereby increasing the confidence of the putative new protein-coding regions found via the whole genome search. At a 1\% false discovery rate, we identified 26,472, 24,406, and 13,128 peptides from the protein, transcript, and whole genome searches, respectively; of these, 481 were found solely via the whole genome search. The proteogenomic mapping data are available on the {UCSC} Genome Browser at http://genome.ucsc.edu/cgi-bin/{hgTrackUi}?db=hg19\&g={wgEncodeUncBsuProt}. {CONCLUSIONS}: The whole genome search revealed that ∼4\% of the uniquely mapping identified peptides were located outside {GENCODE} V7 annotated exons. The comparison of the results from the disparate searches also identified 15\% more spectra than would have been found solely from a protein database search. Therefore, whole genome proteogenomic mapping is a complementary method for genome annotation when performed in conjunction with other searches.},
	pages = {141},
	journaltitle = {{BMC} Genomics},
	author = {Khatun, J and Yu, Y and Wrobel, J A and Risk, B A and Gunawardena, H P and Secrest, A and Spitzer, W J and Xie, L and Wang, L and Chen, X and Giddings, M C},
	date = {2013},
	pmid = {23448259},
	keywords = {Human, {DNA}, Sequence Analysis, Genetic, Humans, *Genome, Computational Biology, *Databases, *Molecular Sequence Annotation, Cell Line, Chromosome Mapping, Mass Spectrometry, Open Reading Frames/*genetics}
}

@article{haug_inflammatory_2003,
	title = {Inflammatory aortic aneurysm is associated with increased incidence of autoimmune disease},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12947264},
	abstract = {{OBJECTIVE}: It has been suggested that certain genetic risk factors indicative of an autoimmune mechanism can be identified in patients with inflammatory aortic aneurysm ({IAA}). We therefore investigated whether there was a higher incidence of autoimmune diseases in patients with {IAA}. Further, we explored risk factors, need for in-hospital resources, and early results of treatment, in a case-control study in a university hospital setting. Material and methods From 1983 to 1994, 520 patients were operated because of abdominal aortic aneurysm ({AAA}). Thirty-one patients had {IAA}. Control subjects were matched for aneurysm rupture, emergency or elective hospital admission, and date of operation. Two noninflammatory {AAA} were included for every {IAA}. {RESULTS}: Of the 31 patients with {IAA}, 6 patients (19\%) had autoimmune disease, compared with none of the control subjects (P =.0017). Two patients had rheumatoid arthritis, 2 patients had systemic lupus erythematosus, 1 had giant cell arteritis, and 1 patient had an undifferentiated seronegative polyarthritis diagnosed as rheumatoid arthritis. Nineteen patients (61\%) with {IAA} had involvement of the duodenum, and 8 patients (26\%) had hydronephrosis with ureteral involvement. Operating time was longer in the {IAA} group, which also had a higher need for blood transfusion. Hospital stay, intensive care unit stay, and 30-day mortality were similar in the two groups. {CONCLUSION}: Except for longer operating time and more need for blood transfusions in the {IAA} group, use of hospital resources was similar after operations to treat {IAA} or noninflammatory {AAA}. The study findings indicate an association between {IAA} and autoimmune disease. This is in accordance with other reports that showed a genetic risk determinant mapped to the human leukocyte antigen ({HLA}) molecule in these patients. Further research is necessary to explore whether {IAA} might be a separate entity with a role of antigen binding in the origin of the disease.},
	pages = {492--497},
	number = {3},
	journaltitle = {J Vasc Surg},
	author = {Haug, E S and Skomsvoll, J F and Jacobsen, G and Halvorsen, T B and Saether, O D and Myhre, H O},
	date = {2003},
	pmid = {12947264},
	keywords = {Humans, 80 and over, Abdominal/*epidemiology/*patholog, Age Distribution, Aged, Aneurysm, Aortic Aneurysm, Autoimmune Diseases/diagnosis/*epidemiology, Case-Control Studies, Comorbidity, Female, Incidence, Infected/*epidemiology/*pathology/surger, Male, Middle Aged, Nonparametric, Norway/epidemiology, Probability, Retrospective Studies, Risk Factors, Severity of Illness Index, Sex Distribution, Statistics, Survival Analysis, Vascular Surgical Procedures}
}

@article{i_jungreis_codalignview:_nodate,
	title = {{CodAlignView}: a tool for visualizing protein-coding constraint},
	journaltitle = {In Preparation},
	author = {{I Jungreis} and {M Lin} and Kellis, M}
}

@article{srikantan_senescence-associated_2011,
	title = {Senescence-associated {microRNAs} linked to tumorigenesis},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21941082},
	doi = {10.4161/cc.10.19.17050},
	pages = {3211--3212},
	number = {19},
	journaltitle = {Cell Cycle},
	author = {Srikantan, S and Gorospe, M and Abdelmohsen, K},
	date = {2011},
	pmid = {21941082},
	keywords = {Humans, *Cell Aging, Cell Transformation, {DNA} Damage, Gene Silencing, {MicroRNAs}/*metabolism, Neoplastic}
}

@article{seshadri_natural_2013,
	title = {Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24285824},
	doi = {10.1093/humupd/dmt056},
	abstract = {{INTRODUCTIONEmbryo} implantation is a complex process involving maternal hormonal changes, immune responses and maturational events in the embryo. A pregnancy could fail when these events are not synchronized. It is speculated that in women, an elevation of natural killer ({NK}) cells may have an effect on reproductive performance, and {NK} cell levels in blood are currently being used as a diagnostic test to guide the initiation of therapies in patients with infertility.{METHODSWe} conducted a systematic review to evaluate the (i) levels of {NK} cells in blood and endometrium in infertile versus fertile women, (ii) association between {NK} cells and {IVF} outcome, (iii) levels of {NK} cells in blood and endometrium in women with recurrent miscarriage ({RM}) versus controls. The following electronic databases were searched: Medline, {EMBASE}, Cochrane Library, Web of Science and National Research Register.{RESULTSA} total of 22 studies were included. Meta-analysis of studies that evaluated peripheral and uterine {NK} ({uNK}) cell percentages in infertile versus fertile women showed no significant difference between the two groups [standardized mean difference ({SMD}) -0.33; 95\% confidence intervals ({CI}) -1.06, 0.4; P = 0.37; {SMD} -1.82; 95\% {CI} -4.80, 1.17; P = 0.23 respectively]. Pooling of studies that reported peripheral {NK} cells as numbers showed significantly higher {NK} cell numbers in infertile women compared with fertile controls ({SMD} 3.16; 95\% {CI} 1.07, 5.24; P = 0.003). Meta-analysis of studies that evaluated the role of {NK} cells in {IVF} outcome showed no significant difference in live birth rates in women with elevated {NK} cells or {NK} cell activity compared with women without elevated peripheral {NK} cells or {NK} cell activity ({NK} activity assessed using a cytotoxicity assay) (relative risk 0.57; 95\% {CI} 0.06, 5.22; P = 0.62). Meta-analysis of studies that evaluated peripheral {NK} cell percentages in women with {RM} versus controls showed significantly higher {NK} cell percentages in women with {RM} ({SMD} 1.36; 95\% {CI} 0.04, 2.69; P = 0.04). Meta-analysis of studies that evaluated peripheral {NK} cell numbers showed significantly higher {NK} cell numbers in women with {RM} compared with controls ({SMD} 0.81; 95\% {CI} 0.47, 1.16; P {\textbackslash}textless 0.00001). Meta-analysis of studies that evaluated {uNK} cells showed no significant difference in women with {RM} compared with controls ({SMD} 0.40; 95\% {CI} -1.24, 2.04; P = 0.63).{CONCLUSIONSFurther} research is needed before {NK} cell assessment can be recommended as a diagnostic tool in the context of female infertility or {RM}. There is no clear explanation as to why the results differ when data for {NK} cells are expressed as numbers or a percentage. On the basis of current evidence, {NK} cell analysis and immune therapy should be offered only in the context of clinical research.},
	journaltitle = {Hum Reprod Update},
	author = {Seshadri, S and Sunkara, S K},
	date = {2013},
	pmid = {24285824}
}

@article{kruman_ii_cell_2004,
	title = {Cell cycle activation linked to neuronal cell death initiated by {DNA} damage},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14980204},
	abstract = {Increasing evidence indicates that neurodegeneration involves the activation of the cell cycle machinery in postmitotic neurons. However, the purpose of these cell cycle-associated events in neuronal apoptosis remains unknown. Here we tested the hypothesis that cell cycle activation is a critical component of the {DNA} damage response in postmitotic neurons. Different genotoxic compounds (etoposide, methotrexate, and homocysteine) induced apoptosis accompanied by cell cycle reentry of terminally differentiated cortical neurons. In contrast, apoptosis initiated by stimuli that do not target {DNA} (staurosporine and colchicine) did not initiate cell cycle activation. Suppression of the function of ataxia telangiectasia mutated ({ATM}), a proximal component of {DNA} damage-induced cell cycle checkpoint pathways, attenuated both apoptosis and cell cycle reentry triggered by {DNA} damage but did not change the fate of neurons exposed to staurosporine and colchicine. Our data suggest that cell cycle activation is a critical element of the {DNA} damage response of postmitotic neurons leading to apoptosis.},
	pages = {549--561},
	number = {4},
	journaltitle = {Neuron},
	author = {{Kruman II} and Wersto, R P and Cardozo-Pelaez, F and Smilenov, L and Chan, S L and Chrest, F J and Emokpae Jr., R and Gorospe, M and Mattson, M P},
	date = {2004},
	pmid = {14980204},
	keywords = {Animals, Mice, Cells, Cultured, Apoptosis/drug effects/*genetics, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Cell Cycle/drug effects/*genetics, Colchicine/pharmacology, {DNA} Damage/drug effects/*genetics, {DNA}-Binding Proteins, Etoposide/pharmacology, Female, Homocysteine/pharmacology, Male, Methotrexate/pharmacology, Nerve Degeneration/*genetics/metabolism, Neurons/drug effects/*metabolism, Protein-Serine-Threonine Kinases/antagonists \& inh, Rats, Staurosporine/pharmacology, Tumor Suppressor Proteins}
}

@article{onoguchi_noncoding_2012,
	title = {A noncoding {RNA} regulates the neurogenin1 gene locus during mouse neocortical development},
	volume = {109},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23027973},
	doi = {10.1073/pnas.1202956109},
	abstract = {The proneural basic helix-loop-helix ({bHLH}) transcription factor neurogenin1 (Neurog1) plays a pivotal role in neuronal differentiation during mammalian development. The spatiotemporal control of the Neurog1 gene expression is mediated by several specific enhancer elements, although how these elements regulate the Neurog1 locus has remained largely unclear. Recently it has been shown that a large number of enhancer elements are transcribed, but the regulation and function of the resulting transcripts have been investigated for only several such elements. We now show that an enhancer element located 5.8-7.0 kb upstream of the mouse Neurog1 locus is transcribed. The production of this transcript, designated {utNgn}1, is highly correlated with that of Neurog1 {mRNA} during neuronal differentiation. Moreover, knockdown of {utNgn}1 by a corresponding short interfering {RNA} inhibits the production of Neurog1 {mRNA} in response to induction of neuronal differentiation. We also found that production of {utNgn}1 is suppressed by polycomb group ({PcG}) proteins, which inhibit the expression of Neurog1. Our results thus suggest that a noncoding {RNA} transcribed from an enhancer element positively regulates transcription at the Neurog1 locus.},
	pages = {16939--16944},
	number = {42},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Onoguchi, M and Hirabayashi, Y and Koseki, H and Gotoh, Y},
	date = {2012},
	pmid = {23027973},
	keywords = {Animals, Mice, {RNA}, Gene Expression Regulation, Basic Helix-Loop-Helix Transcription Factors/genet, Blotting, Cell Differentiation/genetics/*physiology, Chromatin Immunoprecipitation, Developmental/*genetic, {DNA} Primers/genetics, Enhancer Elements, Gene Knockdown Techniques, Genetic/*genetics, In Situ Hybridization, Neocortex/cytology/*embryology, Nerve Tissue Proteins/genetics/*metabolism, Neurons/*physiology, Northern, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, Untranslated/genetics/*metabolism}
}

@article{vidigal_rapid_2015,
	title = {Rapid and efficient one-step generation of paired {gRNA} {CRISPR}-Cas9 libraries},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26278926},
	doi = {10.1038/ncomms9083},
	abstract = {The {CRISPR}-Cas9 system is a powerful tool to edit eukaryotic genomes that has recently been adapted for functional screens. Several of its applications–including the disruption of genes using Cas9-nickase and the generation of large deletions–require co-expression of two distinct guide {RNAs} ({gRNAs}). However, the lack of experimental approaches to generate pools of paired {gRNA} vectors prevents these applications from being scalable. Here we report a simple, inexpensive, one-step method that allows for the rapid and efficient cloning of {gRNA} pairs into expression vectors. We show that this method can be used to generate pooled libraries and is therefore suitable for in vivo and in vitro functional screens.},
	pages = {8083},
	journaltitle = {Nat Commun},
	author = {Vidigal, J A and Ventura, A},
	date = {2015},
	pmid = {26278926}
}

@article{beltran_splicing_2015,
	title = {Splicing of a non-coding antisense transcript controls {LEF}1 gene expression},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25990740},
	doi = {10.1093/nar/gkv502},
	abstract = {In this report we have analyzed the role of antisense transcription in the control of {LEF}1 transcription factor expression. A natural antisense transcript ({NAT}) is transcribed from a promoter present in the first intron of {LEF}1 gene and undergoes splicing in mesenchymal cells. Although this locus is silent in epithelial cells, and neither {NAT} transcript nor {LEF}1 {mRNA} are expressed, in cell lines with an intermediate epithelial-mesenchymal phenotype presenting low {LEF}1 expression, the {NAT} is synthesized and remains unprocessed. Contrarily to the spliced {NAT}, this unspliced {NAT} down-regulates the main {LEF}1 promoter activity and attenuates {LEF}1 {mRNA} transcription. Unspliced {LEF}1 {NAT} interacts with {LEF}1 promoter and facilitates {PRC}2 binding to the {LEF}1 promoter and trimethylation of lysine 27 in histone 3. Expression of the spliced form of {LEF}1 {NAT} in trans prevents the action of unspliced {NAT} by competing for interaction with the promoter. Thus, these results indicate that {LEF}1 gene expression is attenuated by an antisense non-coding {RNA} and that this {NAT} function is regulated by the balance between its spliced and unspliced forms.},
	pages = {5785--5797},
	number = {12},
	journaltitle = {Nucleic Acids Res},
	author = {Beltran, M and Aparicio-Prat, E and Mazzolini, R and Millanes-Romero, A and Masso, P and Jenner, R G and Diaz, V M and Peiro, S and de Herreros, A G},
	date = {2015},
	pmid = {25990740}
}

@article{kim_hur_2009,
	title = {{HuR} recruits let-7/{RISC} to repress c-Myc expression},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19574298},
	doi = {10.1101/gad.1812509},
	abstract = {{RNA}-binding proteins ({RBPs}) and {microRNAs} ({miRNAs}) are potent post-transcriptional regulators of gene expression. Here, we show that the {RBP} {HuR} reduced c-Myc expression by associating with the c-Myc 3' untranslated region ({UTR}) next to a {miRNA} let-7-binding site. Lowering {HuR} or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, {HuR} and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required {HuR} to reduce c-Myc expression and {HuR} required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein {HuR} inhibits c-Myc expression by recruiting let-7-loaded {RISC} ({RNA} {miRNA}-induced silencing complex) to the c-Myc 3'{UTR}.},
	pages = {1743--1748},
	number = {15},
	journaltitle = {Genes Dev},
	author = {Kim, H H and Kuwano, Y and Srikantan, S and Lee, E K and Martindale, J L and Gorospe, M},
	date = {2009},
	pmid = {19574298},
	keywords = {3' Untranslated Regions, Base Sequence, Humans, {RNA}, *Gene Expression Regulation, Antigens, Argonaute Proteins, Eukaryotic Initiation Factor-2/metabolism, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/metabolism, {MicroRNAs}/*metabolism, Molecular Sequence Data, Proto-Oncogene Proteins c-myc/genetics/*metabolism, {RNA}-Binding Proteins/*metabolism, {RNA}-Induced Silencing Complex/*metabolism, Surface/*metabolism}
}

@article{gorospe_inhibition_1996,
	title = {Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8622677},
	abstract = {Prostaglandin A2 ({PGA}2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma {MCF}-7 cells with {PGA}2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in {PGA}2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in {PGA}2-treated cells. Additional experiments with synchronized {MCF}-7 cultures stimulated with serum revealed that treatment with {PGA}2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in {PGA}2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in {PGA}2-treated serum-stimulated cells. These findings indicate that {PGA}2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of {PGA}2, particularly for suppressing growth of tumors lacking p53 function.},
	pages = {762--770},
	number = {3},
	journaltitle = {Mol Cell Biol},
	author = {Gorospe, M and Liu, Y and Xu, Q and Chrest, F J and Holbrook, N J},
	date = {1996},
	pmid = {8622677},
	keywords = {Humans, Gene Expression Regulation, Cultured, *Proto-Oncogene Proteins, Breast Neoplasms/*metabolism/pathology, Carcinoma/*metabolism/pathology, Cell Division/drug effects, Cyclin D1, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases/*biosynthesis, Cyclins/*biosynthesis, G1 Phase, Neoplastic, Oncogene Proteins/*biosynthesis, Prostaglandins A/*pharmacology, Tumor Cells, Tumor Suppressor Protein p53/metabolism}
}

@article{rosa_interplay_2007,
	title = {The interplay between the master transcription factor {PU}.1 and {miR}-424 regulates human monocyte/macrophage differentiation},
	volume = {104},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18056638},
	doi = {10.1073/pnas.0706963104},
	abstract = {We describe a pathway by which the master transcription factor {PU}.1 regulates human monocyte/macrophage differentiation. This includes {miR}-424 and the transcriptional factor {NFI}-A. We show that {PU}.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: {PU}.1 activates the transcription of {miR}-424, and this up-regulation is involved in stimulating monocyte differentiation through {miR}-424-dependent translational repression of {NFI}-A. In turn, the decrease in {NFI}-A levels is important for the activation of differentiation-specific genes such as M-{CSFr}. In line with these data, both {RNAi} against {NFI}-A and ectopic expression of {miR}-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of {NFI}-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human {CD}34+ differentiation. These data point to the important role of {miR}-424 and {NFI}-A in controlling the monocyte/macrophage differentiation program.},
	pages = {19849--19854},
	number = {50},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Rosa, A and Ballarino, M and Sorrentino, A and Sthandier, O and De Angelis, F G and Marchioni, M and Masella, B and Guarini, A and Fatica, A and Peschle, C and Bozzoni, I},
	date = {2007},
	pmid = {18056638},
	keywords = {Base Sequence, Humans, Protein Binding, Cells, Cultured, *Cell Differentiation, *Hematopoiesis, Macrophages/*cytology/*metabolism, {MicroRNAs}/*genetics, Monocytes/*cytology/*metabolism, {NFI} Transcription Factors/genetics/metabolism, Proto-Oncogene Proteins/*metabolism, Trans-Activators/*metabolism, Up-Regulation}
}

@article{xu_acute_1996,
	title = {Acute hypertension activates mitogen-activated protein kinases in arterial wall},
	volume = {97},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8567974},
	doi = {10.1172/JCI118442},
	abstract = {Mitogen-activated protein ({MAP}) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Herein we provide evidence that two distinct classes of {MAP} kinases, the extracellular signal-regulated kinases ({ERK}) and the c-Jun {NH}2-terminal kinases ({JNK}), are transiently activated in rat arteries (aorta, carotid and femoral arteries) in response to an acute elevation in blood pressure induced by either restraint or administration of hypertensive agents (i.e., phenylephrine and angiotensin {II}). Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced activating protein 1 ({AP}-1) {DNA}-binding activity. Activation of {ERK} and {JNK} could contribute to smooth muscle cell hypertrophy/hyperplasia during arterial remodeling due to frequent and/or persistent elevations in blood pressure.},
	pages = {508--514},
	number = {2},
	journaltitle = {J Clin Invest},
	author = {Xu, Q and Liu, Y and Gorospe, M and Udelsman, R and Holbrook, N J},
	date = {1996},
	pmid = {8567974},
	keywords = {Animals, Base Sequence, {RNA}, Messenger/genetics, *Mitogen-Activated Protein Kinases, Acute Disease, Angiotensin {II}/pharmacology, Aorta, Calcium-Calmodulin-Dependent Protein Kinases/*meta, {DNA} Primers/chemistry, Enzyme Activation, fos, Gene Expression, Genes, Hypertension/*enzymology, {JNK} Mitogen-Activated Protein Kinases, jun, Male, Mitogen-Activated Protein Kinase 1, Molecular Sequence Data, Phenylephrine/pharmacology, Physical, Rats, Restraint, Transcription Factor {AP}-1/metabolism, Up-Regulation, Wistar}
}

@article{wang_control_2013,
	title = {Control of myogenesis by rodent {SINE}-containing {lncRNAs}},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23558772},
	doi = {10.1101/gad.212639.112},
	abstract = {Staufen1-mediated {mRNA} decay ({SMD}) degrades {mRNAs} that harbor a Staufen1-binding site ({SBS}) in their 3' untranslated regions ({UTRs}). Human {SBSs} can form by intermolecular base-pairing between a 3' {UTR} Alu element and an Alu element within a long noncoding {RNA} ({lncRNA}) called a \½-{sbsRNA}. Since Alu elements are confined to primates, it was unclear how {SMD} occurs in rodents. Here we identify mouse {mRNA} 3' {UTRs} and {lncRNAs} that contain a B1, B2, B4, or identifier ({ID}) element. We show that {SMD} occurs in mouse cells via {mRNA}-{lncRNA} base-pairing of partially complementary elements and that mouse \½-{sbsRNA} (m\½-{sbsRNA})-triggered {SMD} regulates C2C12 cell myogenesis. Our findings define new roles for {lncRNAs} as well as B and {ID} short interspersed elements ({SINEs}) in mice that undoubtedly influence many developmental and homeostatic pathways.},
	pages = {793--804},
	number = {7},
	journaltitle = {Genes Dev},
	author = {Wang, J and Gong, C and Maquat, L E},
	date = {2013},
	pmid = {23558772},
	keywords = {Animals, Mice, {RNA}, 3' Untranslated Regions/genetics, Base Pairing, Cell Line, Long Untranslated/*genetics/*metabolism, Messenger/genetics/metabolism, Muscle Development/*genetics, {RNA}-Binding Proteins/metabolism, Short Interspersed Nucleotide Elements/*genetics, Trans-Activators/metabolism}
}

@article{ferretti_microrna_2009,
	title = {{MicroRNA} profiling in human medulloblastoma},
	volume = {124},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18973228},
	doi = {10.1002/ijc.23948},
	abstract = {Medulloblastoma is an aggressive brain malignancy with high incidence in childhood. Current treatment approaches have limited efficacy and severe side effects. Therefore, new risk-adapted therapeutic strategies based on molecular classification are required. {MicroRNA} expression analysis has emerged as a powerful tool to identify candidate molecules playing an important role in a large number of malignancies. However, no data are yet available on human primary medulloblastomas. A high throughput {microRNA} expression profiles was performed in human primary medulloblastoma specimens to investigate {microRNA} involvement in medulloblastoma carcinogenesis. We identified specific {microRNA} expression patterns which distinguish medulloblastoma differing in histotypes (anaplastic, classic and desmoplastic), in molecular features ({ErbB}2 or c-Myc overexpressing tumors) and in disease-risk stratification. {MicroRNAs} expression profile clearly differentiates medulloblastoma from either adult or fetal normal cerebellar tissues. Only a few {microRNAs} displayed upregulated expression, while most of them were downregulated in tumor samples, suggesting a tumor growth-inhibitory function. This property has been addressed for {miR}-9 and {miR}-125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated {TrkC} isoform. In conclusion, misregulated {microRNA} expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies.},
	pages = {568--577},
	number = {3},
	journaltitle = {Int J Cancer},
	author = {Ferretti, E and De Smaele, E and Po, A and Di Marcotullio, L and Tosi, E and Espinola, M S and Di Rocco, C and Riccardi, R and Giangaspero, F and Farcomeni, A and Nofroni, I and Laneve, P and Gioia, U and Caffarelli, E and Bozzoni, I and Screpanti, I and Gulino, A},
	date = {2009},
	pmid = {18973228},
	keywords = {Humans, *Gene Expression Profiling, *{MicroRNAs}, Apoptosis/physiology, Biological/*genetics, Blotting, Cell Proliferation, Cerebellar Neoplasms/*genetics/pathology, Child, Female, Male, Medulloblastoma/*genetics/pathology, Northern, Preschool, Receptor, Reverse Transcriptase Polymerase Chain Reaction, {trkC}/genetics, Tumor Markers}
}

@article{gorospe_up-regulation_1996,
	title = {Up-regulation and functional role of p21Waf1/Cip1 during growth arrest of human breast carcinoma {MCF}-7 cells by phenylacetate},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8959328},
	abstract = {Phenylacetate ({PA}) and related aromatic fatty acids constitute a novel class of relatively nontoxic antineoplastic agents. These compounds induce tumor cytostasis and growth inhibition and differentiation of cancer cells, but little is known regarding the molecular events mediating these biological effects. Using human breast carcinoma {MCF}-7 cells as a model, we show here that {PA}-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21Waf1/Cip1 and dephosphorylation of the retinoblastoma protein ({pRB}). The induction of p21WAF1/{CIP}1 {mRNA} by {PA} was independent of the cellular p53 status. To directly assess the contribution of p21Waf1/Cip1 to {PA}-mediated cytostasis, we compared the effects of {PA} in parental {MCF}-7 cells and cells expressing reduced levels of p21Waf1/Cip1 protein (clones {AS}.3 and {AS}.4), accomplished through constitutive expression of antisense p21Waf1/Cip1 transcripts. In contrast to parental cells, {AS}.3 and {AS}.4 cells did not show reduced {pRB} phosphorylation following {PA} treatment, indicating that p21Waf1/Cip1 induction by {PA} is required for dephosphorylation (inactivation) of {pRB}, a known mediator of cell cycle control. A prominent role for p21Waf1/Cip1 in mediating {PA}-induced growth arrest was further supported by the demonstration that embryonal fibroblasts derived from a p21WAF1/{CIP}1 knockout mouse (p21-/- mouse embryonal fibroblasts) did not growth arrest following {PA} treatment, whereas {PA} effectively induced p21WAF1/{CIP}1 {mRNA} and growth inhibition of the wild-type mouse embryonal fibroblasts. Taken together, our findings strongly support a role for p21Waf1/Cip1 in the {PA}-mediated inhibition of cell growth.},
	pages = {1609--1615},
	number = {12},
	journaltitle = {Cell Growth Differ},
	author = {Gorospe, M and Shack, S and Guyton, K Z and Samid, D and Holbrook, N J},
	date = {1996},
	pmid = {8959328},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Regulation, *{CDC}2-{CDC}28 Kinases, Antimetabolites, Antineoplastic/*pharmacology, Antisense Elements (Genetics), Breast Neoplasms, Calcium-Calmodulin-Dependent Protein Kinases/metab, Cell Division/drug effects, Cultured/cytology/drug effects/enzymo, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases/genetics/metabolism, Cyclins/genetics/*metabolism, Enzyme Inhibitors/*metabolism, Female, Fibroblasts/cytology/drug effects/enzymology, Knockout, Messenger/metabolism, Neoplastic/physiology, Phenylacetates/*pharmacology, Phosphorylation, Protein-Serine-Threonine Kinases/genetics/metaboli, Retinoblastoma Protein/metabolism, Signal Transduction/physiology, Tumor Cells, Up-Regulation/drug effects}
}

@article{ikeyama_effects_2003,
	title = {Effects of aging and calorie restriction of Fischer 344 rats on hepatocellular response to proliferative signals},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12670630},
	abstract = {It is well established that the proliferative potential of the liver declines with aging. Epidermal growth factor ({EGF})-stimulated {DNA} synthesis is reduced in hepatocytes from aged rats relative to young rats, and this reduction correlates with diminished activation of the extracellular signal-regulated kinase ({ERK}) pathway and lower phosphorylation of the {EGF} receptor on residue Y1173. Calorie restriction ({CR}) can increase rodent life span and retard many age-associated declines in physiologic function, but its influence on cell proliferation is unknown. Here, we investigated the effects of long-term {CR} on proliferation of hepatocytes derived from young and aged rats following in vitro stimulation with either low-dose hydrogen peroxide or {EGF}. {CR} reduced the proliferative response of hepatocytes derived from young hosts, but long-term {CR} was associated with enhanced proliferation in aged cells relative to that of ad libitum ({AL})-fed animals. {ERK} activation mirrored the effects of {CR} on proliferation, in that young {CR} cells exhibited lower {ERK} activation than young {AL} cells, but old {CR} cells showed higher {ERK} activation than old {AL} cells. Finally, a decline in {EGF} receptor phosphorylation on Y1173, which normally occurs with aging, was absent in cells of old hosts maintained on long-term {CR}, supporting the view that alterations in this early signaling event underlie the age-related decline in proliferative potential in rat hepatocytes.},
	pages = {431--439},
	number = {4},
	journaltitle = {Exp Gerontol},
	author = {Ikeyama, S and Kokkonen, G and Martindale, J L and Wang, X T and Gorospe, M and Holbrook, N J},
	date = {2003},
	pmid = {12670630},
	keywords = {Animals, {RNA}, Cells, Cultured, *Cell Cycle Proteins, *Phosphoprotein Phosphatases, Aging/*physiology, Blotting, Cell Division, Chemical, Dietary Carbohydrates/*administration \& dosage, {DNA}/biosynthesis, Dual Specificity Phosphatase 1, Epidermal Growth Factor/metabolism, Epidermal Growth Factor/pharmacology, Genes, Hepatocytes/*cytology/metabolism, Hydrogen Peroxide/pharmacology, Immediate-Early Proteins/genetics, Inbred F344, jun, Male, Messenger/analysis, Mitogen-Activated Protein Kinases/metabolism, Northern/methods, Phosphorylation, Precipitin Tests/methods, Protein Phosphatase 1, Protein Tyrosine Phosphatases/genetics, Rats, Receptor, Stimulation, Western/methods}
}

@article{plath_xist_2002,
	title = {Xist {RNA} and the mechanism of X chromosome inactivation},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12429693},
	doi = {10.1146/annurev.genet.36.042902.092433},
	abstract = {Dosage compensation in mammals is achieved by the transcriptional inactivation of one X chromosome in female cells. From the time X chromosome inactivation was initially described, it was clear that several mechanisms must be precisely integrated to achieve correct regulation of this complex process. X-inactivation appears to be triggered upon differentiation, suggesting its regulation by developmental cues. Whereas any number of X chromosomes greater than one is silenced, only one X chromosome remains active. Silencing on the inactive X chromosome coincides with the acquisition of a multitude of chromatin modifications, resulting in the formation of extraordinarily stable facultative heterochromatin that is faithfully propagated through subsequent cell divisions. The integration of all these processes requires a region of the X chromosome known as the X-inactivation center, which contains the Xist gene and its cis-regulatory elements. Xist encodes an {RNA} molecule that plays critical roles in the choice of which X chromosome remains active, and in the initial spread and establishment of silencing on the inactive X chromosome. We are now on the threshold of discovering the factors that regulate and interact with Xist to control X-inactivation, and closer to an understanding of the molecular mechanisms that underlie this complex process.},
	pages = {233--278},
	journaltitle = {Annu Rev Genet},
	author = {Plath, K and Mlynarczyk-Evans, S and Nusinow, D A and Panning, B},
	date = {2002},
	pmid = {12429693},
	keywords = {Animals, Base Sequence, Genetic, Mice, {RNA}, Chromatin/genetics, {RNA}/*genetics, Untranslated/*genetics, Long Noncoding, *Dosage Compensation, Gene Silencing}
}

@article{caffarelli_vitro_1994,
	title = {In vitro study of processing of the intron-encoded U16 small nucleolar {RNA} in Xenopus laevis},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7513048},
	abstract = {It was recently shown that a new class of small nuclear {RNAs} is encoded in introns of protein-coding genes and that they originate by processing of the pre-{mRNA} in which they are contained. Little is known about the mechanism and the factors involved in this new type of processing. The L1 ribosomal protein gene of Xenopus laevis is a well-suited system for studying this phenomenon: several different introns encode for two small nucleolar {RNAs} ({snoRNAs}; U16 and U18). In this paper, we analyzed the in vitro processing of these {snoRNAs} and showed that both are released from the pre-{mRNA} by a common mechanism: endonucleolytic cleavages convert the pre-{mRNA} into a precursor {snoRNA} with 5' and 3' trailer sequences. Subsequently, trimming converts the pre-{snoRNAs} into mature molecules. Oocyte and {HeLa} nuclear extracts are able to process X. laevis and human substrates in a similar manner, indicating that the processing of this class of {snoRNAs} relies on a common and evolutionarily conserved mechanism. In addition, we found that the cleavage activity is strongly enhanced in the presence of Mn2+ ions.},
	pages = {2966--2974},
	number = {5},
	journaltitle = {Mol Cell Biol},
	author = {Caffarelli, E and Arese, M and Santoro, B and Fragapane, P and Bozzoni, I},
	date = {1994},
	pmid = {7513048},
	keywords = {Animals, Base Sequence, Genetic, {RNA}, Transcription, *Introns, {DNA} Primers, Female, Manganese/pharmacology, Molecular Sequence Data, Oocytes/metabolism, Polymerase Chain Reaction, Post-Transcriptional, Restriction Mapping, Ribosomal Proteins/biosynthesis/*genetics, {RNA} Precursors/*metabolism, {RNA} Processing, {RNA}-Directed {DNA} Polymerase/metabolism, Small Nuclear/*biosynthesis/*genetics/isolati, Xenopus laevis/*genetics}
}

@article{marques_evidence_2012,
	title = {Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of {mRNAs}},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23153069},
	doi = {10.1186/gb-2012-13-11-r102},
	abstract = {{BACKGROUND}: Recent reports have highlighted instances of {mRNAs} that, in addition to coding for protein, regulate the abundance of related transcripts by altering {microRNA} availability. These two {mRNA} roles - one mediated by {RNA} and the other by protein - are inter-dependent and hence cannot easily be separated. Whether the {RNA}-mediated role of transcripts is important, per se, or whether it is a relatively innocuous consequence of competition by different transcripts for {microRNA} binding remains unknown. {RESULTS}: Here we took advantage of 48 loci that encoded proteins in the earliest eutherian ancestor, but whose protein-coding capability has since been lost specifically during rodent evolution. Sixty-five percent of such loci, which we term 'unitary pseudogenes', have retained their expression in mouse and their transcripts exhibit conserved tissue expression profiles. The maintenance of these unitary pseudogenes' spatial expression profiles is associated with conservation of their {microRNA} response elements and these appear to preserve the post-transcriptional roles of their protein-coding ancestor. We used mouse Pbcas4, an exemplar of these transcribed unitary pseudogenes, to experimentally test our genome-wide predictions. We demonstrate that the role of Pbcas4 as a competitive endogenous {RNA} has been conserved and has outlived its ancestral gene's loss of protein-coding potential. {CONCLUSIONS}: These results show that post-transcriptional regulation by bifunctional {mRNAs} can persist over long evolutionary time periods even after their protein coding ability has been lost.},
	pages = {R102},
	number = {11},
	journaltitle = {Genome Biol},
	author = {Marques, A C and Tan, J and Lee, S and Kong, L and Heger, A and Ponting, C P},
	date = {2012},
	pmid = {23153069}
}

@article{lipovich_novel_2001,
	title = {A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated region: {SLC}4A9 at 5q31},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11305939},
	abstract = {{BACKGROUND}: Sodium bicarbonate cotransporter ({NBC}) genes encode proteins that execute coupled Na+ and {HCO}3- transport across epithelial cell membranes. We report the discovery, characterization, and genomic context of a novel human {NBC}-like gene, {SLC}4A9, on chromosome 5q31. {RESULTS}: {SLC}4A9 was initially discovered by genomic sequence annotation and further characterized by sequencing of long-insert {cDNA} library clones. The predicted protein of 990 amino acids has 12 transmembrane domains and high sequence similarity to other {NBCs}. The 23-exon gene has 14 known {mRNA} isoforms. In three regions, {mRNA} sequence variation is generated by the inclusion or exclusion of portions of an exon. Noncoding {SLC}4A9 {cDNAs} were recovered multiple times from different libraries. The 3' untranslated region is fragmented into six alternatively spliced exons and contains expressed Alu, {LINE} and {MER} repeats. {SLC}4A9 has two alternative stop codons and six polyadenylation sites. Its expression is largely restricted to the kidney. In silico approaches were used to characterize two additional novel {SLC}4A genes and to place {SLC}4A9 within the context of multiple paralogous gene clusters containing members of the epidermal growth factor ({EGF}), ankyrin ({ANK}) and fibroblast growth factor ({FGF}) families. Seven human {EGF}-{SLC}4A-{ANK}-{FGF} clusters were found. {CONCLUSION}: The novel sodium bicarbonate cotransporter-like gene {SLC}4A9 demonstrates abundant alternative {mRNA} processing. It belongs to a growing class of functionally diverse genes characterized by inefficient highly variable splicing. The evolutionary history of the {EGF}-{SLC}4A-{ANK}-{FGF} gene clusters involves multiple rounds of duplication, apparently followed by large insertions and deletions at paralogous loci and genome-wide gene shuffling.},
	pages = {RESEARCH0011},
	number = {4},
	journaltitle = {Genome Biol},
	author = {Lipovich, L and Lynch, E D and Lee, M K and King, M C},
	date = {2001},
	pmid = {11305939},
	keywords = {Human, {DNA}, Sequence Analysis, Humans, {RNA}, Complementary/chemistry/genetics, *Gene Duplication, Adult, Alternative Splicing, Amino Acid, Amino Acid Sequence, Blotting, Chromosomes, Female, Gene Expression, Genes/genetics, Male, Messenger/genetics/metabolism, Molecular Sequence Data, Northern, Pair 5/*genetics, Phylogeny, Sequence Alignment, Sequence Homology, Sodium-Bicarbonate Symporters/*genetics, Tissue Distribution}
}

@article{lal_antiapoptotic_2005,
	title = {Antiapoptotic function of {RNA}-binding protein {HuR} effected through prothymosin alpha},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15861128},
	doi = {10.1038/sj.emboj.7600661},
	abstract = {We report the antiapoptotic effect of {RNA}-binding protein {HuR}, a critical regulator of the post-transcriptional fate of target transcripts. Among the most prominent {mRNAs} complexing with {HuR} is that encoding prothymosin alpha ({ProTalpha}), an inhibitor of the apoptosome. In {HeLa} cells, treatment with the apoptotic stimulus ultraviolet light ({UVC}) triggered the mobilization of {ProTalpha} {mRNA} to the cytoplasm and onto heavier polysomes, where its association with {HuR} increased dramatically. Analysis of a chimeric {ProTalpha} {mRNA} directly implicated {HuR} in regulating {ProTalpha} production: {ProTalpha} translation and cytoplasmic concentration increased in {HuR}-overexpressing cells and declined in cells in which {HuR} levels were lowered by {RNA} interference. Importantly, the antiapoptotic influence engendered by {HuR} was vitally dependent on {ProTalpha} expression, since use of oligomers that blocked {ProTalpha} translation abrogated the protective effect of {HuR}. Together, our data support a regulatory scheme whereby {HuR} binds the {ProTalpha} {mRNA}, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.},
	pages = {1852--1862},
	number = {10},
	journaltitle = {{EMBO} J},
	author = {Lal, A and Kawai, T and Yang, X and Mazan-Mamczarz, K and Gorospe, M},
	date = {2005},
	pmid = {15861128},
	keywords = {Base Sequence, Humans, {RNA}, Antigens, Apoptosis/*physiology/radiation effects, Cell Survival/physiology/radiation effects, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/metabolism, Molecular Sequence Data, Protein Precursors/genetics/*metabolism, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism, Thymosin/*analogs \& derivatives/genetics/*metaboli, Ultraviolet Rays}
}

@article{gutschner_malat1_2013,
	title = {{MALAT}1 – a paradigm for long noncoding {RNA} function in cancer},
	volume = {91},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23529762},
	doi = {10.1007/s00109-013-1028-y},
	abstract = {The metastasis-associated lung adenocarcinoma transcript 1 ({MALAT}1) is a bona fide long noncoding {RNA} ({lncRNA}). {MALAT}1, also known as nuclear-enriched transcript 2 ({NEAT}2), was discovered as a prognostic marker for lung cancer metastasis but also has been linked to several other human tumor entities. Recent work established a critical regulatory function of this {lncRNA} in lung cancer metastasis and cell migration. Moreover, {MALAT}1 is an interesting target for antimetastatic therapy in non-small cell lung carcinoma. Two alternative modes of action have been proposed for {MALAT}1: regulation of gene expression or alternative splicing. Although the exact mechanism of action in different physiological and pathological conditions still needs to be elucidated, {MALAT}1 acts as a regulator of gene expression. Although {MALAT}1 is highly evolutionary conserved in mammals and plays an important role in cancer and metastasis, {MALAT}1 is not essential for development in a knockout mouse model under normal physiological conditions. Hence, one central question for the future is finding the right stressor and the pathological or environmental condition which requires {MALAT}1 expression in vivo and entailing its strong evolutionary conservation. Here, we summarize the current knowledge about this important {lncRNA}. We introduce its discovery, biogenesis, and regulation and describe its known functions, mechanisms of action, and interaction partners.},
	pages = {791--801},
	number = {7},
	journaltitle = {J Mol Med (Berl)},
	author = {Gutschner, T and Hammerle, M and Diederichs, S},
	date = {2013},
	pmid = {23529762},
	keywords = {Animals, Humans, {RNA}, Long Noncoding/*genetics, Neoplasms/*genetics}
}

@article{rinn_functional_2007,
	title = {Functional demarcation of active and silent chromatin domains in human {HOX} loci by noncoding {RNAs}},
	volume = {129},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17604720},
	doi = {10.1016/j.cell.2007.05.022},
	abstract = {Noncoding {RNAs} ({ncRNA}) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human {HOX} loci at five base pair resolution in 11 anatomic sites and identify 231 {HOX} {ncRNAs} that extend known transcribed regions by more than 30 kilobases. {HOX} {ncRNAs} are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and {RNA} polymerase accessibility. We identified a 2.2 kilobase {ncRNA} residing in the {HOXC} locus, termed {HOTAIR}, which represses transcription in trans across 40 kilobases of the {HOXD} locus. {HOTAIR} interacts with Polycomb Repressive Complex 2 ({PRC}2) and is required for {PRC}2 occupancy and histone H3 lysine-27 trimethylation of {HOXD} locus. Thus, transcription of {ncRNA} may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.},
	pages = {1311--1323},
	number = {7},
	journaltitle = {Cell},
	author = {Rinn, J L and Kertesz, M and Wang, J K and Squazzo, S L and Xu, X and Brugmann, S A and Goodnough, L H and Helms, J A and Farnham, P J and Segal, E and Chang, H Y},
	date = {2007},
	pmid = {17604720},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Gene Expression Regulation, Cells, Chromatin/*genetics, Cultured, Genetic/genetics, Base Sequence/genetics, Body Patterning/*genetics, Chromatin, Developmental/genetics, {DNA} Methylation, Embryonic Development, Embryonic Development/*genetics, Epigenesis, Genes, Histones, Histones/genetics, Homeobox/*genetics, Inbred C57BL, Molecular Sequence Data, Polycomb-Group Proteins, Regulatory Elements, Repressor Proteins/genetics, {RNA} Interference, {RNA} Interference/*physiology, Transcriptional/genetics, Untranslated/chemistry/*genetics, Repressor Proteins, Cells, Cultured, {RNA}, Untranslated, Regulatory Elements, Transcriptional, Mice, Inbred C57BL, Gene Expression Regulation, Developmental, Genes, Homeobox, Body Patterning, Epigenesis, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/CL9LM2QC/Rinn et al. - 2007 - Functional demarcation of active and silent chroma.pdf:application/pdf}
}

@article{maher_epidemiologic_2002,
	title = {Epidemiologic study of 203 sibling pairs with Parkinson's disease: the {GenePD} study},
	volume = {58},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11781409},
	abstract = {{OBJECTIVE}: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with {PD}. {METHODS}: Sibling pairs (n = 203) with {PD} were collected as part of the {GenePD} study. Standardized family history, medical history, and risk factor data were collected and analyzed. {RESULTS}: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with {PD}. The frequency of affected parents (7.0\%) and siblings (5.1\%) was increased when compared with frequency in spouses (2.0\%). {CONCLUSIONS}: The greater similarity for age at onset than for year of onset in sibling pairs with {PD}, together with increased risk for biological relatives over spouses of cases, supports a genetic component for {PD}. Risk to siblings in this series is increased over that seen in random series of {PD} cases; however, patients in this sample have similar ages at onset and sex distribution as seen for {PD} generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.},
	pages = {79--84},
	number = {1},
	journaltitle = {Neurology},
	author = {Maher, N E and Golbe, L I and Lazzarini, A M and Mark, M H and Currie, L J and Wooten, G F and Saint-Hilaire, M and Wilk, J B and Volcjak, J and Maher, J E and Feldman, R G and Guttman, M and Lew, M and Waters, C H and Schuman, S and Suchowersky, O and Lafontaine, A L and Labelle, N and Vieregge, P and Pramstaller, P P and Klein, C and Hubble, J and Reider, C and Growdon, J and Watts, R and Montgomery, E and Baker, K and Singer, C and Stacy, M and Myers, R H},
	date = {2002},
	pmid = {11781409},
	keywords = {Humans, Age of Onset, Female, Male, Middle Aged, Parkinson Disease/*epidemiology/*genetics, Risk Factors, Siblings}
}

@article{ellis_indirect_2014,
	title = {Indirect comparison of bazedoxifene vs oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24773456},
	doi = {10.1185/03007995.2014.908279},
	abstract = {{OBJECTIVE}: Compare the efficacy of bazedoxifene with oral bisphosphonates for reduction of vertebral fracture risk in postmenopausal osteoporotic ({PMO}) women and in higher-risk patients based on evidence from randomized controlled trials ({RCTs}). {METHODS}: Eight {RCTs} assessing vertebral fracture risk reduction with oral bisphosphonates (n = 7) or bazedoxifene (n = 1) were identified by a systematic literature review. Individual study results were pooled in a network meta-analysis ({NMA}) to indirectly compare treatment effects for overall {PMO} women and a higher-risk subgroup ({FRAX} {\textbackslash}textgreater/= 20\%). Three sets of {NMA} analyses were conducted: aggregate data ({AD}) from the bisphosphonate {RCTs} and bazedoxifene {RCT} for the full population or the {FRAX} {\textbackslash}textgreater/=20\% subgroup ({NMA} {AD}); bisphosphonate {AD} and bazedoxifene {AD} from each {FRAX} subgroup adjusted for baseline risk ({NMA} {AD} meta-regression); and bisphosphonate {AD} and bazedoxifene individual patient data ({IPD}) adjusted for baseline risk/{FRAX} ({NMA} {AD}/{IPD} meta-regression). {RESULTS}: For the overall population, bisphosphonates had lower fracture risks versus bazedoxifene although there is considerable uncertainty in supporting one intervention over another. The relative risk reduction ({RRR}) for bazedoxifene was -0.23 (95\% {CrI}: -1.11, 0.27) versus ibandronate, -0.17 (-0.76, 0.22) versus alendronate, and -0.06 (-0.62, 0.30) versus risedronate. {RESULTS} from the meta-regression analyses were similar. For the {FRAX} {\textbackslash}textgreater/=20\% population, estimated fracture rates with bazedoxifene were lower than with bisphosphonates, but again the uncertainty limits strong interpretation. The {RRR} for bazedoxifene was 0.51 (-0.31, 0.83) versus ibandronate, 0.53 (-0.18, 0.83) versus alendronate, and 0.57 (-0.07, 0.85) versus risedronate. The meta-regression analyses showed comparable findings. {CONCLUSION}: The analyses only considered vertebral fractures for oral bisphosphonates versus bazedoxifene, and {IPD} was available only for bazedoxifene. In light of this, bazedoxifene is comparable to bisphosphonates in the overall {PMO} population and at least as effective as bisphosphonates for preventing vertebral fractures among higher-risk {PMO} patients. The findings suggest bazedoxifene performs better in higher-risk {PMO} than in the overall {PMO}.},
	pages = {1617--1626},
	number = {8},
	journaltitle = {Curr Med Res Opin},
	author = {Ellis, A G and Reginster, J Y and Luo, X and A, G Bushmakin and Williams, R and Sutradhar, S and Mirkin, S and Jansen, J P},
	date = {2014},
	pmid = {24773456}
}

@article{nissan_colon_2012,
	title = {Colon cancer associated transcript-1: a novel {RNA} expressed in malignant and pre-malignant human tissues},
	volume = {130},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21547902},
	doi = {10.1002/ijc.26170},
	abstract = {Early detection of colorectal cancer ({CRC}) is currently based on fecal occult blood testing ({FOBT}) and colonoscopy, both which can significantly reduce {CRC}-related mortality. However, {FOBT} has low-sensitivity and specificity, whereas colonoscopy is labor- and cost-intensive. Therefore, the discovery of novel biomarkers that can be used for improved {CRC} screening, diagnosis, staging and as targets for novel therapies is of utmost importance. To identify novel {CRC} biomarkers we utilized representational difference analysis ({RDA}) and characterized a colon cancer associated transcript ({CCAT}1), demonstrating consistently strong expression in adenocarcinoma of the colon, while being largely undetectable in normal human tissues (p {\textbackslash}textless 000.1). {CCAT}1 levels in {CRC} are on average 235-fold higher than those found in normal mucosa. Importantly, {CCAT}1 is strongly expressed in tissues representing the early phase of tumorigenesis: in adenomatous polyps and in tumor-proximal colonic epithelium, as well as in later stages of the disease (liver metastasis, for example). In {CRC}-associated lymph nodes, {CCAT}1 overexpression is detectable in all H\&E positive, and 40.0\% of H\&E and immunohistochemistry negative lymph nodes, suggesting very high sensitivity. {CCAT}1 is also overexpressed in 40.0\% of peripheral blood samples of patients with {CRC} but not in healthy controls. {CCAT}1 is therefore a highly specific and readily detectable marker for {CRC} and tumor-associated tissues.},
	pages = {1598--1606},
	number = {7},
	journaltitle = {Int J Cancer},
	author = {Nissan, A and Stojadinovic, A and Mitrani-Rosenbaum, S and Halle, D and Grinbaum, R and Roistacher, M and Bochem, A and Dayanc, B E and Ritter, G and Gomceli, I and Bostanci, E B and Akoglu, M and Chen, Y T and Old, L J and Gure, A O},
	date = {2012},
	pmid = {21547902},
	keywords = {Base Sequence, Humans, {RNA}, Adenocarcinoma/diagnosis/genetics, Adenomatous Polyps/diagnosis/genetics, Adolescent, Amino Acid Sequence, Biomarkers, Cell Line, Cell Transformation, Colonic Neoplasms/diagnosis/*genetics/pathology, Early Detection of Cancer/methods, {HCT}116 Cells, {HT}29 Cells, Intestinal Mucosa/metabolism, Lymph Nodes/metabolism, Molecular Sequence Data, Mucous Membrane/metabolism, Neoplasm Metastasis, Neoplasm/*biosynthesis/genetics, Neoplastic/genetics/pathology, {RNA} Precursors/analysis/*genetics, Sensitivity and Specificity, Tumor, Tumor/analysis/*genetics, Up-Regulation}
}

@article{caffarelli_vivo_1998,
	title = {In vivo identification of nuclear factors interacting with the conserved elements of box C/D small nucleolar {RNAs}},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9447999},
	abstract = {The U16 small nucleolar {RNA} ({snoRNA}) is encoded by the third intron of the L1 (L4, according to the novel nomenclature) ribosomal protein gene of Xenopus laevis and originates from processing of the pre-{mRNA} in which it resides. The U16 {snoRNA} belongs to the box C/D {snoRNA} family, whose members are known to assemble in ribonucleoprotein particles ({snoRNPs}) containing the protein fibrillarin. We have utilized U16 {snoRNA} in order to characterize the factors that interact with the conserved elements common to the other members of the box C/D class. In this study, we have analyzed the in vivo assembly of U16 {snoRNP} particles in X. laevis oocytes and identified the proteins which interact with the {RNA} by label transfer after {UV} cross-linking. This analysis revealed two proteins, of 40- and 68-{kDa} apparent molecular size, which require intact boxes C and D together with the conserved 5',3'-terminal stem for binding. Immunoprecipitation experiments showed that the p40 protein corresponds to fibrillarin, indicating that this protein is intimately associated with the {RNA}. We propose that fibrillarin and p68 represent the {RNA}-binding factors common to box C/D {snoRNPs} and that both proteins are essential for the assembly of {snoRNP} particles and the stabilization of the {snoRNA}.},
	pages = {1023--1028},
	number = {2},
	journaltitle = {Mol Cell Biol},
	author = {Caffarelli, E and Losito, M and Giorgi, C and Fatica, A and Bozzoni, I},
	date = {1998},
	pmid = {9447999},
	keywords = {Animals, {RNA}, Antibodies/metabolism, Autoantigens/immunology, Chromosomal Proteins, Molecular Weight, Non-Histone/immunology, Nuclear Proteins/immunology/*metabolism, Nucleic Acid Conformation, Oocytes/metabolism, Small Nuclear/*metabolism, Ultraviolet Rays, Xenopus laevis}
}

@article{de_marchis_new_2009,
	title = {A new molecular network comprising {PU}.1, interferon regulatory factor proteins and {miR}-342 stimulates {ATRA}-mediated granulocytic differentiation of acute promyelocytic leukemia cells},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19151778},
	doi = {10.1038/leu.2008.372},
	abstract = {In the acute promyelocytic leukemia ({APL}) bearing the t(15;17), all-trans-retinoic acid ({ATRA}) treatment induces granulocytic maturation and complete remission of leukemia. We identified {miR}-342 as one of the {microRNAs} ({miRNAs}) upregulated by {ATRA} during {APL} differentiation. This {miRNA} emerged as a direct transcriptional target of the critical hematopoietic transcription factors {PU}.1 and interferon regulatory factor ({IRF})-1 and {IRF}-9. {IRF}-1 maintains {miR}-342 at low levels, whereas the binding of {PU}.1 and {IRF}-9 in the promoter region following retinoic {ATRA}-mediated differentiation, upregulates {miR}-342 expression. Moreover, we showed that enforced expression of {miR}-342 in {APL} cells stimulated {ATRA}-induced differentiation. These data identified {miR}-342 as a new player in the granulocytic differentiation program activated by {ATRA} in {APL}.},
	pages = {856--862},
	number = {5},
	journaltitle = {Leukemia},
	author = {De Marchis, M L and Ballarino, M and Salvatori, B and Puzzolo, M C and Bozzoni, I and Fatica, A},
	date = {2009},
	pmid = {19151778},
	keywords = {Genetic, Humans, Promoter Regions, {RNA}, Cultured, *Cell Differentiation, Acute/*genetics/metabolis, Antineoplastic Agents/pharmacology, Cell Adhesion Molecules/genetics/metabolism, Chromatin Immunoprecipitation, gamma Subunit, Granulocytes/*cytology/drug effects/metabolism, Immunoblotting, Immunophenotyping, Interferon Regulatory Factor-1/*genetics/metabolis, Interferon-Stimulated Gene Factor 3, Introns/genetics, Leukemia, Messenger/genetics/metabolism, {MicroRNAs}/*genetics/*physiology, Promyelocytic, Proto-Oncogene Proteins/*genetics/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Trans-Activators/*genetics/metabolism, Tretinoin/*pharmacology, Tumor Cells}
}

@article{chueh_line_2009,
	title = {{LINE} retrotransposon {RNA} is an essential structural and functional epigenetic component of a core neocentromeric chromatin},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19180186},
	doi = {10.1371/journal.pgen.1000354},
	abstract = {We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres. Human neocentromeres form epigenetically at euchromatic chromosomal sites and are structurally and functionally similar to normal human centromeres. Recent studies have indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, and speciation. Using a marker chromosome mardel(10) containing a neocentromere formed at the normal chromosomal 10q25 region, we have previously mapped a 330-kb {CENP}-A-binding domain and described an increased prevalence of L1 retrotransposons in the underlying {DNA} sequences of the {CENP}-A-binding clusters. Here, we investigated the potential role of the L1 retrotransposons in the regulation of neocentromere activity. Determination of the transcriptional activity of a panel of full-length L1s ({FL}-L1s) across a 6-Mb region spanning the 10q25 neocentromere chromatin identified one of the {FL}-L1 retrotransposons, designated {FL}-L1b and residing centrally within the {CENP}-A-binding clusters, to be transcriptionally active. We demonstrated the direct incorporation of the {FL}-L1b {RNA} transcripts into the {CENP}-A-associated chromatin. {RNAi}-mediated knockdown of the {FL}-L1b {RNA} transcripts led to a reduction in {CENP}-A binding and an impaired mitotic function of the 10q25 neocentromere. These results indicate that {LINE} retrotransposon {RNA} is a previously undescribed essential structural and functional component of the neocentromeric chromatin and that retrotransposable elements may serve as a critical epigenetic determinant in the chromatin remodelling events leading to neocentromere formation.},
	pages = {e1000354},
	number = {1},
	journaltitle = {{PLoS} Genet},
	author = {Chueh, A C and Northrop, E L and Brettingham-Moore, K H and Choo, K H and Wong, L H},
	date = {2009},
	pmid = {19180186},
	keywords = {Human, Animals, Genetic, Humans, Mice, Transcription, *Epigenesis, *Long Interspersed Nucleotide Elements, Autoantigens/genetics/metabolism, Cell Line, Centromere/chemistry/*genetics/metabolism, Chromatin/chemistry/*metabolism, Chromosomal Proteins, Chromosomes, Cricetinae, Mitosis, Non-Histone/genetics/metabol, Pair 10/genetics, {RNA}/genetics/*metabolism}
}

@article{bird_fast-evolving_2007,
	title = {Fast-evolving noncoding sequences in the human genome},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17578567},
	doi = {10.1186/gb-2007-8-6-r118},
	abstract = {{BACKGROUND}: Gene regulation is considered one of the driving forces of evolution. Although protein-coding {DNA} sequences and {RNA} genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding ({CNC}) sequences may well harbor critical regulatory variants that have driven recent human evolution. {RESULTS}: Here we identify 1,356 {CNC} sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15\% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated {CNC}' ({ANC}) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within {ANC} sequences have a significant excess of high frequency derived alleles and high F({ST}) values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within {ANC} sequences are associated with changes in gene expression. The probability of variation in an {ANC} sequence being associated with a gene expression phenotype is fivefold higher than variation in a control {CNC} sequence. {CONCLUSION}: Our analysis suggests that {ANC} sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation.},
	pages = {R118},
	number = {6},
	journaltitle = {Genome Biol},
	author = {Bird, C P and Stranger, B E and Liu, M and Thomas, D J and Ingle, C E and Beazley, C and Miller, W and Hurles, M E and Dermitzakis, E T},
	date = {2007},
	pmid = {17578567},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Base Sequence, Conserved Sequence, Genetic, Genome, Humans, *Genome, Nucleic Acid, *Evolution, *Gene Expression Regulation, *Regulatory Sequences, Macaca, Molecular, Pan troglodytes, Polymorphism, Selection, Single Nucleotide}
}

@article{pullmann_jr._enhanced_2005,
	title = {Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of {RNA}-binding protein {HuR}},
	volume = {280},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15824116},
	doi = {10.1074/jbc.M501106200},
	abstract = {In dividing cells, the {RNA}-binding protein {HuR} associates with and stabilizes labile {mRNAs} encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of {HuR}. Here, assessment of {HuR} levels in various vascular pathologies (intimal hyperplasia, atherosclerosis and neointimal proliferation, sclerosis of arterialized saphenous venous graft, and fibromuscular dysplasia) revealed a distinct increase in {HuR} expression and cytoplasmic abundance within the intima and neointima layers. On the basis of these observations, we postulated a role for {HuR} in promoting the proliferation of vascular smooth muscle cells. To test this hypothesis directly, we investigated the expression, subcellular localization, and proliferative influence of {HuR} in human vascular smooth muscle cells ({hVSMCs}). Treatment of {hVSMCs} with platelet-derived growth factor increased {HuR} levels in the cytoplasm, thereby influencing the expression of metabolic, proliferative, and structural genes. Importantly, knockdown of {HuR} expression by using {RNA} interference caused a reduction of {hVSMC} proliferation, both basally and following platelet-derived growth factor treatment. We propose that {HuR} contributes to regulating {hVSMC} growth and homeostasis in pathologies associated with vascular smooth muscle proliferation.},
	pages = {22819--22826},
	number = {24},
	journaltitle = {J Biol Chem},
	author = {Pullmann Jr., R and Juhaszova, M and Lopez de Silanes, I and Kawai, T and Mazan-Mamczarz, K and Halushka, M K and Gorospe, M},
	date = {2005},
	pmid = {15824116},
	keywords = {{DNA}, Humans, {RNA}, Protein Binding, Oligonucleotide Array Sequence Analysis, Cells, Cultured, *Gene Expression Regulation, Antigens, Biotinylation, Blotting, Cell Proliferation, Complementary/metabolism, Cytoplasm/metabolism, Extracellular Matrix/metabolism, Fluorescence, Hu Paraneoplastic Encephalomyelitis Antigens, Immunohistochemistry, Messenger/metabolism, Microscopy, Muscle, Platelet-Derived Growth Factor/metabolism, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, {RNA}-Binding Proteins/*chemistry, {RNA}/*chemistry, Smooth, Smooth/metabolism, Surface/*chemistry, Time Factors, Transfection, Vascular/*cytology, Western}
}

@article{kosir_challenging_2013,
	title = {Challenging paradigms: long non-coding {RNAs} in breast ductal carcinoma in situ ({DCIS})},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23577021},
	doi = {10.3389/fgene.2013.00050},
	pages = {50},
	journaltitle = {Front Genet},
	author = {Kosir, M A and Jia, H and Ju, D and Lipovich, L},
	date = {2013},
	pmid = {23577021}
}

@article{srikantan_paradoxical_2011,
	title = {Paradoxical {microRNAs}: individual gene repressors, global translation enhancers},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21311220},
	abstract = {In mammalian cells, {microRNAs} regulate the expression of target {mRNAs} generally by reducing their stability and/or translation, and thereby control diverse cellular processes such as senescence. We recently reported the differential abundance of {microRNAs} in young (early-passage, proliferating) relative to senescent (late-passage, non-proliferating) {WI}-38 human diploid fibroblasts. Here we report that the levels of the vast majority of {mRNAs} were unaltered in senescent compared to young {WI}-38 cells, while overall {mRNA} translation was potently reduced in senescent cells. Downregulation of Dicer or Drosha, two major enzymes in {microRNA} biogenesis, lowered {microRNA} levels, but, unexpectedly, it also reduced global translation. While a reduction in Dicer levels markedly enhanced cellular senescence, reduction of Drosha levels did not, suggesting that the Drosha/Dicer effects on translation may be independent of senescence, and further suggesting that {microRNAs} may directly or indirectly enhance {mRNA} translation in {WI}-38 cells. We discuss possible scenarios through which Dicer/Drosha/{microRNAs} could enhance translation.},
	pages = {751--759},
	number = {5},
	journaltitle = {Cell Cycle},
	author = {Srikantan, S and Marasa, B S and Becker, K G and Gorospe, M and Abdelmohsen, K},
	date = {2011},
	pmid = {21311220},
	keywords = {Humans, {RNA}, Cells, Cultured, *Protein Biosynthesis, Cell Aging, {DEAD}-box {RNA} Helicases/genetics/metabolism, Down-Regulation, Fibroblasts/metabolism, Messenger/metabolism, {MicroRNAs}/*metabolism, Ribonuclease {III}/genetics/metabolism, {RNA} Interference, Small Interfering/metabolism}
}

@article{pervouchine_enhanced_2015,
	title = {Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25582907},
	doi = {10.1038/ncomms6903},
	abstract = {Mice have been a long-standing model for human biology and disease. Here we characterize, by {RNA} sequencing, the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution. This core set of genes captures a substantial fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but is associated with conserved epigenetic marking, as well as with characteristic post-transcriptional regulatory programme, in which sub-cellular localization and alternative splicing play comparatively large roles.},
	pages = {5903},
	journaltitle = {Nat Commun},
	author = {Pervouchine, D D and Djebali, S and Breschi, A and Davis, C A and Barja, P P and Dobin, A and Tanzer, A and Lagarde, J and Zaleski, C and See, L H and Fastuca, M and Drenkow, J and Wang, H and Bussotti, G and Pei, B and Balasubramanian, S and Monlong, J and Harmanci, A and Gerstein, M and Beer, M A and Notredame, C and Guigo, R and Gingeras, T R},
	date = {2015},
	pmid = {25582907}
}

@article{cronstein_mechanistic_2013,
	title = {Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23319019},
	doi = {10.1097/RHU.0b013e31827d8790},
	abstract = {It has been recently demonstrated that interleukin 1beta ({IL}-1beta) plays a central role in monosodium urate crystal-induced inflammation and that the {NALP}3 inflammasome plays a major role in {IL}-1beta production. These discoveries have offered new insights into the pathogenesis of acute gouty arthritis. In this review, we discuss the molecular mechanisms by which monosodium urate crystals induce acute inflammation and examine the mechanisms of action ({MOAs}) of traditional anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids) and biologic agents (e.g., the {IL}-1beta antagonists anakinra, rilonacept, and canakinumab) to understand how their {MOAs} contribute to their safety profiles. Traditional anti-inflammatory agents may act on the {IL}-1beta pathway at some level; however, their {MOAs} are broad-ranging, unspecific, and biologically complex. This lack of specificity may explain the range of systemic adverse effects associated with them. The therapeutic margins of nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids are particularly low in elderly patients and in patients with cardiovascular, metabolic, or renal comorbidities that are frequently associated with gouty arthritis. In contrast, the {IL}-1beta antagonists act on very specific targets of inflammation, which may decrease the potential for systemic adverse effects, although infrequent but serious adverse events (including infection and administration reactions) have been reported. Because these {IL}-1beta antagonists target an early event immediately downstream from {NALP}3 inflammasome activation, they may provide effective alternatives to traditional agents with minimal systemic adverse effects. Results of ongoing trials of {IL}-1beta antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis.},
	pages = {19--29},
	number = {1},
	journaltitle = {J Clin Rheumatol},
	author = {Cronstein, B N and Sunkureddi, P},
	date = {2013},
	pmid = {23319019},
	keywords = {Humans, *Disease Management, Acute Disease, Anti-Inflammatory Agents, Arthritis, Carrier Proteins/physiology, Colchicine/therapeutic use, Glucocorticoids/therapeutic use, Gout Suppressants/*therapeutic use, Gouty/*drug therapy/*physiopathology, Inflammation/*physiopathology, Interleukin-1beta/antagonists \& inhibitors/physiol, Non-Steroidal/therapeuti}
}

@article{engreitz_xist_2013,
	title = {The Xist {lncRNA} exploits three-dimensional genome architecture to spread across the X chromosome},
	volume = {341},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23828888},
	doi = {10.1126/science.1237973},
	abstract = {Many large noncoding {RNAs} ({lncRNAs}) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist {lncRNA} during X-chromosome inactivation ({XCI}), a paradigm of {lncRNA}-mediated chromatin regulation. During the maintenance of {XCI}, Xist binds broadly across the X chromosome. During initiation of {XCI}, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.},
	pages = {1237973},
	number = {6147},
	journaltitle = {Science},
	author = {Engreitz, J M and Pandya-Jones, A and {McDonel}, P and Shishkin, A and Sirokman, K and Surka, C and Kadri, S and Xing, J and Goren, A and Lander, E S and Plath, K and Guttman, M},
	date = {2013},
	pmid = {23828888},
	keywords = {Animals, Genetic, Genome, Mice, {RNA}, Transcription, *Genome, *X Chromosome Inactivation, Cell Differentiation, Cell Line, Chromatin, Chromatin/chemistry/metabolism, Female, Long Untranslated/chemistry/*metabolism, Male, Models, X Chromosome, X Chromosome Inactivation, X Chromosome/*metabolism/ultrastructure, {RNA}, Long Noncoding, Transcription, Genetic, Models, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/APXYCIZW/Engreitz et al. - 2013 - The Xist lncRNA exploits three-dimensional genome .pdf:application/pdf}
}

@article{tilgner_deep_2012,
	title = {Deep sequencing of subcellular {RNA} fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for {lncRNAs}},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22955974},
	doi = {10.1101/gr.134445.111},
	abstract = {Splicing remains an incompletely understood process. Recent findings suggest that chromatin structure participates in its regulation. Here, we analyze the {RNA} from subcellular fractions obtained through {RNA}-seq in the cell line K562. We show that in the human genome, splicing occurs predominantly during transcription. We introduce the {coSI} measure, based on {RNA}-seq reads mapping to exon junctions and borders, to assess the degree of splicing completion around internal exons. We show that, as expected, splicing is almost fully completed in cytosolic {polyA}+ {RNA}. In chromatin-associated {RNA} (which includes the {RNA} that is being transcribed), for 5.6\% of exons, the removal of the surrounding introns is fully completed, compared with 0.3\% of exons for which no intron-removal has occurred. The remaining exons exist as a mixture of spliced and fewer unspliced molecules, with a median {coSI} of 0.75. Thus, most {RNAs} undergo splicing while being transcribed: "co-transcriptional splicing." Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal {snRNAs} in chromatin-associated {RNA} compared with other cellular {RNA} fractions and other nonspliceosomal {snRNAs}. {CoSI} scores decrease along the gene, pointing to a "first transcribed, first spliced" rule, yet more downstream exons carry other characteristics, favoring rapid, co-transcriptional intron removal. Exons with low {coSI} values, that is, in the process of being spliced, are enriched with chromatin marks, consistent with a role for chromatin in splicing during transcription. For alternative exons and long noncoding {RNAs}, splicing tends to occur later, and the latter might remain unspliced in some cases.},
	pages = {1616--1625},
	number = {9},
	journaltitle = {Genome Res},
	author = {Tilgner, H and Knowles, D G and Johnson, R and Davis, C A and Chakrabortty, S and Djebali, S and Curado, J and Snyder, M and Gingeras, T R and Guigo, R},
	date = {2012},
	pmid = {22955974},
	keywords = {Human, Sequence Analysis, Genetic, Humans, {RNA}, *Genome, *Transcription, Exons, *{RNA} Splicing, Chromatin/metabolism, Cluster Analysis, Computational Biology/methods, High-Throughput Nucleotide Sequencing, Long Noncoding/*metabolism, {RNA}/genetics/metabolism, Spliceosomes/genetics/metabolism, Subcellular Fractions/chemistry}
}

@article{hoshi_6-[18f]fluoro-l-dopa_1993,
	title = {6-[18F]fluoro-L-dopa metabolism in living human brain: a comparison of six analytical methods},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8417011},
	doi = {10.1038/jcbfm.1993.8},
	abstract = {In 11 normal volunteers and six patients with Parkinson's disease, we compared six different analyses of dopaminergic function with L-3,4-dihydroxy-6-[18F]fluorophenylalanine ({FDOPA}) and positron emission tomography ({PET}). The caudate nucleus, putamen, and several reference regions were identified in {PET} images, using magnetic resonance imaging ({MRI}). The six analyses included two direct determinations of {DOPA} decarboxylase activity (k3D, k3*), the slope-intercept plot based on plasma concentration (K), two slope-intercept plots based on tissue content (k3r, k3s), and the striato-occipital ratio [R(T)]. For all analyses, the difference between two groups of subjects (normal volunteers and patients with Parkinson's disease) was larger in the putamen than in the caudate. For the caudate nucleus, the {DOPA} decarboxylase activity (k3D, k3*), tissue slope-intercept plots (kr3, ks3); and striato-occipital ratio [R(T)] analyses significantly discriminated between the normal volunteers and the patients with Parkinson's disease (p {\textbackslash}textless 0.005) [with least significance for k3* (p {\textbackslash}textless 0.05)], while the plasma slope-intercept plot (K) failed to do so. For the putamen, the values for k3D, k3*, K, k3r, k3s, and R(T) of normal volunteers were significantly higher than those of patients (p {\textbackslash}textless 0.005) [with least significance for K (p {\textbackslash}textless 0.025)]. Linear correlations were significant between k3D and k3s; k3D and k3r; k3D and R(T); and k3D and k3*, in this order of significance. We found no correlation between k3D and K values in the caudate nucleus.},
	pages = {57--69},
	number = {1},
	journaltitle = {J Cereb Blood Flow Metab},
	author = {Hoshi, H and Kuwabara, H and Leger, G and Cumming, P and Guttman, M and Gjedde, A},
	date = {1993},
	pmid = {8417011},
	keywords = {Humans, Adult, Biological, Caudate Nucleus/*metabolism/radionuclide imaging, Dihydroxyphenylalanine/*analogs \& derivatives/meta, Emission-Computed, Fluorine Radioisotopes/diagnostic use/pharmacokine, Levodopa/*pharmacokinetics, Middle Aged, Models, Parkinson Disease/*metabolism, Putamen/*metabolism/radionuclide imaging, Tomography}
}

@article{presutti_ribosomal_1988,
	title = {Ribosomal protein L2 in Saccharomyces cerevisiae is homologous to ribosomal protein L1 in Xenopus laevis. Isolation and characterization of the genes},
	volume = {263},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2834365},
	abstract = {By cross-hybridization with a {cDNA} probe for the Xenopus laevis ribosomal protein L1 we have been able to isolate the homologous genes from a Saccharomyces cerevisiae genomic library. We have shown that these genes code for a ribosomal protein which was previously named L2. In yeast, like in X. laevis, these genes are present in two copies per haploid genome and, unlike the vertebrate counterpart, they do not contain introns. Amino acid comparison of the X. laevis L1 and S. cerevisiae L2 proteins has shown the presence of a highly conserved protein domain embedded in very divergent sequences. Although these sequences are very poorly homologous, they confer an overall secondary structure and folding highly conserved in the two species.},
	pages = {6188--6192},
	number = {13},
	journaltitle = {J Biol Chem},
	author = {Presutti, C and Lucioli, A and Bozzoni, I},
	date = {1988},
	pmid = {2834365},
	keywords = {Animals, Base Sequence, Amino Acid Sequence, Bacterial Proteins/*genetics, Deoxyribonuclease {BamHI}, Deoxyribonuclease {EcoRI}, {DNA} Restriction Enzymes/metabolism, {DNA}/analysis, Molecular Sequence Data, Nucleic Acid Hybridization, Ribosomal Proteins/*genetics, Saccharomyces cerevisiae/*genetics, Xenopus laevis/*genetics}
}

@article{goodman_phylogenomic_2009,
	title = {Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries},
	volume = {106},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19926857},
	doi = {10.1073/pnas.0911239106},
	abstract = {Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and {dN}/{dS} ratios were determined. Then, from gene ontology information on genes with the higher {dN}/{dS} ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.},
	pages = {20824--20829},
	number = {49},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Goodman, M and Sterner, K N and Islam, M and Uddin, M and Sherwood, C C and Hof, P R and Hou, Z C and Lipovich, L and Jia, H and Grossman, L I and Wildman, D E},
	date = {2009},
	pmid = {19926857},
	keywords = {{DNA}, Animals, Humans, *Evolution, *Phylogeny, Adaptation, Elephants/*genetics, Fossils, Genome/*genetics, Mitochondrial/genetics, Molecular, Open Reading Frames/genetics, Phenotype, Physiological/*genetics}
}

@article{cuomo_italian_2014,
	title = {Italian consensus conference for colonic diverticulosis and diverticular disease},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25360320},
	doi = {10.1177/2050640614547068},
	abstract = {The statements produced by the Consensus Conference on Diverticular Disease promoted by {GRIMAD} (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease ({DD}) in patients with uncomplicated and complicated {DD} were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.},
	pages = {413--442},
	number = {5},
	journaltitle = {United European Gastroenterol J},
	author = {Cuomo, R and Barbara, G and Pace, F and Annese, V and Bassotti, G and Binda, G A and Casetti, T and Colecchia, A and Festi, D and Fiocca, R and Laghi, A and Maconi, G and Nascimbeni, R and Scarpignato, C and Villanacci, V and Annibale, B},
	date = {2014},
	pmid = {25360320}
}

@article{krylov_gene_2003,
	title = {Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14525925},
	doi = {10.1101/gr.1589103},
	abstract = {Lineage-specific gene loss, to a large extent, accounts for the differences in gene repertoires between genomes, particularly among eukaryotes. We derived a parsimonious scenario of gene losses for eukaryotic orthologous groups ({KOGs}) from seven complete eukaryotic genomes. The scenario involves substantial gene loss in fungi, nematodes, and insects. Based on this evolutionary scenario and estimates of the divergence times between major eukaryotic phyla, we introduce a numerical measure, the propensity for gene loss ({PGL}). We explore the connection among the propensity of a gene to be lost in evolution ({PGL} value), protein sequence divergence, the effect of gene knockout on fitness, the number of protein-protein interactions, and expression level for the genes in {KOGs}. Significant correlations between {PGL} and each of these variables were detected. Genes that have a lower propensity to be lost in eukaryotic evolution accumulate fewer substitutions in their protein sequences and tend to be essential for the organism viability, tend to be highly expressed, and have many interaction partners. The dependence between {PGL} and gene dispensability and interactivity is much stronger than that for sequence evolution rate. Thus, propensity of a gene to be lost during evolution seems to be a direct reflection of its biological importance.},
	pages = {2229--2235},
	number = {10},
	journaltitle = {Genome Res},
	author = {Krylov, D M and Wolf, Y I and Rogozin, I B and Koonin, E V},
	date = {2003},
	pmid = {14525925},
	keywords = {Animals, Conserved Sequence, Humans, Gene Expression Regulation, Nucleic Acid, *Evolution, *Gene Deletion, *Genetic Variation, Amino Acid Substitution/genetics, Encephalitozoon cuniculi/cytology/genetics, Essential/genetics, Eukaryotic Cells, Fungal Proteins/chemistry, Fungal/*genetics, Gene Expression Regulation/*genetics, Genes, Molecular, Phylogeny, Protein Interaction Mapping, Protein Structure, Proteins/*chemistry, Protozoan Proteins/chemistry, Protozoan/*genetics, Reference Values, Saccharomyces cerevisiae Proteins/chemistry, Saccharomyces cerevisiae/cytology/genetics, Schizosaccharomyces/cytology/genetics, Secondary/genetics, Sequence Homology}
}

@article{giordano_evolutionary_2007,
	title = {Evolutionary history of mammalian transposons determined by genome-wide defragmentation},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17630829},
	doi = {10.1371/journal.pcbi.0030137},
	abstract = {The constant bombardment of mammalian genomes by transposable elements ({TEs}) has resulted in {TEs} comprising at least 45\% of the human genome. Because of their great age and abundance, {TEs} are important in comparative phylogenomics. However, estimates of {TE} age were previously based on divergence from derived consensus sequences or phylogenetic analysis, which can be unreliable, especially for older more diverged elements. Therefore, a novel genome-wide analysis of {TE} organization and fragmentation was performed to estimate {TE} age independently of sequence composition and divergence or the assumption of a constant molecular clock. Analysis of {TEs} in the human genome revealed approximately 600,000 examples where {TEs} have transposed into and fragmented other {TEs}, covering {\textbackslash}textgreater40\% of all {TEs} or approximately 542 Mbp of genomic sequence. The relative age of these {TEs} over evolutionary time is implicit in their organization, because newer {TEs} have necessarily transposed into older {TEs} that were already present. A matrix of the number of times that each {TE} has transposed into every other {TE} was constructed, and a novel objective function was developed that derived the chronological order and relative ages of human {TEs} spanning {\textbackslash}textgreater100 million years. This method has been used to infer the relative ages across all four major {TE} classes, including the oldest, most diverged elements. Analysis of {DNA} transposons over the history of the human genome has revealed the early activity of some {MER}2 transposons, and the relatively recent activity of {MER}1 transposons during primate lineages. The {TEs} from six additional mammalian genomes were defragmented and analyzed. Pairwise comparison of the independent chronological orders of {TEs} in these mammalian genomes revealed species phylogeny, the fact that transposons shared between genomes are older than species-specific transposons, and a subset of {TEs} that were potentially active during periods of speciation.},
	pages = {e137},
	number = {7},
	journaltitle = {{PLoS} Comput Biol},
	author = {Giordano, J and Ge, Y and Gelfand, Y and Abrusan, G and Benson, G and Warburton, P E},
	date = {2007},
	pmid = {17630829},
	keywords = {Human, Animals, Base Sequence, Genetic, Genome, Humans, Mice, Mammals/*genetics, *Evolution, Base Pairing, Cattle, Chronobiology Phenomena/genetics, {DNA} Mutational Analysis/*methods, {DNA} Transposable Elements/*genetics, Dogs, Genetic Speciation, Haplorhini/genetics, Models, Molecular, Molecular Sequence Data, Phylogeny, Rats}
}

@article{liu_role_1995,
	title = {Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and {AP}-1-dependent gene activation},
	volume = {270},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7721728},
	abstract = {Irradiation of mammalian cells with short wavelength ultraviolet light ({UVC}) evokes a cascade of phosphorylation events leading to altered gene expression. Both the classic mitogen-activated protein ({MAP}) kinases and the distantly related c-Jun N-terminal kinases ({JNK}) contribute to the response via phosphorylation of transcription factors including {AP}-1. These kinases are themselves regulated via reversible phosphorylation, and several recently identified specific {MAP} kinase phosphatases ({MKP}) have been implicated in down-regulating {MAP} kinase-dependent gene expression in response to mitogens. Here, we provide evidence that {MKP}-1 plays a role in regulating transcriptional activation in response to {UVC} as well as another genotoxic agent, methyl methanesulfonate ({MMS}). We further demonstrate that {JNK} is a likely target for {MKP}-1. {JNK} is shown to be activated by {UVC} and {MMS} treatment, while {MAP} kinase activation occurs only with {UVC}. Like {JNK} activation, {MKP}-1 {mRNA} is induced by both treatments, and elevated {MKP}-1 expression coincides with a decline in {JNK} activity. Constitutive expression of {MKP}-1 in vivo inhibits {JNK} activity and reduces {UVC}- and {MMS}-induced activation of {AP}-1-dependent reporter genes.},
	pages = {8377--8380},
	number = {15},
	journaltitle = {J Biol Chem},
	author = {Liu, Y and Gorospe, M and Yang, C and Holbrook, N J},
	date = {1995},
	pmid = {7721728},
	keywords = {Animals, Humans, *Cell Cycle Proteins, *Gene Expression Regulation, *Mitogen-Activated Protein Kinases, *Phosphoprotein Phosphatases, Calcium-Calmodulin-Dependent Protein Kinases/*anta, Dual Specificity Phosphatase 1, Enzyme Induction, Enzymologic, {HeLa} Cells, Immediate-Early Proteins/biosynthesis/genetics/*me, {JNK} Mitogen-Activated Protein Kinases, Methyl Methanesulfonate/toxicity, Mutagens/*toxicity, Protein Phosphatase 1, Protein Tyrosine Phosphatases/biosynthesis/genetic, Rats, Substrate Specificity, Transcription Factor {AP}-1/*metabolism, Transcriptional Activation, Ultraviolet Rays}
}

@article{de_turris_top_2004,
	title = {{TOP} promoter elements control the relative ratio of intron-encoded {snoRNA} versus spliced {mRNA} biosynthesis},
	volume = {344},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15522292},
	doi = {10.1016/j.jmb.2004.09.049},
	abstract = {In vertebrates almost all {snoRNAs} are encoded in introns of a specific subclass of {polII} transcripts: the {TOP} genes. The majority of these {RNAs} originate through debranching of the spliced introns, the rest through endonucleolytic cleavage of the precursor that contains them. In both cases it has been suggested that {snoRNP} factors associate at early steps during transcription and control {snoRNA} biogenesis. Here, we analyzed the specific case of the U16 {snoRNA} that was shown to originate mainly through endonucleolytic cleavage. We show that {TOP} promoter elements determine a specific ratio of {snoRNA} and {mRNA} production. Under the control of these sequences the {snoRNA} is likely to originate from both splicing and cleavage of the pre-{mRNA}. Conversely, canonical {polII} promoter elements seem not to be compatible with {snoRNA} release through the cleavage reaction and produce a lower {snoRNA}/{mRNA} ratio. In addition, we show that the proximal part of the {TOP} promoter is responsible for this peculiar post-transcriptional process that controls the relative ratio between {snoRNA} and {mRNA}.},
	pages = {383--394},
	number = {2},
	journaltitle = {J Mol Biol},
	author = {de Turris, V and Di Leva, G and Caldarola, S and Loreni, F and Amaldi, F and Bozzoni, I},
	date = {2004},
	pmid = {15522292},
	keywords = {Animals, Genetic, Humans, {RNA}, *Promoter Regions, Introns, *{RNA} Splicing, Cell Line, Cell Nucleus/metabolism, Messenger/*biosynthesis, Microinjections, Oocytes/metabolism, Small Nuclear/*genetics/*metabolism, Small Nucleolar/*biosynthesis, Xenopus laevis}
}

@article{chang_efficacy_2013,
	title = {Efficacy of dilute hypochlorite solutions and an electrochemically activated saline solution containing hypochlorous acid for disinfection of methicillin-resistant Staphylococcus aureus in a pig skin model},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24113614},
	doi = {10.1086/673448},
	pages = {1231--1233},
	number = {11},
	journaltitle = {Infect Control Hosp Epidemiol},
	author = {Chang, B and Nerandzic, M M and Kundrapu, S and Sunkesula, V C and Deshpande, A and Donskey, C J},
	date = {2013},
	pmid = {24113614}
}

@article{lal_clean_2005,
	title = {Clean Western blot signals from immunoprecipitated samples},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16146684},
	doi = {10.1016/j.mcp.2005.06.007},
	abstract = {We present a strategy that overcomes the high background arising during Western blotting ({WB}) detection of proteins obtained through immunoprecipitation ({IP}). Traditional {HRP}-conjugated secondary antibodies, which detect the denatured heavy and light antibody chains, produce high background that often mask the signals of interest on {WBs}. Here, we show that {HRP}-conjugated Protein A and Protein G, which detect almost exclusively intact antibody molecules, can be effectively used to obtain clean and specific {WB} signals of target proteins.},
	pages = {385--388},
	number = {6},
	journaltitle = {Mol Cell Probes},
	author = {Lal, A and Haynes, S R and Gorospe, M},
	date = {2005},
	pmid = {16146684},
	keywords = {Protein Binding, Blotting, Horseradish Peroxidase/chemistry, Immunoglobulin Heavy Chains/chemistry/metabolism, Immunoglobulin Light Chains/chemistry/metabolism, Immunoprecipitation/*methods, Nerve Tissue Proteins/chemistry/metabolism, Staphylococcal Protein A/chemistry/metabolism, Western/*methods}
}

@article{ming_genome_2013,
	title = {Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.)},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23663246},
	doi = {10.1186/gb-2013-14-5-r41},
	abstract = {{BACKGROUND}: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. {RESULTS}: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5\% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30\% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 {COG}2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. {CONCLUSIONS}: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.},
	pages = {R41},
	number = {5},
	journaltitle = {Genome Biol},
	author = {Ming, R and Vanburen, R and Liu, Y and Yang, M and Han, Y and Li, L T and Zhang, Q and Kim, M J and Schatz, M C and Campbell, M and Li, J and Bowers, J E and Tang, H and Lyons, E and Ferguson, A A and Narzisi, G and Nelson, D R and Blaby-Haas, C E and Gschwend, A R and Jiao, Y and Der, J P and Zeng, F and Han, J and Min, X J and Hudson, K A and Singh, R and Grennan, A K and Karpowicz, S J and Watling, J R and Ito, K and Robinson, S A and Hudson, M E and Yu, Q and Mockler, T C and Carroll, A and Zheng, Y and Sunkar, R and Jia, R and Chen, N and Arro, J and Wai, C M and Wafula, E and Spence, A and Xu, L and Zhang, J and Peery, R and Haus, M J and Xiong, W and Walsh, J A and Wu, J and Wang, M L and Zhu, Y J and Paull, R E and Britt, A B and Du, C and Downie, S R and Schuler, M A and Michael, T P and Long, S P and Ort, D R and William Schopf, J and Gang, D R and Jiang, N and Yandell, M and Depamphilis, C W and Merchant, S S and Paterson, A H and Buchanan, B B and Li, S and Shen-Miller, J},
	date = {2013},
	pmid = {23663246}
}

@article{gorospe_protective_1999,
	title = {Protective function of von Hippel-Lindau protein against impaired protein processing in renal carcinoma cells},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9891063},
	abstract = {The absence of functional von Hippel-Lindau ({VHL}) tumor suppressor gene leads to the development of neoplasias characteristic of {VHL} disease, including renal cell carcinoma ({RCC}). Here, we compared the sensitivity of {RCC} cells lacking {VHL} gene function with that of {RCC} cells expressing the wild-type {VHL} gene ({wtVHL}) after exposure to various stresses. While the response to most treatments was not affected by the {VHL} gene status, glucose deprivation was found to be much more cytotoxic for {RCC} cells lacking {VHL} gene function than for {wtVHL}-expressing cells. The heightened sensitivity of {VHL}-deficient cells was not attributed to dissimilar energy requirements or to differences in glucose uptake, but more likely reflects a lesser ability of {VHL}-deficient cells to handle abnormally processed proteins arising from impaired glycosylation. In support of this hypothesis, other treatments which act through different mechanisms to interfere with protein processing (i.e., tunicamycin, brefeldin A, and azetidine) were also found to be much more toxic for {VHL}-deficient cells. Furthermore, ubiquitination of cellular proteins was elevated in {VHL}-deficient cells, particularly after glucose deprivation, supporting a role for the {VHL} gene in ubiquitin-mediated proteolysis. Accordingly, the rate of elimination of abnormal proteins was lower in cells lacking a functional {VHL} gene than in {wtVHL}-expressing cells. Thus, {pVHL} appears to participate in the elimination of misprocessed proteins, such as those arising in the cell due to the unavailability of glucose or to other stresses.},
	pages = {1289--1300},
	number = {2},
	journaltitle = {Mol Cell Biol},
	author = {Gorospe, M and Egan, J M and Zbar, B and Lerman, M and Geil, L and Kuzmin, I and Holbrook, N J},
	date = {1999},
	pmid = {9891063},
	keywords = {Base Sequence, Humans, {RNA}, Cultured, *Genes, *Ligases, *Tumor Suppressor Proteins, *Ubiquitin-Protein Ligases, 18S/genetics, Apoptosis, bcl-2, Carcinoma, Energy Metabolism, Genes, Glucose/metabolism, Glycosylation, Kidney Neoplasms/etiology/*genetics/*metabolism, Neoplasm Proteins/genetics/metabolism, Neoplasm/genetics, Post-Translational, Protein Processing, Proteins/*genetics/*metabolism, Renal Cell/etiology/*genetics/*metaboli, Ribosomal, Tumor Cells, Tumor Suppressor, Ubiquitins/metabolism, von Hippel-Lindau Disease/complications/*genetics/, Von Hippel-Lindau Tumor Suppressor Protein}
}

@article{akrami_comprehensive_2013,
	title = {Comprehensive analysis of long non-coding {RNAs} in ovarian cancer reveals global patterns and targeted {DNA} amplification},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24265805},
	doi = {10.1371/journal.pone.0080306},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are emerging as potent regulators of cell physiology, and recent studies highlight their role in tumor development. However, while established protein-coding oncogenes and tumor suppressors often display striking patterns of focal {DNA} copy-number alteration in tumors, similar evidence is largely lacking for {lncRNAs}. Here, we report on a genomic analysis of {GENCODE} {lncRNAs} in high-grade serous ovarian adenocarcinoma, based on The Cancer Genome Atlas ({TCGA}) molecular profiles. Using genomic copy-number data and deep coverage transcriptome sequencing, we derived dual copy-number and expression data for 10,419 {lncRNAs} across 407 primary tumors. We describe global correlations between {lncRNA} copy-number and expression, and associate established expression subtypes with distinct {lncRNA} signatures. By examining regions of focal copy-number change that lack protein-coding targets, we identified an intergenic {lncRNA} on chromosome 1, {OVAL}, that shows narrow focal genomic amplification in a subset of tumors. While weakly expressed in most tumors, focal amplification coincided with strong {OVAL} transcriptional activation. Screening of 16 other cancer types revealed similar patterns in serous endometrial carcinomas. This shows that intergenic {lncRNAs} can be specifically targeted by somatic copy-number amplification, suggestive of functional involvement in tumor initiation or progression. Our analysis provides testable hypotheses and paves the way for further study of {lncRNAs} based on {TCGA} and other large-scale cancer genomics datasets.},
	pages = {e80306},
	number = {11},
	journaltitle = {{PLoS} One},
	author = {Akrami, R and Jacobsen, A and Hoell, J and Schultz, N and Sander, C and Larsson, E},
	date = {2013},
	pmid = {24265805},
	keywords = {Humans, {RNA}, Long Noncoding/*genetics, Gene Expression Profiling, *Gene Amplification, *Transcriptome, Adenocarcinoma/genetics/pathology, Cluster Analysis, Endometrial Neoplasms/genetics/pathology, Female, Gene Dosage, Genetic Loci, Neoplasm Staging, Ovarian Neoplasms/*genetics/pathology}
}

@article{ale-agha_hur_2009,
	title = {{HuR} regulates gap junctional intercellular communication by controlling beta-catenin levels and adherens junction integrity},
	volume = {50},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19676129},
	doi = {10.1002/hep.23146},
	abstract = {Gap junctional intercellular communication ({GJIC}) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstrate that the {RNA}-binding protein {HuR} promotes {GJIC} through two mechanisms. First, {HuR} silencing lowered the levels of Cx43 protein and Cx43 messenger {RNA} ({mRNA}), and decreased Cx43 {mRNA} half-life. This regulation was likely due to the direct stabilization of Cx43 {mRNA} by {HuR}, because {HuR} associated directly with Cx43 {mRNA}, a transcript that bears signature adenylate-uridylate-rich ({AU}-rich) and uridylate-rich (U-rich) sequences in its 3'-untranslated region. Second, {HuR} silencing reduced both half-life and the levels of beta-catenin {mRNA}, also a target of {HuR}; accordingly, {HuR} silencing lowered the levels of whole-cell and membrane-associated beta-catenin. Coimmunoprecipitation experiments showed a direct interaction between beta-catenin and Cx43. Small interfering {RNA} ({siRNA})-mediated depletion of beta-catenin recapitulated the effects of decreasing {HuR} levels: it attenuated {GJIC}, decreased Cx43 levels, and redistributed Cx43 to the cytoplasm, suggesting that depletion of beta-catenin in {HuR}-silenced cells contributed to lowering Cx43 levels at the membrane. Finally, {HuR} was demonstrated to support {GJIC} after exposure to a genotoxic agent, doxorubicin, or an inducer of differentiation processes, retinoic acid, thus pointing to a crucial role of {HuR} in the cellular response to stress and in physiological processes modulated by {GJIC}. {CONCLUSION}: {HuR} promotes gap junctional intercellular communication in rat liver epithelial cells through two related regulatory processes, by enhancing the expression of Cx43 and by increasing the expression of beta-catenin, which, in turn, interacts with Cx43 and is required for proper positioning of Cx43 at the plasma membrane.},
	pages = {1567--1576},
	number = {5},
	journaltitle = {Hepatology},
	author = {Ale-Agha, N and Galban, S and Sobieroy, C and Abdelmohsen, K and Gorospe, M and Sies, H and Klotz, L O},
	date = {2009},
	pmid = {19676129},
	keywords = {Animals, {RNA}, Cells, Cultured, Adherens Junctions/*metabolism, Animal, Antigens, Antineoplastic Agents, beta Catenin/*metabolism, Cell Communication/*physiology, Cell Differentiation, Connexin 43/metabolism, Doxorubicin/pharmacology, Epithelial Cells/cytology/drug effects/*metabolism, Gap Junctions/*metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Inbred F344, Liver/cytology/drug effects/*metabolism, Messenger/metabolism, Models, Rats, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism, Tretinoin/pharmacology}
}

@article{elkan-miller_integration_2011,
	title = {Integration of transcriptomics, proteomics, and {microRNA} analyses reveals novel {microRNA} regulation of targets in the mammalian inner ear},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21483685},
	doi = {10.1371/journal.pone.0018195},
	abstract = {We have employed a novel approach for the identification of functionally important {microRNA} ({miRNA})-target interactions, integrating {miRNA}, transcriptome and proteome profiles and advanced in silico analysis using the {FAME} algorithm. Since {miRNAs} play a crucial role in the inner ear, demonstrated by the discovery of mutations in a {miRNA} leading to human and mouse deafness, we applied this approach to microdissected auditory and vestibular sensory epithelia. We detected the expression of 157 {miRNAs} in the inner ear sensory epithelia, with 53 {miRNAs} differentially expressed between the cochlea and vestibule. Functionally important {miRNAs} were determined by searching for enriched or depleted targets in the transcript and protein datasets with an expression consistent with the dogma of {miRNA} regulation. Importantly, quite a few of the targets were detected only in the protein datasets, attributable to regulation by translational suppression. We identified and experimentally validated the regulation of {PSIP}1-P75, a transcriptional co-activator previously unknown in the inner ear, by {miR}-135b, in vestibular hair cells. Our findings suggest that {miR}-135b serves as a cellular effector, involved in regulating some of the differences between the cochlear and vestibular hair cells.},
	pages = {e18195},
	number = {4},
	journaltitle = {{PLoS} One},
	author = {Elkan-Miller, T and Ulitsky, I and Hertzano, R and Rudnicki, A and Dror, A A and Lenz, D R and Elkon, R and Irmler, M and Beckers, J and Shamir, R and Avraham, K B},
	date = {2011},
	pmid = {21483685},
	keywords = {Gene Expression Profiling/*methods, Animals, Humans, Mice, {RNA}, Organ Specificity, *Systems Integration, 3' Untranslated Regions/genetics, Adaptor Proteins, Cochlea/metabolism, Down-Regulation, Ear, Epithelium/metabolism, Inner/*metabolism, Labyrinth/cytology/metabolism, Messenger/genetics/metabolism, {MicroRNAs}/*genetics/*metabolism, Proteomics/*methods, Signal Transducing/genetics/meta, Transcription Factors/genetics/metabolism, Up-Regulation, Vestibule}
}

@article{washietl_evolutionary_2014,
	title = {Evolutionary dynamics and tissue specificity of human long noncoding {RNAs} in six mammals},
	url = {http://genome.cshlp.org/content/early/2014/01/15/gr.165035.113.abstractN2 - Long intergenic noncoding RNAs (lincRNAs) play diverse regulatory roles in human development and disease, but little is known about their evolutionary history and constraint. Here},
	journaltitle = {Genome Res},
	author = {Washietl, Stefan and Kellis, Manolis and Garber, Manuel},
	date = {2014},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/EUC5JIPM/Washietl et al. - 2014 - Evolutionary dynamics and tissue specificity of hu.pdf:application/pdf}
}

@article{ulveling_identification_2011,
	title = {Identification of potentially new bifunctional {RNA} based on genome-wide data-mining of alternative splicing events},
	volume = {93},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21729736},
	doi = {10.1016/j.biochi.2011.06.019},
	abstract = {It is now evident that the transcriptional output of the genome is much more complex than estimates based on the number of protein-coding genes, and that non-coding {RNA} widely increase the source of regulatory molecules, a role previously ascribed to proteins. Furthermore, the recent characterization of bifunctional {RNA}, i.e. {RNA} for which both coding capacity and activity as functional {RNA} have been reported, adds an additional degree of complexity. Based on the {SRA} (Steroid Receptor {RNA} Activator) model, where bifunctionality is regulated by alternative splicing, we hypothesized that similar cases, not yet formally tested experimentally, might exist. Using freely available data from high-throughput sequencing projects, we propose here a bioinformatical identification of {mRNA} whose {ORF} are disrupted by alternative splicing events, especially by intron retention, and potentially representing a cognate non-coding {RNA}. Our data-mining approach revealed that the human genome contains around 300 possibilities of potentially new bifunctional {RNA}.},
	pages = {2024--2027},
	number = {11},
	journaltitle = {Biochimie},
	author = {Ulveling, D and Francastel, C and Hube, F},
	date = {2011},
	pmid = {21729736},
	keywords = {Human, Genome, Humans, {RNA}, Computational Biology, Exons/genetics, Untranslated/*genetics, Long Noncoding, Alternative Splicing/*genetics, Data Mining, Genome-Wide Association Study, Introns/genetics, Messenger/*genetics, Open Reading Frames/*genetics}
}

@article{maamar_linc-hoxa1_2013,
	title = {linc-{HOXA}1 is a noncoding {RNA} that represses Hoxa1 transcription in cis},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23723417},
	doi = {10.1101/gad.217018.113},
	abstract = {Recently, researchers have uncovered the presence of many long noncoding {RNAs} ({lncRNAs}) in embryonic stem cells and believe they are important regulators of the differentiation process. However, there are only a few examples explicitly linking {lncRNA} activity to transcriptional regulation. Here, we used transcript counting and spatial localization to characterize a {lncRNA} (dubbed linc-{HOXA}1) located approximately 50 kb from the Hoxa gene cluster in mouse embryonic stem cells. Single-cell transcript counting revealed that linc-{HOXA}1 and Hoxa1 {RNA} are highly variable at the single-cell level and that whenever linc-{HOXA}1 {RNA} abundance was high, Hoxa1 {mRNA} abundance was low and vice versa. Knockdown analysis revealed that depletion of linc-{HOXA}1 {RNA} at its site of transcription increased transcription of the Hoxa1 gene cis to the chromosome and that exposure of cells to retinoic acid can disrupt this interaction. We further showed that linc-{HOXA}1 {RNA} represses Hoxa1 by recruiting the protein {PURB} as a transcriptional cofactor. Our results highlight the power of transcript visualization to characterize {lncRNA} function and also suggest that {PURB} can facilitate {lncRNA}-mediated transcriptional regulation.},
	pages = {1260--1271},
	number = {11},
	journaltitle = {Genes Dev},
	author = {Maamar, H and Cabili, M N and Rinn, J and Raj, A},
	date = {2013},
	pmid = {23723417},
	keywords = {Animals, Mice, {RNA}, Transcription, *Gene Silencing, Cell Line, {DNA}-Binding Proteins/genetics/metabolism, Embryonic Stem Cells/metabolism, Gene Expression, Gene Knockdown Techniques, Genes, Genetic/*genetics, Homeobox/*genetics, Homeodomain Proteins/*genetics, Long Untranslated/analysis/biosynthesis/*gene, Multigene Family/genetics, {RNA} Isoforms/analysis/biosynthesis/genetics, Single-Cell Analysis, Transcription Factors/*genetics, Tretinoin}
}

@article{iruarrizaga-lejarreta_rna-binding_2012,
	title = {The {RNA}-binding protein human antigen R controls global changes in gene expression during Schwann cell development},
	volume = {32},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22492050},
	doi = {10.1523/JNEUROSCI.5868-11.2012},
	abstract = {An important prerequisite to myelination in peripheral nerves is the establishment of one-to-one relationships between axons and Schwann cells. This patterning event depends on immature Schwann cell proliferation, apoptosis, and morphogenesis, which are governed by coordinated changes in gene expression. Here, we found that the {RNA}-binding protein human antigen R ({HuR}) was highly expressed in immature Schwann cells, where genome-wide identification of its target {mRNAs} in vivo in mouse sciatic nerves using ribonomics showed an enrichment of functionally related genes regulating these processes. {HuR} coordinately regulated expression of several genes to promote proliferation, apoptosis, and morphogenesis in rat Schwann cells, in response to {NRG}1, {TGFbeta}, and laminins, three major signals implicated in this patterning event. Strikingly, {HuR} also binds to several {mRNAs} encoding myelination-related proteins but, contrary to its typical function, negatively regulated their expression, likely to prevent ectopic myelination during development. These functions of {HuR} correlated with its abundance and subcellular localization, which were regulated by different signals in Schwann cells.},
	pages = {4944--4958},
	number = {14},
	journaltitle = {J Neurosci},
	author = {Iruarrizaga-Lejarreta, M and Varela-Rey, M and Lozano, J J and Fernandez-Ramos, D and Rodriguez-Ezpeleta, N and Embade, N and Lu, S C and van der Kraan, P M and Blaney Davidson, E N and Gorospe, M and Mirsky, R and Jessen, K R and Aransay, A M and Mato, J M and Martinez-Chantar, M L and Woodhoo, A},
	date = {2012},
	pmid = {22492050},
	keywords = {Animals, Humans, Mice, Cells, Cultured, *Gene Expression Regulation, Apoptosis/physiology, Cell Proliferation, Developmental, Female, Hu Paraneoplastic Encephalomyelitis Antigens/biosy, Inbred C57BL, Male, Neurogenesis/*physiology, Newborn, Rats, {RNA}-Binding Proteins/*physiology, Schwann Cells/*cytology/*physiology, Wistar}
}

@article{nagi_n-cadherin_2005,
	title = {N-cadherin expression in breast cancer: correlation with an aggressive histologic variant–invasive micropapillary carcinoma},
	volume = {94},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16258702},
	doi = {10.1007/s10549-005-7727-5},
	abstract = {Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n = 114) for N- and E-cadherin. These specimens compared invasive duct carcinomas ({IDCs}) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast ({MPAP}), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-{MPAP} and {MPAP} {IDCs}, and between the invasive and ductal carcinoma in situ ({DCIS}) of each {IDC} using statistical analysis. We found that N-cadherin was expressed in 76\% of {MPAP} and 52\% of non-{MPAP} carcinomas, and E-cadherin in 57\% of {MPAP} and 36\% of non-{MPAP} tumors. More {MPAP} (25\%) compared to non-{MPAP} (5\%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with {MPAP} tumors (p = 0.033) compared to E-cad (p = 0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the {IDC} relative to intraductal components, and this effect was more dramatic in the {MPAP} carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the {MPAP} group (p = 0.005), whereas such changes were not significant in the non-{MPAP} group (p = 0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression.},
	pages = {225--235},
	number = {3},
	journaltitle = {Breast Cancer Res Treat},
	author = {Nagi, C and Guttman, M and Jaffer, S and Qiao, R and Keren, R and Triana, A and Li, M and Godbold, J and Bleiweiss, I J and Hazan, R B},
	date = {2005},
	pmid = {16258702},
	keywords = {Humans, *Neoplasm Invasiveness, Antigens, Breast Neoplasms/*pathology, Breast/*pathology, Cadherins/*biosynthesis/genetics, Carcinoma, {CD}, Disease Progression, Ductal, Female, Lymphatic Metastasis, Papillary/*pathology, Phenotype, Up-Regulation}
}

@article{yang_paml_2007,
	title = {{PAML} 4: phylogenetic analysis by maximum likelihood},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17483113},
	doi = {10.1093/molbev/msm088},
	abstract = {{PAML}, currently in version 4, is a package of programs for phylogenetic analyses of {DNA} and protein sequences using maximum likelihood ({ML}). The programs may be used to compare and test phylogenetic trees, but their main strengths lie in the rich repertoire of evolutionary models implemented, which can be used to estimate parameters in models of sequence evolution and to test interesting biological hypotheses. Uses of the programs include estimation of synonymous and nonsynonymous rates (d(N) and d(S)) between two protein-coding {DNA} sequences, inference of positive Darwinian selection through phylogenetic comparison of protein-coding genes, reconstruction of ancestral genes and proteins for molecular restoration studies of extinct life forms, combined analysis of heterogeneous data sets from multiple gene loci, and estimation of species divergence times incorporating uncertainties in fossil calibrations. This note discusses some of the major applications of the package, which includes example data sets to demonstrate their use. The package is written in {ANSI} C, and runs under Windows, Mac {OSX}, and {UNIX} systems. It is available at – (http://abacus.gene.ucl.ac.uk/software/paml.html).},
	pages = {1586--1591},
	number = {8},
	journaltitle = {Mol Biol Evol},
	author = {Yang, Z},
	date = {2007},
	pmid = {17483113},
	keywords = {Animals, Genetic, Software, *Likelihood Functions, *Phylogeny, Computer Simulation, Genetic Variation, Models, Selection, Species Specificity}
}

@article{yoon_ms2-trap_2012,
	title = {{MS}2-{TRAP} ({MS}2-tagged {RNA} affinity purification): tagging {RNA} to identify associated {miRNAs}},
	volume = {58},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22813890},
	doi = {10.1016/j.ymeth.2012.07.004},
	abstract = {Cellular transcripts of all types, including coding messenger (m){RNAs} and noncoding (nc){RNAs}, are subject to extensive post-transcriptional regulation. Among the factors that elicit post-transcriptional control, {microRNAs} ({miRNAs}) have emerged as a major class of small regulatory {RNAs}. Since {RNA}-{RNA} interactions can be modeled computationally, several excellent programs have been developed to predict the interaction of {miRNAs} with target transcripts. However, many such predictions are not realized for different reasons, including absent or low-abundance expression of the {miRNA} in the cell, the existence of competing factors or conformational changes masking the {microRNA} site, and the possibility that target transcripts are not present in the prediction databases, as is the case for long {ncRNAs}. Here, we provide a systematic approach termed {MS}2-{TRAP} (tagged {RNA} affinity purification) for identifying {miRNAs} associated with a target transcript in the cellular context. We illustrate the use of this methodology by identifying {microRNAs} that associate with a long intergenic (li){ncRNA}, based on the expression of the {lincRNA} tagged with {MS}2 {RNA} hairpins ({lincRNA}-p21-{MS}2) and the concomitant expression of a fusion protein recognizing the {MS}2 {RNA} hairpins, {MS}2-{GST}. After affinity pulldown of the ribonucleoprotein ({RNP}) complex comprising [{MS}2-{GST}/{lincRNA}-p21-{MS}2], the {RNA} in the pulldown material was isolated and reverse transcribed ({RT}). Subsequent assessment of the {microRNAs} present in the pulldown complex by using real-time quantitative (q){PCR} analysis led to the identification of bona fide {miRNAs} that interact with and control the abundance of {lincRNA}-p21. We describe alternative designs and applications of this approach, and discuss its implications in deciphering post-transcriptional gene regulatory schemes.},
	pages = {81--87},
	number = {2},
	journaltitle = {Methods},
	author = {Yoon, J H and Srikantan, S and Gorospe, M},
	date = {2012},
	pmid = {22813890},
	keywords = {Humans, Gene Expression Regulation, *{MicroRNAs}/chemistry/genetics, *{RNA}, *{RNA}/chemistry/genetics, Affinity, Chromatography, Computational Biology/*methods, Gene Regulatory Networks, Long Noncoding/chemistry/genetics, Messenger/chemistry/genetics}
}

@article{goodier_discrete_2010,
	title = {Discrete subcellular partitioning of human retrotransposon {RNAs} despite a common mechanism of genome insertion},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20147320},
	doi = {10.1093/hmg/ddq048},
	abstract = {Despite the immense significance retrotransposons have had for genome evolution much about their biology is unknown, including the processes of forming their ribonucleoprotein ({RNP}) particles and transporting them about the cell. Suppression of retrotransposon expression, together with the presence of retrotransposon sequence within numerous {mRNAs}, makes tracking endogenous L1 {RNP} particles in cells problematic. We overcame these difficulties by assaying in living and fixed cells tagged-{RNPs} generated from constructs expressing retrotransposition-competent L1s. In this way, we demonstrate for the first time the subcellular colocalization of L1 {RNA} and proteins {ORF}1p and {ORF}2p, and show their targeting together to cytoplasmic foci. Foci are often associated with markers of cytoplasmic stress granules. Furthermore, mutation analyses reveal that {ORF}1p can direct L1 {RNP} distribution within the cell. We also assayed {RNA} localization of the non-autonomous retrotransposons Alu and {SVA}. Despite a requirement for the L1 integration machinery, each manifests unique features of subcellular {RNA} distribution. In nuclei Alu {RNA} forms small round foci partially associated with marker proteins for coiled bodies, suborganelles involved in the processing of non-coding {RNAs}. {SVA} {RNA} patterning is distinctive, being cytoplasmic but without prominent foci and concentrated in large nuclear aggregates that often ring nucleoli. Such variability predicts significant differences in the life cycles of these elements.},
	pages = {1712--1725},
	number = {9},
	journaltitle = {Hum Mol Genet},
	author = {Goodier, J L and Mandal, P K and Zhang, L and Kazazian Jr., H H},
	date = {2010},
	pmid = {20147320},
	keywords = {Humans, Open Reading Frames, Cell Line, Cloning, Cytoplasm/*metabolism, {DNA} Primers, Fluorescence, Fluorescent Antibody Technique, In Situ Hybridization, Molecular, Plasmids/genetics, Retroelements/*genetics, Reverse Transcription/genetics/*physiology, Ribonucleoproteins/genetics/*metabolism, {RNA}/genetics/*metabolism}
}

@article{hsieh_translational_2012,
	title = {The translational landscape of {mTOR} signalling steers cancer initiation and metastasis},
	volume = {485},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22367541},
	doi = {10.1038/nature10912},
	abstract = {The mammalian target of rapamycin ({mTOR}) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic {mTOR} signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger {RNAs} that we show direct prostate cancer invasion and metastasis downstream of oncogenic {mTOR} signalling. Furthermore, we develop a clinically relevant {ATP} site inhibitor of {mTOR}, {INK}128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted.},
	pages = {55--61},
	number = {7396},
	journaltitle = {Nature},
	author = {Hsieh, A C and Liu, Y and Edlind, M P and Ingolia, N T and Janes, M R and Sher, A and Shi, E Y and Stumpf, C R and Christensen, C and Bonham, M J and Wang, S and Ren, P and Martin, M and Jessen, K and Feldman, M E and Weissman, J S and Shokat, K M and Rommel, C and Ruggero, D},
	date = {2012},
	pmid = {22367541},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Regulation, *Neoplasm Metastasis/drug therapy/genetics, *Protein Biosynthesis, *Signal Transduction, Adaptor Proteins, Benzoxazoles/pharmacology, Cell Line, Cell Movement/drug effects/genetics, Eukaryotic Initiation Factor-4E/metabolism, Eukaryotic Initiation Factors/metabolism, Genome/genetics, Inbred C57BL, Male, Messenger/genetics/metabolism, Neoplasm Invasiveness/genetics, Neoplastic/drug effect, Phosphoproteins/metabolism, Prostatic Neoplasms/drug therapy/genetics/*patholo, Pyrimidines/pharmacology, Repressor Proteins/metabolism, Signal Transducing/metabolism, {TOR} Serine-Threonine Kinases/antagonists \& inhibit, Tumor}
}

@article{chang_hur_2010,
	title = {{HuR} uses {AUF}1 as a cofactor to promote p16INK4 {mRNA} decay},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20498276},
	doi = {10.1128/MCB.00169-10},
	abstract = {In this study, we show that {HuR} destabilizes p16({INK}4) {mRNA}. Although the knockdown of {HuR} or {AUF}1 increased p16 expression, concomitant {AUF}1 and {HuR} knockdown had a much weaker effect. The knockdown of Ago2, a component of the {RNA}-induced silencing complex ({RISC}), stabilized p16 {mRNA}. The knockdown of {HuR} diminished the association of the p16 3' untranslated region (3'{UTR}) with {AUF}1 and vice versa. While the knockdown of {HuR} or {AUF}1 reduced the association of Ago2 with the p16 3'{UTR}, Ago2 knockdown had no influence on {HuR} or {AUF}1 binding to the p16 3'{UTR}. The use of {EGFP}-p16 chimeric reporter transcripts revealed that p16 {mRNA} decay depended on a stem-loop structure present in the p16 3'{UTR}, as {HuR} and {AUF}1 destabilized {EGFP}-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and {HuR}-silenced {IDH}4 human diploid fibroblasts, the {EGFP}-p16 3'{UTR} transcript was more stable. Our results suggest that {HuR} destabilizes p16 {mRNA} by recruiting the {RISC}, an effect that depends on the secondary structure of the p16 3'{UTR} and requires {AUF}1 as a cofactor.},
	pages = {3875--3886},
	number = {15},
	journaltitle = {Mol Cell Biol},
	author = {Chang, N and Yi, J and Guo, G and Liu, X and Shang, Y and Tong, T and Cui, Q and Zhan, M and Gorospe, M and Wang, W},
	date = {2010},
	pmid = {20498276},
	keywords = {Base Sequence, Humans, {RNA}, Gene Expression Regulation, Fibroblasts/metabolism, Messenger/genetics/*metabolism, {RNA} Stability/*genetics, {RNA}-Induced Silencing Complex/genetics/metabolism}
}

@article{saade_appropriateness_2013,
	title = {Appropriateness of empiric therapy in patients with suspected Clostridium difficile infection},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23663129},
	doi = {10.1185/03007995.2013.803956},
	abstract = {{OBJECTIVE}: The objective of this study was to test the hypothesis that many patients with suspected Clostridium difficile infection ({CDI}) receive inappropriate empiric therapy and/or receive continued therapy despite negative test results. {METHODS}: We performed a 3 month prospective cohort study at the Cleveland Veteran Affairs Medical Center to assess the appropriateness of empiric {CDI} therapy for all patients with stool samples submitted for {CDI} testing. Empiric therapy for {CDI} was considered appropriate if patients with suspected {CDI} had findings suggestive of severe or complicated illness. {RESULTS}: Of 251 patients tested for {CDI}, 53 (21\%) received empiric treatment, including 45 (85\%) treated with metronidazole and 8 (15\%) treated with vancomycin. Of the 53 empirical therapy regimens, only 20 (38\%) were deemed appropriate based on criteria for severe or severe, complicated {CDI} and 39 (74\%) had negative laboratory testing for {CDI}. Twenty-one of 39 (54\%) patients with negative testing were continued on therapy for three or more days despite the negative results. The key limitations of the study are the fact that it was conducted in a single institution and had a small sample size. {CONCLUSION}: In our facility, empiric treatment for {CDI} was common and more than half of empirical treatment was deemed inappropriate because patients did not meet criteria for severe {CDI}. Because {CDI} therapy may be associated with adverse effects, there is a need for interventions to improve the appropriateness of empiric {CDI} treatment.},
	pages = {985--988},
	number = {8},
	journaltitle = {Curr Med Res Opin},
	author = {Saade, E and Deshpande, A and Kundrapu, S and Sunkesula, V C and Guerrero, D M and Jury, L A and Donskey, C J},
	date = {2013},
	pmid = {23663129},
	keywords = {Humans, Aged, Clostridium difficile/*isolation \& purification, Clostridium Infections/*drug therapy/microbiology, Female, Male}
}

@article{bu_noncode_2012,
	title = {{NONCODE} v3.0: integrative annotation of long noncoding {RNAs}},
	volume = {40},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22135294},
	doi = {10.1093/nar/gkr1175},
	abstract = {Facilitated by the rapid progress of high-throughput sequencing technology, a large number of long noncoding {RNAs} ({lncRNAs}) have been identified in mammalian transcriptomes over the past few years. {LncRNAs} have been shown to play key roles in various biological processes such as imprinting control, circuitry controlling pluripotency and differentiation, immune responses and chromosome dynamics. Notably, a growing number of {lncRNAs} have been implicated in disease etiology. With the increasing number of published {lncRNA} studies, the experimental data on {lncRNAs} (e.g. expression profiles, molecular features and biological functions) have accumulated rapidly. In order to enable a systematic compilation and integration of this information, we have updated the {NONCODE} database (http://www.noncode.org) to version 3.0 to include the first integrated collection of expression and functional {lncRNA} data obtained from re-annotated microarray studies in a single database. {NONCODE} has a user-friendly interface with a variety of search or browse options, a local Genome Browser for visualization and a {BLAST} server for sequence-alignment search. In addition, {NONCODE} provides a platform for the ongoing collation of {ncRNAs} reported in the literature. All data in {NONCODE} are open to users, and can be downloaded through the website or obtained through the {SOAP} {API} and {DAS} services.},
	pages = {D210--5},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Bu, D and Yu, K and Sun, S and Xie, C and Skogerbo, G and Miao, R and Xiao, H and Liao, Q and Luo, H and Zhao, G and Zhao, H and Liu, Z and Liu, C and Chen, R and Zhao, Y},
	date = {2012},
	pmid = {22135294},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Profiling, Nucleic Acid, *Databases, *Molecular Sequence Annotation, Systems Integration, Untranslated/*chemistry/*metabolism}
}

@article{shalem_genome-scale_2014,
	title = {Genome-scale {CRISPR}-Cas9 knockout screening in human cells},
	volume = {343},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24336571},
	doi = {10.1126/science.1247005},
	abstract = {The simplicity of programming the {CRISPR} (clustered regularly interspaced short palindromic repeats)-associated nuclease Cas9 to modify specific genomic loci suggests a new way to interrogate gene function on a genome-wide scale. We show that lentiviral delivery of a genome-scale {CRISPR}-Cas9 knockout ({GeCKO}) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells. First, we used the {GeCKO} library to identify genes essential for cell viability in cancer and pluripotent stem cells. Next, in a melanoma model, we screened for genes whose loss is involved in resistance to vemurafenib, a therapeutic {RAF} inhibitor. Our highest-ranking candidates include previously validated genes {NF}1 and {MED}12, as well as novel hits {NF}2, {CUL}3, {TADA}2B, and {TADA}1. We observe a high level of consistency between independent guide {RNAs} targeting the same gene and a high rate of hit confirmation, demonstrating the promise of genome-scale screening with Cas9.},
	pages = {84--87},
	number = {6166},
	journaltitle = {Science},
	author = {Shalem, O and Sanjana, N E and Hartenian, E and Shi, X and Scott, D A and Mikkelsen, T S and Heckl, D and Ebert, B L and Root, D E and Doench, J G and Zhang, F},
	date = {2014},
	pmid = {24336571},
	keywords = {Genetic, Humans, *Clustered Regularly Interspaced Short Palindromic, Adaptor Proteins, Caspase 9/*genetics, Cell Survival/*genetics, Cullin Proteins/genetics, Drug Resistance, Gene Knockout Techniques, Gene Library, Genes, Genetic Loci, Genetic Testing/*methods, Genome-Wide Association Study, Indoles/therapeutic use, Lentivirus, Mediator Complex/genetics, Melanoma/drug therapy/*genetics, Neoplasm/*genetics, Neurofibromatosis 1, Neurofibromatosis 2, Pluripotent Stem Cells/*metabolism, Protein Kinase Inhibitors/therapeutic use, raf Kinases/antagonists \& inhibitors, Selection, Signal Transducing/genetics, Sulfonamides/therapeutic use, Transcription Factors/genetics}
}

@article{orlov_quality_2007,
	title = {Quality assessment of the Affymetrix U133A\&B probesets by target sequence mapping and expression data analysis},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18415975},
	abstract = {Careful analysis of microarray probe design should be an obligatory component of {MicroArray} Quality Control ({MACQ}) project [Patterson et al., 2006; Shi et al., 2006] initiated by the {FDA} ({USA}) in order to provide quality control tools to researchers of gene expression profiles and to translate the microarray technology from bench to bedside. The identification and filtering of unreliable probesets are important preprocessing steps before analysis of microarray data. These steps may result in an essential improvement in the selection of differentially expressed genes, gene clustering and construction of co-regulatory expression networks. We revised genome localization of the Affymetrix U133A\&B {GeneChip} initial (target) probe sequences, and evaluated the impact of erroneous and poorly annotated target sequences on the quality of gene expression data. We found about 25\% of Affymetrix target sequences overlapping with interspersed repeats that could cause cross-hybridization effects. In total, discrepancies in target sequence annotation account for up to approximately 30\% of 44692 Affymetrix probesets. We introduce a novel quality control algorithm based on target sequence mapping onto genome and {GeneChip} expression data analysis. To validate the quality of probesets we used expression data from large, clinically and genetically distinct groups of breast cancers (249 samples). For the first time, we quantitatively evaluated the effect of repeats and other sources of inadequate probe design on the specificity, reliability and discrimination ability of Affymetrix probesets. We propose that only functionally reliable Affymetrix probesets that passed our quality control algorithm (approximately 86\%) for gene expression analysis should be utilized. The target sequence annotation and filtering is available upon request.},
	pages = {241--260},
	number = {3},
	journaltitle = {In Silico Biol},
	author = {Orlov, Y L and Zhou, J and Lipovich, L and Shahab, A and Kuznetsov, V A},
	date = {2007},
	pmid = {18415975},
	keywords = {Human, Gene Expression Profiling/*methods, Genetic, Humans, {RNA}, Messenger/genetics, *Genome, Reproducibility of Results, *Chromosome Mapping, *Oligonucleotide Array Sequence Analysis, Expressed Sequence Tags, Models}
}

@article{chu_genomic_2011,
	title = {Genomic maps of long noncoding {RNA} occupancy reveal principles of {RNA}-chromatin interactions},
	volume = {44},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21963238},
	doi = {10.1016/j.molcel.2011.08.027},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are key regulators of chromatin state, yet the nature and sites of {RNA}-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by {RNA} Purification ({ChIRP}), where tiling oligonucleotides retrieve specific {lncRNAs} with bound protein and {DNA} sequences, which are enumerated by deep sequencing. {ChIRP}-seq of three {lncRNAs} reveal that {RNA} occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila {roX}2 {RNA} occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at {CES} sites. Human telomerase {RNA} {TERC} occupies telomeres and Wnt pathway genes. {HOTAIR} {lncRNA} preferentially occupies a {GA}-rich {DNA} motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. {HOTAIR} occupancy occurs independently of {EZH}2, suggesting the order of {RNA} guidance of Polycomb occupancy. {ChIRP}-seq is generally applicable to illuminate the intersection of {RNA} and chromatin with newfound precision genome wide.},
	pages = {667--678},
	number = {4},
	journaltitle = {Mol Cell},
	author = {Chu, C and Qu, K and Zhong, F L and Artandi, S E and Chang, H Y},
	date = {2011},
	pmid = {21963238},
	keywords = {Animals, Base Sequence, Humans, {RNA}, *Genomics, *High-Throughput Screening Assays, *{RNA}, Breast Neoplasms/genetics/metabolism, Cell Line, Chromatin Assembly and Disassembly/*genetics, Chromatin/*chemistry/genetics/metabolism, Chromosome Mapping/*methods, {DNA}-Binding Proteins/genetics/metabolism, Drosophila melanogaster/genetics/metabolism, Drosophila Proteins/genetics/metabolism, Female, Genome-Wide Association Study, Histones/genetics/metabolism, Long Untranslated, Male, Molecular Sequence Data, Nucleotide Motifs/genetics, Polycomb Repressive Complex 2, {RNA}-Binding Proteins/genetics/metabolism, {RNA}/genetics/metabolism, Telomerase/genetics/metabolism, Transcription Factors/genetics/metabolism, Tumor, Untranslated/chemistry/genetics/metabolism, Wnt Signaling Pathway/genetics}
}

@article{futreal_census_2004,
	title = {A census of human cancer genes},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14993899},
	doi = {10.1038/nrc1299},
	pages = {177--183},
	number = {3},
	journaltitle = {Nat Rev Cancer},
	author = {Futreal, P A and Coin, L and Marshall, M and Down, T and Hubbard, T and Wooster, R and Rahman, N and Stratton, M R},
	date = {2004},
	pmid = {14993899},
	keywords = {Human, Humans, *Genome, *Mutation, Genes/*genetics, Neoplasms/*genetics, Oncogenes/genetics}
}

@article{mcveigh_real-time_2006,
	title = {Real-time interactive {MRI}-guided cardiac surgery: aortic valve replacement using a direct apical approach},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17036300},
	doi = {10.1002/mrm.21044},
	abstract = {Minimally invasive cardiac surgery requires arresting and emptying of the heart, which compromises visualization of the surgical field. In this feasibility study a novel surgical procedure is demonstrated in which real-time {MRI} is used to guide the placement of a prosthetic aortic valve in the beating heart via direct apical access in eight porcine hearts. A clinical stentless bioprosthetic valve affixed to a platinum stent was compressed onto a balloon-tipped catheter. This was fed through a 15-18-mm delivery port inserted into the left ventricular ({LV}) apex via a minimally invasive subxyphoid incision. Using interactive real-time {MRI}, the surgeon implanted the prosthetic valve in the correct location at the aortic annulus within 90 s. In four of the animals immediately after implantation, ventricular function, blood flow through the valve, and myocardial perfusion were evaluated with {MRI}. {MRI}-guided beating-heart surgery may provide patients with a less morbid and more durable solution to structural heart disease.},
	pages = {958--964},
	number = {5},
	journaltitle = {Magn Reson Med},
	author = {{McVeigh}, E R and Guttman, M A and Lederman, R J and Li, M and Kocaturk, O and Hunt, T and Kozlov, S and Horvath, K A},
	date = {2006},
	pmid = {17036300},
	keywords = {Animals, *Heart Valve Prosthesis, Aortic Valve/*anatomy \& histology/*surgery, Computer Systems, Computer-Assisted/*instrumentation/method, Equipment Design, Equipment Failure Analysis, Heart Valve Prosthesis Implantation/*instrumentati, Magnetic Resonance Imaging/*instrumentation/method, Surgery, Swine, User-Computer Interface}
}

@article{rapicavoli_mammalian_2013,
	title = {A mammalian pseudogene {lncRNA} at the interface of inflammation and anti-inflammatory therapeutics},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23898399},
	doi = {10.7554/eLife.00762},
	abstract = {Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse {lncRNAs} induced by inflammatory signaling via {TNFalpha}. {TNFalpha} regulates hundreds of {lncRNAs}, including 54 pseudogene {lncRNAs}, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a {NF}-{kappaB}-dependent manner. Lethe, a pseudogene {lncRNA}, is selectively induced by proinflammatory cytokines via {NF}-{kappaB} or glucocorticoid receptor agonist, and functions in negative feedback signaling to {NF}-{kappaB}. Lethe interacts with {NF}-{kappaB} subunit {RelA} to inhibit {RelA} {DNA} binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased {NF}-{kappaB} activity. These findings suggest that expression of pseudogenes {lncRNAs} are actively regulated and constitute functional regulators of inflammatory signaling. {DOI}:http://dx.doi.org/10.7554/{eLife}.00762.001.},
	pages = {e00762},
	journaltitle = {Elife},
	author = {Rapicavoli, N A and Qu, K and Zhang, J and Mikhail, M and Laberge, R M and Chang, H Y},
	date = {2013},
	pmid = {23898399}
}

@article{sun_long_2013,
	title = {Long noncoding {RNAs} regulate adipogenesis},
	volume = {110},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23401553},
	doi = {10.1073/pnas.1222643110},
	abstract = {The prevalence of obesity has led to a surge of interest in understanding the detailed mechanisms underlying adipocyte development. Many protein-coding genes, {mRNAs}, and {microRNAs} have been implicated in adipocyte development, but the global expression patterns and functional contributions of long noncoding {RNA} ({lncRNA}) during adipogenesis have not been explored. Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 {lncRNAs} that are specifically regulated during adipogenesis. Many {lncRNAs} are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor gamma ({PPARgamma}) and {CCAAT}/enhancer-binding protein alpha ({CEBPalpha}). {RNAi}-mediated loss of function screens identified functional {lncRNAs} with varying impact on adipogenesis. Collectively, we have identified numerous {lncRNAs} that are functionally required for proper adipogenesis.},
	pages = {3387--3392},
	number = {9},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Sun, L and Goff, L A and Trapnell, C and Alexander, R and Lo, K A and Hacisuleyman, E and Sauvageau, M and Tazon-Vega, B and Kelley, D R and Hendrickson, D G and Yuan, B and Kellis, M and Lodish, H F and Rinn, J L},
	date = {2013},
	pmid = {23401553},
	keywords = {Animals, Mice, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Reproducibility of Results, Adipogenesis/*genetics, Gene Knockdown Techniques, Information Theory, Long Noncoding/genetics/*metabolism, Male, Open Reading Frames/genetics, Phenotype, Transcriptome/genetics}
}

@article{mazan-mamczarz_atm_2011,
	title = {{ATM} regulates a {DNA} damage response posttranscriptional {RNA} operon in lymphocytes},
	volume = {117},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21209379},
	doi = {10.1182/blood-2010-09-310987},
	abstract = {Maintenance of genomic stability depends on the {DNA} damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated ({ATM}) dysfunction. {ATM} activates multiple cell-cycle checkpoints and {DNA} repair after {DNA} damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the {RNA}-binding protein {HuR} with target {mRNAs} in an {ATM}-dependent manner, potentially coordinating the genotoxic response as an {RNA} operon. Pharmacologic {ATM} inhibition and use of {ATM}-null cells revealed a critical role for {ATM} in this process. Numerous {mRNAs} encoding cancer-related proteins were differentially associated with {HuR} depending on the functional state of {ATM}, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of {ATM} in controlling gene expression posttranscriptionally. Dysregulation of this {DNA} damage response {RNA} operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel {RNA} regulatory modules and genetic networks provide critical insight into the function of {ATM} in oncogenesis.},
	pages = {2441--2450},
	number = {8},
	journaltitle = {Blood},
	author = {Mazan-Mamczarz, K and Hagner, P R and Zhang, Y and Dai, B and Lehrmann, E and Becker, K G and Keene, J D and Gorospe, M and Liu, Z and Gartenhaus, R B},
	date = {2011},
	pmid = {21209379},
	keywords = {Humans, {RNA}, *{DNA} Damage, *Gene Expression Regulation, Antigens, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins/*genetics, {DNA} Repair, {DNA}-Binding Proteins/*genetics, Gene Regulatory Networks, Hu Paraneoplastic Encephalomyelitis Antigens, Ionizing, Lymphocytes/*metabolism, Lymphoma/etiology, Messenger/metabolism, Mutant Proteins, Operon/*genetics, Protein Binding/radiation effects, Protein-Serine-Threonine Kinases/*genetics, Radiation, {RNA}-Binding Proteins/metabolism, Surface/metabolism, Tumor Suppressor Proteins/*genetics}
}

@article{amaldi_nucleotide_1982,
	title = {Nucleotide sequences of cloned {cDNA} fragments specific for six Xenopus laevis ribosomal proteins},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7049839},
	abstract = {We have previously constructed and selected six recombinant plasmids containing {cDNA} sequences specific for different ribosomal proteins of Xenopus laevis (Bozzoni et al., 1981). {DNA} cloned in these plasmids have been isolated and sequenced. Amino acid sequences of the corresponding portions of the proteins have been derived from {DNA} sequences; they are arginine- and lysine-rich as expected for ribosomal proteins. One of the {cDNA} sequences has an open reading frame also on the strand complementary to the one coding for the ribosomal protein; this fragment has inverted repeats twenty nucleotides lone at the two ends. The codon usage for the six sequences appears to be non-random with some differences among the ribosomal proteins analysed.},
	pages = {311--316},
	number = {3},
	journaltitle = {Gene},
	author = {Amaldi, F and Beccari, E and Bozzoni, I and Luo, Z X and Pierandrei-Amaldi, P},
	date = {1982},
	pmid = {7049839},
	keywords = {{DNA}, Animals, Base Sequence, Escherichia coli/genetics, Genes, Molecular Sequence Data, Plasmids, Recombinant/*analysis, Ribosomal Proteins/*genetics, Xenopus laevis/*genetics}
}

@article{hall_evolution_1980,
	title = {Evolution of sea urchin non-repetitive {DNA}},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7463491},
	abstract = {New methods have been applied to the determination of single copy {DNA} sequence differences between the sea urchin species Strongylocentrotus purpuratus, S. franciscanus, S. drobachiensis, and Lytechinus pictus. The thermal stability of interspecies {DNA} duplexes was measured in a solvent (2.4 M tetraethylammonium chloride) that suppresses the effect of base composition on melting temperature. The lengths of duplexes were measured after digestion with S1 nuclease and correction made for the effect of length on thermal stability. The degree of base substitution that has occurred in the single copy {DNA} during sea urchin evolution is significantly larger than indicated by earlier measurements. We estimate that 19\% of the nucleotides of the single copy {DNA} are different in the genomes of the two sea urchin congeners, S. purpuratus, and S. franciscanus, which apparently diverged only 15 to 20 million years ago.},
	pages = {95--110},
	number = {2},
	journaltitle = {J Mol Evol},
	author = {Hall, T J and Grula, J W and Davidson, E H and Britten, R J},
	date = {1980},
	pmid = {7463491},
	keywords = {Animals, Base Sequence, *Biological Evolution, {DNA}/*genetics, Drug Stability, Kinetics, Nucleic Acid Denaturation, Sea Urchins/*genetics, Species Specificity}
}

@article{laneve_minicircuitry_2010,
	title = {A minicircuitry involving {REST} and {CREB} controls {miR}-9-2 expression during human neuronal differentiation},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20624818},
	doi = {10.1093/nar/gkq604},
	abstract = {{miRNAs} play key roles in the nervous system, where they mark distinct developmental stages. Accordingly, dysregulation of {miRNA} expression may have profound effects on neuronal physiology and pathology, including cancer. Among the neuronal {miRNAs}, {miR}-9 was shown to be upregulated during in vitro neuronal differentiation and downregulated in 50\% of primary neuroblastoma tumors, suggesting a potential function as an oncosuppressor gene. In this study we characterized the promoter and the transcriptional regulation of the {miR}-9-2 gene during neuronal differentiation. We found that, despite its localization inside an exon of a putative host-gene, {miR}-9-2 is expressed as an independent unit with the promoter located in the upstream intron. By promoter fusion and mutational analyses, together with {RNAi} and Chromatin immunoprecipitation assays, we demonstrated that the concerted action of the master transcriptional factors {RE}1-silencing transcription factor ({REST}) and {cAMP}-response element binding protein ({CREB}) on {miR}-9-2 promoter induces {miRNA} expression during differentiation. We showed that the repressor {REST} inhibits the activity of the {miR}-9-2 promoter in undifferentiated neuroblastoma cells, whereas {REST} dismissal and phosphorylation of {CREB} trigger transcription in differentiating cells. Finally, a regulatory feed-back mechanism, in which the reciprocal action of {miR}-9 and {REST} may be relevant for the maintenance of the neuronal differentiation program, is shown.},
	pages = {6895--6905},
	number = {20},
	journaltitle = {Nucleic Acids Res},
	author = {Laneve, P and Gioia, U and Andriotto, A and Moretti, F and Bozzoni, I and Caffarelli, E},
	date = {2010},
	pmid = {20624818},
	keywords = {Genetic, Humans, Promoter Regions, Transcription, Transcription Initiation Site, Transcription Factors/metabolism, Gene Expression Profiling, Cells, Cultured, *Gene Expression Regulation, Cell Differentiation, Cyclic {AMP} Response Element-Binding Protein/*metab, {MicroRNAs}/*genetics/metabolism, Neurons/cytology/*metabolism, Repressor Proteins/*metabolism}
}

@article{paz_spike:_2011,
	title = {{SPIKE}: a database of highly curated human signaling pathways},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21097778},
	doi = {10.1093/nar/gkq1167},
	abstract = {The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. {SPIKE} (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/\&∼spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator\’s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing {DNA} damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways.},
	pages = {D793--9},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Paz, A and Brownstein, Z and Ber, Y and Bialik, S and David, E and Sagir, D and Ulitsky, I and Elkon, R and Kimchi, A and Avraham, K B and Shiloh, Y and Shamir, R},
	date = {2011},
	pmid = {21097778},
	keywords = {Humans, *Databases, *Signal Transduction, Apoptosis, Cell Cycle, {DNA} Damage, Factual, Intercellular Signaling Peptides and Proteins/*met}
}

@article{ulitsky_towards_2009,
	title = {Towards accurate imputation of quantitative genetic interactions},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20003301},
	doi = {10.1186/gb-2009-10-12-r140},
	abstract = {Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40\% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.},
	pages = {R140},
	number = {12},
	journaltitle = {Genome Biol},
	author = {Ulitsky, I and Krogan, N J and Shamir, R},
	date = {2009},
	pmid = {20003301},
	keywords = {Genomics/*methods, Genetic, Databases, *Genetic Techniques, Epistasis, Fungal/*genetics, Genes, Genetic/*genetics, Linear Models, Saccharomyces cerevisiae/*genetics}
}

@article{srikantan_hur_2012,
	title = {{HuR} function in disease},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22201738},
	abstract = {The cytoplasmic events that control mammalian gene expression, primarily {mRNA} stability and translation, potently influence the cellular response to internal and external signals. The ubiquitous {RNA}-binding protein ({RBP}) {HuR} is one of the best-studied regulators of cytoplasmic {mRNA} fate. Through its post-transcriptional influence on specific target {mRNAs}, {HuR} can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli. In light of its central role in important cellular functions, {HuR}'s role in diseases in which these responses are aberrant is increasingly appreciated. Here, we review the mechanisms that control {HuR} function, its influence on target {mRNAs}, and how impairment in {HuR}-governed gene expression programs impact upon different disease processes. We focus on {HuR}'s well-recognized implication in cancer and chronic inflammation, and discuss emerging studies linking {HuR} to cardiovascular, neurological, and muscular pathologies. We also discuss the progress, potential, and challenges of targeting {HuR} therapeutically.},
	pages = {189--205},
	journaltitle = {Front Biosci (Landmark Ed)},
	author = {Srikantan, S and Gorospe, M},
	date = {2012},
	pmid = {22201738},
	keywords = {Humans, {RNA}, Female, Hu Paraneoplastic Encephalomyelitis Antigens/genet, Inflammation/genetics/metabolism, Male, Messenger/genetics/metabolism, Neoplasm/genetics/metabolism, Neoplasms/genetics/metabolism, Protein Biosynthesis, {RNA} Stability}
}

@article{wani_caspase_2014,
	title = {Caspase inhibition augments Dichlorvos-induced dopaminergic neuronal cell death by increasing {ROS} production and {PARP}1 activation},
	volume = {258},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24231740},
	doi = {10.1016/j.neuroscience.2013.11.004},
	abstract = {Numerous epidemiological studies have shown an association between pesticide exposure and the increased risk of developing Parkinson's disease. Previously we have reported that Dichlorvos exposure can induce oxidative stress, resulting in over-expression of pro-apoptotic genes and finally caspase-dependent nigrostriatal dopaminergic neuronal cell death in rat brain. Here, we examined the effect of caspase inhibition on {PC}12 cell death induced by Dichlorvos (30 {muM}). Reactive oxygen species ({ROS}) generation followed by protein carbonylation, lipid peroxidation, decreased antioxidant defenses (decreased Mn-superoxide dismutase ({MnSOD}) activity and decreased glutathione levels) and subsequent caspase activation mediated the apoptosis. Inhibition of caspase cascade with Boc-aspartyl({OMe})-fluoromethylketone ({BAF}) enhanced the Dichlorvos-induced {PC}12 cell death, as assessed by the increased cellular efflux of lactate dehydrogenase ({LDH}). This increase in cell death was accompanied by a marked increase in poly({ADP}-ribose) polymerase-1 ({PARP}1) activity, increased oxidative stress, a reduction in the mitochondrial membrane potential and reduced cellular {NAD} and {ATP} levels. Pretreatment of cells with {PJ}34, a {PARP}1 inhibitor prevented the cells from undergoing cell death and preserved intracellular {NAD} and {ATP} levels. Subsequent release of the apoptosis-inducing factor ({AIF}) from mitochondria and its translocation into the nucleus was also prevented by {PJ}34 pretreatment. In conclusion, the results of the present study show that caspase inhibition without concurrent inhibition of {PARP}1 is unlikely to be effective in preventing cell death because in the presence of the caspase inhibitor, caspase-independent cell death predominates due to {PARP} activation. These results suggest that combined therapeutic strategies directed at multiple cell death pathways may provide superior neuroprotection than those directed at a single mechanism.},
	pages = {1--15},
	journaltitle = {Neuroscience},
	author = {Wani, W Y and Sunkaria, A and Sharma, D R and Kandimalla, R J and Kaushal, A and Gerace, E and Chiarugi, A and Gill, K D},
	date = {2014},
	pmid = {24231740}
}

@article{smith_signaling_2006,
	title = {Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for Alzheimer's disease},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16787235},
	abstract = {The accumulation of amyloid beta peptide (Abeta) is believed to be an early and critical event leading to synapse and neuronal cell loss in Alzheimer's Disease ({AD}). Abeta itself is toxic to neurons in vitro and the load of Abeta in vivo causes the loss of synapses and neurons in brain in animal models. Therefore, there has been considerable interest in elucidating the mechanism(s) of Abeta neurotoxicity. Here, we review the molecular signaling pathways involved in Abeta-induced cell death, including signaling through the neuronal nicotinic receptor and the Abeta-triggered generation of reactive oxygen species ({ROS}) leading to the activation of the c-jun N-terminal kinase ({JNK}), and the ensuing phosphorylation of p66Shc and inactivation of the Forkhead transcription factors. This focused review not only provides a better understanding of the signaling mechanisms involved in Abeta-induced cell death, but also underscores the potential of {JNK}, p66Shc, Forkhead proteins, p25/cdk5, and neuronal nicotinic receptor, as therapeutic targets for {AD}.},
	pages = {355--361},
	number = {3},
	journaltitle = {{CNS} Neurol Disord Drug Targets},
	author = {Smith, W W and Gorospe, M and Kusiak, J W},
	date = {2006},
	pmid = {16787235},
	keywords = {Animals, Humans, Alzheimer Disease/*drug therapy/metabolism, Amyloid beta-Peptides/metabolism/*toxicity, Drug Delivery Systems/*methods, Signal Transduction/*drug effects/physiology}
}

@article{sunkaria_attenuation_2014,
	title = {Attenuation of Dichlorvos-Induced Microglial Activation and Neuronal Apoptosis by 4-Hydroxy {TEMPO}},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23884618},
	doi = {10.1007/s12035-013-8508-5},
	abstract = {The neurotoxic consequences of acute high-level as well as chronic low-level organophosphates exposure are associated with a range of abnormalities in nerve functions. Previously, we have shown that after 24 h of dichlorvos exposure, microglia become activated and secrete pro-inflammatory molecules like nitric oxide, tumour necrosis factor-alpha and interleukin-1beta. Here, we extended our findings and focused on the neuronal damage caused by dichlorvos via microglial activation. For this, neurons and microglia were isolated separately from 1-day-old Wistar rat pups. Microglia were treated with dichlorvos for 24 h and supernatant was collected (dichlorvos-induced conditioned medium, {DCM}). However, when 4-hydroxy {TEMPO} (4-{HT}) pretreatment was given, we observed significant attenuation of dichlorvos-induced microglial activation; we also collected the supernatant of this culture (4-{HT} + {DCM}, {TDCM}). Next, we checked the effects of {DCM} on neurons and found heavy loss in viability as evident from {NF}-H immunostaining and {MTT} results, whereas dichlorvos alone-treated neurons showed comparatively less damage. However, we observed significant increase in neuronal viability when cells were treated with {TDCM}. Semi-quantitative {PCR} and western blot results revealed significant increase in p53, Bax and cytochrome c levels along with caspase 3 activation after 24 h of {DCM} treatment. However, {TDCM}-treated neurons showed significant decrease in the expression of these pro-apoptotic molecules. Taken together, these findings suggest that 4-{HT} can significantly attenuate dichlorvos-induced microglial activation and prevent apoptotic neuronal cell death.},
	pages = {163--175},
	number = {1},
	journaltitle = {Mol Neurobiol},
	author = {Sunkaria, A and Sharma, D R and Wani, W Y and Gill, K D},
	date = {2014},
	pmid = {23884618}
}

@article{xin_novel_2000,
	title = {A novel imprinted gene, {KCNQ}1DN, within the {WT}2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms' tumors},
	volume = {128},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11056398},
	abstract = {{WT}2 is defined by a maternal-specific loss of heterozygosity on human chromosome 11p15.5 in Wilms' and other embryonal tumors. Therefore, the imprinted genes in this region are candidates for involvement in Wilms' tumorigenesis. We now report a novel imprinted gene, {KCNQ}1DN ({KCNQ}1 downstream neighbor). This gene is located between p57({KIP}2) and {KvLQT}1 ({KCNQ}1) of 11p15.5 within the {WT}2 critical region. {KCNQ}1DN is imprinted and expressed from the maternal allele. We examined the expression of {KCNQ}1DN in Wilms' tumors. Seven of eighteen (39\%) samples showed no expression. In contrast, other maternal imprinted genes in this region, including p57({KIP}2), {IMPT}1, and {IPL} exhibited almost normal expression in these samples, although some samples expressed {IGF}2 biallelically. These results suggest that {KCNQ}1DN existing far from the H19/{IGF}2 region may play some role in Wilms' tumorigenesis along with {IGF}2.},
	pages = {847--853},
	number = {5},
	journaltitle = {J Biochem},
	author = {Xin, Z and Soejima, H and Higashimoto, K and Yatsuki, H and Zhu, X and Satoh, Y and Masaki, Z and Kaneko, Y and Jinno, Y and Fukuzawa, R and Hata, Ji and Mukai, T},
	date = {2000},
	pmid = {11056398},
	keywords = {Human, Humans, *Chromosomes, *Gene Expression Regulation, *Genomic Imprinting, *Potassium Channels, Chromosome Mapping, Female, Gene Library, {KCNQ} Potassium Channels, {KCNQ}1 Potassium Channel, Loss of Heterozygosity, Male, Molecular Sequence Data, Neoplastic, Pair 11, Potassium Channels/*genetics, Testis/chemistry, Voltage-Gated, Wilms Tumor/*genetics}
}

@article{mogilyansky_mir-17/92_2013,
	title = {The {miR}-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24212931},
	doi = {10.1038/cdd.2013.125},
	abstract = {The {miR}-17/92 cluster is among the best-studied {microRNA} clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.},
	pages = {1603--1614},
	number = {12},
	journaltitle = {Cell Death Differ},
	author = {Mogilyansky, E and Rigoutsos, I},
	date = {2013},
	pmid = {24212931},
	keywords = {Base Sequence, Humans, Gene Expression Regulation, Disease/*genetics, *Genomics, *Health, {MicroRNAs}/*genetics/metabolism, Molecular Sequence Data, Oncogenes/genetics}
}

@article{he_nuclear_1994,
	title = {Nuclear export of signal recognition particle {RNA} is a facilitated process that involves the Alu sequence domain},
	volume = {107 ( Pt 4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7520043},
	abstract = {The signal recognition particle is a cytoplasmic {RNA}-protein complex that mediates translocation of secretory polypeptides into the endoplasmic reticulum. We have used a Xenopus oocyte microinjection assay to determine how signal recognition particle ({SRP}) {RNA} is exported from the nucleus. Following nuclear injection, {SRP} {RNA} accumulated in the cytoplasm while cytoplasmically injected {SRP} {RNA} did not enter the nucleus. Cytoplasmic accumulation of {SRP} {RNA} was an apparently facilitated process dependent on limiting trans-acting factors, since nuclear export exhibited saturation kinetics and was completely blocked either at low temperature or by wheat germ agglutinin, a known inhibitor of nuclear pore-mediated transport. At least one target for trans-acting factors that promote nuclear export of {SRP} {RNA} appears to be the Alu element of the molecule, since a transcript consisting of only the Alu sequence was exported from the nucleus in a temperature-dependent manner and the Alu transcript competed in the nucleus for transport with intact {SRP} {RNA}. Although the identities of trans-acting factors responsible for {SRP} {RNA} transport are at present unknown, we suggest that proteins contained within the cytoplasmic form of {SRP} are candidates. Consistent with this idea were the effects of a mutation in {SRP} {RNA} that prevented binding of two known {SRP} proteins to the Alu sequence.},
	pages = {903--912},
	journaltitle = {J Cell Sci},
	author = {He, X P and Bataille, N and Fried, H M},
	date = {1994},
	pmid = {7520043},
	keywords = {Animals, Base Sequence, {RNA}, Nucleic Acid, *Repetitive Sequences, Biological Transport, Cell Nucleus/*metabolism, Cytoplasm/metabolism, Microinjections, Molecular Sequence Data, Nuclear Envelope/metabolism, Nucleic Acid Conformation, Oocytes, Protein Sorting Signals/metabolism, {RNA}-Binding Proteins/metabolism, {RNA}/administration \& dosage/metabolism, Signal Recognition Particle/*metabolism, Small Nuclear/chemistry/*metabolism, Temperature, Xenopus laevis}
}

@article{takacs_identification_2011,
	title = {Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21220547},
	doi = {10.1261/rna.2475211},
	abstract = {Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui(-). No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-{AUG} start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a {UUG}. The compounds were also found to exacerbate increased use of {UUG} as a start codon (Sui(-) phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor ({eIF}) 1, or by mutation in {eIF}1. Furthermore, the effects of the compounds are suppressed by overexpressing {eIF}1, which is known to restore the fidelity of start codon selection in strains harboring Sui(-) mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting {AUG} as the start codon.},
	pages = {439--452},
	number = {3},
	journaltitle = {{RNA}},
	author = {Takacs, J E and Neary, T B and Ingolia, N T and Saini, A K and Martin-Marcos, P and Pelletier, J and Hinnebusch, A G and Lorsch, J R},
	date = {2011},
	pmid = {21220547},
	keywords = {{RNA}, Messenger/genetics, Codon, Eukaryotic Initiation Factor-1/genetics/*metabolis, Eukaryotic/metabolism, Haploinsufficiency, Heterocyclic Compounds/*pharmacology, Initiator/*physiology, Luciferases/metabolism, Mutation/genetics, Peptide Chain Initiation, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, Ribosome Subunits, Saccharomyces cerevisiae Proteins/genetics/*metabo, Saccharomyces cerevisiae/*genetics/growth \& develo, Small, Small Molecule Libraries, Translational/*drug effe}
}

@article{mercer_expression_2011,
	title = {Expression of distinct {RNAs} from 3' untranslated regions},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21075793},
	doi = {10.1093/nar/gkq1158},
	abstract = {The 3' untranslated regions (3'{UTRs}) of eukaryotic genes regulate {mRNA} stability, localization and translation. Here, we present evidence that large numbers of 3'{UTRs} in human, mouse and fly are also expressed separately from the associated protein-coding sequences to which they are normally linked, likely by post-transcriptional cleavage. Analysis of {CAGE} (capped analysis of gene expression), {SAGE} (serial analysis of gene expression) and {cDNA} libraries, as well as microarray expression profiles, demonstrate that the independent expression of 3'{UTRs} is a regulated and conserved genome-wide phenomenon. We characterize the expression of several 3'{UTR}-derived {RNAs} ({uaRNAs}) in detail in mouse embryos, showing by in situ hybridization that these transcripts are expressed in a cell- and subcellular-specific manner. Our results suggest that 3'{UTR} sequences can function not only in cis to regulate protein expression, but also intrinsically and independently in trans, likely as noncoding {RNAs}, a conclusion supported by a number of previous genetic studies. Our findings suggest novel functions for 3'{UTRs}, as well as caution in the use of 3'{UTR} sequence probes to analyze gene expression.},
	pages = {2393--2403},
	number = {6},
	journaltitle = {Nucleic Acids Res},
	author = {Mercer, T R and Wilhelm, D and Dinger, M E and Solda, G and Korbie, D J and Glazov, E A and Truong, V and Schwenke, M and Simons, C and Matthaei, K I and Saint, R and Koopman, P and Mattick, J S},
	date = {2011},
	pmid = {21075793},
	keywords = {Animals, Humans, Mice, {RNA}, Exons, Gene Expression Profiling, *3' Untranslated Regions, Drosophila melanogaster/genetics/metabolism, Embryonic Development/genetics, Post-Transcriptional, {RNA} Processing, Untranslated/*metabolism}
}

@article{de_souza_exaptation_2013,
	title = {Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong?},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23486611},
	doi = {10.1093/molbev/mst045},
	abstract = {Transposable elements ({TEs}) are mobile genetic sequences that can jump around the genome from one location to another, behaving as genomic parasites. {TEs} have been particularly effective in colonizing mammalian genomes, and such heavy {TE} load is expected to have conditioned genome evolution. Indeed, studies conducted both at the gene and genome levels have uncovered {TE} insertions that seem to have been co-opted–or exapted–by providing transcription factor binding sites ({TFBSs}) that serve as promoters and enhancers, leading to the hypothesis that {TE} exaptation is a major factor in the evolution of gene regulation. Here, we critically review the evidence for exaptation of {TE}-derived sequences as {TFBSs}, promoters, enhancers, and silencers/insulators both at the gene and genome levels. We classify the functional impact attributed to {TE} insertions into four categories of increasing complexity and argue that so far very few studies have conclusively demonstrated exaptation of {TEs} as transcriptional regulatory regions. We also contend that many genome-wide studies dealing with {TE} exaptation in recent lineages of mammals are still inconclusive and that the hypothesis of rapid transcriptional regulatory rewiring mediated by {TE} mobilization must be taken with caution. Finally, we suggest experimental approaches that may help attributing higher-order functions to candidate exapted {TEs}.},
	pages = {1239--1251},
	number = {6},
	journaltitle = {Mol Biol Evol},
	author = {de Souza, F S and Franchini, L F and Rubinstein, M},
	date = {2013},
	pmid = {23486611},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, Cell Line, {DNA} Transposable Elements, Phylogeny, Enhancer Elements, Genetic, Regulatory Sequences, Nucleic Acid, gene expression, Embryo, Mammalian, enhancer, exaptation, mobile element},
	file = {Full Text:/home/jlagarde/Zotero/storage/JU9SMY6H/de Souza et al. - 2013 - Exaptation of transposable elements into novel cis.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/U6S7YXEB/de Souza et al. - 2013 - Exaptation of Transposable Elements into Novel Cis.pdf:application/pdf}
}

@article{kim_elucidation_2007,
	title = {Elucidation of a C-rich signature motif in target {mRNAs} of {RNA}-binding protein {TIAR}},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17682065},
	doi = {10.1128/MCB.01036-07},
	abstract = {The {RNA}-binding protein {TIAR} (related to {TIA}-1 [T-cell-restricted intracellular antigen 1]) was shown to associate with subsets of {mRNAs} bearing U-rich sequences in their 3' untranslated regions. {TIAR} can function as a translational repressor, particularly in response to cytotoxic agents. Using unstressed colon cancer cells, collections of {mRNAs} associated with {TIAR} were isolated by immunoprecipitation ({IP}) of ({TIAR}-{RNA}) ribonucleoprotein ({RNP}) complexes, identified by microarray analysis, and used to elucidate a common signature motif present among {TIAR} target transcripts. The predicted {TIAR} motif was an unexpectedly cytosine-rich, 28- to 32-nucleotide-long element forming a stem and a loop of variable size with an additional side loop. The ability of {TIAR} to bind an {RNA} oligonucleotide with a representative C-rich {TIAR} motif sequence was verified in vitro using surface plasmon resonance. By this analysis, {TIAR} containing two or three {RNA} recognition domains ({TIAR}12 and {TIAR}123) showed low but significant binding to the C-rich sequence. In vivo, insertion of the C-rich motif into a heterologous reporter strongly suppressed its translation in cultured cells. Using this signature motif, an additional approximately 2,209 {UniGene} targets were identified (2.0\% of the total {UniGene} database). A subset of specific {mRNAs} were validated by {RNP} {IP} analysis. Interestingly, in response to treatment with short-wavelength {UV} light ({UVC}), a stress agent causing {DNA} damage, each of these target {mRNAs} bearing C-rich motifs dissociated from {TIAR}. In turn, expression of the encoded proteins was elevated in a {TIAR}-dependent manner. In sum, we report the identification of a C-rich signature motif present in {TIAR} target {mRNAs} whose association with {TIAR} decreases following exposure to a stress-causing agent.},
	pages = {6806--6817},
	number = {19},
	journaltitle = {Mol Cell Biol},
	author = {Kim, H S and Kuwano, Y and Zhan, M and Pullmann Jr., R and Mazan-Mamczarz, K and Li, H and Kedersha, N and Anderson, P and Wilce, M C and Gorospe, M and Wilce, J A},
	date = {2007},
	pmid = {17682065},
	keywords = {Animals, Humans, {RNA}, Protein Binding, Oligonucleotide Array Sequence Analysis, *Base Sequence, Antigens, Cell Line, Colonic Neoplasms, {DNA} Damage, Genes, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/*genetics, Molecular Sequence Data, Nucleic Acid Conformation, Protein Biosynthesis, Protein Structure, Reporter, {RNA}-Binding Proteins/*genetics/metabolism, Surface/genetics/metabolism, Tertiary, Tumor, Ultraviolet Rays}
}

@article{cui_mir-503_2012,
	title = {{miR}-503 represses {CUG}-binding protein 1 translation by recruiting {CUGBP}1 {mRNA} to processing bodies},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22072795},
	doi = {10.1091/mbc.E11-05-0456},
	abstract = {{microRNAs} ({miRNAs}) and {RNA}-binding proteins ({RBPs}) jointly regulate gene expression at the posttranscriptional level and are involved in many aspects of cellular functions. The {RBP} {CUG}-binding protein 1 ({CUGBP}1) destabilizes and represses the translation of several target {mRNAs}, but the exact mechanism that regulates {CUGBP}1 abundance remains elusive. In this paper, we show that {miR}-503, computationally predicted to associate with three sites of the {CUGBP}1 {mRNA}, represses {CUGBP}1 expression. Overexpression of an {miR}-503 precursor (pre-{miR}-503) reduced the de novo synthesis of {CUGBP}1 protein, whereas inhibiting {miR}-503 by using an antisense {RNA} (antagomir) enhanced {CUGBP}1 biosynthesis and elevated its abundance; neither intervention changed total {CUGBP}1 {mRNA} levels. Studies using heterologous reporter constructs revealed a greater repressive effect of {miR}-503 through the {CUGBP}1 coding region sites than through the single {CUGBP}1 3'-untranslated region target site. {CUGBP}1 {mRNA} levels in processing bodies (P-bodies) increased in cells transfected with pre-{miR}-503, while silencing P-body resident proteins Ago2, {RCK}, or {LSm}4 decreased {miR}-503-mediated repression of {CUGBP}1 expression. Decreasing the levels of cellular polyamines reduced endogenous {miR}-503 levels and promoted {CUGBP}1 expression, an effect that was prevented by ectopic {miR}-503 overexpression. Repression of {CUGBP}1 by {miR}-503 in turn altered the expression of {CUGBP}1 target {mRNAs} and thus increased the sensitivity of intestinal epithelial cells to apoptosis. These findings identify {miR}-503 as both a novel regulator of {CUGBP}1 expression and a modulator of intestinal epithelial homoeostasis.},
	pages = {151--162},
	number = {1},
	journaltitle = {Mol Biol Cell},
	author = {Cui, Y H and Xiao, L and Rao, J N and Zou, T and Liu, L and Chen, Y and Turner, D J and Gorospe, M and Wang, J Y},
	date = {2012},
	pmid = {22072795},
	keywords = {Animals, Base Sequence, {RNA}, Binding Sites, Gene Expression Regulation, Cells, Cultured, Open Reading Frames, *Protein Biosynthesis, *{RNA} Processing, Apoptosis, Eflornithine/pharmacology, Epithelial Cells/metabolism/physiology, Gene Knockdown Techniques, Genes, Intestines/cytology, Luciferases, Messenger/genetics/*metabolism, {MicroRNAs}/genetics/*metabolism, Ornithine Decarboxylase/antagonists \& inhibitors/g, Polyamines/metabolism, Post-Transcriptional, Rats, Recombinant Proteins/antagonists \& inhibitors/gene, Renilla/biosynthesis/genetics, Reporter, {RNA} Stability, {RNA}-Binding Proteins/*genetics/metabolism, Signal Transduction, Small Nuclear/metabolism}
}

@article{schwartz_cell_2007,
	title = {Cell cycle activation in postmitotic neurons is essential for {DNA} repair},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17297309},
	abstract = {Increasing evidence indicates that maintenance of neuronal homeostasis involves the activation of the cell cycle machinery in postmitotic neurons. Our recent findings suggest that cell cycle activation is essential for {DNA} damage-induced neuronal apoptosis. However, whether the cell division cycle also participates in {DNA} repair and survival of postmitotic, terminally differentiated neurons is unknown. Here, we tested the hypothesis that G(1) phase components contribute to the repair of {DNA} and are involved in the {DNA} damage response of postmitotic neurons. In cortical terminally differentiated neurons, treatment with subtoxic concentrations of hydrogen peroxide (H(2)O(2)) caused repairable {DNA} double strand breaks ({DSBs}) and the activation of G(1) components of the cell cycle machinery. Importantly, {DNA} repair was attenuated if cyclin-dependent kinases {CDK}4 and {CDK}6, essential elements of G(0) –{\textbackslash}textgreater G(1) transition, were suppressed. Our data suggest that G(1) cell cycle components are involved in {DNA} repair and survival of postmitotic neurons.},
	pages = {318--329},
	number = {3},
	journaltitle = {Cell Cycle},
	author = {Schwartz, E I and Smilenov, L B and Price, M A and Osredkar, T and Baker, R A and Ghosh, S and Shi, F D and Vollmer, T L and Lencinas, A and Stearns, D M and Gorospe, M and {Kruman II}},
	date = {2007},
	pmid = {17297309},
	keywords = {Animals, Mice, {RNA}, Cells, Cultured, Apoptosis/drug effects, Cell Cycle/drug effects/genetics/*physiology, Cyclin-Dependent Kinase 4/genetics/metabolism, Cyclin-Dependent Kinase 6/genetics/metabolism, {DNA} Breaks, {DNA} Damage, {DNA} Repair/drug effects/genetics/*physiology, Dose-Response Relationship, Double-Stranded/drug effects, Drug, Flow Cytometry, Fluorescent Antibody Technique, G1 Phase/drug effects/genetics/physiology, Gene Expression Regulation/drug effects, Histones/metabolism, Hydrogen Peroxide/pharmacology, Immunoblotting, Immunoprecipitation, Inbred C57BL, Neurons/cytology/drug effects/*metabolism, Phosphorylation/drug effects, Rats, Small Interfering/genetics, Sprague-Dawley}
}

@article{chen_discordance_2001,
	title = {Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for {MAP} kinase phosphatase-2 and their ability to activate the phosphatase catalytically},
	volume = {276},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11387337},
	doi = {10.1074/jbc.M103463200},
	abstract = {{MKP}-2 is a member of the mitogen-activated protein ({MAP}) kinase phosphatase family which has been suggested to play an important role in the feedback control of {MAP} kinase-mediated gene expression. Although {MKP}-2 preferentially inactivates extracellular signal-regulated kinase ({ERK}) and c-Jun {NH}(2)-terminal kinase ({JNK}) {MAP} kinase subfamilies, the mechanisms underlying its own regulation remain unclear. In this report, we have examined the {MKP}-2 interaction with and catalytic activation by distinct {MAP} kinase subfamilies. We found that the catalytic activity of {MKP}-2 was enhanced dramatically by {ERK} and {JNK} but was affected only minimally by p38. By contrast, p38 and {ERK} bound {MKP}-2 with comparably strong affinities, whereas {JNK} and {MKP}-2 interacted very weakly. Through site-directed mutagenesis, we defined the {ERK}/p38-binding site as a cluster of arginine residues in the {NH}(2)-terminal domain of {MKP}-2. Mutation of the basic motif abrogated its interaction with both {ERK} and p38 and severely compromised the catalytic activation of {MKP}-2 by these kinases. Unexpectedly, such mutations had little effect on {JNK}-triggered catalytic activation. Both in vitro and in vivo, wild type {MKP}-2 effectively inactivated {ERK}2 whereas {MKP}-2 mutants incapable of binding to {ERK}/p38 did not. Finally, in addition to its role as a docking site for {ERK} and p38, the {MKP}-2 basic motif plays a role in regulating its nuclear localization. Our studies provided a mechanistic explanation for the substrate preference of {MKP}-2 and suggest that catalytic activation of {MKP}-2 upon binding to its substrates is crucial for its function.},
	pages = {29440--29449},
	number = {31},
	journaltitle = {J Biol Chem},
	author = {Chen, P and Hutter, D and Yang, X and Gorospe, M and Davis, R J and Liu, Y},
	date = {2001},
	pmid = {11387337},
	keywords = {Humans, Binding Sites, Amino Acid Substitution, Cell Line, Dual-Specificity Phosphatases, Enzyme Activation, Genetic Vectors, Glutathione Transferase/metabolism, {HeLa} Cells, Kinetics, {MAP} Kinase Signaling System/*physiology, Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinase Phosphatases, Mitogen-Activated Protein Kinases/chemistry/*metab, Mutagenesis, p38 Mitogen-Activated Protein Kinases, Protein Phosphatase 2, Protein Tyrosine Phosphatases/chemistry/*metabolis, Recombinant Fusion Proteins/metabolism, Recombinant Proteins/chemistry/metabolism, Site-Directed, Transfection}
}

@article{sunkari_selective_2013,
	title = {Selective blockade of estrogen receptor beta improves wound healing in diabetes},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24366647},
	doi = {10.1007/s12020-013-0144-3},
	journaltitle = {Endocrine},
	author = {Sunkari, V G and Botusan, I R and Savu, O and Grunler, J and Zheng, X and Gustafsson, J A and Brismar, K and Catrina, S B},
	date = {2013},
	pmid = {24366647}
}

@article{smith_deterministic_2002,
	title = {Deterministic mutation rate variation in the human genome},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12213772},
	doi = {10.1101/gr.220502},
	abstract = {Several studies of substitution rate variation have indicated that the local mutation rate varies over the mammalian genome. In the present study, we show significant variation in substitution rates within the noncoding part of the human genome using 4.7 Mb of human-chimpanzee pairwise comparisons. Moreover, we find a significant positive covariation of lineage-specific chimpanzee and human local substitution rates, and very similar mean substitution rates down the two lineages. The substitution rate variation is probably not caused by selection or biased gene conversion, and so we conclude that mutation rates vary deterministically across the noncoding nonrepetitive regions of the human genome. We also show that noncoding substitution rates are significantly affected by G+C base composition, partly because the base composition is not at equilibrium.},
	pages = {1350--1356},
	number = {9},
	journaltitle = {Genome Res},
	author = {Smith, N G and Webster, M T and Ellegren, H},
	date = {2002},
	pmid = {12213772},
	keywords = {Human, Animals, Genetic, Humans, *Genome, *Mutation, Amino Acid Substitution/genetics, Base Composition/genetics, Base Pairing/genetics, {GC} Rich Sequence/genetics, Genetic Variation/*genetics, Pan troglodytes, Selection, Sequence Alignment}
}

@article{durie_rna-binding_2011,
	title = {{RNA}-binding protein {HuR} mediates cytoprotection through stimulation of {XIAP} translation},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21102524},
	doi = {10.1038/onc.2010.527},
	abstract = {Expression of the intrinsic cellular caspase inhibitor {XIAP} is regulated primarily at the level of protein synthesis. The 5' untranslated region harbours an Internal Ribosome Entry Site ({IRES}) motif that supports cap-independent translation of {XIAP} {mRNA} during conditions of cellular stress. In this study, we show that the {RNA}-binding protein {HuR}, which is known to orchestrate an antiapoptotic cellular program, stimulates translation of {XIAP} {mRNA} through {XIAP} {IRES}. We further show that {HuR} binds to {XIAP} {IRES} in vitro and in vivo, and stimulates recruitment of the {XIAP} {mRNA} into polysomes. Importantly, protection from the apoptosis-inducing agent etoposide by overexpression of {HuR} requires the presence of {XIAP}, suggesting that {HuR}-mediated cytoprotection is partially executed through enhanced {XIAP} translation. Our data suggest that {XIAP} belongs to the {HuR}-regulated {RNA} operon of antiapoptotic genes, which, along with Bcl-2, Mcl-1 and {ProTalpha}, contributes to the regulation of cell survival.},
	pages = {1460--1469},
	number = {12},
	journaltitle = {Oncogene},
	author = {Durie, D and Lewis, S M and Liwak, U and Kisilewicz, M and Gorospe, M and Holcik, M},
	date = {2011},
	pmid = {21102524},
	keywords = {Humans, Gene Expression Regulation, *Protein Biosynthesis, Amino Acid Sequence, Antigens, Cell Survival/genetics, Cytoprotection, {HEK}293 Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Molecular Sequence Data, Ribosomes/*metabolism, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism, X-Linked Inhibitor of Apoptosis Protein/*biosynthe}
}

@article{lindblad-toh_high-resolution_2011,
	title = {A high-resolution map of human evolutionary constraint using 29 mammals},
	volume = {478},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21993624},
	doi = {10.1038/nature10530},
	abstract = {The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5\% of the human genome has undergone purifying selection, and locate constrained elements covering approximately 4.2\% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for approximately 60\% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate {RNA} structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.},
	pages = {476--482},
	number = {7370},
	journaltitle = {Nature},
	author = {Lindblad-Toh, K and Garber, M and Zuk, O and Lin, M F and Parker, B J and Washietl, S and Kheradpour, P and Ernst, J and Jordan, G and Mauceli, E and Ward, L D and Lowe, C B and Holloway, A K and Clamp, M and Gnerre, S and Alfoldi, J and Beal, K and Chang, J and Clawson, H and Cuff, J and Di Palma, F and Fitzgerald, S and Flicek, P and Guttman, M and Hubisz, M J and Jaffe, D B and Jungreis, I and Kent, W J and Kostka, D and Lara, M and Martins, A L and Massingham, T and Moltke, I and Raney, B J and Rasmussen, M D and Robinson, J and Stark, A and Vilella, A J and Wen, J and Xie, X and Zody, M C and Baldwin, J and Bloom, T and Chin, C W and Heiman, D and Nicol, R and Nusbaum, C and Young, S and Wilkinson, J and Worley, K C and Kovar, C L and Muzny, D M and Gibbs, R A and Cree, A and Dihn, H H and Fowler, G and Jhangiani, S and Joshi, V and Lee, S and Lewis, L R and Nazareth, L V and Okwuonu, G and Santibanez, J and Warren, W C and Mardis, E R and Weinstock, G M and Wilson, R K and Delehaunty, K and Dooling, D and Fronik, C and Fulton, L and Fulton, B and Graves, T and Minx, P and Sodergren, E and Birney, E and Margulies, E H and Herrero, J and Green, E D and Haussler, D and Siepel, A and Goldman, N and Pollard, K S and Pedersen, J S and Lander, E S and Kellis, M},
	date = {2011},
	pmid = {21993624},
	keywords = {Genomics, {DNA}, Sequence Analysis, Animals, Genome, Humans, {RNA}, Exons, Exons/genetics, Genetic/genetics, Mammals/*genetics, Disease, *Evolution, Genome/*genetics, Health, Human/*genetics, Mammals, Molecular, Molecular Sequence Annotation, Phylogeny, {RNA}/classification/genetics, Selection, Sequence Alignment, Evolution, Molecular, Selection, Genetic, Sequence Analysis, {DNA}, Genome, Human},
	file = {Full Text:/home/jlagarde/Zotero/storage/29MWLJTT/Lindblad-Toh et al. - 2011 - A high-resolution map of human evolutionary constr.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/AHEAIM3D/Lindblad-Toh et al. - 2011 - A high-resolution map of human evolutionary constr.pdf:application/pdf}
}

@article{boyko_assessing_2008,
	title = {Assessing the evolutionary impact of amino acid mutations in the human genome},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18516229},
	doi = {10.1371/journal.pgen.1000083},
	abstract = {Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism ({SNP}) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding {SNPs} found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27-29\% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral ({\textbar}s{\textbar}{\textbackslash}textless0.01\%), 30-42\% are moderately deleterious (0.01\%{\textbackslash}textless{\textbar}s{\textbar}{\textbackslash}textless1\%), and nearly all the remainder are highly deleterious or lethal ({\textbar}s{\textbar}{\textbackslash}textgreater1\%). Our results are consistent with 10-20\% of amino acid differences between humans and chimpanzees having been fixed by positive selection with the remainder of differences being neutral or nearly neutral. Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits.},
	pages = {e1000083},
	number = {5},
	journaltitle = {{PLoS} Genet},
	author = {Boyko, A R and Williamson, S H and Indap, A R and Degenhardt, J D and Hernandez, R D and Lohmueller, K E and Adams, M D and Schmidt, S and Sninsky, J J and Sunyaev, S R and White, T J and Nielsen, R and Clark, A G and Bustamante, C D},
	date = {2008},
	pmid = {18516229},
	keywords = {Human, Animals, Genetic, Humans, *Genome, *Evolution, *Mutation, African Continental Ancestry Group/genetics, Alleles, Amino Acid Substitution, European Continental Ancestry Group/genetics, Female, Genetics, Male, Missense, Molecular, Pan troglodytes/genetics, Polymorphism, Population, Selection, Single Nucleotide}
}

@article{baillie_somatic_2011,
	title = {Somatic retrotransposition alters the genetic landscape of the human brain},
	volume = {479},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22037309},
	doi = {10.1038/nature10531},
	abstract = {Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and {SVA}) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and {SVA} germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 {SVA} insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.},
	pages = {534--537},
	number = {7374},
	journaltitle = {Nature},
	author = {Baillie, J K and Barnett, M W and Upton, K R and Gerhardt, D J and Richmond, T A and De Sapio, F and Brennan, P M and Rizzu, P and Smith, S and Fell, M and Talbot, R T and Gustincich, S and Freeman, T C and Mattick, J S and Hume, D A and Heutink, P and Carninci, P and Jeddeloh, J A and Faulkner, G J},
	date = {2011},
	pmid = {22037309},
	keywords = {Genetic, Genome, Humans, Alu Elements/genetics, Base Sequence/genetics, Brain/*metabolism, Caudate Nucleus/metabolism, Clonal Evolution/genetics, {DNA} Copy Number Variations/genetics, Epistasis, Germ-Line Mutation/*genetics, Hippocampus/metabolism, Histone Deacetylase 1/genetics, Human/genetics, Insertional/*genetics, Mosaicism, Mutagenesis, Nerve Tissue Proteins/genetics, Organ Specificity/genetics, Polymerase Chain Reaction, Retroelements/*genetics, Transcription Factors/genetics}
}

@article{prislei_use_1997,
	title = {Use of adenoviral {VAI} small {RNA} as a carrier for cytoplasmic delivery of ribozymes},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9174101},
	abstract = {The in vivo effectiveness of therapeutic {RNAs}, like antisense molecules and ribozymes, relies on several features: {RNA} molecules need to be expressed at high levels in the correct cellular compartment as stable and active molecules. The exploitation of "natural" small {RNA} coding genes as expressing cassettes gives high chances to fulfill these requirements. We have investigated the utilization of the adenoviral {VAI} {RNA} as a cytoplasmatic carrier for expressing ribozymes against {HIV}-1. The conserved 5' leader sequence of {HIV} was chosen as a target, because it is present in all the viral transcripts and is highly conserved. Hammerhead ribozymes were substituted to different portions of the {VAI} {RNA} and the resulting chimera were tested in the in vivo system of Xenopus laevis oocytes for their level of accumulation, cellular compartmentalization, and assembly in specific ribonucleoparticles containing the La antigen. Interesting differences in the activity of the different chimera were found in both in vitro cleavage assays and S100 extracts of injected oocytes where the catalytic activity of the ribozymes in the {RNP} context can be analyzed.},
	pages = {677--687},
	number = {6},
	journaltitle = {{RNA}},
	author = {Prislei, S and Buonomo, S B and Michienzi, A and Bozzoni, I},
	date = {1997},
	pmid = {9174101},
	keywords = {Animals, Genetic, {RNA}, Transcription, *Genetic Vectors, Adenoviruses, Anti-{HIV} Agents/pharmacology, Autoantigens/metabolism, Catalytic/*genetics/pharmacology, Cell Compartmentation, Cytoplasm/metabolism, Gene Transfer Techniques, {HIV}-1/drug effects, Human/*genetics, Microinjections, Oocytes, Ribonucleoproteins/metabolism, Viral/*genetics, Xenopus laevis}
}

@article{liu_ankrd18a_2012,
	title = {{ANKRD}18A as a novel epigenetic regulation gene in lung cancer},
	volume = {429},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23131552},
	doi = {10.1016/j.bbrc.2012.10.116},
	abstract = {Lung cancer is one of the most common causes of cancer-related mortality worldwide. Effective early diagnosis and targeted therapies for lung cancer to reduce incidence and mortality would benefit from a better understanding of the key molecular changes that occur from normal to malignant tumor cells during lung cancer initiation and development, but these are largely unknown. Previous studies have shown that {DNA} methylation, an important mechanism for the regulation of gene expression, plays a key role in lung carcinogenesis. In this study, we screened a novel methylation gene, {ANKRD}18A, encoding ankyrin repeat domain 18A, to determine whether it is regulated by {DNA} methylation in lung cancer. Methylation-specific {PCR} and bisulfite sequencing {PCR} were used to analyze gene methylation status, and real-time quantitative reverse transcription-polymerase chain reaction ({qRT}-{PCR}) examined {mRNA} levels. Promoter hypermethylation of {ANKRD}18A was detected in 68.4\% (26/38) of lung cancer tissues but not (0/20) in normal lung tissues (P{\textbackslash}textless0.01), whereas {ANKRD}18A {mRNA} expression was significantly decreased in lung cancer tissues compared with adjacent normal tissues. In addition, we found that {ANKRD}18A expression was significantly decreased in 9 of 10 lung cancer cell lines. This was associated with hypermethylation of the {ANKRD}18A promoter region. Moreover, weak expression of {ANKRD}18A in methylated lung cancer cell lines increased markedly after treatment with the {DNA} methylation inhibitor 5-aza-2'-deoxycytidine. These results suggest that {ANKRD}18A hypermethylation and consequent {mRNA} alterations might be a vital molecular mechanism in lung cancer.},
	pages = {180--185},
	number = {3},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Liu, W B and Han, F and Jiang, X and Yang, L J and Li, Y H and Liu, Y and Chen, H Q and Ao, L and Cui, Z H and Cao, J and Liu, J Y},
	date = {2012},
	pmid = {23131552},
	keywords = {Genetic, Humans, Promoter Regions, *Ankyrin Repeat, *Epigenesis, *Gene Expression Regulation, Azacitidine/analogs \& derivatives/pharmacology, {DNA} Methylation, {DNA} Modification Methylases/antagonists \& inhibito, Down-Regulation, Lung Neoplasms/*genetics, Neoplastic}
}

@article{morais_da_silva_tumor_2013,
	title = {A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition},
	volume = {201},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23609535},
	doi = {10.1083/jcb.201210018},
	abstract = {Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint ({SAC}) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down {CENP}-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient {SAC} is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor.},
	pages = {385--393},
	number = {3},
	journaltitle = {J Cell Biol},
	author = {Morais da Silva, S and Moutinho-Santos, T and Sunkel, C E},
	date = {2013},
	pmid = {23609535},
	keywords = {Animals, Drosophila melanogaster, *Apoptosis, Aneuploidy, Cell Cycle Proteins/genetics/*metabolism/physiolog, Cell Transformation, Drosophila Proteins/genetics/*metabolism/physiolog, Gene Knockdown Techniques, Imaginal Discs/metabolism, Kinetochores/metabolism, Mad2 Proteins, Neoplastic, Tumor Suppressor Proteins/genetics/*metabolism/phy}
}

@article{nissim_multiplexed_2014,
	title = {Multiplexed and programmable regulation of gene networks with an integrated {RNA} and {CRISPR}/Cas toolkit in human cells},
	volume = {54},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24837679},
	doi = {10.1016/j.molcel.2014.04.022},
	abstract = {{RNA}-based regulation and {CRISPR}/Cas transcription factors ({CRISPR}-{TFs}) have the potential to be integrated for the tunable modulation of gene networks. A major limitation of this methodology is that guide {RNAs} ({gRNAs}) for {CRISPR}-{TFs} can only be expressed from {RNA} polymerase {III} promoters in human cells, limiting their use for conditional gene regulation. We present new strategies that enable expression of functional {gRNAs} from {RNA} polymerase {II} promoters and multiplexed production of proteins and {gRNAs} from a single transcript in human cells. We use multiple {RNA} regulatory strategies, including {RNA}-triple-helix structures, introns, {microRNAs}, and ribozymes, with Cas9-based {CRISPR}-{TFs} and Cas6/Csy4-based {RNA} processing. Using these tools, we efficiently modulate endogenous promoters and implement tunable synthetic circuits, including multistage cascades and {RNA}-dependent networks that can be rewired with Csy4 to achieve complex behaviors. This toolkit can be used for programming scalable gene circuits and perturbing endogenous networks for biology, therapeutic, and synthetic biology applications.},
	pages = {698--710},
	number = {4},
	journaltitle = {Mol Cell},
	author = {Nissim, L and Perli, S D and Fridkin, A and Perez-Pinera, P and Lu, T K},
	date = {2014},
	pmid = {24837679},
	keywords = {Genetic, Humans, Promoter Regions, {RNA}, *{CRISPR}-Cas Systems, *Gene Expression Regulation/physiology, *Gene Regulatory Networks, Catalytic/metabolism, Guide/genetics, {HEK}293 Cells, Introns/genetics/physiology, {MicroRNAs}/genetics/metabolism, {RNA} Polymerase {II}/genetics/*metabolism, Synthetic Biology, Transcription Factors/genetics/*metabolism}
}

@article{abbott_candidate_2015,
	title = {The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25190456},
	doi = {10.1093/nar/gku770},
	abstract = {Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database ({CCGD}, http://ccgd-starrlab.oit.umn.edu/). The {CCGD} is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites ({CISs}) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using {KEGG} pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The {CCGD} is a novel resource available to scientists interested in the identification of genetic drivers of cancer.},
	pages = {D844--8},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Abbott, K L and Nyre, E T and Abrahante, J and Ho, Y Y and Isaksson Vogel, R and Starr, T K},
	date = {2015},
	pmid = {25190456}
}

@article{remarque_diversity-covering_2008,
	title = {A diversity-covering approach to immunization with Plasmodium falciparum apical membrane antigen 1 induces broader allelic recognition and growth inhibition responses in rabbits},
	volume = {76},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18378635},
	doi = {10.1128/IAI.00170-08},
	abstract = {Plasmodium falciparum apical membrane antigen 1 ({PfAMA}1), a candidate malaria vaccine, is polymorphic. This polymorphism is believed to be generated predominantly under immune selection pressure and, as a result, may compromise attempts at vaccination. Alignment of 355 {PfAMA}1 sequences shows that around 10\% of the 622 amino acid residues can vary between alleles and that linkages between polymorphic residues occur. Using this analysis, we have designed three diversity-covering ({DiCo}) {PfAMA}1 sequences that take account of these linkages and, when taken together, on average incorporate 97\% of amino acid variability observed. For each of the three {DiCo} sequences, a synthetic gene was constructed and used to transform the methylotrophic yeast Pichia pastoris, allowing recombinant expression. All three {DiCo} proteins were reactive with the reduction-sensitive monoclonal antibody 4G2, suggesting the {DiCo} sequences had conformations similar to those of naturally occurring {PfAMA}1. Rabbits were immunized with {FVO} strain {PfAMA}1 or with the {DiCo} proteins either individually or as a mixture. Antibody titers and the ability to inhibit parasite growth in vitro were determined. Animals immunized with the {DiCo} mix performed similarly to animals immunized with {FVO} {AMA}1 when measured against {FCR}3 strain parasites but outperformed animals immunized with {FVO} {AMA}1 when assessed against other strains. The levels of growth inhibition (approximately 70\%) induced by the mix of three {DiCo} proteins were comparable for {FVO}, 3D7, and {HB}3, suggesting that a considerable degree of diversity in {AMA}1 is adequately covered. This suggests that vaccines based upon the {DiCo} mix approach provide a broader functional immunity than immunization with a single allele.},
	pages = {2660--2670},
	number = {6},
	journaltitle = {Infect Immun},
	author = {Remarque, E J and Faber, B W and Kocken, C H and Thomas, A W},
	date = {2008},
	pmid = {18378635},
	keywords = {Animals, Genetic, Alleles, Amino Acid Sequence, Antibodies, Antigens, Immunoglobulin G/blood/immunology, Malaria Vaccines/*immunology, Membrane Proteins/chemistry/genetics/*immunology, Molecular Sequence Data, Plasmodium falciparum/genetics/*immunology, Polymorphism, Protozoan Proteins/chemistry/genetics/*immunology, Protozoan/blood, Protozoan/chemistry/genetics/*immunology, Rabbits, Sequence Alignment}
}

@article{lawrence_mutational_2013,
	title = {Mutational heterogeneity in cancer and the search for new cancer-associated genes},
	volume = {499},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23770567},
	doi = {10.1038/nature12213},
	abstract = {Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, {MutSigCV}, for resolving the problem. We apply {MutSigCV} to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with {DNA} replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, {MutSigCV} is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.},
	pages = {214--218},
	number = {7457},
	journaltitle = {Nature},
	author = {Lawrence, M S and Stojanov, P and Polak, P and Kryukov, G V and Cibulskis, K and Sivachenko, A and Carter, S L and Stewart, C and Mermel, C H and Roberts, S A and Kiezun, A and Hammerman, P S and {McKenna}, A and Drier, Y and Zou, L and Ramos, A H and Pugh, T J and Stransky, N and Helman, E and Kim, J and Sougnez, C and Ambrogio, L and Nickerson, E and Shefler, E and Cortes, M L and Auclair, D and Saksena, G and Voet, D and Noble, M and {DiCara}, D and Lin, P and Lichtenstein, L and Heiman, D I and Fennell, T and Imielinski, M and Hernandez, B and Hodis, E and Baca, S and Dulak, A M and Lohr, J and Landau, D A and Wu, C J and Melendez-Zajgla, J and Hidalgo-Miranda, A and Koren, A and {McCarroll}, S A and Mora, J and Lee, R S and Crompton, B and Onofrio, R and Parkin, M and Winckler, W and Ardlie, K and Gabriel, S B and Roberts, C W and Biegel, J A and Stegmaier, K and Bass, A J and Garraway, L A and Meyerson, M and Golub, T R and Gordenin, D A and Sunyaev, S and Lander, E S and Getz, G},
	date = {2013},
	pmid = {23770567},
	keywords = {Genome, Humans, Reproducibility of Results, *Genetic Heterogeneity, Artifacts, {DNA} Replication Timing, Exome/genetics, False Positive Reactions, Gene Expression, Human/genetics, Lung Neoplasms/genetics, Mutation Rate, Mutation/*genetics, Neoplasms, Neoplasms/classification/*genetics/pathology, Oncogenes/*genetics, Sample Size, Squamous Cell/genetics}
}

@article{becerra_parallel_2013,
	title = {Parallel buprenorphine {phMRI} responses in conscious rodents and healthy human subjects},
	volume = {345},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23370795},
	doi = {10.1124/jpet.112.201145},
	abstract = {Pharmacological magnetic resonance imaging ({phMRI}) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although {phMRI} has been frequently used in preclinical and clinical settings, the extent to which a {phMRI} signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial micro-opioid receptor agonist) was measured in healthy humans. Here, we measured the {phMRI} response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the {phMRI} signature of buprenorphine across species. {PhMRI} of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent {phMRI} activation was observed in the human {phMRI} studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of {phMRI} as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.},
	pages = {41--51},
	number = {1},
	journaltitle = {J Pharmacol Exp Ther},
	author = {Becerra, L and Upadhyay, J and Chang, P C and Bishop, J and Anderson, J and Baumgartner, R and Schwarz, A J and Coimbra, A and Wallin, D and Nutile, L and George, E and Maier, G and Sunkaraneni, S and Iyengar, S and Evelhoch, J L and Bleakman, D and Hargreaves, R and Borsook, D},
	date = {2013},
	pmid = {23370795},
	keywords = {Animals, Humans, *Magnetic Resonance Imaging/instrumentation/method, *Neurosciences/instrumentation/methods, Analgesics, Brain Mapping/methods, Brain/*drug effects, Buprenorphine/*pharmacology, Cross-Over Studies, Dose-Response Relationship, Double-Blind Method, Drug, Infusions, Intravenous, Male, mu/agonists, Opioid, Opioid/*pharmacology, Rats, Receptors, Species Specificity, Sprague-Dawley}
}

@article{helwak_mapping_2013,
	title = {Mapping the human {miRNA} interactome by {CLASH} reveals frequent noncanonical binding},
	volume = {153},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23622248},
	doi = {10.1016/j.cell.2013.03.043},
	abstract = {{MicroRNAs} ({miRNAs}) play key roles in gene regulation, but reliable bioinformatic or experimental identification of their targets remains difficult. To provide an unbiased view of human {miRNA} targets, we developed a technique for ligation and sequencing of {miRNA}-target {RNA} duplexes associated with human {AGO}1. Here, we report data sets of more than 18,000 high-confidence {miRNA}-{mRNA} interactions. The binding of most {miRNAs} includes the 5' seed region, but around 60\% of seed interactions are noncanonical, containing bulged or mismatched nucleotides. Moreover, seed interactions are generally accompanied by specific, nonseed base pairing. 18\% of {miRNA}-{mRNA} interactions involve the {miRNA} 3' end, with little evidence for 5' contacts, and some of these were functionally validated. Analyses of {miRNA}:{mRNA} base pairing showed that {miRNA} species systematically differ in their target {RNA} interactions, and strongly overrepresented motifs were found in the interaction sites of several {miRNAs}. We speculate that these affect the response of {RISC} to {miRNA}-target binding.},
	pages = {654--665},
	number = {3},
	journaltitle = {Cell},
	author = {Helwak, A and Kudla, G and Dudnakova, T and Tollervey, D},
	date = {2013},
	pmid = {23622248},
	keywords = {Humans, {RNA}, *Gene Expression Profiling, *Genetic Techniques, Argonaute Proteins/genetics, Eukaryotic Initiation Factors/genetics, {HEK}293 Cells, High-Throughput Nucleotide Sequencing, Messenger/chemistry/*metabolism, {MicroRNAs}/chemistry/*metabolism, Nucleotide Motifs, {RNA}-Induced Silencing Complex/metabolism, Untranslated/chemistry/metabolism}
}

@article{cazzella_exon_2012,
	title = {Exon 45 skipping through U1-{snRNA} antisense molecules recovers the Dys-{nNOS} pathway and muscle differentiation in human {DMD} myoblasts},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22968481},
	doi = {10.1038/mt.2012.178},
	abstract = {Exon skipping has been demonstrated to be a successful strategy for the gene therapy of Duchenne muscular dystrophy ({DMD}): the rational being to convert severe Duchenne forms into milder Becker ones. Here, we show the selection of U1 {snRNA}-antisense constructs able to confer effective rescue of dystrophin synthesis in a Delta44 Duchenne genetic background, through skipping of exon 45; moreover, we demonstrate that the resulting dystrophin is able to recover timing of myogenic marker expression, to relocalize neuronal nitric oxide synthase ({nNOS}) and to rescue expression of {miRNAs} previously shown to be sensitive to the Dystrophin-{nNOS}-{HDAC}2 pathway. Becker mutations display different phenotypes, likely depending on whether the shorter protein is able to reconstitute the wide range of wild-type functions. Among them, efficient assembly of the dystrophin-associated protein complex ({DAPC}) and {nNOS} localization are important. Comparing different Becker deletions we demonstrate the correlation between the ability of the mutant dystrophin to relocalize {nNOS} and the expression levels of two {miRNAs}, {miR}-1 and {miR}29c, known to be involved in muscle homeostasis and to be controlled by the Dys-{nNOS}-{HDAC}2 pathway.},
	pages = {2134--2142},
	number = {11},
	journaltitle = {Mol Ther},
	author = {Cazzella, V and Martone, J and Pinnaro, C and Santini, T and Twayana, S S and Sthandier, O and D'Amico, A and Ricotti, V and Bertini, E and Muntoni, F and Bozzoni, I},
	date = {2012},
	pmid = {22968481},
	keywords = {Humans, {RNA}, Exons, Cells, Cultured, *Cell Differentiation, Adolescent, Alternative Splicing, Antisense/genetics, Child, Cloning, Duchenne/pathology/*physiopath, Dystrophin/*genetics/metabolism, Genetic Therapy, Lentivirus/genetics, {MicroRNAs}/genetics/metabolism, Molecular, Muscle Development, Muscular Dystrophy, Myoblasts, Nitric Oxide Synthase Type I/*metabolism, Oligoribonucleotides, Preschool, Primary Cell Culture, Protein Transport, {RNA} Interference, Signal Transduction, Skeletal/metabolism/*physiology, Small Nuclear/*genetics}
}

@article{shukla_endogenous_2013,
	title = {Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma},
	volume = {153},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23540693},
	doi = {10.1016/j.cell.2013.02.032},
	abstract = {{LINE}-1 (L1) retrotransposons are mobile genetic elements comprising ∼17\% of the human genome. New L1 insertions can profoundly alter gene function and cause disease, though their significance in cancer remains unclear. Here, we applied enhanced retrotransposon capture sequencing ({RC}-seq) to 19 hepatocellular carcinoma ({HCC}) genomes and elucidated two archetypal L1-mediated mechanisms enabling tumorigenesis. In the first example, 4/19 (21.1\%) donors presented germline retrotransposition events in the tumor suppressor mutated in colorectal cancers ({MCC}). {MCC} expression was ablated in each case, enabling oncogenic beta-catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18 ({ST}18) was activated by a tumor-specific L1 insertion. Experimental assays confirmed that the L1 interrupted a negative feedback loop by blocking {ST}18 repression of its enhancer. {ST}18 was also frequently amplified in {HCC} nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene. These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in {HCC}.},
	pages = {101--111},
	number = {1},
	journaltitle = {Cell},
	author = {Shukla, R and Upton, K R and Munoz-Lopez, M and Gerhardt, D J and Fisher, M E and Nguyen, T and Brennan, P M and Baillie, J K and Collino, A and Ghisletti, S and Sinha, S and Iannelli, F and Radaelli, E and Dos Santos, A and Rapoud, D and Guettier, C and Samuel, D and Natoli, G and Carninci, P and Ciccarelli, F D and Garcia-Perez, J L and Faivre, J and Faulkner, G J},
	date = {2013},
	pmid = {23540693},
	keywords = {Animals, Humans, Mice, *{DNA} Mutational Analysis, *Genes, *Long Interspersed Nucleotide Elements, *Mutagenesis, Adult, Aged, Carcinoma, Cell Line, Cell Transformation, Female, Hepatocellular/*genetics, Insertional, Liver Neoplasms/*genetics, Male, Middle Aged, Neoplastic, P-Glycoproteins/genetics, Repressor Proteins/genetics, Tumor, Tumor Suppressor, Tumor Suppressor Proteins/genetics}
}

@article{thorburn_aneuploid_2013,
	title = {Aneuploid yeast strains exhibit defects in cell growth and passage through {START}},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23468524},
	doi = {10.1091/mbc.E12-07-0520},
	abstract = {Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with many different aneuploid strains exhibiting a delay in G1, a cell cycle stage governed by extracellular cues, growth rate, and cell cycle events. Here we characterize this G1 delay. We show that 10 of 14 aneuploid yeast strains exhibit a growth defect during G1. Furthermore, 10 of 14 aneuploid strains display a cell cycle entry delay that correlates with the size of the additional chromosome. This cell cycle entry delay is due to a delayed accumulation of G1 cyclins that can be suppressed by supplying cells with high levels of a G1 cyclin. Our results indicate that aneuploidy frequently interferes with the ability of cells to grow and, as with many other cellular stresses, entry into the cell cycle.},
	pages = {1274--1289},
	number = {9},
	journaltitle = {Mol Biol Cell},
	author = {Thorburn, R R and Gonzalez, C and Brar, G A and Christen, S and Carlile, T M and Ingolia, N T and Sauer, U and Weissman, J S and Amon, A},
	date = {2013},
	pmid = {23468524},
	keywords = {Genetic, Humans, Transcription, Gene Expression Regulation, Cell Nucleus, *Aneuploidy, *G1 Phase Cell Cycle Checkpoints, Active Transport, Amino Acids/biosynthesis, Artificial, Chromosomes, Cyclin-Dependent Kinases/metabolism, Cyclins/genetics/metabolism, Fungal, Intracellular Signaling Peptides and Proteins/meta, Metabolome, Protein Biosynthesis, Repressor Proteins/metabolism, Saccharomyces cerevisiae Proteins/genetics/metabol, Saccharomyces cerevisiae/*cytology/growth \& develo, Signal Transduction, Yeast/genetics}
}

@article{eissmann_loss_2012,
	title = {Loss of the abundant nuclear non-coding {RNA} {MALAT}1 is compatible with life and development},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22858678},
	doi = {10.4161/rna.21089},
	abstract = {The metastasis-associated lung adenocarcinoma transcript 1, {MALAT}1, is a long non-coding {RNA} ({lncRNA}) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many {RNA} binding proteins and highly conserved throughout evolution. The nuclear transcript {MALAT}-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion. Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important {ncRNA}. In human tumor cells, {MALAT}1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of {MALAT}1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long {ncRNA} {MALAT}1 is compatible with cell viability and normal development.},
	pages = {1076--1087},
	number = {8},
	journaltitle = {{RNA} Biol},
	author = {Eissmann, M and Gutschner, T and Hammerle, M and Gunther, S and Caudron-Herger, M and Gross, M and Schirmacher, P and Rippe, K and Braun, T and Zornig, M and Diederichs, S},
	date = {2012},
	pmid = {22858678},
	keywords = {Animals, Humans, Mice, {RNA}, *Cell Survival, Cell Nucleus/metabolism, Gene Knockout Techniques, Knockout, Liver Neoplasms/metabolism/*pathology, Long Noncoding/genetics/*metabolism, Lung Neoplasms/metabolism/*pathology}
}

@article{michel_observation_2012,
	title = {Observation of dually decoded regions of the human genome using ribosome profiling data},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22593554},
	doi = {10.1101/gr.133249.111},
	abstract = {The recently developed ribosome profiling technique (Ribo-Seq) allows mapping of the locations of translating ribosomes on {mRNAs} with subcodon precision. When ribosome protected fragments ({RPFs}) are aligned to {mRNA}, a characteristic triplet periodicity pattern is revealed. We utilized the triplet periodicity of {RPFs} to develop a computational method for detecting transitions between reading frames that occur during programmed ribosomal frameshifting or in dual coding regions where the same nucleotide sequence codes for multiple proteins in different reading frames. Application of this method to ribosome profiling data obtained for human cells allowed us to detect several human genes where the same genomic segment is translated in more than one reading frame (from different transcripts as well as from the same {mRNA}) and revealed the translation of hitherto unpredicted coding open reading frames.},
	pages = {2219--2229},
	number = {11},
	journaltitle = {Genome Res},
	author = {Michel, A M and Choudhury, K R and Firth, A E and Ingolia, N T and Atkins, J F and Baranov, P V},
	date = {2012},
	pmid = {22593554},
	keywords = {Human, {DNA}, Sequence Analysis, Humans, {RNA}, Binding Sites, *Genome, Open Reading Frames, Complementary/chemistry, Messenger/metabolism, Protein Biosynthesis/*genetics, Ribosomes/*metabolism}
}

@article{bajic_mice_2006,
	title = {Mice and men: their promoter properties},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16683032},
	doi = {10.1371/journal.pgen.0020054},
	abstract = {Using the two largest collections of Mus musculus and Homo sapiens transcription start sites ({TSSs}) determined based on {CAGE} tags, ditags, full-length {cDNAs}, and other transcript data, we describe the compositional landscape surrounding {TSSs} with the aim of gaining better insight into the properties of mammalian promoters. We classified {TSSs} into four types based on compositional properties of regions immediately surrounding them. These properties highlighted distinctive features in the extended core promoters that helped us delineate boundaries of the transcription initiation domain space for both species. The {TSS} types were analyzed for associations with initiating dinucleotides, {CpG} islands, {TATA} boxes, and an extensive collection of statistically significant cis-elements in mouse and human. We found that different {TSS} types show preferences for different sets of initiating dinucleotides and cis-elements. Through Gene Ontology and {eVOC} categories and tissue expression libraries we linked {TSS} characteristics to expression. Moreover, we show a link of {TSS} characteristics to very specific genomic organization in an example of immune-response-related genes ({GO}:0006955). Our results shed light on the global properties of the two transcriptomes not revealed before and therefore provide the framework for better understanding of the transcriptional mechanisms in the two species, as well as a framework for development of new and more efficient promoter- and gene-finding tools.},
	pages = {e54},
	number = {4},
	journaltitle = {{PLoS} Genet},
	author = {Bajic, V B and Tan, S L and Christoffels, A and Schonbach, C and Lipovich, L and Yang, L and Hofmann, O and Kruger, A and Hide, W and Kai, C and Kawai, J and Hume, D A and Carninci, P and Hayashizaki, Y},
	date = {2006},
	pmid = {16683032},
	keywords = {{DNA}, Animals, Genetic, *Promoter Regions, *Transcription, Databases, Nucleic Acid, Base Composition, Complementary/genetics, Dinucleoside Phosphates, Gene Library, Humans/*genetics, Mice/*genetics, {TATA} Box}
}

@article{johnson_microrna-based_2008,
	title = {A {microRNA}-based gene dysregulation pathway in Huntington's disease},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18082412},
	doi = {10.1016/j.nbd.2007.11.001},
	abstract = {Huntington's disease ({HD}) is a dominantly-inherited neurodegenerative disorder which is incurable and ultimately fatal. {HD} is characterised by widespread {mRNA} dysregulation, particularly in neurons of the forebrain, by mechanisms which are not fully understood. Such dysregulation has been demonstrated to result, in part, from aberrant nuclear localisation of the transcriptional repressor, {REST}. Here, we show that expression of a number of neuronal-specific {microRNAs} is also dysregulated in {HD} tissues, probably as a result of increased repression by {REST}. This phenomenon is observed in both murine models of {HD} and in the brains of human {HD} sufferers. {MicroRNA} loss is reflected in increased levels of a number of target messenger {RNAs}. These data are the first to demonstrate a role for {microRNAs} in {HD}, and indicate that the molecular aetiology of {HD} is reflected in a loss of neuronal identity, caused in part by dysregulation of both transcriptional and post-transcriptional mechanisms.},
	pages = {438--445},
	number = {3},
	journaltitle = {Neurobiol Dis},
	author = {Johnson, R and Zuccato, C and Belyaev, N D and Guest, D J and Cattaneo, E and Buckley, N J},
	date = {2008},
	pmid = {18082412},
	keywords = {Animals, Humans, Mice, Cells, Cultured, Brain/pathology/physiology, Gene Targeting/methods, Huntington Disease/*genetics/*metabolism/pathology, {MicroRNAs}/*physiology, Repressor Proteins/biosynthesis/genetics, Signal Transduction/*genetics, Transcription Factors/biosynthesis/genetics, Transgenic}
}

@article{mannironi_acute_2013,
	title = {Acute stress alters amygdala {microRNA} {miR}-135a and {miR}-124 expression: inferences for corticosteroid dependent stress response},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24023867},
	doi = {10.1371/journal.pone.0073385},
	abstract = {The amygdala is a brain structure considered a key node for the regulation of neuroendocrine stress response. Stress-induced response in amygdala is accomplished through neurotransmitter activation and an alteration of gene expression. {MicroRNAs} ({miRNAs}) are important regulators of gene expression in the nervous system and are very well suited effectors of stress response for their ability to reversibly silence specific {mRNAs}. In order to study how acute stress affects {miRNAs} expression in amygdala we analyzed the {miRNA} profile after two hours of mouse restraint, by microarray analysis and reverse transcription real time {PCR}. We found that {miR}-135a and {miR}-124 were negatively regulated. Among in silico predicted targets we identified the mineralocorticoid receptor ({MR}) as a target of both {miR}-135a and {miR}-124. Luciferase experiments and endogenous protein expression analysis upon {miRNA} upregulation and inhibition allowed us to demonstrate that mir-135a and mir-124 are able to negatively affect the expression of the {MR}. The increased levels of the amygdala {MR} protein after two hours of restraint, that we analyzed by western blot, negatively correlate with {miR}-135a and {miR}-124 expression. These findings point to a role of {miR}-135a and {miR}-124 in acute stress as regulators of the {MR}, an important effector of early stress response.},
	pages = {e73385},
	number = {9},
	journaltitle = {{PLoS} One},
	author = {Mannironi, C and Camon, J and De Vito, F and Biundo, A and De Stefano, M E and Persiconi, I and Bozzoni, I and Fragapane, P and Mele, A and Presutti, C},
	date = {2013},
	pmid = {24023867}
}

@article{kravchik_global_2014,
	title = {Global and local perturbation of the tomato {microRNA} pathway by a trans-activated {DICER}-{LIKE} 1 mutant},
	volume = {65},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24376253},
	doi = {10.1093/jxb/ert428},
	abstract = {{DICER}-like 1 ({DCL}1) is a major player in {microRNA} ({miRNA}) biogenesis and accordingly, its few known loss-of-function mutants are either lethal or display arrested development. Consequently, generation of dcl1 mutants by reverse genetics and functional analysis of {DCL}1 in late-developing organs are challenging. Here, these challenges were resolved through the unique use of trans-activated {RNA} interference. Global, as well as organ-specific tomato {DCL}1 ({SlDCL}1) silencing was induced by crossing the generated responder line ({OP}:{SlDCL}1IR) with the appropriate driver line. Constitutive trans-activation knocked down {SlDCL}1 levels by ∼95\%, resulting in severe abnormalities including post-germination growth arrest accompanied by decreased {miRNA} and 21-nucleotide small {RNA} levels, but prominently elevated levels of 22-nucleotide small {RNAs}. The increase in the 22-nucleotide small {RNAs} was correlated with specific up-regulation of {SlDCL}2b and {SlDCL}2d, which are probably involved in their biogenesis. Leaf- and flower-specific {OP}:{SlDCL}1IR trans-activation inhibited blade outgrowth, induced premature bud senescence and produced pale petals, respectively, emphasizing the importance of {SlDCL}1-dependent small {RNAs} in these processes. Together, these results establish {OP}:{SlDCL}1IR as an efficient tool for analysing processes regulated by {SlDCL}1-mediated gene regulation in tomato.},
	pages = {725--739},
	number = {2},
	journaltitle = {J Exp Bot},
	author = {Kravchik, M and Sunkar, R and Damodharan, S and Stav, R and Zohar, M and Isaacson, T and Arazi, T},
	date = {2014},
	pmid = {24376253}
}

@article{vo_oncogenic_2012,
	title = {The oncogenic {RNA}-binding protein Musashi1 is regulated by {HuR} via {mRNA} translation and stability in glioblastoma cells},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22258704},
	doi = {10.1158/1541-7786.MCR-11-0208},
	abstract = {Musashi1 (Msi1) is an evolutionarily conserved {RNA}-binding protein ({RBP}) that has profound implications in cellular processes such as stem cell maintenance, nervous system development, and tumorigenesis. Msi1 is highly expressed in many cancers, including glioblastoma, whereas in normal tissues, its expression is restricted to stem cells. Unfortunately, the factors that modulate Msi1 expression and trigger high levels in tumors are largely unknown. The Msi1 {mRNA} has a long 3' untranslated region ({UTR}) containing several {AU}- and U-rich sequences. This type of sequence motif is often targeted by {HuR}, another important {RBP} known to be highly expressed in tumor tissue such as glioblastoma and to regulate a variety of cancer-related genes. In this report, we show an interaction between {HuR} and the Msi1 3'-{UTR}, resulting in a positive regulation of Msi1 expression. We show that {HuR} increased {MSI}1 {mRNA} stability and promoted its translation. We also present evidence that expression of {HuR} and Msi1 correlate positively in clinical glioblastoma samples. Finally, we show that inhibition of cell proliferation, increased apoptosis, and changes in cell-cycle profile as a result of silencing {HuR} are partially rescued when Msi1 is ectopically expressed. In summary, our results suggest that {HuR} is an important regulator of Msi1 in glioblastoma and that this regulation has important biological consequences during gliomagenesis.},
	pages = {143--155},
	number = {1},
	journaltitle = {Mol Cancer Res},
	author = {Vo, D T and Abdelmohsen, K and Martindale, J L and Qiao, M and Tominaga, K and Burton, T L and Gelfond, J A and Brenner, A J and Patel, V and Trageser, D and Scheffler, B and Gorospe, M and Penalva, L O},
	date = {2012},
	pmid = {22258704},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Cultured, 3' Untranslated Regions/genetics, Brain Neoplasms/*genetics/metabolism/pathology, Glioblastoma/*genetics/metabolism/pathology, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens/antag, inhibitors/genetics/metabolism/*physiology, Neoplastic/drug effect, Nerve Tissue Proteins/*genetics/metabolism, Oncogenes/genetics, Protein Biosynthesis/drug effects/*genetics, {RNA} Stability/drug effects/*genetics, {RNA}-Binding Proteins/antagonists \& inhibitors/*gen, Small Interfering/pharmacology, Tumor Cells}
}

@article{rinn_genome_2012,
	title = {Genome regulation by long noncoding {RNAs}},
	volume = {81},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22663078},
	doi = {10.1146/annurev-biochem-051410-092902},
	abstract = {The central dogma of gene expression is that {DNA} is transcribed into messenger {RNAs}, which in turn serve as the template for protein synthesis. The discovery of extensive transcription of large {RNA} transcripts that do not code for proteins, termed long noncoding {RNAs} ({lncRNAs}), provides an important new perspective on the centrality of {RNA} in gene regulation. Here, we discuss genome-scale strategies to discover and characterize {lncRNAs}. An emerging theme from multiple model systems is that {lncRNAs} form extensive networks of ribonucleoprotein ({RNP}) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, {lncRNAs} can function as modular scaffolds to specify higher-order organization in {RNP} complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long {RNAs} for proper gene control across all kingdoms of life.},
	pages = {145--166},
	journaltitle = {Annu Rev Biochem},
	author = {Rinn, J L and Chang, H Y},
	date = {2012},
	pmid = {22663078},
	keywords = {Human, Animals, Genome, Humans, {RNA}, Gene Expression Regulation, Disease, *Gene Expression Regulation, Disease/genetics, Genome-Wide Association Study, Ribonucleoproteins, Ribonucleoproteins/metabolism, Untranslated/*metabolism, {RNA}, Untranslated, Genome, Human},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/6A32SPPL/Rinn and Chang - 2012 - Genome regulation by long noncoding RNAs.pdf:application/pdf}
}

@article{johnson_human_2010,
	title = {The Human Accelerated Region 1 noncoding {RNA} is repressed by {REST} in Huntington's disease},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20179156},
	doi = {10.1152/physiolgenomics.00019.2010},
	abstract = {In the neurons of Huntington's disease ({HD}) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor, {REST}. Emerging evidence suggests that, in addition to protein-coding genes, non-coding {RNAs} ({ncRNAs}) may also contribute to neurodegenerative processes. To discover {ncRNAs} that are involved in {HD}, we screened genome-wide data for novel, non-coding targets of {REST}. This identified Human Accelerated Region 1 ({HAR}1), a rapidly-evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that {REST} is targeted to the {HAR}1 locus by specific {DNA} regulatory motifs, resulting in potent transcriptional repression. Consistent with other {REST} target genes, {HAR}1 levels are significantly lower in the striatum of {HD} patients compared to unaffected individuals. These data represent further evidence that non-coding gene expression changes accompany neurodegeneration in Huntington's disease. Key words: Huntington's Disease, {HAR}1, noncoding {RNA}.},
	journaltitle = {Physiol Genomics},
	author = {Johnson, R and Richter, N and Jauch, R and Gaughwin, P M and Zuccato, C and Cattaneo, E and Stanton, L W},
	date = {2010},
	pmid = {20179156}
}

@book{nei_molecular_1987,
	title = {Molecular Evolutionary Genetics},
	publisher = {Columbia University Press},
	author = {Nei, M},
	date = {1987}
}

@article{yue_comparative_2014,
	title = {A comparative encyclopedia of {DNA} elements in the mouse genome},
	volume = {515},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25409824},
	doi = {10.1038/nature13992},
	abstract = {The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse {ENCODE} Consortium has mapped transcription, {DNase} I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.},
	pages = {355--364},
	number = {7527},
	journaltitle = {Nature},
	author = {Yue, F and Cheng, Y and Breschi, A and Vierstra, J and Wu, W and Ryba, T and Sandstrom, R and Ma, Z and Davis, C and Pope, B D and Shen, Y and Pervouchine, D D and Djebali, S and Thurman, R E and Kaul, R and Rynes, E and Kirilusha, A and Marinov, G K and Williams, B A and Trout, D and Amrhein, H and Fisher-Aylor, K and Antoshechkin, I and {DeSalvo}, G and See, L H and Fastuca, M and Drenkow, J and Zaleski, C and Dobin, A and Prieto, P and Lagarde, J and Bussotti, G and Tanzer, A and Denas, O and Li, K and Bender, M A and Zhang, M and Byron, R and Groudine, M T and {McCleary}, D and Pham, L and Ye, Z and Kuan, S and Edsall, L and Wu, Y C and Rasmussen, M D and Bansal, M S and Kellis, M and Keller, C A and Morrissey, C S and Mishra, T and Jain, D and Dogan, N and Harris, R S and Cayting, P and Kawli, T and Boyle, A P and Euskirchen, G and Kundaje, A and Lin, S and Lin, Y and Jansen, C and Malladi, V S and Cline, M S and Erickson, D T and Kirkup, V M and Learned, K and Sloan, C A and Rosenbloom, K R and Lacerda de Sousa, B and Beal, K and Pignatelli, M and Flicek, P and Lian, J and Kahveci, T and Lee, D and Kent, W J and Ramalho Santos, M and Herrero, J and Notredame, C and Johnson, A and Vong, S and Lee, K and Bates, D and Neri, F and Diegel, M and Canfield, T and Sabo, P J and Wilken, M S and Reh, T A and Giste, E and Shafer, A and Kutyavin, T and Haugen, E and Dunn, D and Reynolds, A P and Neph, S and Humbert, R and Hansen, R S and De Bruijn, M and Selleri, L and Rudensky, A and Josefowicz, S and Samstein, R and Eichler, E E and Orkin, S H and Levasseur, D and Papayannopoulou, T and Chang, K H and Skoultchi, A and Gosh, S and Disteche, C and Treuting, P and Wang, Y and Weiss, M J and Blobel, G A and Cao, X and Zhong, S and Wang, T and Good, P J and Lowdon, R F and Adams, L B and Zhou, X Q and Pazin, M J and Feingold, E A and Wold, B and Taylor, J and Mortazavi, A and Weissman, S M and Stamatoyannopoulos, J A and Snyder, M P and Guigo, R and Gingeras, T R and Gilbert, D M and Hardison, R C and Beer, M A and Ren, B},
	date = {2014},
	pmid = {25409824},
	keywords = {Animals, Humans, Regulatory Sequences, Transcription Factors/metabolism, *Genomics, *Molecular Sequence Annotation, Cell Lineage/genetics, Chromatin/genetics/metabolism, Conserved Sequence/genetics, Deoxyribonuclease I/metabolism, {DNA} Replication/genetics, Gene Expression Regulation/genetics, Gene Regulatory Networks/genetics, Genome-Wide Association Study, Genome/*genetics, Mice/*genetics, Nucleic Acid/genetics, {RNA}/genetics, Species Specificity, Transcriptome/genetics}
}

@article{sanulli_jarid2_2015,
	title = {Jarid2 Methylation via the {PRC}2 Complex Regulates H3K27me3 Deposition during Cell Differentiation},
	volume = {57},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25620564},
	doi = {10.1016/j.molcel.2014.12.020},
	abstract = {Polycomb Group ({PcG}) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. Polycomb Repressive Complex 2 ({PRC}2), a component of the Polycomb machinery, is responsible for the methylation of histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously identified as a cofactor of {PRC}2, regulating {PRC}2 targeting to chromatin and its enzymatic activity. Deletion of Jarid2 leads to impaired orchestration of gene expression during cell lineage commitment. Here, we reveal an unexpected crosstalk between Jarid2 and {PRC}2, with Jarid2 being methylated by {PRC}2. This modification is recognized by the Eed core component of {PRC}2 and triggers an allosteric activation of {PRC}2's enzymatic activity. We show that Jarid2 methylation is important to promote {PRC}2 activity at a locus devoid of H3K27me3 and for the correct deposition of this mark during cell differentiation. Our results uncover a regulation loop where Jarid2 methylation fine-tunes {PRC}2 activity depending on the chromatin context.},
	pages = {769--783},
	number = {5},
	journaltitle = {Mol Cell},
	author = {Sanulli, S and Justin, N and Teissandier, A and Ancelin, K and Portoso, M and Caron, M and Michaud, A and Lombard, B and da Rocha, S T and Offer, J and Loew, D and Servant, N and Wassef, M and Burlina, F and Gamblin, S J and Heard, E and Margueron, R},
	date = {2015},
	pmid = {25620564},
	keywords = {Animals, Genetic, Humans, Mice, *Cell Differentiation, Cell Line, Chromatin/genetics/metabolism, Drosophila melanogaster/cytology/genetics/metaboli, Drosophila Proteins/genetics/metabolism, Embryonic Stem Cells/cytology/metabolism, Female, {HEK}293 Cells, Histone-Lysine N-Methyltransferase/genetics/*metab, Histones/genetics/*metabolism, Knockout, Lysine/genetics/metabolism, Methylation, Models, Mutation, Polycomb Repressive Complex 2/genetics/*metabolism, {RNA} Interference}
}

@article{ballarino_coupled_2009,
	title = {Coupled {RNA} processing and transcription of intergenic primary {microRNAs}},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19667074},
	doi = {10.1128/MCB.00664-09},
	abstract = {The first step in {microRNA} ({miRNA}) biogenesis occurs in the nucleus and is mediated by the Microprocessor complex containing the {RNase} {III}-like enzyme Drosha and its cofactor {DGCR}8. Here we show that the 5'–{\textbackslash}textgreater3' exonuclease Xrn2 associates with independently transcribed {miRNAs} and, in combination with Drosha processing, attenuates transcription in downstream regions. We suggest that, after Drosha cleavage, a torpedo-like mechanism acts on nascent long precursor {miRNAs}, whereby Xrn2 exonuclease degrades the {RNA} polymerase {II}-associated transcripts inducing its release from the template. While involved in primary transcript termination, this attenuation effect does not restrict clustered {miRNA} expression, which, in the majority of cases, is separated by short spacers. We also show that transcripts originating from a {miRNA} promoter are retained on the chromatin template and are more efficiently processed than those produced from {mRNA} or {snRNA} Pol {II}-dependent promoters. These data imply that coupling between transcription and processing promotes efficient expression of independently transcribed {miRNAs}.},
	pages = {5632--5638},
	number = {20},
	journaltitle = {Mol Cell Biol},
	author = {Ballarino, M and Pagano, F and Girardi, E and Morlando, M and Cacchiarelli, D and Marchioni, M and Proudfoot, N J and Bozzoni, I},
	date = {2009},
	pmid = {19667074},
	keywords = {Humans, Promoter Regions, {RNA}, *{RNA} Processing, Cell Line, Exoribonucleases/genetics/metabolism, Genetic/physiology, {HeLa} Cells, Messenger/genetics/*metabolism, {MicroRNAs}/genetics/*metabolism, Post-Transcriptional, Proteins/genetics/metabolism, Ribonuclease {III}/genetics/*metabolism, {RNA} Polymerase {II}/genetics/metabolism, Small Nuclear/genetics/*metabolism, Tumor}
}

@article{he_anril/cdkn2b-as_2013,
	title = {{ANRIL}/{CDKN}2B-{AS} shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24225082},
	doi = {10.1186/1471-2148-13-247},
	abstract = {{BACKGROUND}: Many long non-coding {RNA} ({lncRNA}) genes identified in mammals have multiple exons and functional domains, allowing them to bind to polycomb proteins, {DNA} methyltransferases, and specific {DNA} sequences to regulate genome methylation. Little is known about the origin and evolution of {lncRNAs}. {ANRIL}/{CDKN}2B-{AS} consists of 19 exons on human chromosome 9p21 and regulates the expression of three cyclin-dependent kinase inhibitors ({CDKN}2A/{ARF}/{CDKN}2B). {RESULTS}: {ANRIL}/{CDKN}2B-{AS} originated in placental mammals, obtained additional exons during mammalian evolution but gradually lost them during rodent evolution, and reached 19 exons only in simians. {ANRIL} lacks splicing signals in mammals. In simians, multiple transposons were inserted and transformed into exons of the {ANRIL} gene, after which {ANRIL} became highly conserved. A further survey reveals that multiple transposons exist in many {lncRNAs}. {CONCLUSIONS}: {ANRIL} shows a two-stage, clade-specific evolutionary process and is fully developed only in simians. The domestication of multiple transposons indicates an impressive pattern of "evolutionary tinkering" and is likely to be important for {ANRIL}'s structure and function. The evolution of {lncRNAs} and that of transposons may be highly co-opted in primates. Many {lncRNAs} may be functional only in simians.},
	pages = {247},
	journaltitle = {{BMC} Evol Biol},
	author = {He, S and Gu, W and Li, Y and Zhu, H},
	date = {2013},
	pmid = {24225082},
	keywords = {Animals, Humans, {RNA} Splicing, Exons, {DNA} Transposable Elements, Mammals, Evolution, Molecular, {RNA}, Long Noncoding, Regulatory Sequences, Nucleic Acid, Cyclin-Dependent Kinase Inhibitor Proteins, Hominidae},
	file = {Full Text:/home/jlagarde/Zotero/storage/25QND2RH/He et al. - 2013 - ANRILCDKN2B-AS shows two-stage clade-specific evo.pdf:application/pdf}
}

@article{fatica_role_2008,
	title = {Role of {microRNAs} in myeloid differentiation},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19021525},
	doi = {10.1042/BST0361201},
	abstract = {All types of blood cell of the body are continuously produced by rare pluripotent self-renewing {HSCs} (haemopoietic stem cells) by a process known as haemopoiesis. This process provides a valuable model for examining how genetic programmes involved in cell differentiation are established, and also how cell-fate specification is altered in leukaemia. Here, we describe examples of how {miRNAs} ({microRNAs}) can influence myelopoiesis and how the identification of their target {mRNAs} has contributed to the understanding of the molecular networks involved in the alternative control between cell growth and differentiation. Ectopic expression and knockdown of specific {miRNAs} have provided powerful molecular tools able to control the switch between proliferation and differentiation, therefore providing new therapeutic tools for interfering with tumorigenesis.},
	pages = {1201--1205},
	issue = {Pt 6},
	journaltitle = {Biochem Soc Trans},
	author = {Fatica, A and Rosa, A and Ballarino, M and De Marchis, M L and Rasmussen, K D and Bozzoni, I},
	date = {2008},
	pmid = {19021525},
	keywords = {Humans, *Cell Differentiation/drug effects, Acute/genetics/pathology, Biological, Cell Line, Granulocytes/cytology/drug effects, Leukemia, {MicroRNAs}/genetics/*metabolism, Models, Monocytes/cytology/drug effects, Myeloid, Myeloid Cells/*cytology/drug effects, Tretinoin/pharmacology}
}

@article{santarius_census_2010,
	title = {A census of amplified and overexpressed human cancer genes},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20029424},
	doi = {10.1038/nrc2771},
	abstract = {Integrated genome-wide screens of {DNA} copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer.},
	pages = {59--64},
	number = {1},
	journaltitle = {Nat Rev Cancer},
	author = {Santarius, T and Shipley, J and Brewer, D and Stratton, M R and Cooper, C S},
	date = {2010},
	pmid = {20029424},
	keywords = {Human, Animals, Genome, Humans, Gene Expression Profiling, *Gene Amplification, *Gene Expression Regulation, Gene Dosage, Molecular Sequence Data, Neoplasms/*genetics, Neoplastic}
}

@article{carlevaro-fita_widespread_2014,
	title = {Widespread localisation of long noncoding {RNAs} to ribosomes: Distinguishing features and evidence for regulatory roles.},
	doi = {http://dx.doi.org/10.1101/013508},
	journaltitle = {Biorxiv},
	author = {Carlevaro-Fita, J and Rahim, A and Guigo, R and Vardy, L A and Johnson, R},
	date = {2014}
}

@article{mathieu_aurora_2013,
	title = {Aurora B and cyclin B have opposite effects on the timing of cytokinesis abscission in Drosophila germ cells and in vertebrate somatic cells},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23948252},
	doi = {10.1016/j.devcel.2013.07.005},
	abstract = {Abscission is the last step of cytokinesis that physically separates the cytoplasm of sister cells. As the final stage of cell division, abscission is poorly characterized during animal development. Here, we show that Aurora B and Survivin regulate the number of germ cells in each Drosophila egg chamber by inhibiting abscission during differentiation. This inhibition is mediated by an Aurora B-dependent phosphorylation of Cyclin B, as a phosphomimic form of Cyclin B rescues premature abscission caused by a loss of function of Aurora B. We show that Cyclin B localizes at the cytokinesis bridge, where it promotes abscission. We propose that mutual inhibitions between Aurora B and Cyclin B regulate the duration of abscission and thereby the number of sister cells in each cyst. Finally, we show that inhibitions of Aurora B and Cyclin-dependent kinase 1 activity in vertebrate cells also have opposite effects on the timing of abscission, suggesting a possible conservation of these mechanisms.},
	pages = {250--265},
	number = {3},
	journaltitle = {Dev Cell},
	author = {Mathieu, J and Cauvin, C and Moch, C and Radford, S J and Sampaio, P and Perdigoto, C N and Schweisguth, F and Bardin, A J and Sunkel, C E and {McKim}, K and Echard, A and Huynh, J R},
	date = {2013},
	pmid = {23948252},
	keywords = {Animals, Humans, Mice, Aurora Kinase B, Aurora Kinases, Cell Differentiation/physiology, Cyclin B/genetics/*metabolism, Cyclin B1/genetics/*metabolism, Cyclin B2/genetics/metabolism, Cytokinesis/*physiology, Drosophila, Drosophila Proteins/genetics/*metabolism, Female, Fibroblasts/cytology/physiology, Germ Cells/cytology/*physiology, Green Fluorescent Proteins/genetics, {HEK}293 Cells, {HeLa} Cells, Inhibitor of Apoptosis Proteins/genetics/metabolis, Knockout, Male, Phosphorylation/physiology, Protein-Serine-Threonine Kinases/genetics/*metabol, Transfection, Vertebrates}
}

@article{gorospe_role_1996,
	title = {Role of p21 in prostaglandin A2-mediated cellular arrest and death},
	volume = {56},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8564956},
	abstract = {Prostaglandin A2 ({PGA}2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma {MCF}-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity. In this study, we demonstrate that, in {RKO} cells, {PGA}2 treatment fails to induce growth arrest, but rather results in significant cell death. These effects are correlated with lack of p21 induction and enhanced cyclin-dependent kinase 2 activity. Reduction of endogenous p21 expression in {MCF}-7 cells through expression of antisense p21 resulted in a response pattern approaching that seen in {RKO} cells, characterized by diminished growth arrest and increased death. These findings support a role for p21 in {PGA}2-mediated growth arrest, which we propose serves to prevent cell death caused by inappropriate cell cycle progression.},
	pages = {475--479},
	number = {3},
	journaltitle = {Cancer Res},
	author = {Gorospe, M and Holbrook, N J},
	date = {1996},
	pmid = {8564956},
	keywords = {Animals, Base Sequence, Humans, Mice, Cultured, *{CDC}2-{CDC}28 Kinases, 3T3 Cells/cytology, Antisense/pharmacology, Cell Count, Cell Cycle/drug effects, Cell Death/drug effects/physiology, Cell Division/drug effects/physiology, Culture Media, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases/metabolism, Cyclins/biosynthesis/*physiology, Experimental/pathology, Flow Cytometry, Molecular Sequence Data, Neoplasms, Neoplasms/pathology, Oligonucleotides, Prostaglandins A/*pharmacology, Protein-Serine-Threonine Kinases/metabolism, Rats, Serum-Free, Tumor Cells}
}

@article{kuwano_protecting_2008,
	title = {Protecting the stress response, guarding the {MKP}-1 {mRNA}},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18728392},
	abstract = {The {RNA}-binding protein ({RBP}) {HuR} plays a vital role in the mammalian stress response, effecting changes in the proliferation and survival of damaged cells. {HuR} prominently influences the stress response by regulating the stability and translation of {mRNAs} encoding stress-response proteins. Recently, {HuR} was found to affect mitogen-activated protein kinase ({MAPK}) signaling, at least in part by post-transcriptionally promoting the expression of {MAPK} phosphatase-1 ({MKP}-1). As anticipated for a pivotal regulator of the {MAPKs} c-jun N-terminal kinase ({JNK}) and p38, {MKP}-1 expression is tightly regulated transcriptionally, post-transcriptionally and post-translationally. {HuR}'s influence on {MKP}-1 expression helps to ensure the appropriate abundance of {MKP}-1 and consequently the appropriate cellular response to stress stimuli.},
	pages = {2640--2642},
	number = {17},
	journaltitle = {Cell Cycle},
	author = {Kuwano, Y and Gorospe, M},
	date = {2008},
	pmid = {18728392},
	keywords = {Animals, Humans, {RNA}, Dual Specificity Phosphatase 1/*genetics/*metaboli, Messenger/genetics/metabolism, Mitogen-Activated Protein Kinases/metabolism, {RNA}-Binding Proteins/metabolism}
}

@article{sunkireddy_natural_2013,
	title = {Natural antioxidant biomolecules promises future nanomedicine based therapy for cataract},
	volume = {112},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24001900},
	doi = {10.1016/j.colsurfb.2013.07.068},
	abstract = {Cataract is an eye disease of major human concern and its prevention is important to control the global incidences of blindness. The emergence of cataract in the eye lens by strong {UV} radiation and growing pollution could be effectively reduced by natural antioxidant biomolecules such as flavonoids, phenolic acids, carotenoids and vitamins. This goal can be achieved either by direct external use of antioxidant biomolecules in the form of topical application as an eye drops, food supplements or through nanobiotechnology based formulation without any side effects. In this manuscript, we have discussed the mechanisms of cataract formation and the preventive role of different classes of natural antioxidant biomolecules. Further, role of nanobiotechnology to enhance therapeutic potential of these natural antioxidant molecules by enhancing solubility, stability, bioavailability and sustained release has been briefly discussed.},
	pages = {554--562},
	journaltitle = {Colloids Surf B Biointerfaces},
	author = {Sunkireddy, P and Jha, S N and Kanwar, J R and Yadav, S C},
	date = {2013},
	pmid = {24001900}
}

@article{lipovich_abundant_2006,
	title = {Abundant novel transcriptional units and unconventional gene pairs on human chromosome 22},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16344557},
	doi = {10.1101/gr.3883606},
	abstract = {Novel transcriptional units ({TUs}) are {EST}-supported transcribed features not corresponding to known genes. Unconventional gene pairs ({UGPs}) are pairs of genes and/or {TUs} sharing exon-to-exon cis-antisense overlaps or putative bidirectional promoters. Computational {TU} and {UGP} discovery followed by manual curation was performed in the entire published 34.9-Mb human chromosome 22 euchromatic sequence. Novel {TUs} (n = 517) were as abundant as known genes (n = 492) and typically did not have nonprimate {DNA} and protein homologies. One hundred seventy-one (33\%) of {TUs}, but only 13 (3\%) of genes, both lacked nonprimate conservation and localized to gaps in the human-mouse {BLASTZ} alignment. Novel {TUs} were richer in exonic primate-specific interspersed repetitive elements (P = 0.001) and were more likely to rely on splice junctions provided by them, than were known genes: 19\% of spliced {TUs}, versus 5\% of spliced genes, had a splice site within a primate-specific repeat. Hence, novel {TUs} and known genes may represent different portions of the transcriptome. Two hundred nine (21\%) of chromosome 22 transcripts participated in 77 cis-antisense and 42 promoter-sharing {UGPs}. Transcripts involved simultaneously in both {UGP} types were more common than was expected (P = 0.01). {UGPs} were nonrandomly distributed along the sequence: 89 (75\%) clustered in distinct regions, the sum of which equaled 4.4 Mb ({\textbackslash}textless13\% of the chromosome). Eighty (67\%) of the {UGPs} possessed significant locus structure differences between primates and rodents. Since some {TUs} may be functional noncoding transcripts and since the cis-regulatory potential of {UGPs} is well recognized, {TUs} and {UGPs} specific to the primate lineage may contribute to the genomic basis for primate-specific phenotypes.},
	pages = {45--54},
	number = {1},
	journaltitle = {Genome Res},
	author = {Lipovich, L and King, M C},
	date = {2006},
	pmid = {16344557},
	keywords = {Human, Animals, Humans, Mice, Transcription, Chromosomes, Euchromatin/*genetics, Genetic/*genetics, Interspersed Repetitive Sequences/*genetics, Open Reading Frames/*genetics, Pair 22/*genetics}
}

@article{lanfear_association_2013,
	title = {Association of genetic variation with gene expression and protein abundance within the natriuretic peptide pathway},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23835779},
	doi = {10.1007/s12265-013-9491-y},
	abstract = {The natriuretic peptide ({NP}) system is a critical physiologic pathway in heart failure with wide individual variability in functioning. We investigated the genetic component by testing the association of single nucleotide polymorphisms ({SNP}) with {RNA} and protein expression. Samples of {DNA}, {RNA}, and tissue from human kidney (n = 103) underwent genotyping, {RT}-{PCR}, and protein quantitation (in lysates), for four candidate genes [{NP} receptor 1 ({NPR}1), {NPR}2, and {NPR}3 and membrane metalloendopeptidase]. The association of genetic variation with expression was tested using linear regression for individual {SNPs}, and a principal components ({PC}) method for overall gene variation. Eleven {SNPs} in {NPR}2 were significantly associated with protein expression (false discovery rate {\textbackslash}textless/=0.05), but not {RNA} quantity. {RNA} and protein quantity correlated poorly with each other. The {PC} analysis showed only {NPR}2 as significant. Assessment of the clinical impact of {NPR}2 genetic variation is needed.},
	pages = {826--833},
	number = {5},
	journaltitle = {J Cardiovasc Transl Res},
	author = {Lanfear, D E and Sunkara, B and Li, J and Rastogi, S and Gupta, R C and Padhukasahasram, B and Williams, L K and Sabbah, H N},
	date = {2013},
	pmid = {23835779}
}

@article{gorospe_assirting_2008,
	title = {{AsSIRTing} the {DNA} damage response},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18215521},
	doi = {10.1016/j.tcb.2007.11.007},
	abstract = {In mammalian cells, changes in signaling networks and expressed proteins ensure the adequate detection and management of damaged macromolecules. Here, we review an emergent pathway of maintenance of homeostasis following genotoxic stress. The {RNA}-binding protein {HuR} associates with sirtuin ({SIRT})1 {mRNA} and maintains constitutively elevated levels of {SIRT}1 protein, a deacetylase that elicits a prosurvival function. {SIRT}1 was recently shown to deacetylate the Nijmegen breakage syndrome ({NBS}1) protein, thereby rendering it phosphorylatable by ataxia telangiectasia mutated protein ({ATM}). A component of the {MRN} ({MRE}11-{RAD}50-{NBS}1) nuclease complex, {NBS}1 is crucial for sensing {DNA} damage and mounting a genotoxic response. This article covers the regulatory pathway of {HuR}–{\textbackslash}{textgreaterSIRT}1–{\textbackslash}{textgreaterNBS}1, through which post-transcriptional and post-translational effectors contribute to the maintenance of genomic integrity.},
	pages = {77--83},
	number = {2},
	journaltitle = {Trends Cell Biol},
	author = {Gorospe, M and de Cabo, R},
	date = {2008},
	pmid = {18215521},
	keywords = {Animals, Humans, Gene Expression Regulation, *{DNA} Damage, *{RNA}, *Sirtuins/genetics/metabolism, Antigens, Cell Cycle Proteins/genetics/metabolism, Cell Survival/physiology, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/genetics/metabolism, Nuclear Proteins/genetics/metabolism, {RNA}-Binding Proteins/genetics/metabolism, Signal Transduction/physiology, Sirtuin 1, Surface/genetics/metabolism}
}

@article{coury_langerhans_2008,
	title = {Langerhans cell histiocytosis reveals a new {IL}-17A-dependent pathway of dendritic cell fusion},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18157139},
	doi = {10.1038/nm1694},
	abstract = {{IL}-17A is a T cell-specific cytokine that is involved in chronic inflammations, such as Mycobacterium infection, Crohn's disease, rheumatoid arthritis and multiple sclerosis. Mouse models have explained the molecular basis of {IL}-17A production and have shown that {IL}-17A has a positive effect not only on granuloma formation and neurodegeneration through unknown mechanisms, but also on bone resorption through Receptor activator of {NF}-{kappaB} ligand ({RANKL}) induction in osteoblasts. Langerhans cell histiocytosis ({LCH}) is a rare disease of unknown etiology, lacking an animal model, that cumulates symptoms that are found separately in various {IL}-17A-related diseases, such as aggressive chronic granuloma formation, bone resorption and soft tissue lesions with occasional neurodegeneration. We examined {IL}-17A in the context of {LCH} and found that there were high serum levels of {IL}-17A during active {LCH} and unexpected {IL}-17A synthesis by dendritic cells ({DCs}), the major cell type in {LCH} lesions. We also found an {IL}-17A-dependent pathway for {DC} fusion, which was highly potentiated by {IFN}-gamma and led to giant cells expressing three major tissue-destructive enzymes: tartrate resistant acidic phosphatase and matrix metalloproteinases 9 and 12. {IFN}-gamma expression has been previously documented in {LCH} and observed in {IL}-17A-related diseases. Notably, serum {IL}-17A-dependent fusion activity correlates with {LCH} activity. Thus, {IL}-17A and {IL}-17A-stimulated {DCs} represent targets that may have clinical value in the treatment of {LCH} and other {IL}-17A-related inflammatory disorders.},
	pages = {81--87},
	number = {1},
	journaltitle = {Nat Med},
	author = {Coury, F and Annels, N and Rivollier, A and Olsson, S and Santoro, A and Speziani, C and Azocar, O and Flacher, M and Djebali, S and Tebib, J and Brytting, M and Egeler, R M and Rabourdin-Combe, C and Henter, J I and Arico, M and Delprat, C},
	date = {2008},
	pmid = {18157139},
	keywords = {Animals, Humans, Mice, Oligonucleotide Array Sequence Analysis, Arthritis, Cell Fusion, Dendritic Cells/*metabolism, Histiocytosis, Inflammation, Interferon-gamma/metabolism, Interleukin-17/*metabolism, Langerhans-Cell/*pathology, Lymphocyte Activation, Lymphocytes/metabolism, Monocytes/metabolism, Mycobacterium/metabolism, Rheumatoid/metabolism}
}

@article{hodis_landscape_2012,
	title = {A landscape of driver mutations in melanoma},
	volume = {150},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22817889},
	doi = {10.1016/j.cell.2012.06.024},
	abstract = {Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic {UV} light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes ({PPP}6C, {RAC}1, {SNX}31, {TACC}1, {STK}19, and {ARID}2), three of which-{RAC}1, {PPP}6C, and {STK}19-harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in {BRAF}- and {NRAS}-driven melanoma as well as those without known {NRAS}/{BRAF} mutations. The landscape also clarified a mutational basis for {RB} and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of {UV} light in melanoma pathogenesis.},
	pages = {251--263},
	number = {2},
	journaltitle = {Cell},
	author = {Hodis, E and Watson, I R and Kryukov, G V and Arold, S T and Imielinski, M and Theurillat, J P and Nickerson, E and Auclair, D and Li, L and Place, C and Dicara, D and Ramos, A H and Lawrence, M S and Cibulskis, K and Sivachenko, A and Voet, D and Saksena, G and Stransky, N and Onofrio, R C and Winckler, W and Ardlie, K and Wagle, N and Wargo, J and Chong, K and Morton, D L and Stemke-Hale, K and Chen, G and Noble, M and Meyerson, M and Ladbury, J E and Davies, M A and Gershenwald, J E and Wagner, S N and Hoon, D S and Schadendorf, D and Lander, E S and Gabriel, S B and Getz, G and Garraway, L A and Chin, L},
	date = {2012},
	pmid = {22817889},
	keywords = {Humans, Cells, Cultured, *Genome-Wide Association Study, *Mutagenesis, *Ultraviolet Rays, Amino Acid Sequence, Exome, Melanocytes/metabolism, Melanoma/*genetics, Models, Molecular, Molecular Sequence Data, Proto-Oncogene Proteins B-raf/genetics, rac1 {GTP}-Binding Protein/genetics, Sequence Alignment}
}

@article{cheadle_control_2005,
	title = {Control of gene expression during T cell activation: alternate regulation of {mRNA} transcription and {mRNA} stability},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15907206},
	doi = {10.1186/1471-2164-6-75},
	abstract = {{BACKGROUND}: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The effective correlation of observed changes in gene expression with shared transcription regulatory elements remains difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and {mRNA} turnover events which, together, directly influence steady-state {mRNA} levels. {RESULTS}: In order to investigate the relative contribution of gene transcription and changes in {mRNA} stability regulation to standard analyses of gene expression, we used two distinct microarray methods which individually measure nuclear gene transcription and changes in {polyA} {mRNA} gene expression. Gene expression profiles were obtained from both {polyA} {mRNA} (whole-cell) and nuclear run-on (newly transcribed) {RNA} across a time course of one hour following the activation of human Jurkat T cells with {PMA} plus ionomycin. Comparative analysis revealed that regulation of {mRNA} stability may account for as much as 50\% of all measurements of changes in {polyA} {mRNA} in this system, as inferred by the absence of any corresponding regulation of nuclear gene transcription activity for these groups of genes. Genes which displayed dramatic elevations in both {mRNA} and nuclear run-on {RNA} were shown to be inhibited by Actinomycin D ({ActD}) pre-treatment of cells while large numbers of genes regulated only through altered {mRNA} turnover (both up and down) were {ActD}-resistant. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. {CONCLUSION}: We propose that regulation of {mRNA} stability contributes significantly to the observed changes in gene expression in response to external stimuli, as measured by high throughput systems.},
	pages = {75},
	journaltitle = {{BMC} Genomics},
	author = {Cheadle, C and Fan, J and Cho-Chung, Y S and Werner, T and Ray, J and Do, L and Gorospe, M and Becker, K G},
	date = {2005},
	pmid = {15907206},
	keywords = {Gene Expression Profiling/*methods, Genomics/*methods, Genetic, Humans, {RNA}, *Transcription, Oligonucleotide Array Sequence Analysis, *Gene Expression Regulation, Cell Nucleus/metabolism, Cluster Analysis, Computational Biology/methods, Dactinomycin/pharmacology, Ionomycin/pharmacology, Jurkat Cells, Lymphocyte Activation, Messenger/*metabolism, {NF}-kappa B/metabolism, Poly A/metabolism, Polymerase Chain Reaction, T-Lymphocytes/*metabolism, Tetradecanoylphorbol Acetate/pharmacology, Time Factors}
}

@article{gorospe_functional_1999,
	title = {Functional role of p21 during the cellular response to stress},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10440238},
	abstract = {A wide range of stress stimuli, including oxidants, genotoxins, metabolic deficiencies, and irradiation, have been shown to induce expression of the cyclin-dependent kinase inhibitor p21. Among the best characterized mediators of p21 induction by stress is the tumor suppressor gene p53, which acts as a transcriptional activator to enhance the expression of the p21 gene. However, many other mechanisms involving transcriptional and posttranscriptional events have been found to participate in the elevation of p21 levels by stressful agents. The significance of the stress-mediated elevation in p21 expression is not fully understood, but it is clear that alterations in p21 expression impact on the ability of the cell to survive the insult. Although a large number of reports have demonstrated correlations between the expression of p21 and cellular outcome, this review will focus only on those reports where the role of p21 in a given stress paradigm has been investigated directly, through use of different strategies to manipulate p21 expression followed by assessment of the consequences of altered p21 expression on cell survival. The majority of such studies have revealed that p21 exerts a protective function against stress, and this property appears to rely, at least in part, on the ability of p21 to suppress cell proliferation. A few exceptions to this universal protective influence of p21 have also been observed and will be discussed.},
	pages = {377--385},
	number = {4},
	journaltitle = {Gene Expr},
	author = {Gorospe, M and Wang, X and Holbrook, N J},
	date = {1999},
	pmid = {10440238},
	keywords = {Animals, Humans, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/*physiology, Gene Expression, Heat-Shock Response}
}

@article{ozturk_magnetic_2005,
	title = {Magnetic resonance imaging-guided vascular interventions},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16924170},
	abstract = {Magnetic resonance imaging ({MRI}), which provides superior soft-tissue imaging and no known harmful effects, has the potential as an alternative modality to guide various medical interventions. This review will focus on {MR}-guided endovascular interventions and present its current state and future outlook. In the first technical part, enabling technologies such as developments in fast imaging, catheter devices, and visualization techniques are examined. This is followed by a clinical survey that includes proof-of-concept procedures in animals and initial experience in human subjects. In preclinical experiments, {MRI} has already proven to be valuable. For example, {MRI} has been used to guide and track targeted cell delivery into or around myocardial infarctions, to guide atrial septal puncture, and to guide the connection of portal and systemic venous circulations. Several investigational {MR}-guided procedures have already been reported in patients, such as {MR}-guided cardiac catheterization, invasive imaging of peripheral artery atheromata, selective intraarterial {MR} angiography, and preliminary angioplasty and stent placement. In addition, {MR}-assisted transjugular intrahepatic portosystemic shunt procedures in patients have been shown in a novel hybrid double-doughnut x-ray/{MRI} system. Numerous additional investigational human {MR}-guided endovascular procedures are now underway in several medical centers around the world. There are also significant hurdles: availability of clinical-grade devices, device-related safety issues, challenges to patient monitoring, and acoustic noise during imaging. The potential of endovascular interventional {MRI} is great because as a single modality, it combines 3-dimensional anatomic imaging, device localization, hemodynamics, tissue composition, and function.},
	pages = {369--381},
	number = {5},
	journaltitle = {Top Magn Reson Imaging},
	author = {Ozturk, C and Guttman, M and {McVeigh}, E R and Lederman, R J},
	date = {2005},
	pmid = {16924170},
	keywords = {Animals, Humans, Blood Vessel Prosthesis Implantation/methods, Catheterization/methods, Contrast Media, Imaging, Magnetic Resonance Imaging/*methods, Minimally Invasive, Surgical Procedures, Three-Dimensional, Vascular Diseases/*diagnosis/*therapy}
}

@article{kim_widespread_2010,
	title = {Widespread transcription at neuronal activity-regulated enhancers},
	volume = {465},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20393465},
	doi = {10.1038/nature09033},
	abstract = {We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator {CBP} in an activity-dependent manner. A function of {CBP} at enhancers may be to recruit {RNA} polymerase {II} ({RNAPII}), as we also observed activity-regulated {RNAPII} binding to thousands of enhancers. Notably, {RNAPII} at enhancers transcribes bi-directionally a novel class of enhancer {RNAs} ({eRNAs}) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of {eRNA} expression at neuronal enhancers positively correlates with the level of messenger {RNA} synthesis at nearby genes, suggesting that {eRNA} synthesis occurs specifically at enhancers that are actively engaged in promoting {mRNA} synthesis. These findings reveal that a widespread mechanism of enhancer activation involves {RNAPII} binding and {eRNA} synthesis.},
	pages = {182--187},
	number = {7295},
	journaltitle = {Nature},
	author = {Kim, T K and Hemberg, M and Gray, J M and Costa, A M and Bear, D M and Wu, J and Harmin, D A and Laptewicz, M and Barbara-Haley, K and Kuersten, S and Markenscoff-Papadimitriou, E and Kuhl, D and Bito, H and Worley, P F and Kreiman, G and Greenberg, M E},
	date = {2010},
	pmid = {20393465},
	keywords = {Animals, Mice, {RNA}, Transcription, Gene Expression Regulation, Basic Helix-Loop-Helix Transcription Factors/genet, Consensus Sequence, Consensus Sequence/genetics, {CREB}-Binding Protein/metabolism, Cytoskeletal Proteins/genetics, Enhancer Elements, fos/genetics, Gene Expression Regulation/*genetics, Genes, Genetic/*genetics, Histones, Histones/metabolism, Inbred C57BL, Methylation, Nerve Tissue Proteins/genetics, Neurons/*metabolism, Reporter, {RNA} Polymerase {II}/metabolism, Untranslated/biosynthesis/genetics, {RNA} Polymerase {II}, Transcription, Genetic, Enhancer Elements, Genetic, {RNA}, Untranslated, Mice, Inbred C57BL, Basic Helix-Loop-Helix Transcription Factors, {CREB}-Binding Protein, Cytoskeletal Proteins, Genes, fos, Genes, Reporter, Nerve Tissue Proteins, Neurons},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/J7H2J8WL/Kim et al. - 2010 - Widespread transcription at neuronal activity-regu.pdf:application/pdf;Accepted Version:/home/jlagarde/Zotero/storage/VPLBZSG4/Kim et al. - 2010 - Widespread transcription at neuronal activity-regu.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/9M5DKE9J/Kim et al. - 2010 - Widespread transcription at neuronal activity-regu.pdf:application/pdf;Widespread transcription at neuronal activity-regulated enhancers:/home/jlagarde/Zotero/storage/KU4MSL5J/kim2010.pdf:application/pdf;Widespread transcription at neuronal activity-regulated enhancers:/home/jlagarde/Zotero/storage/AQ3QCALJ/kim2010.pdf:application/pdf}
}

@article{lipovich_genomic_2002,
	title = {Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor ({hFLVCR}) gene: evidence for block duplications and de novo gene formation within duplicons of the {hFLVCR} locus},
	volume = {286},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11943475},
	abstract = {In this paper we sought to analyze the genomic structure and context of human feline leukemia virus subgroup C receptor ({hFLVCR}), a human glucarate transporter-like gene at chromosome 1q31, and compare it to that of a paralog ({FLVCR}14q) at chromosome 14q24. Splicing, polyadenylation, and expression patterns, as estimated by in silico analysis, differed between the two {FLVCR} genes despite their similar genomic structures, suggesting active and independent evolution of transcriptional and messenger {RNA} processing patterns after gene duplication. Promoter activity was bi-directional for {hFLVCR}, but not for its 14q paralog. The upstream 1q transcribed sequences were determined to comprise a novel gene of unknown function, {LQK}1. Annotation of contigs centered at {hFLVCR} and {FLVCRL}14q also revealed highly conserved gene clusters on chromosomes 1 and 14, inferred to result from a duplication. The clusters contained members of the {FLVCR}, Angel ({KIAA}0759), {JDP}, p21SNFT, and {TGF}- families, as well as two uncharacterized families. The genome-wide locations of both previously recognized and four de novo in silico predicted genes belonging to these seven families were determined. Phylogenetic analyses of these families were consistent with the hypothesis that the 1q/14q duplication occurred early within, or immediately prior to the vertebrate divergence, after the protostome-deuterostome divergence but before the amniote-amphibian divergence.},
	pages = {203--213},
	number = {2},
	journaltitle = {Gene},
	author = {Lipovich, L and Hughes, A L and King, M C and Abkowitz, J L and Quigley, J G},
	date = {2002},
	pmid = {11943475},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Humans, Promoter Regions, Transcription Initiation Site, Genetic/genetics, Complementary/chemistry/genetics, *Evolution, 3' Untranslated Regions/genetics, Alternative Splicing, Cats, Chromosomes, Gene Duplication, Genes/genetics, Molecular, Molecular Sequence Data, Pair 1/genetics, Pair 14/genetics, Phylogeny, Poly A/genetics, Receptors, Time Factors, Virus/*genetics}
}

@article{kondrashov_ribosome-mediated_2011,
	title = {Ribosome-mediated specificity in Hox {mRNA} translation and vertebrate tissue patterning},
	volume = {145},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21529712},
	doi = {10.1016/j.cell.2011.03.028},
	abstract = {Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in {mRNA} translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue-specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged; however the translation of a select subset of Homeobox {mRNAs} is perturbed. Our data reveal that {RPL}38 facilitates 80S complex formation on these {mRNAs} as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein ({RP}) expression screen reveals dynamic regulation of individual {RPs} within the vertebrate embryo. Collectively, these findings suggest that {RP} activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development.},
	pages = {383--397},
	number = {3},
	journaltitle = {Cell},
	author = {Kondrashov, N and Pusic, A and Stumpf, C R and Shimizu, K and Hsieh, A C and Xue, S and Ishijima, J and Shiroishi, T and Barna, M},
	date = {2011},
	pmid = {21529712},
	keywords = {Animals, Humans, Mice, {RNA}, *Body Patterning, *Gene Expression Regulation, *Protein Biosynthesis, Bone Diseases, Developmental, Developmental/*genetics, Homeodomain Proteins/*genetics, Inbred C57BL, Messenger/metabolism, Mutation, Organogenesis, Ribosomal Proteins/genetics/*metabolism, Ribosomes/metabolism, Tail/abnormalities}
}

@article{prado-martinez_great_2013,
	title = {Great ape genetic diversity and population history},
	volume = {499},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23823723},
	doi = {10.1038/nature12228},
	abstract = {Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.},
	pages = {471--475},
	number = {7459},
	journaltitle = {Nature},
	author = {Prado-Martinez, J and Sudmant, P H and Kidd, J M and Li, H and Kelley, J L and Lorente-Galdos, B and Veeramah, K R and Woerner, A E and O'Connor, T D and Santpere, G and Cagan, A and Theunert, C and Casals, F and Laayouni, H and Munch, K and Hobolth, A and Halager, A E and Malig, M and Hernandez-Rodriguez, J and Hernando-Herraez, I and Prufer, K and Pybus, M and Johnstone, L and Lachmann, M and Alkan, C and Twigg, D and Petit, N and Baker, C and Hormozdiari, F and Fernandez-Callejo, M and Dabad, M and Wilson, M L and Stevison, L and Camprubi, C and Carvalho, T and Ruiz-Herrera, A and Vives, L and Mele, M and Abello, T and Kondova, I and Bontrop, R E and Pusey, A and Lankester, F and Kiyang, J A and Bergl, R A and Lonsdorf, E and Myers, S and Ventura, M and Gagneux, P and Comas, D and Siegismund, H and Blanc, J and Agueda-Calpena, L and Gut, M and Fulton, L and Tishkoff, S A and Mullikin, J C and Wilson, R K and Gut, I G and Gonder, M K and Ryder, O A and Hahn, B H and Navarro, A and Akey, J M and Bertranpetit, J and Reich, D and Mailund, T and Schierup, M H and Hvilsom, C and Andres, A M and Wall, J D and Bustamante, C D and Hammer, M F and Eichler, E E and Marques-Bonet, T},
	date = {2013},
	pmid = {23823723},
	keywords = {Animals, Humans, *Genetic Variation, Africa, Asia, Evolution, Gene Flow/genetics, Genetics, Genome/genetics, Gorilla gorilla/classification/genetics, Hominidae/classification/*genetics, Inbreeding, Molecular, Pan paniscus/classification/genetics, Pan troglodytes/classification/genetics, Phylogeny, Polymorphism, Population, Population Density, Single Nucleotide/genetics, Southeastern, Wild/genetics, Zoo/genetics}
}

@article{garcia-garcia_assessment_2016,
	title = {Assessment of the latest {NGS} enrichment capture methods in clinical context},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26864517},
	doi = {10.1038/srep20948},
	abstract = {Enrichment capture methods for {NGS} are widely used, however, they evolve rapidly and it is necessary to periodically measure their strengths and weaknesses before transfer to diagnostic services. We assessed two recently released custom {DNA} solution-capture enrichment methods for {NGS}, namely Illumina {NRCCE} and Agilent {SureSelect}({QXT}), against a reference method {NimbleGen} {SeqCap} {EZ} Choice on a similar gene panel, sharing 678 kb and 110 genes. Two Illumina {MiSeq} runs of 12 samples each have been performed, for each of the three methods, using the same 24 patients (affected with sensorineural disorders). Technical outcomes have been computed and compared, including depth and evenness of coverage, enrichment in targeted regions, performance in {GC}-rich regions and ability to generate consistent variant datasets. While we show that the three methods resulted in suitable datasets for standard {DNA} variant discovery, we describe significant differences between the results for the above parameters. {NimbleGen} offered the best depth of coverage and evenness, while {NRCCE} showed the highest on target levels but high duplicate rates. {SureSelect}({QXT}) showed an overall quality close to that of {NimbleGen}. The new methods exhibit reduced preparation time but behave differently. These findings will guide laboratories in their choice of library enrichment approach.},
	pages = {20948},
	journaltitle = {Sci Rep},
	author = {Garcia-Garcia, G and Baux, D and Faugere, V and Moclyn, M and Koenig, M and Claustres, M and Roux, A F},
	date = {2016},
	pmid = {26864517},
	keywords = {{DNA}, Sequence Analysis, Humans, Base Composition, Functional/diagnosis/*genetics, Genes, Hearing Loss, High-Throughput Nucleotide Sequencing/instrumentat, Recessive, Retinitis Pigmentosa/diagnosis/*genetics, Usher Syndromes/diagnosis/*genetics}
}

@article{cao_inhibition_2014,
	title = {Inhibition of Smurf2 translation by {miR}-322/503 modulates {TGF}-beta/Smad2 signaling and intestinal epithelial homeostasis},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24554769},
	doi = {10.1091/mbc.E13-09-0560},
	abstract = {Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates {TGF}-beta/Smad signaling and is implicated in a wide variety of cellular responses, but the exact mechanisms that control Smurf2 abundance remain largely unknown. Here we identified {microRNA}-322 ({miR}-322) and {miR}-503 as novel factors that regulate Smurf2 expression posttranscriptionally. Both {miR}-322 and {miR}-503 interacted with Smurf2 {mRNA} via its 3'-untranslated region ({UTR}) and repressed Smurf2 translation but did not affect total Smurf2 {mRNA} levels. Studies using heterologous reporter constructs revealed a greater repressive effect of {miR}-322/503 through a single binding site in the Smurf2 3'-{UTR}, whereas point mutation of this site prevented {miR}-322/503-induced repression of Smurf2 translation. Increased levels of endogenous Smurf2 by antagonization of {miR}-322/503 inhibited {TGF}-beta-induced Smad2 activation by increasing the degradation of phosphorylated Smad2. Furthermore, the increase in Smurf2 in intestinal epithelial cells ({IECs}) expressing lower levels of {miR}-322/503 was associated with increased resistance to apoptosis, which was abolished by Smurf2 silencing. These findings indicate {thatmiR}-322/503 represses Smurf2 translation, in turn affecting intestinal epithelial homeostasis by altering {TGF}-beta/Smad2 signaling and {IEC} apoptosis.},
	journaltitle = {Mol Biol Cell},
	author = {Cao, S and Xiao, L and Rao, J N and Zou, T and Liu, L and Zhang, D and Turner, D J and Gorospe, M and Wang, J Y},
	date = {2014},
	pmid = {24554769}
}

@article{han_transcriptional_2004,
	title = {Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes},
	volume = {429},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15152245},
	doi = {10.1038/nature02536},
	abstract = {{LINE}-1 (L1) elements are the most abundant autonomous retrotransposons in the human genome, accounting for about 17\% of human {DNA}. The L1 retrotransposon encodes two proteins, open reading frame ({ORF})1 and the {ORF}2 endonuclease/reverse transcriptase. L1 {RNA} and {ORF}2 protein are difficult to detect in mammalian cells, even in the context of overexpression systems. Here we show that inserting L1 sequences on a transcript significantly decreases {RNA} expression and therefore protein expression. This decreased {RNA} concentration does not result from major effects on the transcription initiation rate or {RNA} stability. Rather, the poor L1 expression is primarily due to inadequate transcriptional elongation. Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a 'molecular rheostat' of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.},
	pages = {268--274},
	number = {6989},
	journaltitle = {Nature},
	author = {Han, J S and Szak, S T and Boeke, J D},
	date = {2004},
	pmid = {15152245},
	keywords = {Animals, Base Sequence, Genetic, Humans, Mice, {RNA}, Transcription, Computational Biology, Cell Line, Down-Regulation/*genetics, Endonucleases/biosynthesis/genetics, Evolution, Feedback, Genetic/*genetics, Half-Life, Long Interspersed Nucleotide Elements/*genetics, Mammals/genetics, Messenger/biosynthesis/genetics/metabolism, Models, Molecular, Open Reading Frames/genetics, Physiological, {RNA} Polymerase {III}/metabolism, {RNA} Stability, {RNA}-Directed {DNA} Polymerase/biosynthesis/genetics}
}

@article{ribeiro-filho_cpg_2002,
	title = {{CpG} hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12203370},
	doi = {10.1002/mc.10064},
	abstract = {Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that {CpG} methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadherin gene expression and methylation status by immunohistochemistry, methylation-specific polymerase chain reaction ({MSP}), and bisulfite genome-sequencing techniques. Ten different {CpG} sites (nt 863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) in the promoter region were studied. Thirty-five of 51 (69\%) bladder cancer samples lacked E-cadherin expression, whereas only six of 51 (12\%) normal bladder samples lacked E-cadherin immunoreactivity. {MSP} analysis of bladder cancer samples suggested that 43 of 51 (84\%) showed methylation of the promoter region, whereas only 12 of 51 (24\%) normal bladder samples showed hypermethylation. Sodium bisulfite genome-sequencing analysis revealed that of 10 {CpG} sites, two sites (nt 892 and nt 940) showed 100\% methylation in all the cancer samples analyzed. Other {CpG} sites were partially methylated (47-91\%). Normal tissue showed only 12\% methylation (range, 1-33\%) on various {CpG} sites. Also supporting these data, E-cadherin-negative bladder cancer cell lines restored expression of the E-cadherin gene after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The present study showed that {CpG} hypermethylation was an important mechanism of E-cadherin gene inactivation in bladder cancer and also that specific {CpG} sites consistently presented higher methylation levels than others. These findings may provide a better strategy for the diagnosis and management of bladder cancer.},
	pages = {187--198},
	number = {4},
	journaltitle = {Mol Carcinog},
	author = {Ribeiro-Filho, L A and Franks, J and Sasaki, M and Shiina, H and Li, L C and Nojima, D and Arap, S and Carroll, P and Enokida, H and Nakagawa, M and Yonezawa, S and Dahiya, R},
	date = {2002},
	pmid = {12203370},
	keywords = {{DNA}, Sequence Analysis, Genetic, Humans, *Promoter Regions, *{CpG} Islands, *{DNA} Methylation, Aged, Cadherins/*genetics, Female, Gene Silencing, Male, Middle Aged, Reference Values, Urinary Bladder Neoplasms/*genetics}
}

@article{vazquez-chantada_hur/methyl-hur_2010,
	title = {{HuR}/methyl-{HuR} and {AUF}1 regulate the {MAT} expressed during liver proliferation, differentiation, and carcinogenesis},
	volume = {138},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20102719},
	doi = {10.1053/j.gastro.2010.01.032},
	abstract = {{BACKGROUND} \& {AIMS}: Hepatic de-differentiation, liver development, and malignant transformation are processes in which the levels of hepatic S-adenosylmethionine are tightly regulated by 2 genes: methionine adenosyltransferase 1A ({MAT}1A) and methionine adenosyltransferase 2A ({MAT}2A). {MAT}1A is expressed in the adult liver, whereas {MAT}2A expression primarily is extrahepatic and is associated strongly with liver proliferation. The mechanisms that regulate these expression patterns are not completely understood. {METHODS}: In silico analysis of the 3' untranslated region of {MAT}1A and {MAT}2A revealed putative binding sites for the {RNA}-binding proteins {AU}-rich {RNA} binding factor 1 ({AUF}1) and {HuR}, respectively. We investigated the posttranscriptional regulation of {MAT}1A and {MAT}2A by {AUF}1, {HuR}, and methyl-{HuR} in the aforementioned biological processes. {RESULTS}: During hepatic de-differentiation, the switch between {MAT}1A and {MAT}2A coincided with an increase in {HuR} and {AUF}1 expression. S-adenosylmethionine treatment altered this homeostasis by shifting the balance of {AUF}1 and methyl-{HuR}/{HuR}, which was identified as an inhibitor of {MAT}2A messenger {RNA} ({mRNA}) stability. We also observed a similar temporal distribution and a functional link between {HuR}, methyl-{HuR}, {AUF}1, and {MAT}1A and {MAT}2A during fetal liver development. Immunofluorescent analysis revealed increased levels of {HuR} and {AUF}1, and a decrease in methyl-{HuR} levels in human livers with hepatocellular carcinoma ({HCC}). {CONCLUSIONS}: Our data strongly support a role for {AUF}1 and {HuR}/methyl-{HuR} in liver de-differentiation, development, and human {HCC} progression through the posttranslational regulation of {MAT}1A and {MAT}2A {mRNAs}.},
	pages = {1943--1953},
	number = {5},
	journaltitle = {Gastroenterology},
	author = {Vazquez-Chantada, M and Fernandez-Ramos, D and Embade, N and Martinez-Lopez, N and Varela-Rey, M and Woodhoo, A and Luka, Z and Wagner, C and Anglim, P P and Finnell, R H and Caballeria, J and Laird-Offringa, I A and Gorospe, M and Lu, S C and Mato, J M and Martinez-Chantar, M L},
	date = {2010},
	pmid = {20102719},
	keywords = {3' Untranslated Regions, Animals, Humans, Mice, {RNA}, Binding Sites, Gene Expression Regulation, Cells, Cultured, *Cell Differentiation, *Cell Proliferation, Antigens, Cell Transformation, Developmental, Enzymologic, Gestational Age, Glycine N-Methyltransferase/deficiency/genetics, Half-Life, Hepatocytes/*metabolism/pathology, Heterogeneous-Nuclear Ribonucleoprotein D/genetics, Hu Paraneoplastic Encephalomyelitis Antigens, Inbred C57BL, Liver Neoplasms/genetics/*metabolism/pathology, Male, Messenger/metabolism, Methionine Adenosyltransferase/genetics/*metabolis, Methylation, Neoplastic/genetics/*metaboli, Post-Transcriptional, Rats, {RNA} Interference, {RNA} Processing, {RNA} Stability, {RNA}-Binding Proteins/genetics/*metabolism, S-Adenosylmethionine/metabolism, Signal Transduction, Surface/genetics/*metabolism, Transfection, Wistar}
}

@article{bozzoni_isolation_1982,
	title = {Isolation and structural analysis of ribosomal protein genes in Xenopus laevis. Homology between sequences present in the gene and in several different messenger {RNAs}},
	volume = {161},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6296397},
	pages = {353--371},
	number = {3},
	journaltitle = {J Mol Biol},
	author = {Bozzoni, I and Tognoni, A and Pierandrei-Amaldi, P and Beccari, E and Buongiorno-Nardelli, M and Amaldi, F},
	date = {1982},
	pmid = {6296397},
	keywords = {{DNA}, Animals, Base Sequence, {RNA}, Messenger, Nucleic Acid, *Genes, Bacterial Proteins/genetics, Bacteriophage lambda/genetics, {DNA} Restriction Enzymes/metabolism, Electrophoresis, Nucleic Acid Hybridization, Protein Biosynthesis, Recombinant, Repetitive Sequences, Ribosomal Proteins/*genetics, Xenopus laevis/*genetics}
}

@article{subramanian_gene_2005,
	title = {Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles},
	volume = {102},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16199517},
	doi = {10.1073/pnas.0506580102},
	abstract = {Although genomewide {RNA} expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis ({GSEA}) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how {GSEA} yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, {GSEA} reveals many biological pathways in common. The {GSEA} method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.},
	pages = {15545--15550},
	number = {43},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Subramanian, A and Tamayo, P and Mootha, V K and Mukherjee, S and Ebert, B L and Gillette, M A and Paulovich, A and Pomeroy, S L and Golub, T R and Lander, E S and Mesirov, J P},
	date = {2005},
	pmid = {16199517},
	keywords = {Gene Expression Profiling/*methods, Genome, Humans, *Oligonucleotide Array Sequence Analysis, Acute/genetics, Cell Line, Female, Genes, Leukemia, Lung Neoplasms/genetics/mortality, Male, Myeloid, p53/physiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma/gen, Tumor}
}

@article{de_koning_repetitive_2011,
	title = {Repetitive elements may comprise over two-thirds of the human genome},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22144907},
	doi = {10.1371/journal.pgen.1002384},
	abstract = {Transposable elements ({TEs}) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as {TEs} and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo "clouds"). We show here that P-clouds predicts {\textbackslash}textgreater840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66\%-69\% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, {RepeatMasker} ({RM}), to detect different sized fragments of the highly abundant human Alu and {MIR} {SINEs}. {RM} can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes ( approximately 25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed "element-specific" P-clouds ({ESPs}) to identify novel Alu and {MIR} {SINE} elements, and using it we identified approximately 100 Mb of previously unannotated human elements. {ESP} estimates of new {MIR} sequences are in good agreement with {RM}-based predictions of the amount that {RM} missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed.},
	pages = {e1002384},
	number = {12},
	journaltitle = {{PLoS} Genet},
	author = {de Koning, A P and Gu, W and Castoe, T A and Batzer, M A and Pollock, D D},
	date = {2011},
	pmid = {22144907},
	keywords = {Genome, Humans, Algorithms, Software, Alu Elements/*genetics, Computational Biology/*methods, Consensus Sequence/genetics, {DNA} Transposable Elements/*genetics, Human/*genetics, Long Interspersed Nucleotide Elements/genetics, Molecular Sequence Annotation, Nucleic Acid/*genetics, Repetitive Sequences}
}

@article{sanjana_improved_2014,
	title = {Improved vectors and genome-wide libraries for {CRISPR} screening},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25075903},
	doi = {10.1038/nmeth.3047},
	pages = {783--784},
	number = {8},
	journaltitle = {Nat Methods},
	author = {Sanjana, N E and Shalem, O and Zhang, F},
	date = {2014},
	pmid = {25075903},
	keywords = {Animals, Genetic, Humans, Mice, *Genome, *Clustered Regularly Interspaced Short Palindromic, *Genetic Vectors, Models, {RNA} Interference}
}

@article{mudge_origins_2011,
	title = {The origins, evolution, and functional potential of alternative splicing in vertebrates},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21551269},
	doi = {10.1093/molbev/msr127},
	abstract = {Alternative splicing ({AS}) has the potential to greatly expand the functional repertoire of mammalian transcriptomes. However, few variant transcripts have been characterized functionally, making it difficult to assess the contribution of {AS} to the generation of phenotypic complexity and to study the evolution of splicing patterns. We have compared the {AS} of 309 protein-coding genes in the human {ENCODE} pilot regions against their mouse orthologs in unprecedented detail, utilizing traditional transcriptomic and {RNAseq} data. The conservation status of every transcript has been investigated, and each functionally categorized as coding (separated into coding sequence [{CDS}] or nonsense-mediated decay [{NMD}] linked) or noncoding. In total, 36.7\% of human and 19.3\% of mouse coding transcripts are species specific, and we observe a 3.6 times excess of human {NMD} transcripts compared with mouse; in contrast to previous studies, the majority of species-specific {AS} is unlinked to transposable elements. We observe one conserved {CDS} variant and one conserved {NMD} variant per 2.3 and 11.4 genes, respectively. Subsequently, we identify and characterize equivalent {AS} patterns for 22.9\% of these {CDS} or {NMD}-linked events in nonmammalian vertebrate genomes, and our data indicate that functional {NMD}-linked {AS} is more widespread and ancient than previously thought. Furthermore, although we observe an association between conserved {AS} and elevated sequence conservation, as previously reported, we emphasize that 30\% of conserved {AS} exons display sequence conservation below the average score for constitutive exons. In conclusion, we demonstrate the value of detailed comparative annotation in generating a comprehensive set of {AS} transcripts, increasing our understanding of {AS} evolution in vertebrates. Our data supports a model whereby the acquisition of functional {AS} has occurred throughout vertebrate evolution and is considered alongside amino acid change as a key mechanism in gene evolution.},
	pages = {2949--2959},
	number = {10},
	journaltitle = {Mol Biol Evol},
	author = {Mudge, J M and Frankish, A and Fernandez-Banet, J and Alioto, T and Derrien, T and Howald, C and Reymond, A and Guigo, R and Hubbard, T and Harrow, J},
	date = {2011},
	pmid = {21551269},
	keywords = {Transcriptome, Animals, Conserved Sequence, Genetic, Humans, Mice, Reproducibility of Results, Databases, *Alternative Splicing, *Evolution, Genome/*genetics, Molecular}
}

@article{kim_rna-binding_2014,
	title = {The {RNA}-binding protein {HuD} regulates autophagosome formation in pancreatic beta cells by promoting autophagy-related gene 5 expression},
	volume = {289},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24275661},
	doi = {10.1074/jbc.M113.474700},
	abstract = {Tight regulation of autophagy is critical for the fate of pancreatic beta cells. The autophagy protein {ATG}5 is essential for the formation of autophagosomes by promoting the lipidation of microtubule-associated protein {LC}3 (light chain 3). However, little is known about the mechanisms that regulate {ATG}5 expression levels. In this study, we investigated the regulation of {ATG}5 expression by {HuD}. The association of {HuD} with {ATG}5 {mRNA} was analyzed by ribonucleoprotein complex immunoprecipitation and biotin pulldown assays. {HuD} expression levels in pancreatic beta cells were knocked down via {siRNA}, elevated by overexpression of a {HuD}-expressing plasmid. The expression levels of {HuD}, {ATG}5, {LC}3, and beta-actin were determined by Western blot and quantitative {RT}-{PCR} analysis. Autophagosome formation was assessed by fluorescence microscopy in {GFP}-{LC}3-expressing cells and in pancreatic tissues from {WT} and {HuD}-null mice. We identified {ATG}5 {mRNA} as a post-transcriptional target of the mammalian {RNA}-binding protein {HuD} in pancreatic beta cells. {HuD} associated with the 3'-{UTR} of the {ATG}5 {mRNA}. Modulating {HuD} abundance did not alter {ATG}5 {mRNA} levels, but {HuD} silencing decreased {ATG}5 {mRNA} translation, and, conversely, {HuD} overexpression enhanced {ATG}5 {mRNA} translation. Through its effect on {ATG}5, {HuD} contributed to the lipidation of {LC}3 and the formation of {LC}3-positive autophagosomes. In keeping with this regulatory paradigm, {HuD}-null mice displayed lower {ATG}5 and {LC}3 levels in pancreatic beta cells. Our results reveal {HuD} to be an inducer of {ATG}5 expression and hence a critical regulator of autophagosome formation in pancreatic beta cells.},
	pages = {112--121},
	number = {1},
	journaltitle = {J Biol Chem},
	author = {Kim, C and Kim, W and Lee, H and Ji, E and Choe, Y J and Martindale, J L and Akamatsu, W and Okano, H and Kim, H S and Nam, S W and Gorospe, M and Lee, E K},
	date = {2014},
	pmid = {24275661}
}

@article{van_der_brug_rna_2008,
	title = {{RNA} binding activity of the recessive parkinsonism protein {DJ}-1 supports involvement in multiple cellular pathways},
	volume = {105},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18626009},
	doi = {10.1073/pnas.0708518105},
	abstract = {Parkinson's disease ({PD}) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of {PD} but the molecular mechanisms involved in the degeneration of neurons remain unclear. {DJ}-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing {PTEN}-induced apoptosis. The specific function of {DJ}-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that {DJ}-1 associates with {RNA} targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the {PTEN}/{PI}3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that {DJ}-1 is sufficient for {RNA} binding at nanomolar concentrations. Further, we show that {DJ}-1 binds {RNA} but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of {DJ}-1 in different model systems, namely that the protein binds multiple {RNA} targets in an oxidation-dependent manner.},
	pages = {10244--10249},
	number = {29},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {van der Brug, M P and Blackinton, J and Chandran, J and Hao, L Y and Lal, A and Mazan-Mamczarz, K and Martindale, J and Xie, C and Ahmad, R and Thomas, K J and Beilina, A and Gibbs, J R and Ding, J and Myers, A J and Zhan, M and Cai, H and Bonini, N M and Gorospe, M and Cookson, M R},
	date = {2008},
	pmid = {18626009},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, Brain/metabolism, Cell Line, Drosophila Proteins/deficiency/genetics, Drosophila/genetics/metabolism, Genes, Glutathione/metabolism, inhibitors/genetics/*metabolism, Intracellular Signaling Peptides and Proteins/anta, Knockout, {MAP} Kinase Signaling System, Messenger/genetics/*metabolism, Mitochondrial, Molecular Sequence Data, Oncogene Proteins/antagonists \& inhibitors/deficie, Oxidative Stress, Parkinsonian Disorders/genetics/*metabolism, Phosphatidylinositol 3-Kinases/metabolism, {PTEN} Phosphohydrolase/metabolism, Recessive, Recombinant Proteins/genetics/metabolism, {RNA}-Binding Proteins/genetics/*metabolism, Small Interfering/genetics, Transfection}
}

@article{reveille_genome-wide_2010,
	title = {Genome-wide association study of ankylosing spondylitis identifies non-{MHC} susceptibility loci},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20062062},
	doi = {10.1038/ng.513},
	abstract = {To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina {HumHap}370 genotyping chips. In addition to strong association with the major histocompatibility complex ({MHC}; P {\textbackslash}textless 10(-800)), we found association with {SNPs} in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes {ANTXR}2 (rs4333130; P = 9.3 x 10(-8)) and {IL}1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at {IL}23R (rs11209026; P = 9.1 x 10(-14)) and {ERAP}1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin ({IL})-23 and {IL}-1 cytokine pathways in disease susceptibility.},
	pages = {123--127},
	number = {2},
	journaltitle = {Nat Genet},
	author = {Reveille, J D and Sims, A M and Danoy, P and Evans, D M and Leo, P and Pointon, J J and Jin, R and Zhou, X and Bradbury, L A and Appleton, L H and Davis, J C and Diekman, L and Doan, T and Dowling, A and Duan, R and Duncan, E L and Farrar, C and Hadler, J and Harvey, D and Karaderi, T and Mogg, R and Pomeroy, E and Pryce, K and Taylor, J and Savage, L and Deloukas, P and Kumanduri, V and Peltonen, L and Ring, S M and Whittaker, P and Glazov, E and Thomas, G P and Maksymowych, W P and Inman, R D and Ward, M M and Stone, M A and Weisman, M H and Wordsworth, B P and Brown, M A},
	date = {2010},
	pmid = {20062062},
	keywords = {Humans, Reproducibility of Results, *Genetic Predisposition to Disease, *Genome-Wide Association Study, Ankylosing/*genetics, Cohort Studies, Genetic Loci/*genetics, Major Histocompatibility Complex/*genetics, Polymorphism, Single Nucleotide/genetics, Spondylitis}
}

@article{mercken_age-associated_2013,
	title = {Age-associated {miRNA} alterations in skeletal muscle from rhesus monkeys reversed by caloric restriction},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24036467},
	abstract = {The levels of {microRNAs} ({miRNAs}) are altered under different conditions such as cancer, senescence, and aging. Here, we have identified differentially expressed {miRNAs} in skeletal muscle from young and old rhesus monkeys using {RNA} sequencing. In old muscle, several {miRNAs} were upregulated, including {miR}-451, {miR}-144, {miR}-18a and {miR}-15a, while a few {miRNAs} were downregulated, including {miR}-181a and {miR}-181b. A number of novel {miRNAs} were also identified, particularly in old muscle. We also examined the impact of caloric restriction ({CR}) on {miRNA} abundance by reverse transcription ({RT}) followed by real-time, quantitative (q){PCR} analysis and found that {CR} rescued the levels of {miR}-181b and chr1:205580546, and also dampened the age-induced increase in {miR}-451 and {miR}-144 levels. Our results reveal that there are changes in expression of known and novel {miRNAs} with skeletal muscle aging and that {CR} may reverse some of these changes to a younger phenotype.},
	pages = {692--703},
	number = {9},
	journaltitle = {Aging (Albany {NY})},
	author = {Mercken, E M and Majounie, E and Ding, J and Guo, R and Kim, J and Bernier, M and Mattison, J and Cookson, M R and Gorospe, M and de Cabo, R and Abdelmohsen, K},
	date = {2013},
	pmid = {24036467}
}

@article{kim_flow-enhanced_2013,
	title = {Flow-enhanced electrochemical immunosensors on centrifugal microfluidic platforms},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23900555},
	doi = {10.1039/c3lc50374g},
	abstract = {We present a novel fully integrated centrifugal microfluidic device with features for target antigen capture from biological samples, via a bead-based enzyme-linked immune-sorbent assay, and flow-enhanced electrochemical detection. The limit of detection ({LOD}) of our device for the C-reactive protein ({CRP}) was determined to be 4.9 pg {mL}(-1), a 17-fold improvement over quantification by optical density. The complete sample-to-answer protocol of our device is fully automated and takes less than 20 min. Overall, the presented microfluidic disc adds to the comparatively small number of fully integrated microfluidic-based platforms that utilize electrochemical detection and exemplifies how electrochemical detection can be enhanced by flow to successfully detect very low levels of biomarkers (e.g. pg {mL}(-1)).},
	pages = {3747--3754},
	number = {18},
	journaltitle = {Lab Chip},
	author = {Kim, T H and Abi-Samra, K and Sunkara, V and Park, D K and Amasia, M and Kim, N and Kim, J and Kim, H and Madou, M and Cho, Y K},
	date = {2013},
	pmid = {23900555}
}

@article{loreni_nucleotide_1985,
	title = {Nucleotide sequence of the L1 ribosomal protein gene of Xenopus laevis: remarkable sequence homology among introns},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3841512},
	abstract = {Ribosomal protein L1 is encoded by two genes in Xenopus laevis. The comparison of two {cDNA} sequences shows that the two L1 gene copies (L1a and L1b) have diverged in many silent sites and very few substitution sites; moreover a small duplication occurred at the very end of the coding region of the L1b gene which thus codes for a product five amino acids longer than that coded by L1a. Quantitatively the divergence between the two L1 genes confirms that a whole genome duplication took place in Xenopus laevis approximately 30 million years ago. A genomic fragment containing one of the two L1 gene copies (L1a), with its nine introns and flanking regions, has been completely sequenced. The 5' end of this gene has been mapped within a 20-pyridimine stretch as already found for other vertebrate ribosomal protein genes. Four of the nine introns have a 60-nucleotide sequence with 80\% homology; within this region some boxes, one of which is 16 nucleotides long, are 100\% homologous among the four introns. This feature of L1a gene introns is interesting since we have previously shown that the activity of this gene is regulated at a post-transcriptional level and it involves the block of the normal splicing of some intron sequences.},
	pages = {3483--3488},
	number = {13},
	journaltitle = {{EMBO} J},
	author = {Loreni, F and Ruberti, I and Bozzoni, I and Pierandrei-Amaldi, P and Amaldi, F},
	date = {1985},
	pmid = {3841512},
	keywords = {Animals, Base Sequence, Nucleic Acid, Cloning, {DNA}/genetics, Genes, Molecular, Ribosomal Proteins/*genetics, Sequence Homology, Xenopus laevis/*genetics}
}

@article{buljan_quantifying_2010,
	title = {Quantifying the mechanisms of domain gain in animal proteins},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20633280},
	doi = {10.1186/gb-2010-11-7-r74},
	abstract = {{BACKGROUND}: Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding {DNA} investigate the causative mechanisms. {RESULTS}: Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1\% and 10\% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80\% of the gain events. {CONCLUSIONS}: The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.},
	pages = {R74},
	number = {7},
	journaltitle = {Genome Biol},
	author = {Buljan, M and Frankish, A and Bateman, A},
	date = {2010},
	pmid = {20633280},
	keywords = {Animals, Genetic, Humans, {RNA}, Exons/genetics, *Protein Structure, Amino Acids/genetics, Chromosomes/genetics, Evolution, Gene Duplication/genetics, Gene Fusion/genetics, Genes/genetics, Insertional/genetics, Introns/genetics, Messenger/genetics/metabolism, Molecular, Mutagenesis, Proteins/*chemistry, Recombination, Tertiary, Time Factors}
}

@article{smith_phosphorylation_2005,
	title = {Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicity},
	volume = {169},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15837797},
	doi = {10.1083/jcb.200410041},
	abstract = {Excessive accumulation of amyloid beta-peptide (Abeta) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease ({AD}). Increased oxidative stress is one of the mechanisms whereby Abeta induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Abeta toxicity. Treatment of cells and primary neuronal cultures with Abeta caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative {SEK}1 mutant or chemical {JNK} inhibition reduced Abeta-induced {JNK} activation and p66Shc phosphorylation (Ser36), suggesting that {JNK} phosphorylates p66Shc. Abeta induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against Abeta-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies Abeta toxicity. These findings underscore the potential usefulness of {JNK}, p66Shc, and forkhead proteins as therapeutic targets for {AD}.},
	pages = {331--339},
	number = {2},
	journaltitle = {J Cell Biol},
	author = {Smith, W W and Norton, D D and Gorospe, M and Jiang, H and Nemoto, S and Holbrook, N J and Finkel, T and Kusiak, J W},
	date = {2005},
	pmid = {15837797},
	keywords = {Animals, Humans, Mice, Adaptor Proteins, Alzheimer Disease/physiopathology, Amino Acid Substitution, Amyloid beta-Peptides/*toxicity, Apoptosis/*drug effects, Forkhead Transcription Factors, {JNK} Mitogen-Activated Protein Kinases/metabolism, {MAP} Kinase Kinase 4, Mitogen-Activated Protein Kinase Kinases/metabolis, Neurons/metabolism, Nuclear Proteins/*metabolism, Oxidation-Reduction/drug effects, {PC}12 Cells, Phosphorylation/drug effects, Point Mutation, Rats, Serine/metabolism, Shc Signaling Adaptor Proteins, Signal Transducing/genetics/*met, Signal Transduction/*drug effects, Transcription Factors/*metabolism}
}

@article{habib_blood_2013,
	title = {Blood transfusion requirements for endoscopic sinonasal inverted papilloma resections},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23866296},
	doi = {10.1186/1916-0216-42-44},
	abstract = {{BACKGROUND}: Endoscopic resection of sinonasal Inverted Papilloma ({SNIP}) tumors has been shown to reduce intra-operative blood loss and recovery time compared to open approaches. The purpose of this study is to investigate the incidence and requirements of blood transfusion for endoscopic {SNIP} surgeries. {METHODS}: An individual retrospective cohort study of endoscopic {SNIP} surgeries over a 10-year period was performed. Age, sex, pre-existing co-morbidity, use of anti-coagulants, tumor type and stage, time of surgery, estimated blood loss and the requirement for blood transfusion were recorded. {RESULTS}: 82 patients were included (57 males, 25 females). 4 (5\%) Stage 1, 7 (8.5\%) Stage 2, 62 (75.5\%) Stage 3 and 9 (11\%) Stage 4 {SNIP} tumors were identified according to the Krouse staging system. 3 (4\%) patients required blood transfusion. 3 of the 9 (33\%) Stage 4 tumors required blood transfusion. Stage 4 tumors were significantly associated with blood transfusion (p {\textbackslash}textless 0.05). Higher staged tumors were associated with greater blood loss (p {\textbackslash}textless 0.05) than lower staged cases. No other tumor stage required blood transfusion and no other pre-operative variable was associated with requirement for blood transfusion. {CONCLUSION}: Endoscopic {SNIP} resections rarely require blood transfusions. No pre-operative factor other than tumor stage is associated with the requirement for blood transfusion. We would therefore suggest that only Stage 4 {SNIP} tumors require pre-operative type and screen.},
	pages = {44},
	journaltitle = {J Otolaryngol Head Neck Surg},
	author = {Habib, A R and Hathorn, I and Sunkaraneni, V S and Srubiski, A and Javer, A R},
	date = {2013},
	pmid = {23866296}
}

@article{lal_concurrent_2004,
	title = {Concurrent versus individual binding of {HuR} and {AUF}1 to common labile target {mRNAs}},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15257295},
	doi = {10.1038/sj.emboj.7600305},
	abstract = {{RNA}-binding proteins {HuR} and {AUF}1 bind to many common {AU}-rich target {mRNAs} and exert opposing influence on target {mRNA} stability, but the functional interactions between {HuR} and {AUF}1 have not been systematically studied. Here, using common target {RNAs} encoding p21 and cyclin D1, we provide evidence that {HuR} and {AUF}1 can bind target transcripts on both distinct, nonoverlapping sites, and on common sites in a competitive fashion. In the nucleus, both proteins were found together within stable ribonucleoprotein complexes; in the cytoplasm, {HuR} and {AUF}1 were found to bind to target {mRNAs} individually, {HuR} colocalizing with the translational apparatus and {AUF}1 with the exosome. Our results indicate that the composition and fate (stability, translation) of {HuR}- and/or {AUF}1-containing ribonucleoprotein complexes depend on the target {mRNA} of interest, {RNA}-binding protein abundance, stress condition, and subcellular compartment.},
	pages = {3092--3102},
	number = {15},
	journaltitle = {{EMBO} J},
	author = {Lal, A and Mazan-Mamczarz, K and Kawai, T and Yang, X and Martindale, J L and Gorospe, M},
	date = {2004},
	pmid = {15257295},
	keywords = {Humans, {RNA}, Transcription, *{RNA} Stability, Antigens, Cell Cycle Proteins/genetics, Cyclin D1/genetics, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Regulation/radiation effects, Genetic/radiation effects, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoprotein D/genetics, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/chemical synthesis/genetics/*metabo, {RNA}-Binding Proteins/genetics/*metabolism, Small Interfering/genetics/metabolism, Substrate Specificity, Surface/genetics/*metabolism, Ultraviolet Rays}
}

@article{pullmann_jr._differential_2006,
	title = {Differential stability of thymidylate synthase 3'-untranslated region polymorphic variants regulated by {AUF}1},
	volume = {281},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16787927},
	doi = {10.1074/jbc.M600282200},
	abstract = {A 6-nucleotide insertion (I)/deletion (D) polymorphism in the 3'-untranslated region of the thymidylate synthase gene was shown to influence {mRNA} stability, but the molecular basis of this effect has not been elucidated. Here, studies of both endogenous and ectopically expressed thymidylate synthase alleles revealed that the {mRNA}-binding, decay-promoting protein {AUF}1 has higher affinity for allele D {mRNA}. {AUF}1 overexpression preferentially suppressed D allele {mRNA} levels, whereas {AUF}1 silencing selectively elevated D allele {mRNA} levels. Our results illustrate the functional consequences of ribonucleoprotein associations involving a polymorphic {RNA} sequence and uncover a novel mechanism of action for non-coding {RNA} polymorphisms.},
	pages = {23456--23463},
	number = {33},
	journaltitle = {J Biol Chem},
	author = {Pullmann Jr., R and Abdelmohsen, K and Lal, A and Martindale, J L and Ladner, R D and Gorospe, M},
	date = {2006},
	pmid = {16787927},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, *Genetic Variation, *Polymorphism, 3' Untranslated Regions/*genetics, Alleles, Cell Line, Enzyme Stability/genetics, Gene Silencing, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoprotein D/antagoni, inhibitors/biosynthesis/genetics/*physiology, Messenger/biosynthesis/metabolism, Molecular Sequence Data, {RNA} Stability, Thymidylate Synthase/*genetics/*metabolism, Tumor, Up-Regulation/genetics}
}

@article{dimitrieva_ucnebasedatabase_2013,
	title = {{UCNEbase}–a database of ultraconserved non-coding elements and genomic regulatory blocks},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23193254},
	doi = {10.1093/nar/gks1092},
	abstract = {{UCNEbase} (http://ccg.vital-it.ch/{UCNEbase}) is a free, web-accessible information resource on the evolution and genomic organization of ultra-conserved non-coding elements ({UCNEs}). It currently covers 4351 such elements in 18 different species. The majority of {UCNEs} are supposed to be transcriptional regulators of key developmental genes. As most of them occur as clusters near potential target genes, the database is organized along two hierarchical levels: individual {UCNEs} and ultra-conserved genomic regulatory blocks ({UGRBs}). {UCNEbase} introduces a coherent nomenclature for {UCNEs} reflecting their respective associations with likely target genes. Orthologous and paralogous {UCNEs} share components of their names and are systematically cross-linked. Detailed synteny maps between the human and other genomes are provided for all {UGRBs}. {UCNEbase} is managed by a relational database system and can be accessed by a variety of web-based query pages. As it relies on the {UCSC} genome browser as visualization platform, a large part of its data content is also available as browser viewable custom track files. {UCNEbase} is potentially useful to any computational, experimental or evolutionary biologist interested in conserved non-coding {DNA} elements in vertebrates.},
	pages = {D101--9},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Dimitrieva, S and Bucher, P},
	date = {2013},
	pmid = {23193254},
	keywords = {{DNA}, Animals, Base Sequence, Conserved Sequence, Genome, Humans, Nucleic Acid, *Databases, *Regulatory Elements, Computer Graphics, Evolution, Intergenic/*chemistry, Internet, Molecular, Synteny, Terminology as Topic, Transcriptional, User-Computer Interface, Vertebrates/genetics}
}

@article{laurent_dynamic_2011,
	title = {Dynamic changes in the copy number of pluripotency and cell proliferation genes in human {ESCs} and {iPSCs} during reprogramming and time in culture},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21211785},
	doi = {10.1016/j.stem.2010.12.003},
	abstract = {Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high-resolution {SNP} (single-nucleotide polymorphism) analysis on 186 pluripotent and 119 nonpluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to nonpluripotent samples, with variations enriched in specific genomic regions. The distribution of these variations differed between {hESCs} and {hiPSCs}, characterized by large numbers of duplications found in a few {hESC} samples and moderate numbers of deletions distributed across many {hiPSC} samples. For {hiPSCs}, the reprogramming process was associated with deletions of tumor-suppressor genes, whereas time in culture was associated with duplications of oncogenic genes. We also observed duplications that arose during a differentiation protocol. Our results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.},
	pages = {106--118},
	number = {1},
	journaltitle = {Cell Stem Cell},
	author = {Laurent, L C and Ulitsky, I and Slavin, I and Tran, H and Schork, A and Morey, R and Lynch, C and Harness, J V and Lee, S and Barrero, M J and Ku, S and Martynova, M and Semechkin, R and Galat, V and Gottesfeld, J and Izpisua Belmonte, J C and Murry, C and Keirstead, H S and Park, H S and Schmidt, U and Laslett, A L and Muller, F J and Nievergelt, C M and Shamir, R and Loring, J F},
	date = {2011},
	pmid = {21211785},
	keywords = {Human, Genome, Humans, Cells, Cultured, *Cell Proliferation, *Gene Dosage, *Nuclear Reprogramming, Cell Differentiation, Embryonic Stem Cells/*cytology/metabolism, Induced Pluripotent Stem Cells/*cytology/metabolis, Phenotype, Pluripotent Stem Cells/*cytology/metabolism}
}

@article{presutti_identification_1995,
	title = {Identification of the cis-elements mediating the autogenous control of ribosomal protein L2 {mRNA} stability in yeast},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7664741},
	abstract = {The ribosomal protein L2 ({rpL}2) of Saccharomyces cerevisiae regulates the accumulation of its own {mRNA} by a feedback mechanism. An {RNA} sequence is responsible for this control, initially characterized as a 360 nucleotide-long region, localized at the 5' end of the transcript. This region, fused to an unrelated coding sequence, is able to down-regulate the accumulation of the chimeric transcript when increased levels of {rpL}2 are induced in the cell. The target regulatory region also responds to regulation when inserted inside an intron, demonstrating that the control process can take place inside the nucleus. Deletion analysis from the 5' and 3' borders have restricted the responsive region to approximately 200 nt. The insertion of a poly-G cassette downstream of the regulatory region allowed the identification of truncated 3' cut-off poly(A)+ {RNA} molecules. The parallel identification of cut-off molecules containing the 5' portion of the transcript allowed us to deduce that the truncated products originate by endonucleolytic cleavage. Altogether, these results are consistent with a mechanism by which the presence of excess amounts of {rpL}2 in the cell triggers its own {mRNA} to a degradative pathway; this involves an initial endonucleolytic cleavage that is followed by exonucleolytic trimming. Such a regulatory mechanism shows interesting analogies with the translational regulation of r-proteins in Escherichia coli.},
	pages = {4022--4030},
	number = {16},
	journaltitle = {{EMBO} J},
	author = {Presutti, C and Villa, T and Hall, D and Pertica, C and Bozzoni, I},
	date = {1995},
	pmid = {7664741},
	keywords = {Base Sequence, Regulatory Sequences, {RNA}, {RNA} Splicing, Gene Expression Regulation, beta-Galactosidase/genetics, Endoribonucleases/metabolism, Exoribonucleases/metabolism, Feedback, Fungal/genetics, Fungal/genetics/*metabolism, Introns/genetics, Messenger/genetics/*metabolism, Molecular Sequence Data, Nucleic Acid/genetics, Poly G, Post-Transcriptional/*genetics, Recombinant Fusion Proteins/biosynthesis/metabolis, Ribosomal Proteins/*genetics, {RNA} Precursors/metabolism, {RNA} Processing, Saccharomyces cerevisiae/*genetics, Sequence Deletion}
}

@article{maenner_2-d_2010,
	title = {2-D structure of the A region of Xist {RNA} and its implication for {PRC}2 association},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20052282},
	doi = {10.1371/journal.pbio.1000276},
	abstract = {In placental mammals, inactivation of one of the X chromosomes in female cells ensures sex chromosome dosage compensation. The 17 kb non-coding Xist {RNA} is crucial to this process and accumulates on the future inactive X chromosome. The most conserved Xist {RNA} region, the A region, contains eight or nine repeats separated by U-rich spacers. It is implicated in the recruitment of late inactivated X genes to the silencing compartment and likely in the recruitment of complex {PRC}2. Little is known about the structure of the A region and more generally about Xist {RNA} structure. Knowledge of its structure is restricted to an {NMR} study of a single A repeat element. Our study is the first experimental analysis of the structure of the entire A region in solution. By the use of chemical and enzymatic probes and {FRET} experiments, using oligonucleotides carrying fluorescent dyes, we resolved problems linked to sequence redundancies and established a 2-D structure for the A region that contains two long stem-loop structures each including four repeats. Interactions formed between repeats and between repeats and spacers stabilize these structures. Conservation of the spacer terminal sequences allows formation of such structures in all sequenced Xist {RNAs}. By combination of {RNP} affinity chromatography, immunoprecipitation assays, mass spectrometry, and Western blot analysis, we demonstrate that the A region can associate with components of the {PRC}2 complex in mouse {ES} cell nuclear extracts. Whilst a single four-repeat motif is able to associate with components of this complex, recruitment of Suz12 is clearly more efficient when the entire A region is present. Our data with their emphasis on the importance of inter-repeat pairing change fundamentally our conception of the 2-D structure of the A region of Xist {RNA} and support its possible implication in recruitment of the {PRC}2 complex.},
	pages = {e1000276},
	number = {1},
	journaltitle = {{PLoS} Biol},
	author = {Maenner, S and Blaud, M and Fouillen, L and Savoye, A and Marchand, V and Dubois, A and Sanglier-Cianferani, S and Van Dorsselaer, A and Clerc, P and Avner, P and Visvikis, A and Branlant, C},
	date = {2010},
	pmid = {20052282},
	keywords = {Human, Animals, Humans, Mice, {RNA}, Untranslated/*genetics, Chromosomes, Female, {HeLa} Cells, Interspersed Repetitive Sequences/genetics, Long Untranslated, Nucleic Acid Conformation, Phylogeny, Polycomb-Group Proteins, Repressor Proteins/*genetics, X Chromosome Inactivation/genetics, X Chromosome/*genetics, X/genetics}
}

@article{shaaban_herbimycins_2013,
	title = {Herbimycins D-F, ansamycin analogues from Streptomyces sp. {RM}-7-15},
	volume = {76},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23947794},
	doi = {10.1021/np400308w},
	abstract = {Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian Mountains of eastern Kentucky). High-resolution electrospray ionization mass spectrometry and ultraviolet absorption profiles of metabolites from one of the isolates (Streptomyces sp. {RM}-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1-3). In addition, herbimycin A (4), dihydroherbimycin A ({TAN} 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. {RM}-7-15. Herbimycins A and D-F (1-3) displayed comparable binding affinities to the Hsp90alpha. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of nontoxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.},
	pages = {1619--1626},
	number = {9},
	journaltitle = {J Nat Prod},
	author = {Shaaban, K A and Wang, X and Elshahawi, S I and Ponomareva, L V and Sunkara, M and Copley, G C and Hower, J C and Morris, A J and Kharel, M K and Thorson, J S},
	date = {2013},
	pmid = {23947794},
	keywords = {Humans, *Rifabutin/analogs \& derivatives/chemistry/isolati, Anti-Bacterial Agents/chemistry/isolation \& purifi, Biomolecular, Cell Survival/drug effects, {HSP}90 Heat-Shock Proteins/antagonists \& inhibitors, Microbial Sensitivity Tests, Nuclear Magnetic Resonance, Saccharomyces cerevisiae/drug effects, Salmonella enterica/drug effects, Staphylococcus aureus/drug effects, Streptomyces/chemistry}
}

@article{ulitsky_degas:_2010,
	title = {{DEGAS}: de novo discovery of dysregulated pathways in human diseases},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20976054},
	doi = {10.1371/journal.pone.0013367},
	abstract = {{BACKGROUND}: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. {METHODOLOGY}/{PRINCIPAL} {FINDINGS}: We present {DEGAS} ({DysrEgulated} Gene set Analysis via Subnetworks), a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied {DEGAS} to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of {mRNA} splicing, cell proliferation, and the 14-3-3 complex in the disease progression. {DEGAS} is available as part of the {MATISSE} software package (http://acgt.cs.tau.ac.il/matisse). {CONCLUSIONS}/{SIGNIFICANCE}: The subnetworks identified by {DEGAS} can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.},
	pages = {e13367},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Ulitsky, I and Krishnamurthy, A and Karp, R M and Shamir, R},
	date = {2010},
	pmid = {20976054},
	keywords = {Humans, Gene Expression Profiling, Disease/*genetics, Algorithms, *Gene Expression Regulation, Up-Regulation}
}

@article{cacchiarelli_micrornas_2010,
	title = {{MicroRNAs} involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/{nNOS} pathway},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20727829},
	doi = {10.1016/j.cmet.2010.07.008},
	abstract = {In Duchenne muscular dystrophy ({DMD}) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase ({nNOS}); this alters S-nitrosylation of {HDAC}2 and its chromatin association. We show that the differential {HDAC}2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of {microRNA} genes. Several circuitries controlled by the identified {microRNAs}, such as the one linking {miR}-1 to the G6PD enzyme and the redox state of cell, or {miR}-29 to extracellular proteins and the fibrotic process, explain some of the {DMD} pathogenetic traits. We also show that, at variance with other {myomiRs}, {miR}-206 escapes from the dystrophin-{nNOS} control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/{nNOS} controls several important circuitries increasing the robustness of the muscle differentiation program.},
	pages = {341--351},
	number = {4},
	journaltitle = {Cell Metab},
	author = {Cacchiarelli, D and Martone, J and Girardi, E and Cesana, M and Incitti, T and Morlando, M and Nicoletti, C and Santini, T and Sthandier, O and Barberi, L and Auricchio, A and Musaro, A and Bozzoni, I},
	date = {2010},
	pmid = {20727829},
	keywords = {Animals, Mice, Gene Expression Regulation, Animal/*enzymology, Dystrophin/*metabolism/physiology, Histone Deacetylase 2/metabolism, Inbred mdx, {MicroRNAs}/genetics/*physiology, Muscle, Muscular Dystrophy, Nitric Oxide Synthase Type I/*metabolism, Regeneration, Satellite Cells, Skeletal Muscle/physiology, Skeletal/cytology/physiology}
}

@article{starnes_nfi-directs_2009,
	title = {{NFI}-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-{CSF} receptor expression},
	volume = {114},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19542302},
	doi = {10.1182/blood-2008-12-196196},
	abstract = {It is generally conceded that selective combinations of transcription factors determine hematopoietic lineage commitment and differentiation. Here we show that in normal human hematopoiesis the transcription factor nuclear factor I-A ({NFI}-A) exhibits a marked lineage-specific expression pattern: it is upmodulated in the erythroid (E) lineage while fully suppressed in the granulopoietic (G) series. In unilineage E culture of hematopoietic progenitor cells ({HPCs}), {NFI}-A overexpression or knockdown accelerates or blocks erythropoiesis, respectively: notably, {NFI}-A overexpression restores E differentiation in the presence of low or minimal erythropoietin stimulus. Conversely, {NFI}-A ectopic expression in unilineage G culture induces a sharp inhibition of granulopoiesis. Finally, in bilineage E + G culture, {NFI}-A overexpression or suppression drives {HPCs} into the E or G differentiation pathways, respectively. These {NFI}-A actions are mediated, at least in part, by a dual and opposite transcriptional action: direct binding and activation or repression of the promoters of the beta-globin and G-{CSF} receptor gene, respectively. Altogether, these results indicate that, in early hematopoiesis, the {NFI}-A expression level acts as a novel factor channeling {HPCs} into either the E or G lineage.},
	pages = {1753--1763},
	number = {9},
	journaltitle = {Blood},
	author = {Starnes, L M and Sorrentino, A and Pelosi, E and Ballarino, M and Morsilli, O and Biffoni, M and Santoro, S and Felli, N and Castelli, G and De Marchis, M L and Mastroberardino, G and Gabbianelli, M and Fatica, A and Bozzoni, I and Nervi, C and Peschle, C},
	date = {2009},
	pmid = {19542302},
	keywords = {Genetic, Humans, Promoter Regions, *Gene Expression Regulation, Antigens, beta-Globins/*metabolism, Biological, {CD}34/biosynthesis, Cell Differentiation, Cell Lineage, Erythrocytes/*metabolism, Erythropoietin/metabolism, Fetal Blood/metabolism, Granulocyte Colony-Stimulating Factor/*, Granulocytes/*metabolism, Hematopoietic Stem Cells/*cytology, Models, {NFI} Transcription Factors/*metabolism, Receptors}
}

@article{liu_differential_1996,
	title = {Differential activation of {ERK}, {JNK}/{SAPK} and P38/{CSBP}/{RK} map kinase family members during the cellular response to arsenite},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8902523},
	abstract = {Exposure of cells to either proliferative or stressful stimuli elicits a complex response involving one or more distinct phosphorylation cascades culminating in the activation of multiple members of the mitogen-activated protein kinase ({MAPK}) family, including extracellular signal regulated kinase ({ERK}), stress-activated c-Jun N-terminal kinase ({JNK}/{SAPK}), and p38/{RK}/{CSBP} protein kinase. While the pathways transducing mitogenic stimuli to these kinases are relatively well established, the early signalling events leading to their activation in response to stress are poorly understood. In the present study, we examined {ERK}, {JNK}/{SAPK}, and p38 activation in cells treated with the sulfhydryl-reactive agent sodium arsenite. Arsenite treatment potently activated both {JNK}/{SAPK} and p38, but only moderately activated {ERK}. Activation of all three kinases was prevented by the free radical scavenger N-Acetyl-L-cysteine, suggesting that an oxidative signal initiates the responses. Suramin, a growth factor receptor poison, significantly inhibited {ERK} activation by arsenite, but had little effect on either {JNK}/{SAPK} or p38 activity. In contrast, suramin inhibited the activation of all three kinases by short wavelength ultraviolet light ({UVC}) irradiation. In addition, comparative studies with wild-type {PC}12 cells and {PC}12 cells expressing a dominant negative Ras mutant allele indicated that arsenite activates {ERK} primarily through a Ras-dependent pathway(s), while activation of both {JNK}/{SAPK} and p38 occurs through a mechanism relatively independent of Ras. These results suggest that {JNK}/{SAPK} and p38 may share common upstream regulators distinct from those involved in {ERK} activation.},
	pages = {771--781},
	number = {6},
	journaltitle = {Free Radic Biol Med},
	author = {Liu, Y and Guyton, K Z and Gorospe, M and Xu, Q and Lee, J C and Holbrook, N J},
	date = {1996},
	pmid = {8902523},
	keywords = {Animals, *Mitogen-Activated Protein Kinases, Acetylcysteine/pharmacology, Arsenites/*pharmacology, Blotting, Calcium-Calmodulin-Dependent Protein Kinases/*meta, Cell Line, Embryo, Enzyme Activation/drug effects, Fibroblasts, Free Radical Scavengers/pharmacology, {JNK} Mitogen-Activated Protein Kinases, Mammalian, p38 Mitogen-Activated Protein Kinases, {PC}12 Cells, ras Proteins/physiology, Rats, Sodium Compounds/*pharmacology, Suramin/pharmacology, Ultraviolet Rays, Western}
}

@article{wang_high_2013,
	title = {High expression of class {III} beta-tubulin predicts good response to neoadjuvant taxane and doxorubicin/cyclophosphamide-based chemotherapy in estrogen receptor-negative breast cancer},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23218766},
	doi = {10.1016/j.clbc.2012.11.003},
	abstract = {{BACKGROUND}: Expression of class {IotaIotaIota} beta-tubulin ({betaIotaIotaIota}-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies including breast cancer. However its predictive value in a neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether {betaIotaIotaIota}-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy. {PATIENTS} {AND} {METHODS}: We determined {betaIotaIotaIota}-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. {betaIotaIotaIota}-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden ({RCB}) score. {RESULTS}: High {betaIotaIotaIota}-tubulin expression was significantly associated with poorly differentiated high-grade breast cancers (P = .003) but not with tumor size, estrogen receptor ({ER}) status, or human epidermal growth factor receptor 2 ({HER}2)/neu overexpression. In {ER}(-) tumors treated with neoadjuvant chemotherapy, high {betaIotaIotaIota}-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower {RCB} scores (P = .021). {CONCLUSION}: This study reveals differential {betaIotaIotaIota}-tubulin expression in breast cancers of different histologic grades, hormone receptors, and {HER}2/neu status. It also suggests a potential role for {betaIotaIotaIota}-tubulin as a predictive biomarker for response in neoadjuvant chemotherapy for {ER}(-) breast cancer, which has not been previously reported. These data provide a strong rationale for considering {betaIotaIotaIota}-tubulin status and further validation of this marker in a large study.},
	pages = {103--108},
	number = {2},
	journaltitle = {Clin Breast Cancer},
	author = {Wang, Y and Sparano, J A and Fineberg, S and Stead, L and Sunkara, J and Horwitz, S B and {McDaid}, H M},
	date = {2013},
	pmid = {23218766},
	keywords = {Humans, *Neoadjuvant Therapy, 80 and over, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/*th, Biological/*metabolism, Breast Neoplasms/drug therapy/*metabolism/patholog, Breast/drug therapy/*metabolism, Bridged Compounds/administration \& dosage, Carcinoma, Cyclophosphamide/administration \& dosage, Doxorubicin/administration \& dosage, Ductal, {erbB}-2/metabolism, Estrogen/*metabolism, Female, Follow-Up Studies, Immunoenzyme Techniques, Middle Aged, Neoplasm Grading, Neoplasm Staging, Prognosis, Receptor, Receptors, Retrospective Studies, Taxoids/administration \& dosage, Tubulin/*metabolism, Tumor Markers}
}

@article{hindorff_potential_2009,
	title = {Potential etiologic and functional implications of genome-wide association loci for human diseases and traits},
	volume = {106},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19474294},
	doi = {10.1073/pnas.0903103106},
	abstract = {We have developed an online catalog of {SNP}-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated {SNPs} ({TASs}). Reported {TASs} were common [median risk allele frequency 36\%, interquartile range ({IQR}) 21\%-53\%] and were associated with modest effect sizes [median odds ratio ({OR}) 1.33, {IQR} 1.20-1.61]. Among 20 genomic annotation sets, reported {TASs} were significantly overrepresented only in nonsynonymous sites [{OR} = 3.9 (2.2-7.0), p = 3.5 x 10(-7)] and 5kb-promoter regions [{OR} = 2.3 (1.5-3.6), p = 3 x 10(-4)] compared to {SNPs} randomly selected from genotyping arrays. Although 88\% of {TASs} were intronic (45\%) or intergenic (43\%), {TASs} were not overrepresented in introns and were significantly depleted in intergenic regions [{OR} = 0.44 (0.34-0.58), p = 2.0 x 10(-9)]. Only slightly more {TASs} than expected by chance were predicted to be in regions under positive selection [{OR} = 1.3 (0.8-2.1), p = 0.2]. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology.},
	pages = {9362--9367},
	number = {23},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Hindorff, L A and Sethupathy, P and Junkins, H A and Ramos, E M and Mehta, J P and Collins, F S and Manolio, T A},
	date = {2009},
	pmid = {19474294},
	keywords = {Genetic, Humans, *Genetic Predisposition to Disease, *Genome-Wide Association Study, *Polymorphism, Disease/genetics, Polymorphism, Single Nucleotide}
}

@article{yang_protein_1996,
	title = {Protein tyrosine phosphatase regulation of endothelial cell apoptosis and differentiation},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8822199},
	abstract = {Apoptosis, or programmed cell death, occurs during development and may also be an important factor in many diseases. However, little is known about the signal transduction pathways regulating apoptosis. In these studies, loss of endothelial cell-substrate attachment and apoptosis after removal of growth factors was associated with dephosphorylation of tyrosine residues at the cell periphery. Dephosphorylation of total cellular proteins accompanied apoptosis and was reduced by orthovanadate, an inhibitor of protein tyrosine phosphatases. Orthovanadate blocked the fragmentation of nuclear {DNA}, inhibited {DNA} laddering, and suppressed the expression of {TRPM}-2, an apoptosis-associated gene. The tyrosine phosphorylation levels of {FAK}125, erk1 (mitogen-activated kinase kinase), and cdc-2 were reduced during apoptosis. {FAK}125 dephosphorylation was inhibited by orthovanadate, but premature activation (tyrosine dephosphorylation) of cdc-2 was not. Orthovanadate was as effective as basic fibroblast growth factor in activating erk1 without increasing cell proliferation and in preventing the apoptosis of endothelial cells after treatment with tumor necrosis factor alpha. Endothelial cell differentiation on extracellular matrix (Matrigel) was also stimulated by orthovanadate in the absence of basic fibroblast growth factor without affecting growth arrest and inhibition of {DNA} synthesis. Expression of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1) was down-regulated during the early stages of differentiation, remained low for at least 6 hours as differentiation proceeded, and increased upon completion of differentiation. Cells that failed to down-regulate p21 {mRNA} on Matrigel in the absence of angiogenic factors underwent apoptosis. These results suggest that protein tyrosine phosphatases are actively involved in signal transduction during apoptosis and may regulate p21 expression to inhibit endothelial cell differentiation.},
	pages = {161--171},
	number = {2},
	journaltitle = {Cell Growth Differ},
	author = {Yang, C and Chang, J and Gorospe, M and Passaniti, A},
	date = {1996},
	pmid = {8822199},
	keywords = {Humans, Cells, Cultured, Apoptosis/drug effects/physiology, Cell Adhesion/drug effects, Cell Cycle/drug effects/physiology, Cell Differentiation/drug effects/physiology, Cell Division/drug effects/physiology, Collagen/pharmacology, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/pharmacology, Drug Combinations, Electrophoresis, Endothelium, Enzyme Inhibitors/pharmacology, Fibroblast Growth Factor 2/pharmacology, Growth Substances/pharmacology, Laminin/pharmacology, Phosphorylation, Polyacrylamide Gel, Protein Tyrosine Phosphatases/antagonists \& inhibi, Proteoglycans/pharmacology, Signal Transduction/physiology, Time Factors, Umbilical Veins/cytology, Vanadates/pharmacology, Vascular/*cytology/metabolism}
}

@article{ferdin_hincuts_2013,
	title = {{HINCUTs} in cancer: hypoxia-induced noncoding ultraconserved transcripts},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24037088},
	doi = {10.1038/cdd.2013.119},
	abstract = {Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific {microRNAs} ({miRNAs}); however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-{UCRs}). Interestingly, several hypoxia-upregulated T-{UCRs}, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' ({HINCUTs}), are also overexpressed in clinical samples from colon cancer patients. We show that these T-{UCRs} are predominantly nuclear and that the hypoxia-inducible factor ({HIF}) is at least partly responsible for the induction of several members of this group. One specific {HINCUT}, uc.475 (or {HINCUT}-1) is part of a retained intron of the host protein-coding gene, O-linked N-acetylglucosamine transferase, which is overexpressed in epithelial cancer types. Consistent with the hypothesis that T-{UCRs} have important function in tumor formation, {HINCUT}-1 supports cell proliferation specifically under hypoxic conditions and may be critical for optimal O-{GlcNAcylation} of proteins when oxygen tension is limiting. Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding {RNAs} ({ncRNAs}) from the T-{UCRs} category.},
	pages = {1675--1687},
	number = {12},
	journaltitle = {Cell Death Differ},
	author = {Ferdin, J and Nishida, N and Wu, X and Nicoloso, M S and Shah, M Y and Devlin, C and Ling, H and Shimizu, M and Kumar, K and Cortez, M A and Ferracin, M and Bi, Y and Yang, D and Czerniak, B and Zhang, W and Schmittgen, T D and Voorhoeve, M P and Reginato, M J and Negrini, M and Davuluri, R V and Kunej, T and Ivan, M and Calin, G A},
	date = {2013},
	pmid = {24037088},
	keywords = {{DNA}, Genetic, Humans, {RNA}, Transcription, Gene Expression Regulation, Genetic/genetics, Reproducibility of Results, Untranslated/*genetics, alpha Subunit/metaboli, Cell Hypoxia/genetics, Cell Line, Conserved Sequence/*genetics, Down-Regulation/genetics, Enhancer Elements, Genetic Loci/genetics, Hypoxia-Inducible Factor 1, Messenger/genetics/metabolism, N-Acetylglucosaminyltransferases/genetics/metaboli, Neoplasm/genetics, Neoplasms/enzymology/*genetics/pathology, Neoplastic, Tumor}
}

@article{pryde_53bp1_2005,
	title = {53BP1 exchanges slowly at the sites of {DNA} damage and appears to require {RNA} for its association with chromatin},
	volume = {118},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15840649},
	doi = {10.1242/jcs.02336},
	abstract = {53BP1 protein is re-localized to the sites of {DNA} damage after ionizing radiation ({IR}) and is involved in {DNA}-damage-checkpoint signal transduction. We examined the dynamics of {GFP}-53BP1 in living cells. The protein starts to accumulate at the sites of {DNA} damage 2-3 minutes after damage induction. Fluorescence recovery after photobleaching experiments showed that {GFP}-53BP1 is highly mobile in non-irradiated cells. Upon binding to the {IR}-induced nuclear foci, the mobility of 53BP1 reduces greatly. The minimum (M) domain of 53BP1 essential for targeting to {IR} induced foci consists of residues 1220-1703. {GFP}-M protein forms foci in mouse embryonic fibroblast cells lacking functional endogenous 53BP1. The M domain contains a tandem repeat of Tudor motifs and an arginine- and glycine-rich domain ({RG} stretch), which are often found in proteins involved in {RNA} metabolism, the former being essential for targeting. {RNase} A treatment dissociates 53BP1 from {IR}-induced foci. In {HeLa} cells, dissociation of the M domain without the {RG} stretch by {RNase} A treatment can be restored by re-addition of nuclear {RNA} in the early stages of post-irradiation. 53BP1 immunoprecipitates contain some {RNA} molecules. Our results suggest a possible involvement of {RNA} in the binding of 53BP1 to chromatin damaged by {IR}.},
	pages = {2043--2055},
	issue = {Pt 9},
	journaltitle = {J Cell Sci},
	author = {Pryde, F and Khalili, S and Robertson, K and Selfridge, J and Ritchie, A M and Melton, D W and Jullien, D and Adachi, Y},
	date = {2005},
	pmid = {15840649},
	keywords = {Animals, Humans, Mice, Protein Binding, *{DNA} Damage, Amino Acid Sequence, Chromatin/*chemistry, {DNA} Repair, Fibroblasts/metabolism, Fluorescence, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins/metabolism, {HeLa} Cells, Homozygote, Immunoprecipitation, Intracellular Signaling Peptides and Proteins/*gen, Microscopy, Molecular Sequence Data, Mutation, Pancreatic/metabolism, Phosphoproteins/*genetics/metabolism/*physiology, Plasmids/metabolism, Protein Structure, Ribonuclease, Ribonucleases/metabolism, {RNA}/*chemistry, Signal Transduction, Tertiary, Time Factors, Transgenic}
}

@article{reimand_mutational_2013,
	title = {The mutational landscape of phosphorylation signaling in cancer},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24089029},
	doi = {10.1038/srep02651},
	abstract = {Somatic mutations in cancer genomes include drivers that provide selective advantages to tumor cells and passengers present due to genome instability. Discovery of pan-cancer drivers will help characterize biological systems important in multiple cancers and lead to development of better therapies. Driver genes are most often identified by their recurrent mutations across tumor samples. However, some mutations are more important for protein function than others. Thus considering the location of mutations with respect to functional protein sites can predict their mechanisms of action and improve the sensitivity of driver gene detection. Protein phosphorylation is a post-translational modification central to cancer biology and treatment, and frequently altered by driver mutations. Here we used our {ActiveDriver} method to analyze known phosphorylation sites mutated by single nucleotide variants ({SNVs}) in The Cancer Genome Atlas Research Network ({TCGA}) pan-cancer dataset of 3,185 genomes and 12 cancer types. Phosphorylation-related {SNVs} ({pSNVs}) occur in ∼90\% of tumors, show increased conservation and functional mutation impact compared to other protein-coding mutations, and are enriched in cancer genes and pathways. Gene-centric analysis found 150 known and candidate cancer genes with significant {pSNV} recurrence. Using a novel computational method, we predict that 29\% of these mutations directly abolish phosphorylation or modify kinase target sites to rewire signaling pathways. This analysis shows that incorporation of information about protein signaling sites will improve computational pipelines for variant function prediction.},
	pages = {2651},
	journaltitle = {Sci Rep},
	author = {Reimand, J and Wagih, O and Bader, G D},
	date = {2013},
	pmid = {24089029},
	keywords = {Human, Genome, Humans, Computational Biology, Algorithms, *Protein Processing, *Signal Transduction, Gene Regulatory Networks, Mutation/*genetics, Neoplasm Proteins/genetics/*metabolism, Neoplasms/*genetics/*metabolism, Phosphorylation, Polymorphism, Post-Translational, Protein Kinases/genetics/metabolism, Single Nucleotide/*genetics}
}

@article{fragapane_splicing_1990,
	title = {Splicing control of the L1 ribosomal protein gene of X.laevis: structural similarities between sequences present in the regulatory intron and in the 28S ribosomal {RNA}},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2362566},
	pages = {111--112},
	number = {2},
	journaltitle = {Mol Biol Rep},
	author = {Fragapane, P and Caffarelli, E and Santoro, B and Sperandio, S and Lener, M and Bozzoni, I},
	date = {1990},
	pmid = {2362566},
	keywords = {Animals, Base Sequence, {RNA}, Gene Expression Regulation, Nucleic Acid, Introns, *{RNA} Splicing, 28S/*genetics, Bacterial Proteins/*genetics, Feedback, Genes, Molecular Sequence Data, Nucleic Acid Conformation, Ribosomal, Ribosomal Proteins/*genetics, Ribosomal/*genetics, Sequence Homology, Xenopus laevis/*genetics}
}

@article{johnson_evolution_2009,
	title = {Evolution of the vertebrate gene regulatory network controlled by the transcriptional repressor {REST}},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19318521},
	doi = {10.1093/molbev/msp058},
	abstract = {Specific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor {REST} ({RE}1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate {DNA} motif, the {RE}1 (Repressor Element 1). Here we present a comparative genomic analysis of {REST} recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify {REST} binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human {RE}1 elements. We validate these findings using experimental data of {REST} binding across the whole genomes of human and mouse. We show that one-third of human {RE}1s are unique to primates: These sites recruit {REST} in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient {RE}1s to have higher affinity for {REST} than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.},
	pages = {1491--1507},
	number = {7},
	journaltitle = {Mol Biol Evol},
	author = {Johnson, R and Samuel, J and Ng, C K and Jauch, R and Stanton, L W and Wood, I C},
	date = {2009},
	pmid = {19318521},
	keywords = {Human, Animals, Base Sequence, Genome, Humans, Protein Binding, *Gene Regulatory Networks, Co-Repressor Proteins, {DNA}-Binding Proteins/*genetics, Molecular Sequence Data, Nerve Tissue Proteins/*genetics, Repressor Proteins/*genetics, Sequence Alignment, Vertebrates/*genetics}
}

@article{tarallo_dicer1_2012,
	title = {{DICER}1 loss and Alu {RNA} induce age-related macular degeneration via the {NLRP}3 inflammasome and {MyD}88},
	volume = {149},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22541070},
	doi = {10.1016/j.cell.2012.03.036},
	abstract = {Alu {RNA} accumulation due to {DICER}1 deficiency in the retinal pigmented epithelium ({RPE}) is implicated in geographic atrophy ({GA}), an advanced form of age-related macular degeneration that causes blindness in millions of individuals. The mechanism of Alu {RNA}-induced cytotoxicity is unknown. Here we show that {DICER}1 deficit or Alu {RNA} exposure activates the {NLRP}3 inflammasome and triggers {TLR}-independent {MyD}88 signaling via {IL}18 in the {RPE}. Genetic or pharmacological inhibition of inflammasome components ({NLRP}3, Pycard, Caspase-1), {MyD}88, or {IL}18 prevents {RPE} degeneration induced by {DICER}1 loss or Alu {RNA} exposure. These findings, coupled with our observation that human {GA} {RPE} contains elevated amounts of {NLRP}3, {PYCARD}, and {IL}18 and evidence of increased Caspase-1 and {MyD}88 activation, provide a rationale for targeting this pathway in {GA}. Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements.},
	pages = {847--859},
	number = {4},
	journaltitle = {Cell},
	author = {Tarallo, V and Hirano, Y and Gelfand, B D and Dridi, S and Kerur, N and Kim, Y and Cho, W G and Kaneko, H and Fowler, B J and Bogdanovich, S and Albuquerque, R J and Hauswirth, W W and Chiodo, V A and Kugel, J F and Goodrich, J A and Ponicsan, S L and Chaudhuri, G and Murphy, M P and Dunaief, J L and Ambati, B K and Ogura, Y and Yoo, J W and Lee, D K and Provost, P and Hinton, D R and Nunez, G and Baffi, J Z and Kleinman, M E and Ambati, J},
	date = {2012},
	pmid = {22541070},
	keywords = {Animals, Humans, Mice, *Alu Elements, Carrier Proteins/metabolism, {DEAD}-box {RNA} Helicases/*metabolism, Geographic Atrophy/*immunology/metabolism/*patholo, Inflammasomes/*immunology/metabolism, Myeloid Differentiation Factor 88/*metabolism, Retinal Pigment Epithelium/*metabolism/pathology, Ribonuclease {III}/*metabolism, Toll-Like Receptors/metabolism}
}

@article{buonomo_rev_1999,
	title = {The Rev protein is able to transport to the cytoplasm small nucleolar {RNAs} containing a Rev binding element},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10445874},
	abstract = {Small nucleolar {RNAs} ({snoRNAs}) were utilized to express Rev-binding sequences inside the nucleolus and to test whether they are substrates for Rev binding and transport. We show that U16 {snoRNA} containing the minimal binding site for Rev stably accumulates inside the nucleolus maintaining the interaction with the basic C/D {snoRNA}-specific factors. Upon Rev expression, the chimeric {RNA} is exported to the cytoplasm, where it remains bound to Rev in a particle devoid of {snoRNP}-specific factors. These data indicate that Rev can elicit the functions of {RNA} binding and transport inside the nucleolus.},
	pages = {993--1002},
	number = {8},
	journaltitle = {{RNA}},
	author = {Buonomo, S B and Michienzi, A and De Angelis, F G and Bozzoni, I},
	date = {1999},
	pmid = {10445874},
	keywords = {Animals, Base Sequence, Genetic, {RNA}, *{RNA} Helicases, Cell Line, Cell Nucleus/genetics/metabolism, Chromosomal Proteins, Cytoplasm/*metabolism, {DEAD}-box {RNA} Helicases, env/*genetics, Gene Products, Genes, Models, Molecular Sequence Data, Non-Histone/metabolism, Precipitin Tests, Protein Kinases/metabolism, rev/pharmacology/*physiology, Small Nuclear/analysis/*metabolism, Time Factors, Transfection, Xenopus/genetics}
}

@article{martone_u1_2012,
	title = {U1 {snRNA} as an effective vector for stable expression of antisense molecules and for the inhibition of the splicing reaction},
	volume = {867},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22454066},
	doi = {10.1007/978-1-61779-767-5_16},
	abstract = {We report the use of the U1 {snRNA} as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons. The single-stranded 5' terminus of U1 can be replaced by unrelated sequences as long as 50 nucleotides without affecting both the stability and the ability to assemble into {snRNP} particles. Effective exon skipping has been obtained for different dystrophin exons by antisense sequences against 5' and 3' splice sites alone or in combination with {ESE} sequences. The efficacy of these molecules has been studied both in in vitro systems and in animals. In both cases the chimeric molecules, delivered as part of lentiviral or {AAV} vectors (De Angelis et al. Proc Natl Acad Sci {USA} 99:9456-9461, 2002; Denti et al. Proc Natl Acad Sci {USA} 103: 3758-3763, 2006; Denti et al. Hum Gene Ther 17: 565-743, 2006; Denti et al. Hum Gene Ther 19: 601-608, 2008; Incitti et al. Mol Ther 18: 1675-1682, 2010), provided high skipping activity and efficient rescue of dystrophin synthesis. Moreover, the U1-antisense molecules, delivered to mice via systemic injection of recombinant {AAV} viruses, displayed body wide transduction, long-term expression, dystrophin rescue as well as morphological and functional benefit (Denti et al. Hum Gene Ther 19: 601-608, 2008). In this Chapter we report methods for producing U1-antisense expression cassettes in the backbone of lentiviral constructs and for testing their activity both in patients' derived myoblasts as well as in fibroblasts reprogrammed to muscle differentiation.},
	pages = {239--257},
	journaltitle = {Methods Mol Biol},
	author = {Martone, J and De Angelis, F G and Bozzoni, I},
	date = {2012},
	pmid = {22454066},
	keywords = {Animals, Humans, Mice, {RNA}, {RNA} Splicing, Cells, Cultured, *Exons, Antisense/*genetics, Cloning, Duchenne/*genetics/therapy, Dystrophin/*genetics, Fibroblasts/metabolism, Firefly/genetics, Genetic Therapy/methods, Genetic Vectors/*genetics, {HeLa} Cells, Lentivirus/genetics, Luciferases, Molecular/methods, Muscular Dystrophy, Myoblasts/metabolism, Small Nuclear/*genetics}
}

@article{caldwell_serial_2002,
	title = {Serial analysis of gene expression in renal carcinoma cells reveals {VHL}-dependent sensitivity to {TNFalpha} cytotoxicity},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11840338},
	doi = {10.1038/sj.onc.1205140},
	abstract = {We have used serial analysis of gene expression ({SAGE}) to investigate the influence of the von Hippel-Lindau ({VHL}) gene on global gene expression profiles. {SAGE} libraries were prepared from renal cell carcinoma ({RCC}) lines that either lack (parental) or express wild-type {VHL} ({wtVHL}). Comparison of these libraries revealed some differentially expressed genes (Glut-1, for example) that were known to be influenced by {VHL}, but the majority of genes had not previously been reported to be affected by the cell's {VHL} status. The identification of several genes involved in {TNFalpha}-mediated events prompted us to compare the sensitivity of cells with different {VHL} status in {TNFalpha} cytotoxicity assays. Strikingly, {VHL}-deficient cells were much more resistant to the toxic influence of {TNFalpha}. We propose that {VHL}-dependent sensitization of {RCC} cells to {TNFalpha}-mediated killing may contribute to {VHL}'s growth suppressive function.},
	pages = {929--936},
	number = {6},
	journaltitle = {Oncogene},
	author = {Caldwell, M C and Hough, C and Furer, S and Linehan, W M and Morin, P J and Gorospe, M},
	date = {2002},
	pmid = {11840338},
	keywords = {Gene Expression Profiling/*methods, Humans, {RNA}, Gene Expression Regulation, *Tumor Suppressor Proteins, *Ubiquitin-Protein Ligases, Blotting, Carcinoma, Computer Systems, Cultured/drug effects/metabolism, Drug Resistance/genetics, Gene Library, Kidney Neoplasms/*genetics/metabolism/pathology, Ligases/deficiency/genetics/*physiology, Messenger/biosynthesis/genetics, Neoplasm Proteins/genetics/*physiology, Neoplasm/biosynthesis/genetics, Neoplastic/genetics/*p, Northern, Polymerase Chain Reaction, Recombinant Fusion Proteins/physiology, Renal Cell/*genetics/metabolism/patholo, Transfection, Tumor Cells, Tumor Necrosis Factor-alpha/*toxicity, Von Hippel-Lindau Tumor Suppressor Protein, Western}
}

@article{de_angelis_chimeric_2002,
	title = {Chimeric {snRNA} molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-{mRNA} induce exon skipping and restoration of a dystrophin synthesis in Delta 48-50 {DMD} cells},
	volume = {99},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12077324},
	doi = {10.1073/pnas.142302299},
	abstract = {Deletions and point mutations in the dystrophin gene cause either the severe progressive myopathy Duchenne muscular dystrophy ({DMD}) or the milder Becker muscular dystrophy, depending on whether the translational reading frame is lost or maintained. Because internal in-frame deletions in the protein produce only mild myopathic symptoms, it should be possible, by preventing the inclusion of specific mutated exon(s) in the mature dystrophin {mRNA}, to restore a partially corrected phenotype. Such control has been previously accomplished by the use of synthetic oligonucleotides; nevertheless, a significant drawback to this approach is caused by the fact that oligonucleotides would require periodic administrations. To circumvent this problem, we have produced several constructs able to express in vivo, in a stable fashion, large amounts of chimeric {RNAs} containing antisense sequences. In this paper we show that antisense molecules against exon 51 splice junctions are able to direct skipping of this exon in the human {DMD} deletion 48-50 and to rescue dystrophin synthesis. We also show that the highest skipping activity was found when antisense constructs against the 5' and 3' splice sites are coexpressed in the same cell.},
	pages = {9456--9461},
	number = {14},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {De Angelis, F G and Sthandier, O and Berarducci, B and Toso, S and Galluzzi, G and Ricci, E and Cossu, G and Bozzoni, I},
	date = {2002},
	pmid = {12077324},
	keywords = {Animals, Genetic, Humans, {RNA}, {RNA} Splicing, Exons, Antisense/genetics/pharmacology, Duchenne/*genetics/metabolism/, Dystrophin/*biosynthesis/*genetics, Female, Genetic Therapy, Male, Muscular Dystrophy, Oocytes/metabolism, {RNA} Precursors/genetics, {RNA}/genetics/pharmacology, Sequence Deletion, Small Nuclear/*genetics/pharmacology, Transduction, Xenopus laevis}
}

@article{gutschner_hallmarks_2012,
	title = {The hallmarks of cancer: a long non-coding {RNA} point of view},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22664915},
	doi = {10.4161/rna.20481},
	abstract = {With the advent of next generation sequencing methods and progress in transcriptome analysis, it became obvious that the human genome contains much more than just protein-coding genes. In fact, up to 70\% of our genome is transcribed into {RNA} that does not serve as templates for proteins. In this review, we focus on the emerging roles of these long non-coding {RNAs} ({lncRNAs}) in the field of tumor biology. Long {ncRNAs} were found to be deregulated in several human cancers and show tissue-specific expression. Functional studies revealed a broad spectrum of mechanisms applied by {lncRNAs} such as {HOTAIR}, {MALAT}1, {ANRIL} or {lincRNA}-p21 to fulfill their functions. Here, we link the cellular processes influenced by long {ncRNAs} to the hallmarks of cancer and therefore provide an {ncRNA} point-of-view on tumor biology. This should stimulate new research directions and therapeutic options considering long {ncRNAs} as novel prognostic markers and therapeutic targets.},
	pages = {703--719},
	number = {6},
	journaltitle = {{RNA} Biol},
	author = {Gutschner, T and Diederichs, S},
	date = {2012},
	pmid = {22664915},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation, Cell Death, Cell Proliferation, Cell Transformation, Long Noncoding/metabolism/*physiology, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms/genetics/*metabolism/*pathology, Neoplastic, Neoplastic/genetics/metabolis, Neovascularization, Pathologic/genetics/metabolism}
}

@article{srikantan_functional_2012,
	title = {Functional interplay between {RNA}-binding protein {HuR} and {microRNAs}},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22708488},
	abstract = {The mammalian {RNA}-binding protein ({RBP}) {HuR} associates with numerous {mRNAs} encoding proteins with roles in cell division, cell survival, immune response, and differentiation. {HuR} was known to stabilize many of these {mRNAs} and/or modulated their translation, but the molecular processes by which {HuR} affected the fate of target {mRNAs} was largely unknown. Evidence accumulated over the past five years has revealed that the influence of {HuR} on many bound transcripts depends on {HuR}'s interplay with {microRNAs} which associate with the same {mRNAs}. Here, we review the interactions of {HuR} and {microRNAs} - both competitive and cooperative - that govern expression of shared target {mRNAs}. Competition between {HuR} and {microRNAs} typically results in enhanced gene expression if the {HuR}-{mRNA} interaction prevails, and in repression if the {microRNA} remains associated. Cooperation between {HuR} and {microRNAs} leads to lower expression of the shared {mRNA}. We also describe the regulation of {HuR} levels by {microRNAs} as well as the regulation of {microRNA} levels by {HuR}. Finally, we discuss transcriptome-wide analyses of {HuR}-bound {mRNAs} with neighboring {microRNA} sites, and review the emerging mechanisms whereby {microRNAs} confer versatility and robustness to the post-transcriptional outcomes of {HuR} targets.},
	pages = {372--379},
	number = {4},
	journaltitle = {Curr Protein Pept Sci},
	author = {Srikantan, S and Tominaga, K and Gorospe, M},
	date = {2012},
	pmid = {22708488},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Hu Paraneoplastic Encephalomyelitis Antigens/genet, Messenger/genetics/metabolism, {MicroRNAs}/genetics/*metabolism, Protein Binding/genetics}
}

@article{liu_polyamines_2009,
	title = {Polyamines regulate c-Myc translation through Chk2-dependent {HuR} phosphorylation},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19812253},
	doi = {10.1091/mbc.E09-07-0550},
	abstract = {All mammalian cells depend on polyamines for normal growth and proliferation, but the exact roles of polyamines at the molecular level remain largely unknown. The {RNA}-binding protein {HuR} modulates the stability and translation of many target {mRNAs}. Here, we show that in rat intestinal epithelial cells ({IECs}), polyamines enhanced {HuR} association with the 3'-untranslated region of the c-Myc {mRNA} by increasing {HuR} phosphorylation by Chk2, in turn promoting c-Myc translation. Depletion of cellular polyamines inhibited Chk2 and reduced the affinity of {HuR} for c-Myc {mRNA}; these effects were completely reversed by addition of the polyamine putrescine or by Chk2 overexpression. In cells with high content of cellular polyamines, {HuR} silencing or Chk2 silencing reduced c-Myc translation and c-Myc expression levels. Our findings demonstrate that polyamines regulate c-Myc translation in {IECs} through {HuR} phosphorylation by Chk2 and provide new insight into the molecular functions of cellular polyamines.},
	pages = {4885--4898},
	number = {23},
	journaltitle = {Mol Biol Cell},
	author = {Liu, L and Rao, J N and Zou, T and Xiao, L and Wang, P Y and Turner, D J and Gorospe, M and Wang, J Y},
	date = {2009},
	pmid = {19812253},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, {RNA}, *Protein Biosynthesis, Antigens, Checkpoint Kinase 2, Epithelial Cells/cytology/drug effects/physiology, Gene Expression Regulation/*drug effects, Gene Silencing, Hu Paraneoplastic Encephalomyelitis Antigens, Intestinal Mucosa/cytology, Messenger/genetics/metabolism, Molecular Sequence Data, Phosphorylation, Point Mutation, Polyamines/*metabolism/pharmacology, Polyribosomes/chemistry/metabolism, Protein-Serine-Threonine Kinases/genetics/*metabol, Proto-Oncogene Proteins c-myc/genetics/*metabolism, Rats, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism}
}

@article{hall_aurkb-mediated_2009,
	title = {{AURKB}-mediated effects on chromatin regulate binding versus release of {XIST} {RNA} to the inactive chromosome},
	volume = {186},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19704020},
	doi = {10.1083/jcb.200811143},
	abstract = {How {XIST} {RNA} strictly localizes across the inactive X chromosome is unknown; however, prophase release of human {XIST} {RNA} provides a clue. Tests of inhibitors that mimic mitotic chromatin modifications implicated an indirect role of {PP}1 (protein phosphatase 1), potentially via its interphase repression of Aurora B kinase ({AURKB}), which phosphorylates H3 and chromosomal proteins at prophase. {RNA} interference to {AURKB} causes mitotic retention of {XIST} {RNA}, unlike other mitotic or broad kinase inhibitors. Thus, {AURKB} plays an unexpected role in regulating {RNA} binding to heterochromatin, independent of mechanics of mitosis. H3 phosphorylation (H3ph) was shown to precede {XIST} {RNA} release, whereas results exclude H1ph involvement. Of numerous Xi chromatin (chromosomal protein) hallmarks, ubiquitination closely follows {XIST} {RNA} retention or release. Surprisingly, H3S10ph staining (but not H3S28ph) is excluded from Xi and is potentially linked to ubiquitination. Results suggest a model of multiple distinct anchor points for {XIST} {RNA}. This study advances understanding of {RNA} chromosome binding and the roles of {AURKB} and demonstrates a novel approach to manipulate and study {XIST} {RNA}.},
	pages = {491--507},
	number = {4},
	journaltitle = {J Cell Biol},
	author = {Hall, L L and Byron, M and Pageau, G and Lawrence, J B},
	date = {2009},
	pmid = {19704020},
	keywords = {Animals, Humans, {RNA}, Long Noncoding, Aurora Kinase B, Aurora Kinases, Cell Cycle/physiology, Cell Line, Chromatin/*metabolism, Chromosomal Proteins, Chromosomes/genetics/*metabolism, Enzyme Activation, Enzyme Inhibitors/metabolism, Female, Indoles/metabolism, Male, Mediator Complex, Models, Molecular, Non-Histone/genetics/metabol, Protein Phosphatase 1/antagonists \& inhibitors, Protein-Serine-Threonine Kinases/antagonists \& inh, {RNA} Interference, {RNA}/genetics/*metabolism, Sulfonamides/metabolism, Transcription Factors/genetics/metabolism, Transgenes, Untranslated/genetics/*metabolism}
}

@article{dreszer_biased_2007,
	title = {Biased clustered substitutions in the human genome: the footprints of male-driven biased gene conversion},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17785536},
	doi = {10.1101/gr.6395807},
	abstract = {We examined fixed substitutions in the human lineage since divergence from the common ancestor with the chimpanzee, and determined what fraction are {AT} to {GC} (weak-to-strong). Substitutions that are densely clustered on the chromosomes show a remarkable excess of weak-to-strong "biased" substitutions. These unexpected biased clustered substitutions ({UBCS}) are common near the telomeres of all autosomes but not the sex chromosomes. Regions of extreme bias are enriched for genes. Human and chimp orthologous regions show a striking similarity in the shape and magnitude of their respective {UBCS} maps, suggesting a relatively stable force leads to clustered bias. The strong and stable signal near telomeres may have participated in the evolution of isochores. One exception to the {UBCS} pattern found in all autosomes is chromosome 2, which shows a {UBCS} peak midchromosome, mapping to the fusion site of two ancestral chromosomes. This provides evidence that the fusion occurred as recently as 740,000 years ago and no more than approximately 3 million years ago. No biased clustering was found in {SNPs}, suggesting that clusters of biased substitutions are selected from mutations. {UBCS} is strongly correlated with male (and not female) recombination rates, which explains the lack of {UBCS} signal on chromosome X. These observations support the hypothesis that biased gene conversion ({BGC}), specifically in the male germline, played a significant role in the evolution of the human genome.},
	pages = {1420--1430},
	number = {10},
	journaltitle = {Genome Res},
	author = {Dreszer, T R and Wall, G D and Haussler, D and Pollard, K S},
	date = {2007},
	pmid = {17785536},
	keywords = {Human, Animals, Genetic, Humans, *Genome, *Gene Conversion, Chromosomes, Evolution, Female, Gene Fusion, Male, Models, Molecular, Pair 2/genetics, Pan troglodytes/genetics, Polymorphism, Recombination, Sex Characteristics, Single Nucleotide, Species Specificity, Telomere/genetics, Time Factors, X/genetics, Y/genetics}
}

@article{lai_activating_2013,
	title = {Activating {RNAs} associate with Mediator to enhance chromatin architecture and transcription},
	volume = {494},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23417068},
	doi = {10.1038/nature11884},
	abstract = {Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding {RNAs} ({lncRNAs}) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of {lncRNAs} may have varied biological functions. We and others have identified a class of {lncRNAs}, termed {ncRNA}-activating ({ncRNA}-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like {RNAs} function, we depleted factors with known roles in transcriptional activation and assessed their role in {RNA}-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the {ncRNA}-induced activation of transcription in a heterologous reporter assay using human {HEK}293 cells. In vivo, Mediator is recruited to {ncRNA}-a target genes and regulates their expression. We show that {ncRNA}-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating {ncRNAs}. Chromosome conformation capture confirmed the presence of {DNA} looping between the {ncRNA}-a loci and its targets. Importantly, depletion of Mediator subunits or {ncRNA}-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating {ncRNAs} and highlight the importance of Mediator and activating {ncRNA} association in human disease.},
	pages = {497--501},
	number = {7438},
	journaltitle = {Nature},
	author = {Lai, F and Orom, U A and Cesaroni, M and Beringer, M and Taatjes, D J and Blobel, G A and Shiekhattar, R},
	date = {2013},
	pmid = {23417068},
	keywords = {Humans, {RNA}, *Transcription, Genetic/genetics, Agenesis of Corpus Callosum/genetics, Anus, Chromatin/chemistry/*genetics/*metabolism, Constipation/genetics, Gene Knockdown Techniques, Genes, Imperforate/genetics, Long Noncoding/*genetics/*metabolism, Mediator Complex/chemistry/deficiency/genetics/*me, Mental Retardation, Molecular Conformation, Muscle Hypotonia/congenital/genetics, Protein Subunits/genetics/metabolism, Reporter/genetics, {RNA}-Binding Proteins/chemistry/genetics/metabolism, X-Linked/genetics}
}

@article{bassik_rapid_2009,
	title = {Rapid creation and quantitative monitoring of high coverage {shRNA} libraries},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19448642},
	doi = {10.1038/nmeth.1330},
	abstract = {Short hairpin {RNA} libraries are limited by low efficacy of many {shRNAs} and by off-target effects, which give rise to false negatives and false positives, respectively. Here we present a strategy for rapidly creating expanded {shRNA} pools (approximately 30 {shRNAs} per gene) that are analyzed by deep sequencing ({EXPAND}). This approach enables identification of multiple effective target-specific {shRNAs} from a complex pool, allowing a rigorous statistical evaluation of true hits.},
	pages = {443--445},
	number = {6},
	journaltitle = {Nat Methods},
	author = {Bassik, M C and Lebbink, R J and Churchman, L S and Ingolia, N T and Patena, W and {LeProust}, E M and Schuldiner, M and Weissman, J S and {McManus}, M T},
	date = {2009},
	pmid = {19448642},
	keywords = {Sequence Analysis, Base Sequence, Humans, {RNA}, *Gene Library, Messenger/*genetics, Molecular Sequence Data, Polymerase Chain Reaction/*methods, {RNA}/*methods}
}

@article{chen_jund_2008,
	title = {{JunD} represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18562690},
	doi = {10.1091/mbc.E08-02-0175},
	abstract = {The {AP}-1 transcription factor {JunD} is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction ({TJ}) protein zonula occludens ({ZO})-1 links the intracellular domain of {TJ}-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the {TJ} complex. Here, we show that {JunD} negatively regulates expression of {ZO}-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased {JunD} levels by ectopic overexpression of the {junD} gene or by depleting cellular polyamines repressed {ZO}-1 expression and increased epithelial paracellular permeability. {JunD} regulated {ZO}-1 expression at the levels of transcription and translation. Transcriptional repression of {ZO}-1 by {JunD} was mediated through {cAMP} response element-binding protein-binding site within its proximal region of the {ZO}-1-promoter, whereas induced {JunD} inhibited {ZO}-1 {mRNA} translation by enhancing the interaction of the {ZO}-1 3'-untranslated region with {RNA}-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that {JunD} is a biological suppressor of {ZO}-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.},
	pages = {3701--3712},
	number = {9},
	journaltitle = {Mol Biol Cell},
	author = {Chen, J and Xiao, L and Rao, J N and Zou, T and Liu, L and Bellavance, E and Gorospe, M and Wang, J Y},
	date = {2008},
	pmid = {18562690},
	keywords = {Genetic, Humans, Binding Sites, Protein Binding, *Transcription, *Protein Biosynthesis, Cell Line, Colonic Neoplasms/metabolism, Cyclic {AMP}/metabolism, Epithelial Cells/metabolism, Epithelium/*metabolism, Gene Deletion, Membrane Proteins/metabolism/*physiology, Phosphoproteins/metabolism/*physiology, Polyamines/metabolism, Tight Junctions, Transcription Factor {AP}-1/*metabolism, Tumor, Zonula Occludens-1 Protein}
}

@article{johnson_rest_2008,
	title = {{REST} regulates distinct transcriptional networks in embryonic and neural stem cells},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18959480},
	doi = {10.1371/journal.pbio.0060256},
	abstract = {The maintenance of pluripotency and specification of cellular lineages during embryonic development are controlled by transcriptional regulatory networks, which coordinate specific sets of genes through both activation and repression. The transcriptional repressor {RE}1-silencing transcription factor ({REST}) plays important but distinct regulatory roles in embryonic ({ESC}) and neural ({NSC}) stem cells. We investigated how these distinct biological roles are effected at a genomic level. We present integrated, comparative genome- and transcriptome-wide analyses of transcriptional networks governed by {REST} in mouse {ESC} and {NSC}. The {REST} recruitment profile has dual components: a developmentally independent core that is common to {ESC}, {NSC}, and differentiated cells; and a large, {ESC}-specific set of target genes. In {ESC}, the {REST} regulatory network is highly integrated into that of pluripotency factors Oct4-Sox2-Nanog. We propose that an extensive, pluripotency-specific recruitment profile lends {REST} a key role in the maintenance of the {ESC} phenotype.},
	pages = {e256},
	number = {10},
	journaltitle = {{PLoS} Biol},
	author = {Johnson, R and Teh, C H and Kunarso, G and Wong, K Y and Srinivasan, G and Cooper, M L and Volta, M and Chan, S S and Lipovich, L and Pollard, S M and Karuturi, R K and Wei, C L and Buckley, N J and Stanton, L W},
	date = {2008},
	pmid = {18959480},
	keywords = {Animals, Mice, Binding Sites, Gene Expression Regulation, Oligonucleotide Array Sequence Analysis, *Gene Regulatory Networks, Cell Differentiation/genetics/physiology, Cell Line, Chromatin Immunoprecipitation, Developmental, Embryonic Stem Cells/cytology/*metabolism, Fibroblasts/cytology/metabolism, Neurons/cytology/*metabolism, {NIH} 3T3 Cells, Repressor Proteins/genetics/metabolism/*physiology, Stem Cells/cytology/*metabolism}
}

@article{brar_high-resolution_2012,
	title = {High-resolution view of the yeast meiotic program revealed by ribosome profiling},
	volume = {335},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22194413},
	doi = {10.1126/science.1215110},
	abstract = {Meiosis is a complex developmental process that generates haploid cells from diploid progenitors. We measured messenger {RNA} ({mRNA}) abundance and protein production through the yeast meiotic sporulation program and found strong, stage-specific expression for most genes, achieved through control of both {mRNA} levels and translational efficiency. Monitoring of protein production timing revealed uncharacterized recombination factors and extensive organellar remodeling. Meiotic translation is also shifted toward noncanonical sites, including short open reading frames ({ORFs}) on unannnotated transcripts and upstream regions of known transcripts ({uORFs}). Ribosome occupancy at near-cognate {uORFs} was associated with more efficient {ORF} translation; by contrast, some {AUG} {uORFs}, often exposed by regulated 5' leader extensions, acted competitively. This work reveals pervasive translational control in meiosis and helps to illuminate the molecular basis of the broad restructuring of meiotic cells.},
	pages = {552--557},
	number = {6068},
	journaltitle = {Science},
	author = {Brar, G A and Yassour, M and Friedman, N and Regev, A and Ingolia, N T and Weissman, J S},
	date = {2012},
	pmid = {22194413},
	keywords = {{RNA}, Gene Expression Profiling, Open Reading Frames, *Gene Expression Regulation, *Meiosis, *Protein Biosynthesis, 5' Untranslated Regions, Fungal, Fungal/genetics/metabolism, Fungal/physiology, High-Throughput Nucleotide Sequencing, Messenger/genetics/metabolism, Ribosomes/*metabolism, Saccharomyces cerevisiae Proteins/*biosynthesis/ge, Saccharomyces cerevisiae/cytology/*genetics/*physi, Spores}
}

@article{brawand_evolution_2011,
	title = {The evolution of gene expression levels in mammalian organs},
	volume = {478},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22012392},
	doi = {10.1038/nature10532},
	abstract = {Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated {RNA} from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.},
	pages = {343--348},
	number = {7369},
	journaltitle = {Nature},
	author = {Brawand, D and Soumillon, M and Necsulea, A and Julien, P and Csardi, G and Harrigan, P and Weier, M and Liechti, A and Aximu-Petri, A and Kircher, M and Albert, F W and Zeller, U and Khaitovich, P and Grutzner, F and Bergmann, S and Nielsen, R and Paabo, S and Kaessmann, H},
	date = {2011},
	pmid = {22012392},
	keywords = {Animals, Humans, {RNA}, *Evolution, *Gene Expression Profiling, Messenger/*genetics, Molecular, Phylogeny, Principal Component Analysis, X Chromosome/genetics}
}

@article{sela_comparative_2007,
	title = {Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17594509},
	doi = {10.1186/gb-2007-8-6-r127},
	abstract = {{BACKGROUND}: Transposed elements ({TEs}) have a substantial impact on mammalian evolution and are involved in numerous genetic diseases. We compared the impact of {TEs} on the human transcriptome and the mouse transcriptome. {RESULTS}: We compiled a dataset of all {TEs} in the human and mouse genomes, identifying 3,932,058 and 3,122,416 {TEs}, respectively. We than extracted {TEs} located within human and mouse genes and, surprisingly, we found that 60\% of {TEs} in both human and mouse are located in intronic sequences, even though introns comprise only 24\% of the human genome. All {TE} families in both human and mouse can exonize. {TE} families that are shared between human and mouse exhibit the same percentage of {TE} exonization in the two species, but the exonization level of Alu, a primate-specific retroelement, is significantly greater than that of other {TEs} within the human genome, leading to a higher level of {TE} exonization in human than in mouse (1,824 exons compared with 506 exons, respectively). We detected a primate-specific mechanism for intron gain, in which Alu insertion into an exon creates a new intron located in the 3' untranslated region (termed 'intronization'). Finally, the insertion of {TEs} into the first and last exons of a gene is more frequent in human than in mouse, leading to longer exons in human. {CONCLUSION}: Our findings reveal many effects of {TEs} on these two transcriptomes. These effects are substantially greater in human than in mouse, which is due to the presence of Alu elements in human.},
	pages = {R127},
	number = {6},
	journaltitle = {Genome Biol},
	author = {Sela, N and Mersch, B and Gal-Mark, N and Lev-Maor, G and Hotz-Wagenblatt, A and Ast, G},
	date = {2007},
	pmid = {17594509},
	keywords = {Animals, Base Sequence, Humans, Mice, Exons, Gene Expression Profiling, Introns, *Alu Elements, *{DNA} Transposable Elements, *Gene Expression Profiling, Alternative Splicing, {DNA} Transposable Elements, Molecular Sequence Data, Sequence Alignment, Alu Elements},
	file = {Full Text:/home/jlagarde/Zotero/storage/UZRMQMWX/Sela et al. - 2007 - Comparative analysis of transposed element inserti.pdf:application/pdf}
}

@article{ost_laparoscopic_2005,
	title = {Laparoscopic pyeloplasty versus antegrade endopyelotomy: comparison in 100 patients and a new algorithm for the minimally invasive treatment of ureteropelvic junction obstruction},
	volume = {66},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16194707},
	doi = {10.1016/j.urology.2005.06.115},
	abstract = {The aim of this article is to assess the treatment efficacy of percutaneous endopyelotomy and laparoscopic pyeloplasty to establish a new algorithm in the minimally invasive treatment of ureteropelvic junction obstruction ({UPJO}). Hospital records, office charts, and radiographic studies of patients with {UPJO} treated either endoscopically (n = 50), laparoscopically (n = 50), or by endopyeloplasty (n = 5) were reviewed. All percutaneous endopyelotomies were performed with a cold hook-knife technique, and all laparoscopic pyeloplasties were performed transperitoneally using an Anderson-Hynes dismembered anastomosis. Successful outcomes were defined as relief of obstruction as quantified by diuretic renal scans and/or relief of obstructive symptoms. All patients were followed for an average of 16.0 months (range, 2 to 42 months). In the endoscopically treated group, the average age was 44.6 +/- 15.6 years, estimated blood loss ({EBL}) was 152.1 +/- 112.8 {mL}, and the hospital stay was 2.5 +/- 1.0 days. There was no significant change from preoperative to postoperative creatinine (1.2 +/- 0.7 mg/{dL} to 1.2 +/- 0.7 [106 +/- 62 micromol/L +/- 106 +/- 62 micromol/L]). Success rates included 92\% (35 of 38) for primary percutaneous antegrade endopyelotomy and 58\% (7 of 12) for secondary percutaneous antegrade endopyelotomy. All of the primary percutaneous antegrade endopyelotomy failures (n = 3) had either grade 3 or grade 4 hydronephrosis. In the laparoscopic pyeloplasty group the average age was 37.9 +/- 14.8 years, {EBL} was 108.3 +/- 109.4 {mL}, and the average hospital stay was 2.6 +/- 0.9 days. There was no significant change from preoperative to postoperative creatinine (1.1 +/- 0.4 mg/{dL} to 1.0 +/- 0.4 mg/{dL} [97 +/- 35 micromol/L to 97 +/- 35 micromol/L]). Success rates included 100\% (29 of 29) for primary repair and 95.2\% (20 of 21) for secondary repair. There was no statistical difference in preoperative patient parameters or objective outcomes when comparing primary endopyelotomy and primary laparoscopic pyeloplasty. In skilled hands, highly successful outcomes can be expected when either antegrade endopyelotomy or laparoscopic pyeloplasty is used to treat a primary {UPJO}. In the instance of a {UPJO} associated with a high degree of hydronephrosis, patients may be better served with a laparoscopic pyeloplasty. To maximize an efficacious outcome, minimally invasive {UPJO} treatment decisions should be based on patient and surgeon preference, as directed by the presented algorithm.},
	pages = {47--51},
	number = {5},
	journaltitle = {Urology},
	author = {Ost, M C and Kaye, J D and Guttman, M J and Lee, B R and Smith, A D},
	date = {2005},
	pmid = {16194707},
	keywords = {Humans, *Algorithms, *Laparoscopy, *Ureteroscopy, Adult, Female, Kidney Pelvis/*surgery, Male, Ureteral Obstruction/*surgery, Urologic Surgical Procedures/methods}
}

@article{pierini_asc_2013,
	title = {{ASC} Controls {IFN}-gamma Levels in an {IL}-18-Dependent Manner in Caspase-1-Deficient Mice Infected with Francisella novicida},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23975862},
	doi = {10.4049/jimmunol.1203326},
	abstract = {The inflammasome is a signaling platform that is central to the innate immune responses to bacterial infections. Francisella tularensis is a bacterium replicating within the host cytosol. During F. tularensis subspecies novicida infection, {AIM}2, an inflammasome receptor sensing cytosolic {DNA}, activates caspase-1 in an {ASC}-dependent manner, leading to both pyroptosis and release of the proinflammatory cytokines {IL}-1beta and {IL}-18. Activation of this canonical inflammasome pathway is key to limit F. novicida infection. In this study, by comparing the immune responses of {AIM}2 knockout ({KO}), {ASCKO}, and Casp1KO mice in response to F. novicida infection, we observed that {IFN}-gamma levels in the serum of Casp1KO mice were much higher than the levels observed in {AIM}2KO and {ASCKO} mice. This difference in {IFN}-gamma production was due to a large production of {IFN}-gamma by {NK} cells in Casp1KO mice that was not observed in {ASCKO} mice. The deficit in {IFN}-gamma production observed in {ASCKO} mice was not due to a reduced Dock2 expression or to an intrinsic defect of {ASCKO} {NK} cells. We demonstrate that in infected Casp1KO mice, {IFN}-gamma production is due to an {ASC}-dependent caspase-1-independent pathway generating {IL}-18. Furthermore, we present in vitro data suggesting that the recently described {AIM}2/{ASC}/caspase-8 noncanonical pathway is responsible for the caspase-1-independent {IL}-18 releasing activity. To our knowledge, this study is the first in vivo evidence of an alternative pathway able to generate in a caspase-1-independent pathway bioactive {IL}-18 to boost the production of {IFN}-gamma, a cytokine critical for the host antibacterial response.},
	journaltitle = {J Immunol},
	author = {Pierini, R and Perret, M and Djebali, S and Juruj, C and Michallet, M C and Forster, I and Marvel, J and Walzer, T and Henry, T},
	date = {2013},
	pmid = {23975862}
}

@article{fatica_micrornas_2006,
	title = {{MicroRNAs} and hematopoietic differentiation},
	volume = {71},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17381298},
	doi = {10.1101/sqb.2006.71.014},
	abstract = {The discovery of {microRNAS} ({miRNAs}) and of their mechanism of action has provided some very new clues on how gene expression is regulated. These studies established new concepts on how posttranscriptional control can fine-tune gene expression during differentiation and allowed the identification of new regulatory circuitries as well as factors involved therein. Because of the wealth of information available about the transcriptional and cellular networks involved in hematopoietic differentiation, the hematopoietic system is ideal for studying cell lineage specification. An interesting interplay between {miRNAs} and lineage-specific transcriptional factors has been found, and this can help us to understand how terminal differentiation is accomplished.},
	pages = {205--210},
	journaltitle = {Cold Spring Harb Symp Quant Biol},
	author = {Fatica, A and Rosa, A and Fazi, F and Ballarino, M and Morlando, M and De Angelis, F G and Caffarelli, E and Nervi, C and Bozzoni, I},
	date = {2006},
	pmid = {17381298},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Transcription Factors/metabolism, Biological, Cell Differentiation/genetics/physiology, Developmental, Hematopoiesis/*genetics/*physiology, Leukemia/genetics/metabolism, {MicroRNAs}/*genetics/*metabolism, Models, Neoplasm/genetics/metabolism}
}

@article{marin-bejar_pint_2013,
	title = {Pint {lincRNA} connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24070194},
	doi = {10.1186/gb-2013-14-9-r104},
	abstract = {{BACKGROUND}: The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding {RNAs} ({lincRNAs}). However, relatively little is known about the role that {lincRNAs} play in this pathway. {RESULTS}: Here we characterize a {lincRNA} named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed {lincRNA} that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the {TGF}-beta, {MAPK} and p53 pathways. Pint is a nuclear {lincRNA} that directly interacts with the Polycomb repressive complex 2 ({PRC}2), and is required for {PRC}2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on {PRC}2 expression. We have also identified Pint human ortholog ({PINT}), which presents suggestive analogies with the murine {lincRNA}. {PINT} is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, {PINT} is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. {CONCLUSIONS}: Our results reveal a p53 autoregulatory negative mechanism where a {lincRNA} connects p53 activation with epigenetic silencing by {PRC}2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate {lincRNA}.},
	pages = {R104},
	number = {9},
	journaltitle = {Genome Biol},
	author = {Marin-Bejar, O and Marchese, F P and Athie, A and Sanchez, Y and Gonzalez, J and Segura, V and Huang, L and Moreno, I and Navarro, A and Monzo, M and Garcia-Foncillas, J and Rinn, J L and Guo, S and Huarte, M},
	date = {2013},
	pmid = {24070194}
}

@article{amaldi_expression_1989,
	title = {Expression of ribosomal protein genes and regulation of ribosome biosynthesis in Xenopus development},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2672437},
	abstract = {Studies on ribosome biosynthesis in developing Xenopus oocytes and embryos, and after microinjection of cloned ribosomal-protein genes, have revealed that the synthesis of ribosomal proteins (r-proteins) is controlled by two types of regulation: (1) a post-transcriptional regulation, operated by feedback of the r-proteins themselves, controls processing and stability of r-protein transcripts and thus the amount of the corresponding {mRNA} present in the cell; and (2) a translational regulation controls the efficiency of utilization of r-protein {mRNA} (rp-{mRNA}) in response to the cellular needs for new ribosomes.},
	pages = {175--178},
	number = {5},
	journaltitle = {Trends Biochem Sci},
	author = {Amaldi, F and Bozzoni, I and Beccari, E and Pierandrei-Amaldi, P},
	date = {1989},
	pmid = {2672437},
	keywords = {Animals, Ribosomal Proteins/*biosynthesis, Ribosomes/*metabolism, Xenopus/*genetics}
}

@article{li_efficient_2015,
	title = {Efficient inversions and duplications of mammalian regulatory {DNA} elements and gene clusters by {CRISPR}/Cas9},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25757625},
	doi = {10.1093/jmcb/mjv016},
	abstract = {The human genome contains millions of {DNA} regulatory elements and a large number of gene clusters, most of which have not been tested experimentally. The clustered regularly interspaced short palindromic repeats ({CRISPR})/{CRISPR}-associated nuclease 9 (Cas9) programed with a synthetic single-guide {RNA} ({sgRNA}) emerges as a method for genome editing in virtually any organisms. Here we report that targeted {DNA} fragment inversions and duplications could easily be achieved in human and mouse genomes by {CRISPR} with two {sgRNAs}. Specifically, we found that, in cultured human cells and mice, efficient precise inversions of {DNA} fragments ranging in size from a few tens of bp to hundreds of kb could be generated. In addition, {DNA} fragment duplications and deletions could also be generated by {CRISPR} through trans-allelic recombination between the Cas9-induced double-strand breaks ({DSBs}) on two homologous chromosomes (chromatids). Moreover, junctions of combinatorial inversions and duplications of the protocadherin (Pcdh) gene clusters induced by Cas9 with four {sgRNAs} could be detected. In mice, we obtained founders with alleles of precise inversions, duplications, and deletions of {DNA} fragments of variable sizes by {CRISPR}. Interestingly, we found that very efficient inversions were mediated by microhomology-mediated end joining ({MMEJ}) through short inverted repeats. We showed for the first time that {DNA} fragment inversions could be transmitted through germlines in mice. Finally, we applied this {CRISPR} method to a regulatory element of the Pcdhalpha cluster and found a new role in the regulation of members of the Pcdhgamma cluster. This simple and efficient method should be useful in manipulating mammalian genomes to study millions of regulatory {DNA} elements as well as vast numbers of gene clusters.},
	pages = {284--298},
	number = {4},
	journaltitle = {J Mol Cell Biol},
	author = {Li, J and Shou, J and Guo, Y and Tang, Y and Wu, Y and Jia, Z and Zhai, Y and Chen, Z and Xu, Q and Wu, Q},
	date = {2015},
	pmid = {25757625}
}

@article{ulitsky_pathway_2007,
	title = {Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17437029},
	doi = {10.1038/msb4100144},
	abstract = {The biological interpretation of genetic interactions is a major challenge. Recently, Kelley and Ideker proposed a method to analyze together genetic and physical networks, which explains many of the known genetic interactions as linking different pathways in the physical network. Here, we extend this method and devise novel analytic tools for interpreting genetic interactions in a physical context. Applying these tools on a large-scale Saccharomyces cerevisiae data set, our analysis reveals 140 between-pathway models that explain 3765 genetic interactions, roughly doubling those that were previously explained. Model genes tend to have short {mRNA} half-lives and many phosphorylation sites, suggesting that their stringent regulation is linked to pathway redundancy. We also identify 'pivot' proteins that have many physical interactions with both pathways in our models, and show that pivots tend to be essential and highly conserved. Our analysis of models and pivots sheds light on the organization of the cellular machinery as well as on the roles of individual proteins.},
	pages = {104},
	journaltitle = {Mol Syst Biol},
	author = {Ulitsky, I and Shamir, R},
	date = {2007},
	pmid = {17437029},
	keywords = {{RNA}, Messenger/genetics, Half-Life, Saccharomyces cerevisiae Proteins/genetics/*metabo, Saccharomyces cerevisiae/genetics/*metabolism}
}

@article{bozzoni_expression_1984,
	title = {Expression of two Xenopus laevis ribosomal protein genes in injected frog oocytes. A specific splicing block interferes with the L1 {RNA} maturation},
	volume = {180},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6084725},
	abstract = {The expression of two Xenopus laevis ribosomal protein genes (L1 and L14) has been analysed by microinjection of the cloned genomic sequences into frog oocyte nuclei. While the injection of the L14 gene causes the accumulation of the corresponding protein in large excess with respect to that synthesized endogenously, the L1 gene does not. Analysis of the {RNA} shows that both genes are actively transcribed. The seven-intron-containing L14 transcript is completely processed to a mature form, while two out of nine intron sequences persist in the L1 transcript. This precursor {RNA} is confined to the nucleus; its accumulation is due to a specific block of splicing operating at the level of two defined introns and not to saturation of the processing apparatus of the oocyte. The different behaviour of the two genes may reflect different mechanisms of regulation which, in the case of the L1 gene, could operate at the level of splicing.},
	pages = {987--1005},
	number = {4},
	journaltitle = {J Mol Biol},
	author = {Bozzoni, I and Fragapane, P and Annesi, F and Pierandrei-Amaldi, P and Amaldi, F and Beccari, E},
	date = {1984},
	pmid = {6084725},
	keywords = {Animals, Base Sequence, Genetic, {RNA} Splicing, Transcription, Gene Expression Regulation, *{RNA} Processing, Cloning, Dna, Electron, Electrophoresis, Microscopy, Molecular, Nucleic Acid Hybridization, Polyacrylamide Gel, Post-Transcriptional, Protein Biosynthesis, Ribosomal Proteins/*genetics, {RNA}/*metabolism, Xenopus laevis}
}

@article{johnson_identification_2006,
	title = {Identification of the {REST} regulon reveals extensive transposable element-mediated binding site duplication},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16899447},
	doi = {10.1093/nar/gkl525},
	abstract = {The genome-wide mapping of gene-regulatory motifs remains a major goal that will facilitate the modelling of gene-regulatory networks and their evolution. The repressor element 1 is a long, conserved transcription factor-binding site which recruits the transcriptional repressor {REST} to numerous neuron-specific target genes. {REST} plays important roles in multiple biological processes and disease states. To map {RE}1 sites and target genes, we created a position specific scoring matrix representing the {RE}1 and used it to search the human and mouse genomes. We identified 1301 and 997 {RE}1s inhuman and mouse genomes, respectively, of which {\textbackslash}textgreater40\% are novel. By employing an ontological analysis we show that {REST} target genes are significantly enriched in a number of functional classes. Taking the novel {REST} target gene {CACNA}1A as an experimental model, we show that it can be regulated by multiple {RE}1s of different binding affinities, which are only partially conserved between human and mouse. A novel {BLAST} methodology indicated that many {RE}1s belong to closely related families. Most of these sequences are associated with transposable elements, leading us to propose that transposon-mediated duplication and insertion of {RE}1s has led to the acquisition of novel target genes by {REST} during evolution.},
	pages = {3862--3877},
	number = {14},
	journaltitle = {Nucleic Acids Res},
	author = {Johnson, R and Gamblin, R J and Ooi, L and Bruce, A W and Donaldson, I J and Westhead, D R and Wood, I C and Jackson, R M and Buckley, N J},
	date = {2006},
	pmid = {16899447},
	keywords = {Genomics/*methods, Animals, Humans, Mice, Binding Sites, Gene Expression Regulation, Introns, *Regulatory Elements, *Regulon, *Retroelements, Calcium Channels, Calcium Channels/genetics, Evolution, {HeLa} Cells, Molecular, Mutation, P-Type/genetics, Q-Type/genetics, Repressor Proteins/*metabolism, Transcription Factors/*metabolism, Transcriptional}
}

@article{visel_vista_2007,
	title = {{VISTA} Enhancer Browser–a database of tissue-specific human enhancers},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17130149},
	doi = {10.1093/nar/gkl822},
	abstract = {Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This paucity of enhancer collections with defined activities has thus hindered computational approaches for the genome-wide prediction of enhancers and their functions. To fill this void, we utilize comparative genome analysis to identify candidate enhancer elements in the human genome coupled with the experimental determination of their in vivo enhancer activity in transgenic mice [L. A. Pennacchio et al. (2006) Nature, in press]. These data are available through the {VISTA} Enhancer Browser (http://enhancer.lbl.gov). This growing database currently contains over 250 experimentally tested {DNA} fragments, of which more than 100 have been validated as tissue-specific enhancers. For each positive enhancer, we provide digital images of whole-mount embryo staining at embryonic day 11.5 and an anatomical description of the reporter gene expression pattern. Users can retrieve elements near single genes of interest, search for enhancers that target reporter gene expression to a particular tissue, or download entire collections of enhancers with a defined tissue specificity or conservation depth. These experimentally validated training sets are expected to provide a basis for a wide range of downstream computational and functional studies of enhancer function.},
	pages = {D88--92},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Visel, A and Minovitsky, S and Dubchak, I and Pennacchio, L A},
	date = {2007},
	pmid = {17130149},
	keywords = {Human, Genomics, Animals, Genetic, Genome, Humans, Mice, Computational Biology, Nucleic Acid, *Databases, *Enhancer Elements, Embryo, Gene Expression, Internet, Mammalian/metabolism, User-Computer Interface}
}

@article{lee_coding_2011,
	title = {Coding region: the neglected post-transcriptional code},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21289484},
	abstract = {The control of mammalian {mRNA} turnover and translation has been linked almost exclusively to specific cis-elements within the 5'- and 3'-untranslated regions ({UTRs}) of the mature {mRNA}. However, instances of regulated turnover and translation via cis-elements within the coding region ({CR}) of {mRNAs} are accumulating. Here, we describe the regulation of post-transcriptional fate through trans-binding factors ({RNA}-binding proteins and {microRNAs}) that function via {CR} sequences. We discuss how the {CR} enriches the post-transcriptional control of gene expression, and predict that new high-throughput technologies will enable a more mainstream study of {CR}-governed gene regulation.},
	pages = {44--48},
	number = {1},
	journaltitle = {{RNA} Biol},
	author = {Lee, E K and Gorospe, M},
	date = {2011},
	pmid = {21289484},
	keywords = {Gene Expression Regulation, *Open Reading Frames, *{RNA} Processing, *Untranslated Regions, Fragile X Mental Retardation Protein/metabolism, {MicroRNAs}/*metabolism, Post-Transcriptional, Ribosomes/genetics/metabolism, {RNA} Stability, {RNA}-Binding Proteins/metabolism, {RNA}-Induced Silencing Complex/metabolism}
}

@article{michienzi_u1_1996,
	title = {U1 small nuclear {RNA} chimeric ribozymes with substrate specificity for the Rev pre-{mRNA} of human immunodeficiency virus},
	volume = {93},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8692972},
	abstract = {The in vivo effectiveness of ribozymes strongly depends on the correct choice of the vector molecule. High levels of expression, stability, active conformation, and correct cellular localization are the most important features for a ribozyme vector. We have exploited the utilization of the U1 small nuclear {RNA} ({snRNA}) as a vector for specifically targeting a ribozyme into the nucleus. The Rev pre-{mRNA} of human immunodeficiency virus type 1 was chosen as target for testing the activity of the Ul-ribozyme. The catalytic core of the hammerhead motif, plus the recognition sequences, substituted the stem-loop {III} of the U1 {snRNA}. The resulting construct displays efficient cleavage activity in vitro. In addition, in the in vivo system of Xenopus laevis oocytes, the Ul-chimeric ribozyme accumulates in large amounts in the nucleus and produces a considerable reduction of Rev pre-{mRNA} levels. The Rev-specific ribozyme was also inserted in a derivative of the Ul {snRNA} mutated in the region of pairing with the 5' splice site, such as to match it with the suboptimal splice junction of the Rev precursor. This construct shows more efficient reduction of Rev pre-{mRNA} in vivo than the wild-type U1 vector.},
	pages = {7219--7224},
	number = {14},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Michienzi, A and Prislei, S and Bozzoni, I},
	date = {1996},
	pmid = {8692972},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, Transcription, Catalytic/biosynthesis/chemistry/*metabolism, Chimera, {DNA} Primers, Gene Products, {HIV}/*metabolism, Human Immunodeficiency Virus, Models, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Polymerase Chain Reaction, rev Gene Products, rev/*biosynthesis, {RNA} Precursors/*metabolism, Small Nuclear/biosynthesis/chemistry/*metabol, Structural, Substrate Specificity, Viral/*metabolism}
}

@article{masuda_global_2011,
	title = {Global dissociation of {HuR}-{mRNA} complexes promotes cell survival after ionizing radiation},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21317874},
	doi = {10.1038/emboj.2011.24},
	abstract = {Ionizing radiation ({IR}) triggers adaptive changes in gene expression. Here, we show that survival after {IR} strongly depends on the checkpoint kinase Chk2 acting upon its substrate {HuR}, an {RNA}-binding protein that stabilizes and/or modulates the translation of target {mRNAs}. Microarray analysis showed that in human {HCT}116 colorectal carcinoma cells ({WT}), {IR}-activated Chk2 triggered the dissociation of virtually all of {HuR}-bound {mRNAs}, since {IR} did not dissociate {HuR} target {mRNAs} in Chk2-null ({CHK}2-/-) {HCT}116 cells. Accordingly, several {HuR}-interacting {mRNAs} encoding apoptosis- and proliferation-related proteins ({TJP}1, Mdm2, {TP}53BP2, Bax, K-Ras) dissociated from {HuR} in {WT} cells, but remained bound and showed altered post-transcriptional regulation in {CHK}2-/- cells. Use of {HuR} mutants that were not phosphorylatable by Chk2 ({HuR}(3A)) and {HuR} mutants mimicking constitutive phosphorylation by Chk2 ({HuR}(3D)) revealed that dissociation of {HuR} target transcripts enhanced cell survival. We propose that the release of {HuR}-bound {mRNAs} via an {IR}-Chk2-{HuR} regulatory axis improves cell outcome following {IR}.},
	pages = {1040--1053},
	number = {6},
	journaltitle = {{EMBO} J},
	author = {Masuda, K and Abdelmohsen, K and Kim, M M and Srikantan, S and Lee, E K and Tominaga, K and Selimyan, R and Martindale, J L and Yang, X and Lehrmann, E and Zhang, Y and Becker, K G and Wang, J Y and Kim, H H and Gorospe, M},
	date = {2011},
	pmid = {21317874},
	keywords = {Humans, {RNA}, *Gene Expression Regulation, *Radiation, Antigens, Cell Line, Cell Survival, Checkpoint Kinase 2, Epithelial Cells/*radiation effects, Gene Knockout Techniques, Hu Paraneoplastic Encephalomyelitis Antigens, Ionizing, Messenger/*metabolism, Protein-Serine-Threonine Kinases/*metabolism, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism}
}

@article{kim_modification_2008,
	title = {Modification at {HuR}(S242) alters {HuR} localization and proliferative influence},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18948743},
	abstract = {{HuR} is predominantly nuclear but following exposure to stress and mitogens, it can translocate to the cytoplasm where it stabilizes target {mRNAs} and/or modulates their translation. Several phosphorylation sites in a central 'hinge" region of {HuR} have been reported to affect its nucleocytoplasmic shuttle: phosphorylation by {PKC} at serine (S)221 and by Cdk1 at S202. Here, we investigated if there are additional putative phosphorylation sites within the {HuR} hinge region capable of influencing its cytoplasmic abundance. We systematically mutated all seven serine residues within the shuttling hinge domain to the nonphosphorylatable residue alanine (A), S197A, S202A, S221A, S229A, S232A, S241A and S242A. Using {HeLa} cells as the study system, we found that the {HuR}(S242A) mutant was more abundant in the cytoplasm in both untreated cells and in cells treated with short-wavelength ultraviolet light or with an inhibitor of Cdk1. Conversely, mutation of S242 to aspartic acid (D), rendered the phosphomimetic {HuR}(S242D) nuclear under all treatment conditions. S242 mutations did not influence {HuR} stability, but {HuR}(S242A) showed increased association with target cyclin A2 and cyclin B1 {mRNAs}. Accordingly, expression of {HuR}(S242A) led to increased cyclin {mRNA} stability and heightened cell proliferation rates. Our findings suggest that {HuR} phosphorylation at S242 hinders its cytoplasmic localization, its function as a posttranscriptional regulator, and its proliferative influence.},
	pages = {3371--3377},
	number = {21},
	journaltitle = {Cell Cycle},
	author = {Kim, H H and Yang, X and Kuwano, Y and Gorospe, M},
	date = {2008},
	pmid = {18948743},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Amino Acid Sequence, Amino Acid Substitution, Cell Proliferation, Cyclins/genetics/metabolism, Cytoplasm/metabolism, {DNA} Mutational Analysis, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoproteins/chemistry, Messenger/genetics/metabolism, Molecular Sequence Data, Mutagenesis, Mutant Proteins/metabolism, Mutation/*genetics, Neoplastic, Protein Stability, Protein Transport, {RNA} Stability, Serine/*genetics}
}

@article{ghorecha_analysis_2014,
	title = {Analysis of biochemical variations and {microRNA} expression in wild ( Ipomoea campanulata ) and cultivated ( Jacquemontia pentantha ) species exposed to in vivo water stress},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24554839},
	doi = {10.1007/s12298-013-0207-1},
	abstract = {The current study analyses few important biochemical parameters and {microRNA} expression in two closely related species (wild but tolerant Ipomoea campanulata L. and cultivated but sensitive Jacquemontia pentantha Jacq.G.Don) exposed to water deficit conditions naturally occurring in the field. Under soil water deficit, both the species showed reduction in their leaf area and {SLA} as compared to well-watered condition. A greater decrease in chlorophyll was noticed in J. pentantha (∼50 \%) as compared to I. campanulata (20 \%) under stress. By contrast, anthocyanin and {MDA} accumulation was greater in J. pentantha as compared to I. campanulata. Multiple isoforms of superoxide dismutases ({SODs}) with differing activities were observed under stress in these two plant species. {CuZnSOD} isoforms showed comparatively higher induction (∼10-40 \%) in I. campanulata than J. pentantha. {MicroRNAs}, {miR}398, {miR}319, {miR}395 {miR}172, and {miR}408 showed opposing expression under water deficit in these two plant species. Expression of {miR}156, {miR}168, {miR}171, {miR}172, {miR}393, {miR}319, {miR}396, {miR}397 and {miR}408 from either I. campanulata or J. pentantha or both demonstrated opposite pattern of expression to that of drought stressed Arabidopsis. The better tolerance of the wild species (I. campanulata) to water deficit could be attributed to lesser variations in chlorophyll and anthocyanin levels; and relatively higher levels of {SODs} than J. pentantha. {miRNA} expression was different in I. campanulata than J. pentantha.},
	pages = {57--67},
	number = {1},
	journaltitle = {Physiol Mol Biol Plants},
	author = {Ghorecha, V and Patel, K and Ingle, S and Sunkar, R and Krishnayya, N S},
	date = {2014},
	pmid = {24554839}
}

@article{kabadi_multiplex_2014,
	title = {Multiplex {CRISPR}/Cas9-based genome engineering from a single lentiviral vector},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25122746},
	doi = {10.1093/nar/gku749},
	abstract = {Engineered {DNA}-binding proteins that manipulate the human genome and transcriptome have enabled rapid advances in biomedical research. In particular, the {RNA}-guided {CRISPR}/Cas9 system has recently been engineered to create site-specific double-strand breaks for genome editing or to direct targeted transcriptional regulation. A unique capability of the {CRISPR}/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide {RNAs} ({sgRNAs}) targeted to distinct genomic sites. This approach can be used to simultaneously create multiple {DNA} breaks or to target multiple transcriptional activators to a single promoter for synergistic enhancement of gene induction. To address the need for uniform and sustained delivery of multiplex {CRISPR}/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four {sgRNAs} from independent {RNA} polymerase {III} promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each {sgRNA} is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of {CRISPR}/Cas9-based multiplex genome engineering in diverse cell types.},
	pages = {e147},
	number = {19},
	journaltitle = {Nucleic Acids Res},
	author = {Kabadi, A M and Ousterout, D G and Hilton, I B and Gersbach, C A},
	date = {2014},
	pmid = {25122746},
	keywords = {Genome, Humans, {RNA}, Cells, Cultured, *Cell Engineering, *{CRISPR}-Cas Systems, *Genetic Vectors, {CRISPR}-Associated Proteins/*genetics/metabolism, {DNA}-Binding Proteins/*genetics/metabolism, Fibroblasts/metabolism, Guide/metabolism, {HEK}293 Cells, Lentivirus/*genetics, Trans-Activators/genetics, Transcriptional Activation}
}

@article{ishmael_human_2011,
	title = {The human glucocorticoid receptor as an {RNA}-binding protein: global analysis of glucocorticoid receptor-associated transcripts and identification of a target {RNA} motif},
	volume = {186},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21148795},
	doi = {10.4049/jimmunol.1001794},
	abstract = {Posttranscriptional regulation is emerging as a key factor in glucocorticoid ({GC})-mediated gene regulation. We investigated the role of the human {GC} receptor ({GR}) as an {RNA}-binding protein and its effect on {mRNA} turnover in human airway epithelial cells. Cell treatment with the potent {GC} budesonide accelerated the decay of {CCL}2 {mRNA} (t(1/2) = 8 +/- 1 min versus 62 +/- 17 min in {DMSO}-treated cells) and {CCL}7 {mRNA} (t(1/2) = 15 +/- 4 min versus 114 +/- 37 min), but not that of {CCL}5 {mRNA} (t(1/2)=231 +/- 8 min versus 266 +/- 5 min) in the {BEAS}-2B cell line. This effect was inhibited by preincubation with an anti-{GR} Ab, indicating that {GR} itself plays a role in the turnover of these transcripts. Coimmunoprecipitation and biotin pulldown experiments showed that {GR} associates with {CCL}2 and {CCL}7 {mRNAs}, but not {CCL}5 {mRNA}. These methods confirmed {CCL}2 {mRNA} targeting by {GR} in human primary airway epithelial cells. Association of the {GR} was localized to the 5' untranslated region of {CCL}2 {mRNA} and further mapped to nt 44-60. The collection of transcripts associated with {GR}, identified by immunoprecipitation of {GR}-{mRNA} complexes followed by microarray analysis, revealed 479 transcripts that associated with {GR}. Computational analysis of the primary sequence and secondary structures of these transcripts yielded a {GC}-rich motif, which was shown to bind to {GR} in vitro. This motif was used to predict binding of {GR} to an additional 7889 transcripts. These results indicate that cytoplasmic {GR} interacts with a subset of {mRNA} through specific sequences and can regulate turnover rates, suggesting a novel posttranscriptional role for {GR} as an {RNA}-binding protein.},
	pages = {1189--1198},
	number = {2},
	journaltitle = {J Immunol},
	author = {Ishmael, F T and Fang, X and Houser, K R and Pearce, K and Abdelmohsen, K and Zhan, M and Gorospe, M and Stellato, C},
	date = {2011},
	pmid = {21148795},
	keywords = {Humans, {RNA}, Transcription, Computational Biology, Oligonucleotide Array Sequence Analysis, *Drug Delivery Systems, Cell Line, Cell-Free System/immunology/metabolism, Chemokine {CCL}2/genetics/*metabolism, Chemokine {CCL}7/genetics/*metabolism, Cytoplasm/genetics/immunology/metabolism, Gene Expression Regulation/immunology, Genetic/*immunology, Glucocorticoid/*genetics/*metabolism, Messenger/genetics/*metabolism, Receptors, {RNA} Stability/genetics/immunology, {RNA}-Binding Proteins/genetics/*metabolism}
}

@article{zuker_mfold_2003,
	title = {Mfold web server for nucleic acid folding and hybridization prediction},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12824337},
	abstract = {The abbreviated name, 'mfold web server', describes a number of closely related software applications available on the World Wide Web ({WWW}) for the prediction of the secondary structure of single stranded nucleic acids. The objective of this web server is to provide easy access to {RNA} and {DNA} folding and hybridization software to the scientific community at large. By making use of universally available web {GUIs} (Graphical User Interfaces), the server circumvents the problem of portability of this software. Detailed output, in the form of structure plots with or without reliability information, single strand frequency plots and 'energy dot plots', are available for the folding of single sequences. A variety of 'bulk' servers give less information, but in a shorter time and for up to hundreds of sequences at once. The portal for the mfold web server is http://www.bioinfo.rpi.edu/applications/mfold. This {URL} will be referred to as '{MFOLDROOT}'.},
	pages = {3406--3415},
	number = {13},
	journaltitle = {Nucleic Acids Res},
	author = {Zuker, M},
	date = {2003},
	pmid = {12824337},
	keywords = {*Software, {DNA}, Base Sequence, Databases, Nucleic Acid, *Nucleic Acid Hybridization, Computer Graphics, {DNA}/*chemistry, Internet, Models, Molecular, Nucleic Acid Conformation, Nucleic Acid Denaturation, {RNA}/*chemistry, Single-Stranded/chemistry, Thermodynamics, User-Computer Interface}
}

@article{wang_evidence_2006,
	title = {Evidence of influence of genomic {DNA} sequence on human X chromosome inactivation},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16948528},
	doi = {10.1371/journal.pcbi.0020113},
	abstract = {A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the potential role of the X chromosome primary {DNA} sequence in determining a gene's X inactivation status is unclear. Using a combination of the X chromosome sequence and a comprehensive X inactivation profile of more than 600 genes, two independent yet complementary approaches were used to systematically investigate the relationship between X inactivation and {DNA} sequence features. First, statistical analyses revealed that a number of repeat features, including long interspersed nuclear element ({LINE}) and mammalian-wide interspersed repeat repetitive elements, are significantly enriched in regions surrounding transcription start sites of genes that are subject to inactivation, while Alu repetitive elements and short motifs containing {ACG}/{CGT} are significantly enriched in those that escape inactivation. Second, linear support vector machine classifiers constructed using primary {DNA} sequence features were used to correctly predict the X inactivation status for {\textbackslash}textgreater80\% of all X-linked genes. We further identified a small set of features that are important for accurate classification, among which {LINE}-1 and {LINE}-2 content show the greatest individual discriminatory power. Finally, as few as 12 features can be used for accurate support vector machine classification. Taken together, these results suggest that features of the underlying primary {DNA} sequence of the human X chromosome may influence the spreading and/or maintenance of X inactivation.},
	pages = {e113},
	number = {9},
	journaltitle = {{PLoS} Comput Biol},
	author = {Wang, Z and Willard, H F and Mukherjee, S and Furey, T S},
	date = {2006},
	pmid = {16948528},
	keywords = {Human, Base Sequence, Genetic, Genome, Humans, Transcription, Computational Biology, Genetic/genetics, Chromosomes, Human/*genetics, Probability, Selection, X Chromosome Inactivation/*genetics, X/*genetics}
}

@article{lal_posttranscriptional_2006,
	title = {Posttranscriptional derepression of {GADD}45alpha by genotoxic stress},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16600875},
	doi = {10.1016/j.molcel.2006.03.016},
	abstract = {The growth arrest- and {DNA} damage-inducible gene {GADD}45alpha is potently upregulated in response to stress stimuli. Here, two {RNA} binding proteins, the {mRNA} decay-promoting {AUF}1 and the translational suppressor {TIAR}, were found to interact specifically with the 3' untranslated region ({UTR}) of the {GADD}45alpha {mRNA} in {HeLa} cells. These associations were prominent in unstimulated cells, decreasing dramatically after treatment with the genotoxin methyl methanesulfonate ({MMS}). Analysis of both endogenous and chimeric {GADD}45alpha {mRNA} revealed that in untreated cells {AUF}1 strongly reduced {GADD}45alpha {mRNA} stability, whereas {TIAR} potently inhibited {GADD}45alpha translation. After genotoxic stress, {AUF}1 and {TIAR} dissociated from the {GADD}45alpha {mRNA}, thereby allowing coordinated elevations in both {GADD}45alpha {mRNA} half-life and translation rate, respectively. We propose that the posttranscriptional derepression of {GADD}45alpha critically contributes to its potent upregulation after {DNA} damage.},
	pages = {117--128},
	number = {1},
	journaltitle = {Mol Cell},
	author = {Lal, A and Abdelmohsen, K and Pullmann, R and Kawai, T and Galban, S and Yang, X and Brewer, G and Gorospe, M},
	date = {2006},
	pmid = {16600875},
	keywords = {Humans, *{RNA} Stability, 3' Untranslated Regions/*genetics/metabolism, Cell Cycle Proteins/antagonists \& inhibitors/*meta, {DNA} Damage/drug effects, Half-Life, {HeLa} Cells/drug effects/metabolism, Heterogeneous-Nuclear Ribonucleoprotein D/metaboli, Methyl Methanesulfonate/toxicity, Mutagens/toxicity, Nuclear Proteins/antagonists \& inhibitors/*metabol, Protein Biosynthesis, {RNA} 3' End Processing, {RNA}-Binding Proteins/metabolism}
}

@article{routray_carcinoma-associated_2013,
	title = {Carcinoma-associated fibroblasts, its implication in head and neck squamous cell carcinoma: a mini review},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23574536},
	doi = {10.1111/odi.12107},
	abstract = {The communication between tumor stromal and parenchymal cells provides an insight to tumor progression. One of the main elements of the stroma, a major contributor to the extracellular environment of tumors, is carcinoma-associated fibroblasts. They can originate from either normal fibroblasts in the immediate vicinity of the tumor or from circulating bone marrow-derived mesenchymal stem cells. These myofibroblasts can arise locally from an endothelial-mesenchymal transformation at the invasive edge of the cancer and are physically associated with carcinoma cells, that is, in the development of high-grade malignancies and poor prognosis. These carcinoma-associated fibroblasts feed the epithelial tumor cells in a host-parasite relationship establishing its role in head and neck squamous cell carcinoma progression.},
	journaltitle = {Oral Dis},
	author = {Routray, S and Sunkavali, A and Bari, K},
	date = {2013},
	pmid = {23574536}
}

@article{de_cabo_vitro_2003,
	title = {An in vitro model of caloric restriction},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12814798},
	abstract = {The mechanisms underlying the ability of caloric restriction ({CR}) to extend life span and enhance stress responsiveness remain elusive. Progress in this area has been slow due to the complexities of using animals for {CR} studies and assessing life span as the measure of {CR} effectiveness. It is therefore of great interest to develop in vitro models of {CR}. Here we use sera obtained from either Fisher 344 rats or Rhesus monkeys that were fed ad libitum ({AL}) or {CR} diets to culture various cell types. We show that treatment of cultured cells with {CR} sera caused reduced cell proliferation, enhanced tolerance to oxidants and heat, and heightened expression of stress-response genes. These phenotypic features mirror the effects of {CR} in animals. Supplementation of {CR} serum with insulin and insulin-like growth factor ({IGF})-1 partially restored the proliferative and stress-response phenotype that was seen in cells cultured with {AL} serum, indicating that reduced levels of insulin and {IGF}-1 likely contribute to the {CR}-related effects. This in vitro cell culture model recapitulates key in vivo proliferative and stress-response phenotypic features of {CR}, and further suggests that endocrine mechanisms contribute to the enhanced stress responsiveness observed in {CR} animals.},
	pages = {631--639},
	number = {6},
	journaltitle = {Exp Gerontol},
	author = {de Cabo, R and Furer-Galban, S and Anson, R M and Gilman, C and Gorospe, M and Lane, M A},
	date = {2003},
	pmid = {12814798},
	keywords = {Animals, Cultured, *Caloric Restriction, *Models, Biological, Cell Division/drug effects/physiology, Hepatocytes/cytology/drug effects/metabolism, {HSP}70 Heat-Shock Proteins/metabolism, Hydrogen Peroxide/pharmacology, Inbred F344, Insulin-Like Growth Factor I/pharmacology, Insulin/pharmacology, Longevity/*physiology, Macaca mulatta, Male, Oxidative Stress/drug effects/physiology, Rats, Tumor Cells}
}

@article{managadze_negative_2011,
	title = {Negative correlation between expression level and evolutionary rate of long intergenic noncoding {RNAs}},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22071789},
	doi = {10.1093/gbe/evr116},
	abstract = {Mammalian genomes contain numerous genes for long noncoding {RNAs} ({lncRNAs}). The functions of the {lncRNAs} remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the {lncRNA}, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic {ncRNAs} ({lincRNAs}) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse {lincRNA} genes. The magnitude of the correlation for the {lincRNAs} is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the {lincRNAs} is significantly and positively correlated with the predicted extent of {lincRNA} molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and {RNA} misfolding and/or other factors, for example, the number of interacting partners of the gene product.},
	pages = {1390--1404},
	journaltitle = {Genome Biol Evol},
	author = {Managadze, D and Rogozin, I B and Chernikova, D and Shabalina, S A and Koonin, E V},
	date = {2011},
	pmid = {22071789},
	keywords = {Sequence Analysis, Animals, Conserved Sequence, Humans, Mice, {RNA}, Gene Expression Regulation, Proteins/genetics, Exons, Mammals/*genetics, Untranslated/*genetics, *Evolution, Molecular, Sequence Alignment}
}

@article{chew_ribosome_2013,
	title = {Ribosome profiling reveals resemblance between long non-coding {RNAs} and 5' leaders of coding {RNAs}},
	volume = {140},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23698349},
	doi = {10.1242/dev.098343},
	abstract = {Large-scale genomics and computational approaches have identified thousands of putative long non-coding {RNAs} ({lncRNAs}). It has been controversial, however, as to what fraction of these {RNAs} is truly non-coding. Here, we combine ribosome profiling with a machine-learning approach to validate {lncRNAs} during zebrafish development in a high throughput manner. We find that dozens of proposed {lncRNAs} are protein-coding contaminants and that many {lncRNAs} have ribosome profiles that resemble the 5' leaders of coding {RNAs}. Analysis of ribosome profiling data from embryonic stem cells reveals similar properties for mammalian {lncRNAs}. These results clarify the annotation of developmental {lncRNAs} and suggest a potential role for translation in {lncRNA} regulation. In addition, our computational pipeline and ribosome profiling data provide a powerful resource for the identification of translated open reading frames during zebrafish development.},
	pages = {2828--2834},
	number = {13},
	journaltitle = {Development},
	author = {Chew, G L and Pauli, A and Rinn, J L and Regev, A and Schier, A F and Valen, E},
	date = {2013},
	pmid = {23698349},
	keywords = {Animals, {RNA}, Long Noncoding/*genetics, {RNA}/*genetics, Embryonic Development/genetics/physiology, Ribosomes/*genetics, Zebrafish/genetics/growth \& development}
}

@article{gallmeier_targeted_2006,
	title = {Targeted disruption of {FANCC} and {FANCG} in human cancer provides a preclinical model for specific therapeutic options},
	volume = {130},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16762635},
	doi = {10.1053/j.gastro.2006.03.016},
	abstract = {{BACKGROUND} \& {AIMS}: How specifically to treat pancreatic and other cancers harboring Fanconi anemia gene mutations has raised great interest recently, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. {METHODS}: We endogenously disrupted {FANCC} and {FANCG} in a human adenocarcinoma cell line and determined the impact of these genes on drug sensitivity, irradiation sensitivity, and genome maintenance. {RESULTS}: {FANCC} and {FANCG} disruption abrogated {FANCD}2 monoubiquitination, confirming an impaired Fanconi anemia pathway function. On treatment with {DNA} interstrand-cross-linking agents, {FANCC} and {FANCG} disruption caused increased clastogenic damage, G2/M arrest, and decreased proliferation. The extent of hypersensitivity varied among agents, with ratios of inhibitory concentration 50\% ranging from 2-fold for oxaliplatin to 14-fold for melphalan, a drug infrequently used in solid tumors. No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, {NU}1025, or hydrogen peroxide. {FANCC} and {FANCG} disruption also resulted in increased clastogenic damage on irradiation, but only {FANCG} disruption caused a subsequent decrease in relative survival. Finally, {FANCC} and {FANCG} disruption increased spontaneous chromosomal breakage, supporting the role of these genes in genome maintenance and likely explaining why they are mutated in sporadic cancer. {CONCLUSIONS}: Our human cancer cell model provides optimal controls to elucidate fundamental biologic features of individual Fanconi anemia gene defects and facilitates preclinical studies of therapeutic options. The impact of Fanconi gene defects on drug and irradiation sensitivity renders these genes promising targets for a specific, genotype-based therapy for individual cancer patients, providing a strong rationale for clinical trials.},
	pages = {2145--2154},
	number = {7},
	journaltitle = {Gastroenterology},
	author = {Gallmeier, E and Calhoun, E S and Rago, C and Brody, J R and Cunningham, S C and Hucl, T and Gorospe, M and Kohli, M and Lengauer, C and Kern, S E},
	date = {2006},
	pmid = {16762635},
	keywords = {Humans, Adenocarcinoma/drug therapy/*genetics, Alleles, Antineoplastic Agents/pharmacology, Blotting, Cell Line, Cell Proliferation/drug effects, Chromosome Breakage/*genetics, Fanconi Anemia Complementation Group C Protein/dru, Fanconi Anemia Complementation Group G Protein/dru, Immunoprecipitation, In Situ Hybridization, Karyotyping, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Tumor, Western}
}

@article{yang_decay_2003,
	title = {Decay rates of human {mRNAs}: correlation with functional characteristics and sequence attributes},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12902380},
	doi = {10.1101/gr.1272403},
	abstract = {Although {mRNA} decay rates are a key determinant of the steady-state concentration for any given {mRNA} species, relatively little is known, on a population level, about what factors influence turnover rates and how these rates are integrated into cellular decisions. We decided to measure {mRNA} decay rates in two human cell lines with high-density oligonucleotide arrays that enable the measurement of decay rates simultaneously for thousands of {mRNA} species. Using existing annotation and the Gene Ontology hierarchy of biological processes, we assign {mRNAs} to functional classes at various levels of resolution and compare the decay rate statistics between these classes. The results show statistically significant organizational principles in the variation of decay rates among functional classes. In particular, transcription factor {mRNAs} have increased average decay rates compared with other transcripts and are enriched in "fast-decaying" {mRNAs} with half-lives {\textbackslash}textless2 h. In contrast, we find that {mRNAs} for biosynthetic proteins have decreased average decay rates and are deficient in fast-decaying {mRNAs}. Our analysis of data from a previously published study of Saccharomyces cerevisiae {mRNA} decay shows the same functional organization of decay rates, implying that it is a general organizational scheme for eukaryotes. Additionally, we investigated the dependence of decay rates on sequence composition, that is, the presence or absence of short {mRNA} motifs in various regions of the {mRNA} transcript. Our analysis recovers the positive correlation of {mRNA} decay with known {AU}-rich {mRNA} motifs, but we also uncover further short {mRNA} motifs that show statistically significant correlation with decay. However, we also note that none of these motifs are strong predictors of {mRNA} decay rate, indicating that the regulation of {mRNA} decay is more complex and may involve the cooperative binding of several {RNA}-binding proteins at different sites.},
	pages = {1863--1872},
	number = {8},
	journaltitle = {Genome Res},
	author = {Yang, E and van Nimwegen, E and Zavolan, M and Rajewsky, N and Schroeder, M and Magnasco, M and Darnell Jr., J E},
	date = {2003},
	pmid = {12902380},
	keywords = {Humans, {RNA}, Cultured, Base Composition, Carcinoma, Cell Line, Fibroblasts/chemistry/cytology/metabolism, Genetic Variation, Half-Life, Hepatocellular/genetics/pathology, Liver Neoplasms/genetics/pathology, Messenger/*chemistry/genetics/*metabolism/phy, Neoplasm/classification/genetics/metabolism/p, Oligonucleotide Array Sequence Analysis/methods/st, Tumor Cells}
}

@article{sunkesula_does_2013,
	title = {Does empirical Clostridium difficile infection ({CDI}) therapy result in false-negative {CDI} diagnostic test results?},
	volume = {57},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23645849},
	doi = {10.1093/cid/cit286},
	abstract = {{BACKGROUND}: Patients with suspected Clostridium difficile infection ({CDI}) often receive empirical therapy prior to collection of stool specimens for diagnostic testing. The likelihood that such empirical therapy might result in false-negative {CDI} test results is unknown. {METHODS}: We conducted a prospective study of {CDI} patients to determine the time to conversion of {CDI} test results, including polymerase chain reaction ({PCR}) for toxin B genes, glutamate dehydrogenase, and toxigenic culture, from positive to negative during {CDI} therapy. We evaluated the frequency of and risk factors for persistence of positive {CDI} tests. For patients receiving empirical therapy, we assessed the frequency of conversion of positive {CDI} test results at the time of the test order to negative by the time clinical staff collected stool specimens for testing. {RESULTS}: For 51 {CDI} patients, {PCR}, glutamate dehydrogenase, and toxigenic culture results converted to negative at similar rates. For {PCR}, 14\%, 35\%, and 45\% of positive {CDI} tests converted to negative after 1, 2, and 3 days of treatment, respectively. Increased age and infection with North American pulsed-field gel electrophoresis strains were associated with persistent positive {PCR} results. For {CDI} patients diagnosed at the time of the test order, conversion to negative {PCR} results by the time clinical stool specimens were collected occurred in 4 of 9 (44\%) patients who were prescribed empirical {CDI} therapy versus 0 of 23 (0\%) who were not (P = .004). {CONCLUSIONS}: Empirical treatment for suspected {CDI} cases may result in false-negative {PCR} results if there are delays in stool specimen collection.},
	pages = {494--500},
	number = {4},
	journaltitle = {Clin Infect Dis},
	author = {Sunkesula, V C and Kundrapu, S and Muganda, C and Sethi, A K and Donskey, C J},
	date = {2013},
	pmid = {23645849},
	keywords = {Humans, *Diagnostic Errors/statistics \& numerical data, 80 and over, Adult, Aged, Anti-Bacterial Agents/*therapeutic use, Clostridium difficile/*isolation \& purification, Clostridium Infections/*diagnosis/*drug therapy/mi, Diagnostic Tests, Feces/microbiology, Female, Male, Middle Aged, Polymerase Chain Reaction/methods, Prospective Studies, Routine/*methods}
}

@article{davidson_general_1973,
	title = {General interspersion of repetitive with non-repetitive sequence elements in the {DNA} of Xenopus},
	volume = {77},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/4769838},
	pages = {1--23},
	number = {1},
	journaltitle = {J Mol Biol},
	author = {Davidson, E H and Hough, B R and Amenson, C S and Britten, R J},
	date = {1973},
	pmid = {4769838},
	keywords = {Animals, Base Sequence, Binding Sites, Centrifugation, Density Gradient, Deoxyribonucleotides/analysis, {DNA}/analysis/*blood, Erythrocytes/*analysis, Genes, Hydroxyapatites, Kinetics, Mathematics, Molecular Weight, Pressure, Spectrophotometry, Temperature, Time Factors, Tritium, Ultraviolet, Xenopus}
}

@article{lopez_de_silanes_hur:_2005,
	title = {{HuR}: post-transcriptional paths to malignancy},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17132932},
	abstract = {The {RNA}-binding protein {HuR} regulates the stability and translation of target {mRNAs}. While no {HuR} mutations have been found in cancer, a link between {HuR} and malignant transformation has been suggested in cancers of the breast, colon, lung and ovary. We describe a paradigm consistent with a central role of {HuR} in oncogenesis.},
	pages = {11--13},
	number = {1},
	journaltitle = {{RNA} Biol},
	author = {Lopez de Silanes, I and Lal, A and Gorospe, M},
	date = {2005},
	pmid = {17132932},
	keywords = {Human, Animals, Humans, Mice, {RNA}, *Cell Transformation, *{RNA} Processing, Antigens, Carcinoma, Cell Line, Cell Nucleus/metabolism, Chromosomes, Colonic Neoplasms/metabolism, Cytoplasm/metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/metabolism, Neoplastic, Non-Small-Cell Lung/metabolism, Nude, Pair 19, Post-Transcriptional, Protein Biosynthesis, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism, Tumor}
}

@article{piriyapongsa_family_2007,
	title = {A family of human {microRNA} genes from miniature inverted-repeat transposable elements},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17301878},
	doi = {10.1371/journal.pone.0000203},
	abstract = {While hundreds of novel {microRNA} ({miRNA}) genes have been discovered in the last few years alone, the origin and evolution of these non-coding regulatory sequences remain largely obscure. In this report, we demonstrate that members of a recently discovered family of human {miRNA} genes, hsa-mir-548, are derived from Made1 transposable elements. Made1 elements are short miniature inverted-repeat transposable elements ({MITEs}), which consist of two 37 base pair (bp) terminal inverted repeats that flank 6 bp of internal sequence. Thus, Made1 elements are nearly perfect palindromes, and when expressed as {RNA} they form highly stable hairpin loops. Apparently, these Made1-related structures are recognized by the {RNA} interference enzymatic machinery and processed to form 22 bp mature {miRNA} sequences. Consistent with their origin from {MITEs}, hsa-mir-548 genes are primate-specific and have many potential paralogs in the human genome. There are more than 3,500 putative hsa-mir-548 target genes; analysis of their expression profiles and functional affinities suggests cancer-related regulatory roles for hsa-mir-548. Taken together, the characteristics of Made1 elements, and {MITEs} in general, point to a specific mechanism for the generation of numerous small regulatory {RNAs} and target sites throughout the genome. The evolutionary lineage-specific nature of {MITEs} could also provide for the generation of novel regulatory phenotypes related to species diversification. Finally, we propose that {MITEs} may represent an evolutionary link between {siRNAs} and {miRNAs}.},
	pages = {e203},
	number = {2},
	journaltitle = {{PLoS} One},
	author = {Piriyapongsa, J and Jordan, I K},
	date = {2007},
	pmid = {17301878},
	keywords = {Animals, Base Sequence, Humans, {RNA}, Nucleic Acid, *Multigene Family, Comparative Genomic Hybridization, {DNA} Transposable Elements/*genetics, Expressed Sequence Tags, Inverted Repeat Sequences/*genetics, Mammals/genetics, {MicroRNAs}/*genetics/isolation \& purification, Molecular Sequence Data, {RNA} Interference, Sequence Alignment, Sequence Homology, Small Interfering/genetics}
}

@article{sela_characteristics_2010,
	title = {Characteristics of transposable element exonization within human and mouse},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20532223},
	doi = {10.1371/journal.pone.0010907},
	abstract = {Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms ({SNPs}) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. {SNP} density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on {RNA} editing for their exonization. These results shed light on {TE} fixation and the exonization process within human and mouse genes.},
	pages = {e10907},
	number = {6},
	journaltitle = {{PLoS} One},
	author = {Sela, N and Mersch, B and Hotz-Wagenblatt, A and Ast, G},
	date = {2010},
	pmid = {20532223},
	keywords = {Animals, Humans, Mice, Exons, Introns, *{DNA} Transposable Elements, Polymorphism, {RNA} Editing, Single Nucleotide}
}

@article{puetz_intracranial_2008,
	title = {Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18811738},
	doi = {10.1111/j.1747-4949.2008.00221.x},
	abstract = {{BACKGROUND}: In ischemic stroke, functional outcomes vary depending on site of intracranial occlusion. We tested the prognostic value of a semiquantitative computed tomography angiography-based clot burden score. {METHODS}: Clot burden score allots major anterior circulation arteries 10 points for presence of contrast opacification on computed tomography angiography. Two points each are subtracted for thrombus preventing contrast opacification in the proximal M1, distal M1 or supraclinoid internal carotid artery and one point each for M2 branches, A1 and infraclinoid internal carotid artery. We retrospectively studied patients with disabling neurological deficits (National Institute of Health Stroke Scale score {\textbackslash}textgreateror=5) and computed tomography angiography within 24-hours from symptom onset. We analyzed percentages independent functional outcome (modified Rankin Scale score {\textbackslash}textlessor=2), final infarct Alberta Stroke Program Early Computed Tomography Score and parenchymal hematoma rates across categorized clot burden score groups and performed multivariable analysis. {RESULTS}: We identified 263 patients (median age 73-years, National Institute of Health Stroke Scale score 10, onset-to-computed tomography angiography time 165 min). Clot burden score{\textbackslash}textless10 was associated with reduced odds of independent functional outcome (odds ratio 0.09 for clot burden score{\textbackslash}textlessor=5; odds ratio 0.22 for clot burden score 6-7; odds ratio 0.48 for clot burden score 8-9; all versus clot burden score 10; P{\textbackslash}textless0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early Computed Tomography Scores (P{\textbackslash}textless0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early {CT} Scores (P{\textbackslash}textless0.001) and higher parenchymal hematoma rates (P=0.008). Inter-rater reliability for clot burden score was 0.87 (lower 95\% confidence interval 0.71) and intra-rater reliability 0.96 (lower 95\% confidence interval 0.92). {CONCLUSION}: The quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The score needs external validation and could be useful for patient stratification in stroke trials.},
	pages = {230--236},
	number = {4},
	journaltitle = {Int J Stroke},
	author = {Puetz, V and Dzialowski, I and Hill, M D and Subramaniam, S and Sylaja, P N and Krol, A and O'Reilly, C and Hudon, M E and Hu, W Y and Coutts, S B and Barber, P A and Watson, T and Roy, J and Demchuk, A M},
	date = {2008},
	pmid = {18811738},
	keywords = {Humans, Reproducibility of Results, *Cerebral Angiography, *Tomography, Aged, Brain Infarction/etiology/*radiography, Computer-Assisted, Female, Image Interpretation, Intracranial Thrombosis/complications/*radiography, Male, Recovery of Function, Retrospective Studies, Severity of Illness Index, X-Ray Computed}
}

@article{morlando_fus_2012,
	title = {{FUS} stimulates {microRNA} biogenesis by facilitating co-transcriptional Drosha recruitment},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23232809},
	doi = {10.1038/emboj.2012.319},
	abstract = {{microRNA} abundance has been shown to depend on the amount of the microprocessor components or, in some cases, on specific auxiliary co-factors. In this paper, we show that the {FUS}/{TLS} (fused in sarcoma/translocated in liposarcoma) protein, associated with familial forms of Amyotrophic Lateral Sclerosis ({ALS}), contributes to the biogenesis of a specific subset of {microRNAs}. Among them, species with roles in neuronal function, differentiation and synaptogenesis were identified. We also show that {FUS}/{TLS} is recruited to chromatin at sites of their transcription and binds the corresponding pri-{microRNAs}. Moreover, {FUS}/{TLS} depletion leads to decreased Drosha level at the same chromatin loci. Limited {FUS}/{TLS} depletion leads to a reduced {microRNA} biogenesis and we suggest a possible link between {FUS} mutations affecting nuclear/cytoplasmic partitioning of the protein and altered neuronal {microRNA} biogenesis in {ALS} pathogenesis.},
	pages = {4502--4510},
	number = {24},
	journaltitle = {{EMBO} J},
	author = {Morlando, M and Dini Modigliani, S and Torrelli, G and Rosa, A and Di Carlo, V and Caffarelli, E and Bozzoni, I},
	date = {2012},
	pmid = {23232809},
	keywords = {Humans, Blotting, Cell Line, Chromatin Immunoprecipitation, Chromatin/*metabolism, Electrophoretic Mobility Shift Assay, Immunoprecipitation, {MicroRNAs}/*biosynthesis, Neurons/*cytology/physiology, Oligonucleotides/genetics, Plasmids/genetics, Real-Time Polymerase Chain Reaction, Ribonuclease {III}/*metabolism, {RNA}-Binding Protein {FUS}/*metabolism, Synapses/genetics/*physiology, Tumor, Western}
}

@article{bozzoni_splicing_1984,
	title = {Splicing of Xenopus laevis ribosomal protein {RNAs} is inhibited in vivo by antisera to ribonucleoproteins containing U1 small nuclear {RNA}},
	volume = {180},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6084721},
	abstract = {The activity of antisera against ribonucleoproteins containing U1 small nuclear {RNA} (Sm and {RNP}) has been analysed on pol {II} transcripts in an in vivo system. Xenopus laevis ribosomal protein gene transcripts are accumulated in the form of precursor {RNA} when either of the two kinds of antisera are injected into the germinal vesicles of X. laevis oocytes before the injection of purified L1 and L14 ribosomal protein genes. No effect on the accumulation of mature histone {mRNA} is detected when X. laevis histone genes are injected together with the {RNP} antiserum. These results strongly suggest that U1-{RNP} complexes play an essential role in intron removal in vivo.},
	pages = {1173--1178},
	number = {4},
	journaltitle = {J Mol Biol},
	author = {Bozzoni, I and Annesi, F and Beccari, E and Fragapane, P and Pierandrei-Amaldi, P and Amaldi, F},
	date = {1984},
	pmid = {6084721},
	keywords = {Animals, Genetic, {RNA}, Transcription, *Immune Sera, *{RNA} Splicing, Nucleic Acid Hybridization, Ribonucleoproteins, Ribonucleoproteins/*immunology, Ribosomal Proteins/*genetics, Ribosomal/*genetics, {RNA}/*immunology, Small Nuclear, Xenopus laevis}
}

@article{amaral_lncrnadb:_2011,
	title = {{lncRNAdb}: a reference database for long noncoding {RNAs}},
	volume = {39},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21112873},
	doi = {10.1093/nar/gkq1138},
	abstract = {Large numbers of long {RNAs} with little or no protein-coding potential [long noncoding {RNAs} ({lncRNAs})] are being identified in eukaryotes. In parallel, increasing data describing the expression profiles, molecular features and functions of individual {lncRNAs} in a variety of systems are accumulating. To enable the systematic compilation and updating of this information, we have developed a database ({lncRNAdb}) containing a comprehensive list of {lncRNAs} that have been shown to have, or to be associated with, biological functions in eukaryotes, as well as messenger {RNAs} that have regulatory roles. Each entry contains referenced information about the {RNA}, including sequences, structural information, genomic context, expression, subcellular localization, conservation, functional evidence and other relevant information. {lncRNAdb} can be searched by querying published {RNA} names and aliases, sequences, species and associated protein-coding genes, as well as terms contained in the annotations, such as the tissues in which the transcripts are expressed and associated diseases. In addition, {lncRNAdb} is linked to the {UCSC} Genome Browser for visualization and Noncoding {RNA} Expression Database ({NRED}) for expression information from a variety of sources. {lncRNAdb} provides a platform for the ongoing collation of the literature pertaining to {lncRNAs} and their association with other genomic elements. {lncRNAdb} can be accessed at: http://www.lncrnadb.org/.},
	pages = {D146--51},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Amaral, P P and Clark, M B and Gascoigne, D K and Dinger, M E and Mattick, J S},
	date = {2011},
	pmid = {21112873},
	keywords = {Humans, {RNA}, Nucleic Acid, *Databases, Disease/genetics, Host-Pathogen Interactions, Untranslated/*chemistry/metabolism/*physiolog}
}

@article{odonnell_c-myc-regulated_2005,
	title = {c-Myc-regulated {microRNAs} modulate E2F1 expression},
	volume = {435},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15944709},
	doi = {10.1038/nature03677},
	abstract = {{MicroRNAs} ({miRNAs}) are 21-23 nucleotide {RNA} molecules that regulate the stability or translational efficiency of target messenger {RNAs}. {miRNAs} have diverse functions, including the regulation of cellular differentiation, proliferation and apoptosis. Although strict tissue- and developmental-stage-specific expression is critical for appropriate {miRNA} function, mammalian transcription factors that regulate {miRNAs} have not yet been identified. The proto-oncogene c-{MYC} encodes a transcription factor that regulates cell proliferation, growth and apoptosis. Dysregulated expression or function of c-Myc is one of the most common abnormalities in human malignancy. Here we show that c-Myc activates expression of a cluster of six {miRNAs} on human chromosome 13. Chromatin immunoprecipation experiments show that c-Myc binds directly to this locus. The transcription factor E2F1 is an additional target of c-Myc that promotes cell cycle progression. We find that expression of E2F1 is negatively regulated by two {miRNAs} in this cluster, {miR}-17-5p and {miR}-20a. These findings expand the known classes of transcripts within the c-Myc target gene network, and reveal a mechanism through which c-Myc simultaneously activates E2F1 transcription and limits its translation, allowing a tightly controlled proliferative signal.},
	pages = {839--843},
	number = {7043},
	journaltitle = {Nature},
	author = {O'Donnell, K A and Wentzel, E A and Zeller, K I and Dang, C V and Mendell, J T},
	date = {2005},
	pmid = {15944709},
	keywords = {Human, Animals, Humans, Protein Binding, *Gene Expression Regulation, Cell Cycle Proteins/*biosynthesis, Cell Line, Chromatin Immunoprecipitation, Chromosomes, {DNA}-Binding Proteins/*biosynthesis, E2F Transcription Factors, E2F1 Transcription Factor, {MicroRNAs}/*genetics/metabolism, Pair 13/genetics, Proto-Oncogene Proteins c-myc/genetics/*metabolism, Rats, Transcription Factors/*biosynthesis}
}

@article{costantino_role_2009,
	title = {The role of {HuR} in gemcitabine efficacy in pancreatic cancer: {HuR} Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase},
	volume = {69},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19487279},
	doi = {10.1158/0008-5472.CAN-09-0371},
	abstract = {{RNA}-binding protein {HuR} binds U- or {AU}-rich sequences in the 3'-untranslated regions of target {mRNAs}, stabilizing them and/or modulating their translation. Given the links of {HuR} with cancer, we studied the consequences of modulating {HuR} levels in pancreatic cancer cells. {HuR}-overexpressing cancer cells, in some instances, are roughly up to 30-fold more sensitive to treatment with gemcitabine, the main chemotherapeutic component of treatment regimens for pancreatic ductal adenocarcinoma ({PDA}), compared with control cells. In pancreatic cancer cells, {HuR} associates with deoxycytidine kinase ({dCK}) {mRNA}, which encodes the enzyme that metabolizes and thereby activates gemcitabine. Gemcitabine exposure to pancreatic cancer cells enriches the association between {HuR} and {dCK} {mRNA} and increases cytoplasmic {HuR} levels. Accordingly, {HuR} overexpression elevates, whereas {HuR} silencing reduces, {dCK} protein expression in pancreatic cancer cells. In a clinical correlate study of gemcitabine treatment, we found a 7-fold increase in risk of mortality in {PDA} patients with low cytoplasmic {HuR} levels compared with patients with high {HuR} levels, after adjusting for other treatments and demographic variables. These data support the notion that {HuR} is a key mediator of gemcitabine efficacy in cancer cells, at least in part through its ability to regulate {dCK} levels posttranscriptionally. We propose that {HuR} levels in {PDA} modulate the therapeutic efficacy of gemcitabine, thus serving as a marker of the clinical utility of this common chemotherapeutic agent and a potential target for intervention in pancreatic cancer.},
	pages = {4567--4572},
	number = {11},
	journaltitle = {Cancer Res},
	author = {Costantino, C L and Witkiewicz, A K and Kuwano, Y and Cozzitorto, J A and Kennedy, E P and Dasgupta, A and Keen, J C and Yeo, C J and Gorospe, M and Brody, J R},
	date = {2009},
	pmid = {19487279},
	keywords = {Humans, Gene Expression Regulation, Cultured, Antigens, Antimetabolites, Antineoplastic/therapeutic use, Biological/genetics/physiology, Carcinoma, Cytarabine/therapeutic use, Deoxycytidine Kinase/*genetics/metabolism, Deoxycytidine/*analogs \& derivatives/pharmacokinet, Drug Resistance, Drug/genetics, Hu Paraneoplastic Encephalomyelitis Antigens, Metabolic Detoxication, Neoplasm/genetics, Neoplastic/drug effect, Pancreatic Ductal/*drug therapy/*geneti, Pancreatic Neoplasms/*drug therapy/*genetics, {RNA}-Binding Proteins/genetics/*physiology, Surface/genetics/*physiology, Time Factors, Treatment Outcome, Tumor Cells, Tumor Markers, Up-Regulation/drug effects}
}

@article{pierandrei-amaldi_ribosomal-protein_1985,
	title = {Ribosomal-protein synthesis is not autogenously regulated at the translational level in Xenopus laevis},
	volume = {107},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3972154},
	abstract = {Whether ribosomal-protein synthesis in Xenopus laevis is autogenously controlled at the translational level as is known to occur in prokaryotes has been studied. For this purpose ribosomal (r) proteins were prepared from X. laevis ribosomal subunits and group fractionated by ion-exchange chromatography. They were then added to an in vitro translation system directed by an oocyte {mRNA} fraction which contains template activity for r proteins. The synthesized radioactive products were analyzed by 2D gel electrophoresis and compared with controls. Similarly in vivo experiments were performed by microinjection of the fractionated proteins into the cytoplasm of Xenopus oocytes followed by incubation with [35S]methionine for different times. In all the experiments no evident effect of r proteins on the translation of their own {mRNA} was observed.},
	pages = {281--289},
	number = {2},
	journaltitle = {Dev Biol},
	author = {Pierandrei-Amaldi, P and Campioni, N and Gallinari, P and Beccari, E and Bozzoni, I and Amaldi, F},
	date = {1985},
	pmid = {3972154},
	keywords = {Animals, Gene Expression Regulation, Cell-Free System, Protein Biosynthesis, Ribosomal Proteins/*biosynthesis/genetics, Xenopus laevis/*embryology}
}

@article{spengler_functional_2014,
	title = {Functional {microRNAs} and target sites are created by lineage-specific transposition},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24234653},
	doi = {10.1093/hmg/ddt569},
	abstract = {Transposable elements ({TEs}) account for nearly one-half of the sequence content in the human genome, and de novo germline transposition into regulatory or coding sequences of protein-coding genes can cause heritable disorders. {TEs} are prevalent in and around protein-coding genes, providing an opportunity to impart regulation. Computational studies reveal that {microRNA} ({miRNA}) genes and {miRNA} target sites reside within {TE} sequences, but there is little experimental evidence supporting a role for {TEs} in the birth of {miRNAs}, or as platform for gene regulation by {miRNAs}. In this work, we validate {miRNAs} and target sites derived from {TE} families prevalent in the human genome, including the ancient long interspersed nuclear element 2 ({LINE}2/L2), mammalian-wide interspersed repeat ({MIR}) retrotransposons and the primate-specific Alu family. We show that genes with 3' untranslated region (3' {UTR}) {MIR} elements are enriched for let-7 targets and that these sites are conserved and responsive to let-7 expression. We also demonstrate that 3' {UTR}-embedded Alus are a source of {miR}-24 and {miR}-122 target sites and that a subset of active genomic Alus provide for de novo target site creation. Finally, we report that although the creation of {miRNA} genes by Alu elements is relatively uncommon relative to their overall genomic abundance, Alu-derived {miR}-1285-1 is efficiently processed from its genomic locus and regulates genes with target sites contained within homologous elements. Taken together, our data provide additional evidence for {TEs} as a source for {miRNAs} and {miRNA} target sites, with instances of conservation through the course of mammalian evolution.},
	pages = {1783--1793},
	number = {7},
	journaltitle = {Hum Mol Genet},
	author = {Spengler, R M and Oakley, C K and Davidson, B L},
	date = {2014},
	pmid = {24234653}
}

@article{hanahan_hallmarks_2011,
	title = {Hallmarks of cancer: the next generation},
	volume = {144},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21376230},
	doi = {10.1016/j.cell.2011.02.013},
	abstract = {The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.},
	pages = {646--674},
	number = {5},
	journaltitle = {Cell},
	author = {Hanahan, D and Weinberg, R A},
	date = {2011},
	pmid = {21376230},
	keywords = {Animals, Humans, Genomic Instability, Neoplasm Invasiveness, Neoplasms/metabolism/*pathology/*physiopathology, Signal Transduction, Stromal Cells/pathology}
}

@article{santoni_herv-h_2012,
	title = {{HERV}-H {RNA} is abundant in human embryonic stem cells and a precise marker for pluripotency},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23253934},
	doi = {10.1186/1742-4690-9-111},
	abstract = {{BACKGROUND}: Certain post-translational modifications to histones, including H3K4me3, as well as binding sites for the transcription factor {STAT}1, predict the site of integration of exogenous gamma-retroviruses with great accuracy and cell-type specificity. Statistical methods that were used to identify chromatin features that predict exogenous gamma-retrovirus integration site selection were exploited here to determine whether cell type-specific chromatin markers are enriched in the vicinity of endogenous retroviruses ({ERVs}). {RESULTS}: Among retro-elements in the human genome, the gamma-retrovirus {HERV}-H was highly associated with H3K4me3, though this association was only observed in embryonic stem ({ES}) cells (p {\textbackslash}textless 10-300) and, to a lesser extent, in induced pluripotent stem ({iPS}) cells. No significant association was observed in nearly 40 differentiated cell types, nor was any association observed with other retro-elements. Similar strong association was observed between {HERV}-H and the binding sites within {ES} cells for the pluripotency transcription factors {NANOG}, {OCT}4, and {SOX}2. {NANOG} binding sites were located within the {HERV}-H 5'{LTR} itself. {OCT}4 and {SOX}2 binding sites were within 1 {kB} and 2 {kB} of the 5'{LTR}, respectively. In keeping with these observations, {HERV}-H {RNA} constituted 2\% of all poly A {RNA} in {ES} cells. As {ES} cells progressed down a differentiation pathway, the levels of {HERV}-H {RNA} decreased progressively. {RNA}-Seq datasets showed {HERV}-H transcripts to be over 5 {kB} in length and to have the structure 5'{LTR}-gag-pro-3'{LTR}, with no evidence of splicing and no intact open reading frames. {CONCLUSION}: The developmental regulation of {HERV}-H expression, the association of {HERV}-H with binding sites for pluripotency transcription factors, and the extremely high levels of {HERV}-H {RNA} in human {ES} cells suggest that {HERV}-H contributes to pluripotency in human cells. Proximity of {HERV}-H to binding sites for pluripotency transcription factors within {ES} cells might be due to retention of the same chromatin features that determined the site of integration of the ancestral, exogenous, gamma-retrovirus that gave rise to {HERV}-H in the distant past. Retention of these markers, or, alternatively, recruitment of them to the site of the established provirus, may have acted post-integration to fix the provirus within the germ-line of the host species. Either way, {HERV}-H {RNA} provides a specific marker for pluripotency in human cells.},
	pages = {111},
	journaltitle = {Retrovirology},
	author = {Santoni, F A and Guerra, J and Luban, J},
	date = {2012},
	pmid = {23253934},
	keywords = {Humans, {RNA}, Binding Sites, Gene Expression Regulation, Protein Binding, Organ Specificity, Algorithms, *Protein Processing, Biological Markers/metabolism, Chromatin/chemistry, Embryonic Stem Cells/cytology/*metabolism/virology, Endogenous Retroviruses/*genetics, Histones/genetics/*metabolism, Homeodomain Proteins/genetics/metabolism, Induced Pluripotent Stem Cells/cytology/*metabolis, Octamer Transcription Factor-3/genetics/metabolism, Post-Translational, Signal Transduction, {SOXB}1 Transcription Factors/genetics/metabolism, {STAT}1 Transcription Factor/genetics/metabolism, Terminal Repeat Sequences, Viral/*genetics}
}

@article{blackwell_protein_2012,
	title = {Protein interactions with {piALU} {RNA} indicates putative participation of {retroRNA} in the cell cycle, {DNA} repair and chromatin assembly},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22754750},
	doi = {10.4161/mge.19032},
	abstract = {Recent analyses suggest that transposable element-derived transcripts are processed to yield a variety of small {RNA} species that play critical functional roles in gene regulation and chromatin organization as well as genome stability and maintenance. Here we report a mass spectrometry analysis of an {RNA}-affinity complex isolation using a {piRNA} homologous sequence derived from Alu retrotransposal {RNA}. Our data point to potential roles for {piALU} {RNAs} in {DNA} repair, cell cycle and chromatin regulations.},
	pages = {26--35},
	number = {1},
	journaltitle = {Mob Genet Elements},
	author = {Blackwell, B J and Lopez, M F and Wang, J and Krastins, B and Sarracino, D and Tollervey, J R and Dobke, M and Jordan, I K and Lunyak, V V},
	date = {2012},
	pmid = {22754750}
}

@article{martin_de_hijas_large_1993,
	title = {Large peristomal pyoderma gangrenosum successfully treated with cyclosporine and corticosteroids},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7902367},
	pages = {1034--1035},
	number = {6},
	journaltitle = {J Am Acad Dermatol},
	author = {Martin de Hijas, C and Del-Rio, E and Gorospe, M A and Velez, A and Garcia del Pozo, J A},
	date = {1993},
	pmid = {7902367},
	keywords = {Humans, Abdominal Muscles, Administration, Aged, Combination, Cyclosporine/*therapeutic use, Drug Therapy, Female, Oral, Prednisone/*therapeutic use, Pyoderma Gangrenosum/*drug therapy/etiology, Sulfasalazine/*therapeutic use}
}

@article{banfai_long_2012,
	title = {Long noncoding {RNAs} are rarely translated in two human cell lines},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22955977},
	doi = {10.1101/gr.134767.111},
	abstract = {Data from the Encyclopedia of {DNA} Elements ({ENCODE}) project show over 9640 human genome loci classified as long noncoding {RNAs} ({lncRNAs}), yet only ∼100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these {RNAs}, we jointly analyzed two recent data sets produced in the {ENCODE} project: tandem mass spectrometry ({MS}/{MS}) data mapping expressed peptides to their encoding genomic loci, and {RNA}-seq data generated by {ENCODE} in long {polyA}+ and {polyA}- fractions in the cell lines K562 and {GM}12878. We used the machine-learning algorithm {RuleFit}3 to regress the peptide data against {RNA} expression data. The most important covariate for predicting translation was, surprisingly, the Cytosol {polyA}- fraction in both cell lines. {LncRNAs} are ∼13-fold less likely to produce detectable peptides than similar {mRNAs}, indicating that ∼92\% of {GENCODE} v7 {lncRNAs} are not translated in these two {ENCODE} cell lines. Intersecting 9640 {lncRNA} loci with 79,333 peptides yielded 85 unique peptides matching 69 {lncRNAs}. Most cases were due to a coding transcript misannotated as {lncRNA}. Two exceptions were an unprocessed pseudogene and a bona fide {lncRNA} gene, both with open reading frames ({ORFs}) compromised by upstream stop codons. All potentially translatable {lncRNA} {ORFs} had only a single peptide match, indicating low protein abundance and/or false-positive peptide matches. We conclude that with very few exceptions, ribosomes are able to distinguish coding from noncoding transcripts and, hence, that ectopic translation and cryptic {mRNAs} are rare in the human {lncRNAome}.},
	pages = {1646--1657},
	number = {9},
	journaltitle = {Genome Res},
	author = {Banfai, B and Jia, H and Khatun, J and Wood, E and Risk, B and Gundling Jr., W E and Kundaje, A and Gunawardena, H P and Yu, Y and Xie, L and Krajewski, K and Strahl, B D and Chen, X and Bickel, P and Giddings, M C and Brown, J B and Lipovich, L},
	date = {2012},
	pmid = {22955977},
	keywords = {Base Sequence, Humans, {RNA}, Gene Expression Regulation, Gene Expression Profiling, *Protein Biosynthesis, Amino Acid Sequence, Cell Line, Gene Expression, K562 Cells, Long Untranslated/*genetics/metabolism, Messenger/genetics/metabolism, Molecular Sequence Annotation, Molecular Sequence Data, Peptides/genetics, Sequence Alignment, Tandem Mass Spectrometry/methods}
}

@article{melo_ernas_2013,
	title = {{eRNAs} are required for p53-dependent enhancer activity and gene transcription},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23273978},
	doi = {10.1016/j.molcel.2012.11.021},
	abstract = {Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression. Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene. Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions. We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation. Furthermore, p53BERs produce, in a p53-dependent manner, enhancer {RNAs} ({eRNAs}) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest. Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site. Moreover, {eRNA} production from p53BERs is required for efficient p53 transcription enhancement.},
	pages = {524--535},
	number = {3},
	journaltitle = {Mol Cell},
	author = {Melo, C A and Drost, J and Wijchers, P J and van de Werken, H and de Wit, E and Oude Vrielink, J A and Elkon, R and Melo, S A and Leveille, N and Kalluri, R and de Laat, W and Agami, R},
	date = {2013},
	pmid = {23273978},
	keywords = {Genetic, Humans, {RNA}, Gene Expression Regulation, *Transcription, *Enhancer Elements, Cell Cycle Checkpoints/genetics, Chromatin/metabolism, Chromosomes, Genes, Human/metabolism, {MCF}-7 Cells, Messenger/genetics/metabolism, Models, Neoplastic, Protein Binding/genetics, {RNA}/*metabolism, Tumor Suppressor Protein p53/*metabolism, Untranslated/metabolism}
}

@article{galtier_adaptation_2007,
	title = {Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17418442},
	doi = {10.1016/j.tig.2007.03.011},
	abstract = {The analysis of evolutionary rates is a popular approach to characterizing the effect of natural selection at the molecular level. Sequences contributing to species adaptation are expected to evolve faster than nonfunctional sequences because favourable mutations have a higher fixation probability than neutral ones. Such an accelerated rate of evolution might be due to factors other than natural selection, in particular {GC}-biased gene conversion. This is true of neutral sequences, but also of constrained sequences, which can be illustrated using the mouse Fxy gene. Several criteria can discriminate between the natural selection and biased gene conversion models. These criteria suggest that the recently reported human accelerated regions are most likely the result of biased gene conversion. We argue that these regions, far from contributing to human adaptation, might represent the Achilles' heel of our genome.},
	pages = {273--277},
	number = {6},
	journaltitle = {Trends Genet},
	author = {Galtier, N and Duret, L},
	date = {2007},
	pmid = {17418442},
	keywords = {Animals, Genetic, Humans, *Adaptation, *Evolution, *Gene Conversion, *Selection, Biological, {GC} Rich Sequence, Genes, Genetics, Models, Molecular, Physiological, Polymorphism, Population}
}

@article{bustamante_natural_2005,
	title = {Natural selection on protein-coding genes in the human genome},
	volume = {437},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16237444},
	doi = {10.1038/nature04240},
	abstract = {Comparisons of {DNA} polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0\%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5\%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.},
	pages = {1153--1157},
	number = {7062},
	journaltitle = {Nature},
	author = {Bustamante, C D and Fledel-Alon, A and Williamson, S and Nielsen, R and Hubisz, M T and Glanowski, S and Tanenbaum, D M and White, T J and Sninsky, J J and Hernandez, R D and Civello, D and Adams, M D and Cargill, M and Clark, A G},
	date = {2005},
	pmid = {16237444},
	keywords = {Human, Genomics, Animals, Genetic, Humans, *Genome, Computational Biology, Genetic/genetics, Disease, *Evolution, *Genes, *Selection, Amino Acid Substitution/genetics, Continental Population Groups/genetics, Cytoskeleton/metabolism, Genetic Predisposition to Disease/genetics, Male, Molecular, Pan troglodytes/genetics, Polymorphism, Proteins/*genetics}
}

@article{gibson_enzymatic_2009,
	title = {Enzymatic assembly of {DNA} molecules up to several hundred kilobases},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19363495},
	doi = {10.1038/nmeth.1318},
	abstract = {We describe an isothermal, single-reaction method for assembling multiple overlapping {DNA} molecules by the concerted action of a 5' exonuclease, a {DNA} polymerase and a {DNA} ligase. First we recessed {DNA} fragments, yielding single-stranded {DNA} overhangs that specifically annealed, and then covalently joined them. This assembly method can be used to seamlessly construct synthetic and natural genes, genetic pathways and entire genomes, and could be a useful molecular engineering tool.},
	pages = {343--345},
	number = {5},
	journaltitle = {Nat Methods},
	author = {Gibson, D G and Young, L and Chuang, R Y and Venter, J C and Hutchison 3rd, C A and Smith, H O},
	date = {2009},
	pmid = {19363495},
	keywords = {{DNA}, Circular/biosynthesis, Cloning, {DNA} Ligases/metabolism, {DNA}-Directed {DNA} Polymerase/metabolism, Escherichia coli/genetics, Genes/genetics, Genetic Engineering/*methods, Genetic Techniques, Genetic Vectors/biosynthesis, Genome/genetics, Molecular/methods, Mycoplasma genitalium/genetics, Phosphodiesterase I/metabolism, Plasmids/biosynthesis, Recombinant/*biosynthesis/*chemistry}
}

@article{zhang_mammalian_2004,
	title = {Mammalian housekeeping genes evolve more slowly than tissue-specific genes},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14595094},
	doi = {10.1093/molbev/msh010},
	abstract = {Do housekeeping genes, which are turned on most of the time in almost every tissue, evolve more slowly than genes that are turned on only at specific developmental times or tissues? Recent large-scale gene expression studies enable us to have a better definition of housekeeping genes and to address the above question in detail. In this study, we examined 1581 human-mouse orthologous gene pairs for their patterns of sequence evolution, contrasting housekeeping genes with tissue-specific genes. Our results show that, in comparison to tissue-specific genes, housekeeping genes on average evolve more slowly and are under stronger selective constraints as reflected by significantly smaller values of Ka/Ks. Besides stronger purifying selection, we explored several other factors that can possibly slow down nonsynonymous rates in housekeeping genes. Although mutational bias might slightly slow the nonsynonymous rates in housekeeping genes, it is unlikely to be the major cause of the rate difference between the two types of genes. The codon usage pattern of housekeeping genes does not seem to differ from that of tissue-specific genes. Moreover, contrary to the old textbook concept, we found that approximately 74\% of the housekeeping genes in our study belong to multigene families, not significantly different from that of the tissue-specific genes ( approximately 70\%). Therefore, the stronger selective constraints on housekeeping genes are not due to a lower degree of genetic redundancy.},
	pages = {236--239},
	number = {2},
	journaltitle = {Mol Biol Evol},
	author = {Zhang, L and Li, W H},
	date = {2004},
	pmid = {14595094},
	keywords = {Animals, Humans, Mice, *Genome, Databases, Nucleic Acid, *Evolution, *Gene Expression Regulation, Mammals, Molecular, Mutation, Organ Specificity/*genetics}
}

@article{mitchell_splice-mediated_1991,
	title = {Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation},
	volume = {88},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1992472},
	abstract = {In studies of mutations causing deficiency of ornithine delta-aminotransferase ({EC} 2.6.1.13), we found an allele whose mature {mRNA} has a 142-nucleotide insertion at the junction of sequences from exons 3 and 4. The insert derives from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the direction opposite to transcription (an "antisense Alu"). A guanine—-cytosine transversion creates a donor splice site in this Alu, activating a cryptic acceptor splice site at its 5' end and causing splice-mediated insertion of an Alu fragment into the mature ornithine-delta-aminotransferase {mRNA}. We note that the complement of the Alu consensus sequence has at least two cryptic acceptor sites and several potential donor sequences and predict that similar mutations will be found in other genes.},
	pages = {815--819},
	number = {3},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Mitchell, G A and Labuda, D and Fontaine, G and Saudubray, J M and Bonnefont, J P and Lyonnet, S and Brody, L C and Steel, G and Obie, C and Valle, D},
	date = {1991},
	pmid = {1992472},
	keywords = {Humans, {RNA}, {RNA} Splicing, Messenger/genetics, Cells, Cultured, Nucleic Acid, *Mutagenesis, *Mutation, *Repetitive Sequences, Amino Acid Sequence, {DNA} Probes, Female, Insertional, Male, Molecular Sequence Data, Oligonucleotide Probes, Ornithine-Oxo-Acid Transaminase/antagonists \& inhi, Pedigree, Plasmids, Polymerase Chain Reaction/methods, Reference Values, Skin/enzymology}
}

@article{fazi_minicircuitry_2005,
	title = {A minicircuitry comprised of {microRNA}-223 and transcription factors {NFI}-A and C/{EBPalpha} regulates human granulopoiesis},
	volume = {123},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16325577},
	doi = {10.1016/j.cell.2005.09.023},
	abstract = {{MicroRNAs} play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving {miR}-223 and two transcriptional factors, {NFI}-A and C/{EBPalpha}. The two factors compete for binding to the {miR}-223 promoter: {NFI}-A maintains {miR}-223 at low levels, whereas its replacement by C/{EBPalpha}, following retinoic acid ({RA})-induced differentiation, upregulates {miR}-223 expression. The competition by C/{EBPalpha} and the granulocytic differentiation are favored by a negative-feedback loop in which {miR}-223 represses {NFI}-A translation. In line with this, both {RNAi} against {NFI}-A and ectopic expression of {miR}-223 in acute promyelocytic leukemia ({APL}) cells enhance differentiation, whereas {miR}-223 knockdown inhibits the differentiation response to {RA}. Altogether, our data indicate that {miR}-223 plays a crucial role during granulopoiesis and point to the {NFI}-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage.},
	pages = {819--831},
	number = {5},
	journaltitle = {Cell},
	author = {Fazi, F and Rosa, A and Fatica, A and Gelmetti, V and De Marchis, M L and Nervi, C and Bozzoni, I},
	date = {2005},
	pmid = {16325577},
	keywords = {Genetic, Humans, Promoter Regions, Binding Sites, Gene Expression Regulation, *{MicroRNAs}, Biological, {CCAAT}-Enhancer-Binding Protein-alpha/genetics/*met, Cell Differentiation/*physiology, Cell Line, Cell Lineage, Granulocytes/drug effects/*physiology, Models, Myelopoiesis/*physiology, {NFI} Transcription Factors/genetics/*metabolism, {RNA} Interference, Tretinoin/pharmacology}
}

@article{filion_systematic_2010,
	title = {Systematic protein location mapping reveals five principal chromatin types in Drosophila cells},
	volume = {143},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20888037},
	doi = {10.1016/j.cell.2010.09.009},
	abstract = {Chromatin is important for the regulation of transcription and other functions, yet the diversity of chromatin composition and the distribution along chromosomes are still poorly characterized. By integrative analysis of genome-wide binding maps of 53 broadly selected chromatin components in Drosophila cells, we show that the genome is segmented into five principal chromatin types that are defined by unique yet overlapping combinations of proteins and form domains that can extend over {\textbackslash}textgreater 100 kb. We identify a repressive chromatin type that covers about half of the genome and lacks classic heterochromatin markers. Furthermore, transcriptionally active euchromatin consists of two types that differ in molecular organization and H3K36 methylation and regulate distinct classes of genes. Finally, we provide evidence that the different chromatin types help to target {DNA}-binding factors to specific genomic regions. These results provide a global view of chromatin diversity and domain organization in a metazoan cell.},
	pages = {212--224},
	number = {2},
	journaltitle = {Cell},
	author = {Filion, G J and van Bemmel, J G and Braunschweig, U and Talhout, W and Kind, J and Ward, L D and Brugman, W and de Castro, I J and Kerkhoven, R M and Bussemaker, H J and van Steensel, B},
	date = {2010},
	pmid = {20888037},
	keywords = {Animals, Cell Line, Chromatin/*classification/metabolism, {DNA}-Binding Proteins/*analysis/metabolism, Drosophila melanogaster/*genetics/metabolism, Drosophila Proteins/*analysis/metabolism, Euchromatin/metabolism, Heterochromatin/metabolism, Histones/metabolism, Principal Component Analysis}
}

@article{ritter_transcriptional_2012,
	title = {Transcriptional enhancers in protein-coding exons of vertebrate developmental genes},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22567096},
	doi = {10.1371/journal.pone.0035202},
	abstract = {Many conserved noncoding sequences function as transcriptional enhancers that regulate gene expression. Here, we report that protein-coding {DNA} also frequently contains enhancers functioning at the transcriptional level. We tested the enhancer activity of 31 protein-coding exons, which we chose based on strong sequence conservation between zebrafish and human, and occurrence in developmental genes, using a Tol2 transposable {GFP} reporter assay in zebrafish. For each exon we measured {GFP} expression in hundreds of embryos in 10 anatomies via a novel system that implements the voice-recognition capabilities of a cellular phone. We find that 24/31 (77\%) exons drive {GFP} expression compared to a minimal promoter control, and 14/24 are anatomy-specific (expression in four anatomies or less). {GFP} expression driven by these coding enhancers frequently overlaps the anatomies where the host gene is expressed (60\%), suggesting self-regulation. Highly conserved coding sequences and highly conserved noncoding sequences do not significantly differ in enhancer activity (coding: 24/31 vs. noncoding: 105/147) or tissue-specificity (coding: 14/24 vs. noncoding: 50/105). Furthermore, coding and noncoding enhancers display similar levels of the enhancer-related histone modification H3K4me1 (coding: 9/24 vs noncoding: 34/81). Meanwhile, coding enhancers are over three times as likely to contain an H3K4me1 mark as other exons of the host gene. Our work suggests that developmental transcriptional enhancers do not discriminate between coding and noncoding {DNA} and reveals widespread dual functions in protein-coding {DNA}.},
	pages = {e35202},
	number = {5},
	journaltitle = {{PLoS} One},
	author = {Ritter, D I and Dong, Z and Guo, S and Chuang, J H},
	date = {2012},
	pmid = {22567096},
	keywords = {Animals, Humans, Developmental/*genetics, Enhancer Elements, Exons/*genetics, Genes, Genetic/*genetics, Vertebrates/*genetics, Zebrafish}
}

@article{newsome_green_2014,
	title = {Green tea diet decreases {PCB} 126-induced oxidative stress in mice by up-regulating antioxidant enzymes},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24378064},
	doi = {10.1016/j.jnutbio.2013.10.003},
	abstract = {Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate {PCB} toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar {PCB} exhibit decreased overall oxidative stress primarily due to the up-regulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low-fat diet supplemented with green tea extract ({GTE}) for 12 weeks and exposed to 5 mumol {PCB} 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via {HPLC}-{MS}/{MS} exhibited fivefold decreased levels in mice supplemented with {GTE} and subsequently exposed to {PCB} compared to animals on a control diet exposed to {PCB}. Livers were collected and harvested for both messenger {RNA} and protein analyses, and it was determined that many genes transcriptionally controlled by aryl hydrocarbon receptor and nuclear factor (erythroid-derived 2)-like 2 proteins were up-regulated in {PCB}-exposed mice fed the green tea-supplemented diet. An increased induction of genes such as {SOD}1, {GSR}, {NQO}1 and {GST}, key antioxidant enzymes, in these mice (green tea plus {PCB}) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of {PCB} 126, which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants.},
	pages = {126--135},
	number = {2},
	journaltitle = {J Nutr Biochem},
	author = {Newsome, B J and Petriello, M C and Han, S G and Murphy, M O and Eske, K E and Sunkara, M and Morris, A J and Hennig, B},
	date = {2014},
	pmid = {24378064}
}

@article{ingolia_topology_2004,
	title = {Topology and robustness in the Drosophila segment polarity network},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15208707},
	doi = {10.1371/journal.pbio.0020123},
	abstract = {A complex hierarchy of genetic interactions converts a single-celled Drosophila melanogaster egg into a multicellular embryo with 14 segments. Previously, von Dassow et al. reported that a mathematical model of the genetic interactions that defined the polarity of segments (the segment polarity network) was robust (von Dassow et al. 2000). As quantitative information about the system was unavailable, parameters were sampled randomly. A surprisingly large fraction of these parameter sets allowed the model to maintain and elaborate on the segment polarity pattern. This robustness is due to the positive feedback of gene products on their own expression, which induces individual cells in a model segment to adopt different stable expression states (bistability) corresponding to different cell types in the segment polarity pattern. A positive feedback loop will only yield multiple stable states when the parameters that describe it satisfy a particular inequality. By testing which random parameter sets satisfy these inequalities, I show that bistability is necessary to form the segment polarity pattern and serves as a strong predictor of which parameter sets will succeed in forming the pattern. Although the original model was robust to parameter variation, it could not reproduce the observed effects of cell division on the pattern of gene expression. I present a modified version that incorporates recent experimental evidence and does successfully mimic the consequences of cell division. The behavior of this modified model can also be understood in terms of bistability in positive feedback of gene expression. I discuss how this topological property of networks provides robust pattern formation and how large changes in parameters can change the specific pattern produced by a network.},
	pages = {e123},
	number = {6},
	journaltitle = {{PLoS} Biol},
	author = {Ingolia, N T},
	date = {2004},
	pmid = {15208707},
	keywords = {Animals, Gene Expression Regulation, Transcription Factors/metabolism, Computational Biology, *Models, Biological, Body Patterning/genetics/*physiology, Computer Simulation, Developmental/*genetic, Drosophila melanogaster/*embryology/metabolism, Drosophila Proteins/metabolism, Embryo, Homeodomain Proteins/metabolism, Likelihood Functions, Nonmammalian/metabolism, Proto-Oncogene Proteins/metabolism, Wnt1 Protein}
}

@article{fatica_fibrillarin_2000,
	title = {Fibrillarin binds directly and specifically to U16 box C/D {snoRNA}},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10668801},
	abstract = {Eukaryotic nucleoli contain a large family of box C/D small nucleolar ribonucleoprotein complexes ({snoRNPs}) that are involved in processing and site-specific methylation of pre-{rRNA}. Several proteins have been reported to be common factors of box C/D {snoRNPs} in lower and higher eukaryotes; nevertheless none of them has been clearly shown to directly interact with {RNA}. We previously identified in Xenopus laevis, by means of {UV} crosslinking in vivo, two proteins associated with box C/D {snoRNAs}, fibrillarin and p68. Here we show that fibrillarin interacts directly and specifically with the U16 box C/D {snoRNA} in a X. laevis oocyte nuclear extract and that it does not require p68 for binding. Specific binding is also obtained with a recombinant fibrillarin demonstrating that the protein is able to bind directly and specifically to U16 {snoRNA} by itself.},
	pages = {88--95},
	number = {1},
	journaltitle = {{RNA}},
	author = {Fatica, A and Galardi, S and Altieri, F and Bozzoni, I},
	date = {2000},
	pmid = {10668801},
	keywords = {Animals, {RNA}, Protein Binding, *{RNA} Helicases, Cell Extracts, Chromosomal Proteins, Cross-Linking Reagents, {DEAD}-box {RNA} Helicases, Non-Histone/*metabolism, Oocytes/metabolism/radiation effects/ultrastructur, Protein Kinases/*metabolism, Ribonucleoproteins/*metabolism, Small Nucleolar/*metabolism, Ultraviolet Rays, Xenopus laevis}
}

@article{huang_david_2007-1,
	title = {{DAVID} Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17576678},
	doi = {10.1093/nar/gkm415},
	abstract = {All tools in the {DAVID} Bioinformatics Resources aim to provide functional interpretation of large lists of genes derived from genomic studies. The newly updated {DAVID} Bioinformatics Resources consists of the {DAVID} Knowledgebase and five integrated, web-based functional annotation tool suites: the {DAVID} Gene Functional Classification Tool, the {DAVID} Functional Annotation Tool, the {DAVID} Gene {ID} Conversion Tool, the {DAVID} Gene Name Viewer and the {DAVID} {NIAID} Pathogen Genome Browser. The expanded {DAVID} Knowledgebase now integrates almost all major and well-known public bioinformatics resources centralized by the {DAVID} Gene Concept, a single-linkage method to agglomerate tens of millions of diverse gene/protein identifiers and annotation terms from a variety of public bioinformatics databases. For any uploaded gene list, the {DAVID} Resources now provides not only the typical gene-term enrichment analysis, but also new tools and functions that allow users to condense large gene lists into gene functional groups, convert between gene/protein identifiers, visualize many-genes-to-many-terms relationships, cluster redundant and heterogeneous terms into groups, search for interesting and related genes or terms, dynamically view genes from their lists on bio-pathways and more. With {DAVID} (http://david.niaid.nih.gov), investigators gain more power to interpret the biological mechanisms associated with large gene lists.},
	pages = {W169--75},
	issue = {Web Server issue},
	journaltitle = {Nucleic Acids Res},
	author = {Huang, D W and Sherman, B T and Tan, Q and Kir, J and Liu, D and Bryant, D and Guo, Y and Stephens, R and Baseler, M W and Lane, H C and Lempicki, R A},
	date = {2007},
	pmid = {17576678},
	keywords = {Genomics, Genetic, Humans, Nucleic Acid, Algorithms, Software, *Databases, Automated, Computational Biology/*methods, Data Interpretation, Gene Expression Profiling/*statistics \& numerical, Information Storage and Retrieval/*methods, Internet, Oligonucleotide Array Sequence Analysis/methods, Pattern Recognition, Statistical}
}

@article{garber_identifying_2009,
	title = {Identifying novel constrained elements by exploiting biased substitution patterns},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19478016},
	doi = {10.1093/bioinformatics/btp190},
	abstract = {{MOTIVATION}: Comparing the genomes from closely related species provides a powerful tool to identify functional elements in a reference genome. Many methods have been developed to identify conserved sequences across species; however, existing methods only model conservation as a decrease in the rate of mutation and have ignored selection acting on the pattern of mutations. {RESULTS}: We present a new approach that takes advantage of deeply sequenced clades to identify evolutionary selection by uncovering not only signatures of rate-based conservation but also substitution patterns characteristic of sequence undergoing natural selection. We describe a new statistical method for modeling biased nucleotide substitutions, a learning algorithm for inferring site-specific substitution biases directly from sequence alignments and a hidden Markov model for detecting constrained elements characterized by biased substitutions. We show that the new approach can identify significantly more degenerate constrained sequences than rate-based methods. Applying it to the {ENCODE} regions, we identify as much as 10.2\% of these regions are under selection. {AVAILABILITY}: The algorithms are implemented in a Java software package, called {SiPhy}, freely available at http://www.broadinstitute.org/science/software/. {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at Bioinformatics online.},
	pages = {i54--62},
	number = {12},
	journaltitle = {Bioinformatics},
	author = {Garber, M and Guttman, M and Clamp, M and Zody, M C and Friedman, N and Xie, X},
	date = {2009},
	pmid = {19478016},
	keywords = {Genomics/*methods, Base Sequence, Software, *Algorithms, Evolution, Molecular, Sequence Alignment/*methods}
}

@article{orom_long_2010,
	title = {Long noncoding {RNAs} with enhancer-like function in human cells},
	volume = {143},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20887892},
	doi = {10.1016/j.cell.2010.09.001},
	abstract = {While the long noncoding {RNAs} ({ncRNAs}) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long {ncRNAs} that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a {GENCODE} annotation of the human genome to characterize over a thousand long {ncRNAs} that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long {ncRNAs} in human cell lines. Depletion of a number of {ncRNAs} led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, {SCL} (also called {TAL}1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the {ncRNAs} in activation of gene expression. These results reveal an unanticipated role for a class of long {ncRNAs} in activation of critical regulators of development and differentiation.},
	pages = {46--58},
	number = {1},
	journaltitle = {Cell},
	author = {Orom, U A and Derrien, T and Beringer, M and Gumireddy, K and Gardini, A and Bussotti, G and Lai, F and Zytnicki, M and Notredame, C and Huang, Q and Guigo, R and Shiekhattar, R},
	date = {2010},
	pmid = {20887892},
	keywords = {Human, Genetic, Humans, {RNA}, Messenger/genetics, *Genome, Cells, Cultured, *Enhancer Elements, Cell Line, Transcription Factors/genetics, Transcriptional Activation, Tumor, Untranslated/*metabolism}
}

@article{york_steroid_2010,
	title = {Steroid receptor coactivator ({SRC}) family: masters of systems biology},
	volume = {285},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20956538},
	doi = {10.1074/jbc.R110.193367},
	abstract = {The three members of the p160 family of steroid receptor coactivators ({SRC}-1, {SRC}-2, and {SRC}-3) steer the functional output of numerous genetic programs and serve as pleiotropic rheostats for diverse physiological processes. Since their discovery approximately 15 years ago, the extraordinary sum of examination of {SRC} function has shaped the foundation of our knowledge for the now 350+ coregulators that have been identified to date. In this perspective, we retrace our steps into the field of coregulators and provide a summary of selected seminal work that helped define the {SRCs} as masters of systems biology.},
	pages = {38743--38750},
	number = {50},
	journaltitle = {J Biol Chem},
	author = {York, B and O'Malley, B W},
	date = {2010},
	pmid = {20956538},
	keywords = {Animals, Genetic, Humans, Transcription, Bibliometrics, Biological, Biological Markers, Cytoplasmic and Nuclear/*metabolism, Ligands, Models, Neoplasms/metabolism, Nuclear Receptor Coactivator 1/*metabolism, Nuclear Receptor Coactivator 2/*metabolism, Nuclear Receptor Coactivator 3/*metabolism, Receptors, Systems Biology}
}

@article{victor_prospective_2014,
	title = {A prospective, observational, multicentre study comparing tenecteplase facilitated {PCI} versus primary {PCI} in Indian patients with {STEMI} ({STEPP}-{AMI})},
	volume = {1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25332825},
	doi = {10.1136/openhrt-2014-000133},
	abstract = {{OBJECTIVE}: To compare the efficacy of pharmacoinvasive strategy versus primary percutaneous coronary intervention ({PCI}) in patients with {ST}-segment elevation myocardial infarction ({STEMI}). Primary {PCI} is the preferred treatment for {STEMI}, but it is not a feasible option for many. A pharmacoinvasive strategy might be a practical solution in the Indian context, although few empirical data exist to guide this approach. {METHODS}: This is a prospective, observational, multicentre pilot study. Two hundred consecutive patients with {STEMI} aged 18-75 years, presenting within 12 h of onset of symptoms and requiring a reperfusion strategy, were studied from five primary {PCI} capable centres in South India. Patients who opted for pharmacoinvasive strategy (n=45) formed group A. Group B consisted of patients treated with primary {PCI} (n=155). One patient was lost to follow-up at 1 year. The primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularisation of a culprit artery and congestive heart failure at 30 days. {RESULTS}: The primary end point occurred in 11.1\% in group A and in 3.9\% in group B, p=0.07 ({RR}=2.87; 95\% {CI} 0.92 to 8.97). The infarct-related artery patency at angiogram was 82.2\% in group A and 22.6\% in group B (p{\textbackslash}textless0.001). {PCI} was performed in 73.3\% in group A versus 100\% in group B (p{\textbackslash}textless0.001), and a thrombus was present in 26.7\% in group A versus 63.2\% in group B (p{\textbackslash}textless0.001). Failed fibrinolysis occurred in 12.1\% in group A. There was no difference in bleeding risk, 2.2\% in group A versus 0.6\% in group B, (p=0.4). {CONCLUSIONS}: This pilot study shows that a pharmacoinvasive strategy can be implemented in patients not selected for primary {PCI} in India and hints at the possibility of similar outcomes. Larger studies are required to confirm these findings. {TRIAL} {REGISTRATION} {NUMBER}: {TRIAL} {IS} {REGISTERED} {WITH} {CLINICAL} {TRIAL} {REGISTRY} {OF} {INDIA}, {CTRI} {NUMBER}: {REF}/2011/07/002556.},
	pages = {e000133},
	number = {1},
	journaltitle = {Open Heart},
	author = {Victor, S M and Subban, V and Alexander, T and G, B C and Srinivas, A and S, S and Mullasari, A S},
	date = {2014},
	pmid = {25332825}
}

@article{carpenter_long_2013,
	title = {A long noncoding {RNA} mediates both activation and repression of immune response genes},
	volume = {341},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23907535},
	doi = {10.1126/science.1240925},
	abstract = {An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding {RNA} ({lncRNA}) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous {lncRNAs}. One of these, {lincRNA}-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of {lincRNA}-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of {lincRNA}-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.},
	pages = {789--792},
	number = {6147},
	journaltitle = {Science},
	author = {Carpenter, S and Aiello, D and Atianand, M K and Ricci, E P and Gandhi, P and Hall, L L and Byron, M and Monks, B and Henry-Bezy, M and Lawrence, J B and O'Neill, L A and Moore, M J and Caffrey, D R and Fitzgerald, K A},
	date = {2013},
	pmid = {23907535},
	keywords = {Animals, Genetic, Mice, {RNA}, Transcription, *Gene Expression Regulation, Cell Line, Cell Nucleus/metabolism, Cyclooxygenase 2/genetics, Cytokines/genetics/metabolism, Cytosol/metabolism, Heterogeneous-Nuclear Ribonucleoproteins/metabolis, Immunity, Immunological, Inflammation/*genetics, Innate/*genetics, Long Noncoding/*genetics/metabolism, Macrophage Activation, Macrophages/*immunology/*metabolism, Models, {RNA} Interference, Toll-Like Receptors/genetics/metabolism, Transcription Factors/genetics/metabolism, Transcriptional Activation}
}

@article{mcnicoll_huntington_2008,
	title = {Huntington {CAG} repeat size does not modify onset age in familial Parkinson's disease: the {GenePD} study},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18649400},
	doi = {10.1002/mds.22186},
	abstract = {The {ATP}/{ADP} ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene ({HD}) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease ({PD}), and therefore, we evaluated the relationship of the {HD} {CAG} repeat size to {PD} onset age in a large sample of familial {PD} cases. {PD} affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the {HD} {CAG} repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 {LRRK}2 carriers. All cases had {HD} {CAG} repeats (range, 15-34) below the clinical range for {HD}, although 5.2\% of the sample (n = 25) had repeats in the intermediate range (the intermediate range lower limit = 27; upper limit = 35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the {HD} {CAG} repeat size and the age at onset for {PD} was found in this sample of familial {PD}.},
	pages = {1596--1601},
	number = {11},
	journaltitle = {Mov Disord},
	author = {{McNicoll}, C F and Latourelle, J C and {MacDonald}, M E and Lew, M F and Suchowersky, O and Klein, C and Golbe, L I and Mark, M H and Growdon, J H and Wooten, G F and Watts, R L and Guttman, M and Racette, B A and Perlmutter, J S and Ahmed, A and Shill, H A and Singer, C and Saint-Hilaire, M H and Massood, T and Huskey, K W and {DeStefano}, A L and Gillis, T and Mysore, J and Goldwurm, S and Pezzoli, G and Baker, K B and Itin, I and Litvan, I and Nicholson, G and Corbett, A and Nance, M and Drasby, E and Isaacson, S and Burn, D J and Chinnery, P F and Pramstaller, P P and Al-Hinti, J and Moller, A T and Ostergaard, K and Sherman, S J and Roxburgh, R and Snow, B and Slevin, J T and Cambi, F and Gusella, J F and Myers, R H},
	date = {2008},
	pmid = {18649400},
	keywords = {Humans, *Family Health, 80 and over, Adult, Age of Onset, Aged, Female, Genotype, Huntington Disease/epidemiology/*genetics, Male, Middle Aged, Nerve Tissue Proteins/*genetics, Nuclear Proteins/*genetics, Parkinson Disease/*genetics/*physiopathology, Trinucleotide Repeats/*genetics}
}

@article{hucl_syngeneic_2008,
	title = {A syngeneic variance library for functional annotation of human variation: application to {BRCA}2},
	volume = {68},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18593900},
	doi = {10.1158/0008-5472.CAN-07-6189},
	abstract = {The enormous scope of natural human genetic variation is now becoming defined. To accurately annotate these variants, and to identify those with clinical importance, is often difficult to assess through functional assays. We explored systematic annotation by using homologous recombination to modify a native gene in hemizygous (wt/Deltaexon) human cancer cells, generating a novel syngeneic variance library ({SyVaL}). We created a {SyVaL} of {BRCA}2 variants: nondeleterious, proposed deleterious, deleterious, and of uncertain significance. We found that the null states {BRCA}2(Deltaex11/Deltaex11) and {BRCA}2(Deltaex11/Y3308X) were deleterious as assessed by a loss of {RAD}51 focus formation on genotoxic damage and by acquisition of toxic hypersensitivity to mitomycin C and etoposide, whereas {BRCA}2(Deltaex11/Y3308Y), {BRCA}2(Deltaex11/P3292L), and {BRCA}2(Deltaex11/P3280H) had wild-type function. A proposed phosphorylation site at codon 3291 affecting function was confirmed by substitution of an acidic residue (glutamate, {BRCA}2(Deltaex11/S3291E)) for the native serine, but in contrast to a prior report, phosphorylation was dispensable (alanine, {BRCA}2(Deltaex11/S3291A)) for {BRCA}2-governed cellular phenotypes. These results show that {SyVaLs} offer a means to comprehensively annotate gene function, facilitating numerical and unambiguous readouts. {SyVaLs} may be especially useful for genes in which functional assays using exogenous expression are toxic or otherwise unreliable. They also offer a stable, distributable cellular resource for further research.},
	pages = {5023--5030},
	number = {13},
	journaltitle = {Cancer Res},
	author = {Hucl, T and Rago, C and Gallmeier, E and Brody, J R and Gorospe, M and Kern, S E},
	date = {2008},
	pmid = {18593900},
	keywords = {Humans, Cells, Cultured, *Gene Library, *Genes, Antineoplastic Agents/pharmacology, Biological, {BRCA}2, Cell Proliferation/drug effects/radiation effects, Cell Survival/drug effects, Chromosomal Instability/drug effects/radiation eff, Clone Cells, Drug Resistance, Etoposide/pharmacology, Genetic Variation/*physiology, Mitomycin/pharmacology, Models, Mutagenesis, Neoplasm/drug effects/genetics, Rad51 Recombinase/genetics/physiology, Site-Directed, Tumor Stem Cell Assay}
}

@article{vallender_positive_2004,
	title = {Positive selection on the human genome},
	volume = {13 Spec No},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15358731},
	doi = {10.1093/hmg/ddh253},
	abstract = {Positive selection has undoubtedly played a critical role in the evolution of Homo sapiens. Of the many phenotypic traits that define our species–notably the enormous brain, advanced cognitive abilities, complex vocal organs, bipedalism and opposable thumbs–most (if not all) are likely the product of strong positive selection. Many other aspects of human biology not necessarily related to the 'branding' of our species, such as host-pathogen interactions, reproduction, dietary adaptation and physical appearance, have also been the substrate of varying levels of positive selection. Comparative genetics/genomics studies in recent years have uncovered a growing list of genes that might have experienced positive selection during the evolution of human and/or primates. These genes offer valuable inroads into understanding the biological processes specific to humans, and the evolutionary forces that gave rise to them. Here, we present a comprehensive review of these genes, and their implications for human evolution.},
	pages = {R245--54},
	journaltitle = {Hum Mol Genet},
	author = {Vallender, E J and Lahn, B T},
	date = {2004},
	pmid = {15358731},
	keywords = {Human, Genetic, Humans, *Genome, *Selection}
}

@article{raval_real-time_2006-1,
	title = {Real-time magnetic resonance imaging-guided endovascular recanalization of chronic total arterial occlusion in a swine model},
	volume = {113},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16490819},
	doi = {10.1161/CIRCULATIONAHA.105.586727},
	abstract = {{BACKGROUND}: Endovascular recanalization (guidewire traversal) of peripheral artery chronic total occlusion ({CTO}) can be challenging. X-ray angiography resolves {CTO} poorly. Virtually "blind" device advancement during x-ray-guided interventions can lead to procedure failure, perforation, and hemorrhage. Alternatively, {MRI} may delineate the artery within the occluded segment to enhance procedural safety and success. We hypothesized that real-time {MRI} ({rtMRI})-guided {CTO} recanalization can be accomplished in an animal model. {METHODS} {AND} {RESULTS}: Carotid artery {CTO} was created by balloon injury in 19 lipid-overfed swine. After 6 to 8 weeks, 2 underwent direct necropsy analysis for histology, 3 underwent primary x-ray-guided {CTO} recanalization attempts, and the remaining 14 underwent {rtMRI}-guided recanalization attempts in a 1.5-T interventional {MRI} system. Real-time {MRI} intervention used custom {CTO} catheters and guidewires that incorporated {MRI} receiver antennae to enhance device visibility. The mean length of the occluded segments was 13.3+/-1.6 cm. The {rtMRI}-guided {CTO} recanalization was successful in 11 of 14 swine and in only 1 of 3 swine with the use of x-ray alone. After unsuccessful {rtMRI} (n=3), x-ray-guided attempts were also unsuccessful. {CONCLUSIONS}: Recanalization of long {CTO} is entirely feasible with the use of {rtMRI} guidance. Low-profile clinical-grade devices will be required to translate this experience to humans.},
	pages = {1101--1107},
	number = {8},
	journaltitle = {Circulation},
	author = {Raval, A N and Karmarkar, P V and Guttman, M A and Ozturk, C and Sampath, S and {DeSilva}, R and Aviles, R J and Xu, M and Wright, V J and Schenke, W H and Kocaturk, O and Dick, A J and Raman, V K and Atalar, E and {McVeigh}, E R and Lederman, R J},
	date = {2006},
	pmid = {16490819},
	keywords = {Animals, *Magnetic Resonance Imaging/instrumentation/method, Angioplasty/instrumentation/methods, Animal, Arterial Occlusive Diseases/pathology/*therapy, Carotid Artery Diseases/pathology/therapy, Catheterization/instrumentation/*methods, Chronic Disease, Disease Models, Equipment Design, Peripheral Vascular Diseases/pathology/therapy, Swine, Treatment Outcome}
}

@article{laurent_comprehensive_2008,
	title = {Comprehensive {microRNA} profiling reveals a unique human embryonic stem cell signature dominated by a single seed sequence},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18403753},
	doi = {10.1634/stemcells.2007-1081},
	abstract = {Embryonic stem cells are unique among cultured cells in their ability to self-renew and differentiate into a wide diversity of cell types, suggesting that a specific molecular control network underlies these features. Human embryonic stem cells ({hESCs}) are known to have distinct {mRNA} expression, global {DNA} methylation, and chromatin profiles, but the involvement of high-level regulators, such as {microRNAs} ({miRNA}), in the {hESC}-specific molecular network is poorly understood. We report that global {miRNA} expression profiling of {hESCs} and a variety of stem cell and differentiated cell types using a novel microarray platform revealed a unique set of {miRNAs} differentially regulated in {hESCs}, including numerous {miRNAs} not previously linked to {hESCs}. These {hESC}-associated {miRNAs} were more likely to be located in large genomic clusters, and less likely to be located in introns of coding genes. {hESCs} had higher expression of oncogenic {miRNAs} and lower expression of tumor suppressor {miRNAs} than the other cell types. Many {miRNAs} upregulated in {hESCs} share a common consensus seed sequence, suggesting that there is cooperative regulation of a critical set of target {miRNAs}. We propose that {miRNAs} are coordinately controlled in {hESCs}, and are key regulators of pluripotence and differentiation. Disclosure of potential conflicts of interest is found at the end of this article.},
	pages = {1506--1516},
	number = {6},
	journaltitle = {Stem Cells},
	author = {Laurent, L C and Chen, J and Ulitsky, I and Mueller, F J and Lu, C and Shamir, R and Fan, J B and Loring, J F},
	date = {2008},
	pmid = {18403753},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Oligonucleotide Array Sequence Analysis, *Gene Expression Profiling, Cell Culture Techniques/methods, Cell Differentiation, Cell Line, Collagen, Consensus Sequence, {DNA}/genetics/isolation \& purification, Drug Combinations, Embryonic Stem Cells/*cytology/*physiology, Endoderm/cytology/physiology, Female, Laminin, Male, Messenger/*genetics, {MicroRNAs}/*genetics, Neurons/cytology/physiology, Proteoglycans}
}

@article{kawai_translational_2006,
	title = {Translational control of cytochrome c by {RNA}-binding proteins {TIA}-1 and {HuR}},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16581801},
	doi = {10.1128/MCB.26.8.3295-3307.2006},
	abstract = {Stresses affecting the endoplasmic reticulum ({ER}) globally modulate gene expression patterns by altering posttranscriptional processes such as translation. Here, we use tunicamycin (Tn) to investigate {ER} stress-triggered changes in the translation of cytochrome c, a pivotal regulator of apoptosis. We identified two {RNA}-binding proteins that associate with its approximately 900-bp-long, adenine- and uridine-rich 3' untranslated region ({UTR}): {HuR}, which displayed affinity for several regions of the cytochrome c 3'{UTR}, and T-cell-restricted intracellular antigen 1 ({TIA}-1), which preferentially bound the segment proximal to the coding region. {HuR} did not appear to influence the cytochrome c {mRNA} levels but instead promoted cytochrome c translation, as {HuR} silencing greatly diminished the levels of nascent cytochrome c protein. By contrast, {TIA}-1 functioned as a translational repressor of cytochrome c, with interventions to silence {TIA}-1 dramatically increasing cytochrome c translation. Following treatment with Tn, {HuR} binding to cytochrome c {mRNA} decreased, and both the presence of cytochrome c {mRNA} within actively translating polysomes and the rate of cytochrome c translation declined. Taken together, our data suggest that the translation rate of cytochrome c is determined by the opposing influences of {HuR} and {TIA}-1 upon the cytochrome c {mRNA}. Under unstressed conditions, cytochrome c {mRNA} is actively translated, but in response to {ER} stress agents, both {HuR} and {TIA}-1 contribute to lowering its biosynthesis rate. We propose that {HuR} and {TIA}-1 function coordinately to maintain precise levels of cytochrome c production under unstimulated conditions and to modify cytochrome c translation when damaged cells are faced with molecular decisions to follow a prosurvival or a prodeath path.},
	pages = {3295--3307},
	number = {8},
	journaltitle = {Mol Cell Biol},
	author = {Kawai, T and Lal, A and Yang, X and Galban, S and Mazan-Mamczarz, K and Gorospe, M},
	date = {2006},
	pmid = {16581801},
	keywords = {3' Untranslated Regions, Humans, {RNA}, Gene Expression Regulation, Protein Binding, *Protein Biosynthesis, Antigens, Blotting, Cytochromes c/analysis/*biosynthesis, Electrophoresis, Fluorescence, Fluorescent Antibody Technique, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Indirect, Messenger/metabolism, Microscopy, Northern, Polyacrylamide Gel, Precipitin Tests, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, {RNA}-Binding Proteins/genetics/*metabolism, Small Interfering/metabolism, Surface/*metabolism, Western}
}

@article{fan_role_2005,
	title = {The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16264057},
	doi = {10.1183/09031936.05.00120204},
	abstract = {The aim of this review is to discuss recent advances in the understanding of the regulation of chemokine expression occurring during chronic inflammatory conditions, such as allergic diseases. The focus will be on current data, which suggest that post-transcriptional regulation plays a larger role in chemokine gene regulation than previously recognised. In particular, a growing body of data indicates that mechanisms controlling {mRNA} stability may be relevant in determining, or maintaining, the increased levels of chemokine gene expression in this context. Such regulatory pathways may be important targets of novel anti-inflammatory strategies.},
	pages = {933--947},
	number = {5},
	journaltitle = {Eur Respir J},
	author = {Fan, J and Heller, N M and Gorospe, M and Atasoy, U and Stellato, C},
	date = {2005},
	pmid = {16264057},
	keywords = {Animals, Humans, *Models, Chemokines/*immunology, Gene Expression Regulation/*immunology, Hypersensitivity/*immunology, Immunological, Inflammation/*immunology, Post-Transcriptional/*immunology, Post-Translational/*immunology, Protein Processing, {RNA} Processing}
}

@article{gorospe_degradation_1994,
	title = {Degradation of unstable interleukin-1 alpha {mRNA} in a rabbit reticulocyte cell-free system. Localization of an instability determinant to a cluster of {AUUUA} motifs},
	volume = {269},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8163483},
	abstract = {Labeled transcripts of interleukin-1 alpha ({IL}-1 alpha) {cDNA} were rapidly degraded in incubations with rabbit reticulocyte lysate ({RRL}). In contrast, a transcript of superoxide dismutase {cDNA} was stable in control incubations. A transcript of the 3'-untranslated region ({UTR}) of {IL}-1 alpha was rapidly degraded while that of the 5'-{UTR} and coding region was stable. This degradative activity was present in the post-ribosomal supernatant. Degradation of the 3'-{UTR} transcript was inhibited by the addition of a large excess of an 80-base {RNA} containing four {AUUUA} repeats, but not by the same {RNA} without such repeats. This suggested that {AUUUA} motifs were responsible for the instability of the 3'-{UTR} transcript. The 80-base {RNA} did not act as a competitive substrate for a nuclease since it was not degraded. Partial transcripts of {IL}-1 alpha 3'-{UTR} were incubated with {RRL} to localize instability determinants. Transcripts containing at least three clustered {AUUUA} motifs were rapidly degraded, while transcripts containing four scattered {AUUUA} motifs were stable. To study the mechanism of {RNA} degradation, the {RRL} was passed through an affinity column that retained {AUUUA}-binding proteins. The flow-through or the fraction eluted from such a column were inactive, but the two fractions together degraded the 3'-{UTR} transcript. This indicated that proteins bound by the affinity column did not have nuclease activity but targeted this {RNA} for degradation.},
	pages = {11845--11851},
	number = {16},
	journaltitle = {J Biol Chem},
	author = {Gorospe, M and Baglioni, C},
	date = {1994},
	pmid = {8163483},
	keywords = {{DNA}, Animals, Base Sequence, Genetic, {RNA}, Transcription, Nucleic Acid, *Repetitive Sequences, Cell-Free System, Complementary/metabolism, {DNA} Primers, Ethylmaleimide/pharmacology, Interleukin-1/*biosynthesis, Kinetics, Messenger/chemistry/drug effects/*metabolism, Molecular Sequence Data, Polymerase Chain Reaction, Rabbits, Reticulocytes/*metabolism}
}

@article{elisaphenko_dual_2008,
	title = {A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18575625},
	doi = {10.1371/journal.pone.0002521},
	abstract = {X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center ({XIC}). Previously it was proposed that genes of the {XIC} evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key {XIC} gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other {XIC} genes producing non-coding nuclear {RNA}.},
	pages = {e2521},
	number = {6},
	journaltitle = {{PLoS} One},
	author = {Elisaphenko, E A and Kolesnikov, N N and Shevchenko, A I and Rogozin, I B and Nesterova, T B and Brockdorff, N and Zakian, S M},
	date = {2008},
	pmid = {18575625},
	keywords = {Animals, Mice, {RNA}, Exons, Nucleic Acid, Untranslated/*genetics, *{DNA} Transposable Elements, {DNA} Transposable Elements, Female, Long Untranslated, Sequence Homology, Tandem Repeat Sequences, X Chromosome Inactivation, {RNA}, Long Noncoding, {RNA}, Untranslated, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/ZZIJ3WFG/Elisaphenko et al. - 2008 - A dual origin of the Xist gene from a protein-codi.pdf:application/pdf}
}

@article{kim_distinct_2013,
	title = {Distinct binding properties of {TIAR} {RRMs} and linker region},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23603827},
	doi = {10.4161/rna.24341},
	abstract = {The {RNA}-binding protein {TIAR} is an {mRNA}-binding protein that acts as a translational repressor, particularly important under conditions of cellular stress. It binds to target {mRNA} and {DNA} via its {RNA} recognition motif ({RRM}) domains and is involved in both splicing regulation and translational repression via the formation of "stress granules." {TIAR} has also been shown to bind {ssDNA} and play a role in the regulation of transcription. Here we show, using surface plasmon resonance and nuclear magnetic resonance spectroscopy, specific roles of individual {TIAR} domains for high-affinity binding to {RNA} and {DNA} targets. We confirm that {RRM}2 of {TIAR} is the major {RNA}- and {DNA}-binding domain. However, the strong nanomolar affinity binding to U-rich {RNA} and T-rich {DNA} depends on the presence of the six amino acid residues found in the linker region C-terminal to {RRM}2. On its own, {RRM}1 shows preferred binding to {DNA} over {RNA}. We further characterize the interaction between {RRM}2 with the C-terminal extension and an {AU}-rich target {RNA} sequence using {NMR} spectroscopy to identify the amino acid residues involved in binding. We demonstrate that {TIAR} {RRM}2, together with its C-terminal extension, is the major contributor for the high-affinity ({nM}) interactions of {TIAR} with target {RNA} sequences.},
	pages = {579--589},
	number = {4},
	journaltitle = {{RNA} Biol},
	author = {Kim, H S and Headey, S J and Yoga, Y M and Scanlon, M J and Gorospe, M and Wilce, M C and Wilce, J A},
	date = {2013},
	pmid = {23603827},
	keywords = {Humans, {RNA}, {RNA} Splicing, Binding Sites, Gene Expression Regulation, Protein Binding, *Amino Acid Motifs, Amino Acid Sequence, {DNA}-Binding Proteins/chemistry/genetics/*metabolis, {DNA}/genetics/*metabolism, Magnetic Resonance Spectroscopy, Messenger/genetics/*metabolism, Models, Molecular, {RNA}-Binding Proteins/*chemistry/genetics/*metaboli, Sequence Alignment, Surface Plasmon Resonance}
}

@article{kavanagh_hallmarks_2011,
	title = {The hallmarks of {CDKN}1C (p57, {KIP}2) in cancer},
	volume = {1816},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21447370},
	doi = {10.1016/j.bbcan.2011.03.002},
	abstract = {Cyclin-dependent kinase inhibitor 1C {CDKN}1C (p57({KIP}2)) regulates several hallmarks of cancer, including apoptosis, cell invasion and metastasis, tumor differentiation and angiogenesis. p57({KIP}2) is generally not mutated in cancer, but its expression is downregulated through epigenetic changes such as {DNA} methylation and repressive histone marks at the promoter. This opens up possibilities for therapeutic intervention through reactivation of p57({KIP}2) gene expression. Furthermore, p57({KIP}2) has been tested as a prognostic factor for many types of cancer, even differentiating between early and late stage cancer. In this review, the multifunctional tumor suppressor capabilities of p57({KIP}2), the mechanisms of p57({KIP}2) transcriptional repression in cancer, and the therapeutic potential of reactivation of p57({KIP}2) protein expression will be discussed.},
	pages = {50--56},
	number = {1},
	journaltitle = {Biochim Biophys Acta},
	author = {Kavanagh, E and Joseph, B},
	date = {2011},
	pmid = {21447370},
	keywords = {Animals, Humans, Cell Differentiation, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p57/*physiology, Neoplasm Invasiveness, Neoplasms/*etiology/pathology/therapy}
}

@article{dubois_multiple_2010,
	title = {Multiple common variants for celiac disease influencing immune gene expression},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20190752},
	doi = {10.1038/ng.543},
	abstract = {We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected {SNPs} with P({GWAS}) {\textbackslash}textless 10(-4) and 18 {SNPs} from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) {\textbackslash}textless 5 x 10(-8)); most contain genes with immune functions ({BACH}2, {CCR}4, {CD}80, {CIITA}-{SOCS}1-{CLEC}16A, {ICOSLG} and {ZMIZ}1), with {ETS}1, {RUNX}3, {THEMIS} and {TNFRSF}14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6\%) tested loci had celiac risk variants correlated (P {\textbackslash}textless 0.0028, {FDR} 5\%) with cis gene expression.},
	pages = {295--302},
	number = {4},
	journaltitle = {Nat Genet},
	author = {Dubois, P C and Trynka, G and Franke, L and Hunt, K A and Romanos, J and Curtotti, A and Zhernakova, A and Heap, G A and Adany, R and Aromaa, A and Bardella, M T and van den Berg, L H and Bockett, N A and de la Concha, E G and Dema, B and Fehrmann, R S and Fernandez-Arquero, M and Fiatal, S and Grandone, E and Green, P M and Groen, H J and Gwilliam, R and Houwen, R H and Hunt, S E and Kaukinen, K and Kelleher, D and Korponay-Szabo, I and Kurppa, K and {MacMathuna}, P and Maki, M and Mazzilli, M C and {McCann}, O T and Mearin, M L and Mein, C A and Mirza, M M and Mistry, V and Mora, B and Morley, K I and Mulder, C J and Murray, J A and Nunez, C and Oosterom, E and Ophoff, R A and Polanco, I and Peltonen, L and Platteel, M and Rybak, A and Salomaa, V and Schweizer, J J and Sperandeo, M P and Tack, G J and Turner, G and Veldink, J H and Verbeek, W H and Weersma, R K and Wolters, V M and Urcelay, E and Cukrowska, B and Greco, L and Neuhausen, S L and {McManus}, R and Barisani, D and Deloukas, P and Barrett, J C and Saavalainen, P and Wijmenga, C and van Heel, D A},
	date = {2010},
	pmid = {20190752},
	keywords = {Humans, Gene Expression Profiling, *Genes, *Polymorphism, Case-Control Studies, Celiac Disease/*genetics, Gene Expression, Genome-Wide Association Study, Meta-Analysis as Topic, {MHC} Class I, Risk, Single Nucleotide}
}

@article{ishmael_role_2008,
	title = {Role of the {RNA}-binding protein tristetraprolin in glucocorticoid-mediated gene regulation},
	volume = {180},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18523301},
	abstract = {Glucocorticoids ({GCs}) are the mainstay of anti-inflammatory therapy. Modulation of posttranscriptional regulation ({PTR}) of gene expression by {GCs} is a relevant yet poorly characterized mechanism of their action. The {RNA}-binding protein tristetraprolin ({TTP}) plays a central role in {PTR} by binding to {AU}-rich elements in the 3'-untranslated region of proinflammatory transcripts and accelerating their decay. We found that {GCs} induce {TTP} expression in primary and immortalized human bronchial epithelial cells. To investigate the importance of {PTR} and the role of {TTP} in {GC} function, we compared the effect of {GC} treatment on genome-wide gene expression using mouse embryonic fibroblasts ({MEFs}) obtained from wild-type and {TTP}(-/-) mice. We confirmed that {GCs} induce {TTP} in {MEFs} and observed in {TTP}(-/-) {MEFs} a striking loss of up to 85\% of {GC}-mediated gene expression. Gene regulation by {TNF}-alpha was similarly affected, as was the antagonistic effect of {GC} on {TNF}-alpha-induced response. Inflammatory genes, including cytokines and chemokines, were among the genes whose sensitivity to {GCs} was affected by lack of {TTP}. Silencing of {TTP} in {WT} {MEFs} by small interfering {RNA} confirmed loss of {GC} response in selected targets. Immunoprecipitation of ribonucleoprotein complexes revealed binding of {TTP} to several validated transcripts. Changes in the rate of transcript degradation studied by actinomycin D were documented for only a subset of transcripts bound to {TTP}. These results reveal a strong and previously unrecognized contribution of {PTR} to the anti-inflammatory action of {GCs} and point at {TTP} as a key factor mediating this process through a complex mechanism of action.},
	pages = {8342--8353},
	number = {12},
	journaltitle = {J Immunol},
	author = {Ishmael, F T and Fang, X and Galdiero, M R and Atasoy, U and Rigby, W F and Gorospe, M and Cheadle, C and Stellato, C},
	date = {2008},
	pmid = {18523301},
	keywords = {Animals, Humans, Mice, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Cells, Cultured, Budesonide/pharmacology, Cell Line, Embryonic Stem Cells/drug effects/metabolism, Fibroblasts/drug effects/metabolism, Gene Expression Regulation/*drug effects/physiolog, Gene Silencing/drug effects, Glucocorticoids/*pharmacology, Knockout, {RNA} Stability/drug effects/physiology, {RNA}-Binding Proteins/antagonists \& inhibitors/gene, Tristetraprolin/antagonists \& inhibitors/deficienc, Up-Regulation/drug effects/physiology}
}

@article{gorospe_p21waf1/cip1_1997,
	title = {p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9050992},
	doi = {10.1038/sj.onc.1200897},
	abstract = {The tumor suppressive effect of p53 is believed to be rooted in its two primary functions: the implementation of cellular growth arrest and the execution of apoptotic cell death. While p53-regulated expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) appears to be central for the implementation of G1 arrest, the participation of p21(Waf1/Cip1) in p53-triggered cell death remains controversial. In the present study, overexpression of p53 in human melanoma {SK}-{MEL}-110 cells through use of an adenoviral expression vector ({AdCMV}.p53) was found to result in apoptosis, while similar infection of primary vascular smooth muscle cells ({VSMC}) instead resulted in a moderate inhibition of growth. Expression of p21(Waf1/Cip1) was strongly elevated in {VSMC}, but showed little change in {SK}-{MEL}-110 cells, although expression of another p53-regulated gene ({GADD}45) was comparable in both {AdCMV}.p53-infected cell types. Evidence that p21(Waf1/Cip1) expression may be required for surviving p53-induced cell death was further supported by the finding that p53 overexpression was highly toxic for p21-deficient mouse embryonal fibroblasts (p21-/- {MEFs}). In both {SK}-{MEL}-110 and p21-/- {MEFs}, adenovirus-driven ectopic expression of p21(Waf1/Cip1) resulted in a substantial protection against p53-induced apoptosis, indicating that p21(Waf1/Cip1) rescued cells from a path of programmed cell death to one of enhanced survival.},
	pages = {929--935},
	number = {8},
	journaltitle = {Oncogene},
	author = {Gorospe, M and Cirielli, C and Wang, X and Seth, P and Capogrossi, M C and Holbrook, N J},
	date = {1997},
	pmid = {9050992},
	keywords = {Animals, Humans, Mice, {RNA}, Messenger/genetics, Proteins/genetics, Cells, Cultured, *Apoptosis, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/*physiology, Gene Expression, Intracellular Signaling Peptides and Proteins, Knockout, Melanoma/*pathology, Tumor Cells, Tumor Suppressor Protein p53/*physiology}
}

@article{tay_global_2009,
	title = {Global discovery of primate-specific genes in the human genome},
	volume = {106},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19581580},
	doi = {10.1073/pnas.0904569106},
	abstract = {The genomic basis of primate phenotypic uniqueness remains obscure, despite increasing genome and transcriptome sequence data availability. Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes are poorly characterized. To discover such genes genomewide, we screened a catalog of 38,037 human transcriptional units ({TUs}), compiled from {EST} and {cDNA} sequences in conjunction with the {FANTOM}3 transcriptome project. We identified 131 {TUs} from transcribed sequences residing within primate-specific insertions in 9-species sequence alignments and outside of segmental duplications. Exons of 120 (92\%) of the {TUs} contained interspersed repeats, indicating that repeat insertions may have contributed to primate-specific gene genesis. Fifty-nine (46\%) primate-specific {TUs} may encode proteins. Although primate-specific {TU} transcript lengths were comparable to known human gene {mRNA} lengths overall, 92 (70\%) primate-specific {TUs} were single-exon. Thirty-two (24\%) primate-specific {TUs} were localized to subtelomeric and pericentromeric regions. Forty (31\%) of the {TUs} were nested in introns of known genes, indicating that primate-specific {TUs} may arise within older, protein-coding regions. Primate-specific {TUs} were preferentially expressed in reproductive organs and tissues (P {\textbackslash}textless 0.011), consistent with the expectation that emergence of new, lineage-specific genes may accompany speciation or reproduction. Of the 33 primate-specific {TUs} with human Affymetrix microarray probe support, 21 were differentially expressed in human teratozoospermia. In addition to elucidating the likely functional relevance of primate-specific {TUs} to reproduction, we present a set of primate-specific genes for future functional studies, and we implicate nonduplicated pericentromeric and subtelomeric regions in gene genesis.},
	pages = {12019--12024},
	number = {29},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Tay, S K and Blythe, J and Lipovich, L},
	date = {2009},
	pmid = {19581580},
	keywords = {{DNA}, Animals, Conserved Sequence, Genetic, Genome, Humans, Promoter Regions, {RNA}, Transcription, Gene Expression Regulation, Exons/genetics, Genetic/genetics, Chromosomes, Complementary/genetics, Human/*genetics, Interspersed Repetitive Sequences/genetics, Introns/genetics, Macaca mulatta/genetics, Mammalian/genetics, Messenger/genetics/metabolism, Open Reading Frames/genetics, Pan troglodytes/genetics, Primates/*genetics, Reproduction/genetics, Species Specificity, Transcription Factors/genetics}
}

@article{mattick_deconstructing_2009,
	title = {Deconstructing the dogma: a new view of the evolution and genetic programming of complex organisms},
	volume = {1178},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19845626},
	doi = {10.1111/j.1749-6632.2009.04991.x},
	abstract = {Since the birth of molecular biology it has been generally assumed that most genetic information is transacted by proteins, and that {RNA} plays an intermediary role. This led to the subsidiary assumption that the vast tracts of noncoding sequences in the genomes of higher organisms are largely nonfunctional, despite the fact that they are transcribed. These assumptions have since become articles of faith, but they are not necessarily correct. I propose an alternative evolutionary history whereby developmental and cognitive complexity has arisen by constructing sophisticated {RNA}-based regulatory networks that interact with generic effector complexes to control gene expression patterns and the epigenetic trajectories of differentiation and development. Environmental information can also be conveyed into this regulatory system via {RNA} editing, especially in the brain. Moreover, the observations that {RNA}-directed epigenetic changes can be inherited raises the intriguing question: has evolution learnt how to learn?},
	pages = {29--46},
	journaltitle = {Ann N Y Acad Sci},
	author = {Mattick, J S},
	date = {2009},
	pmid = {19845626},
	keywords = {Animals, Humans, {RNA}, *Genome, Introns, *Evolution, Developmental Biology, Molecular, {RNA} Editing, Untranslated/metabolism}
}

@article{murthy_value_2013,
	title = {Value of isolated {IgA} anti-beta2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome},
	volume = {65},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23983008},
	doi = {10.1002/art.38131},
	abstract = {{OBJECTIVE}: To examine the prevalence of isolated {IgA} anti-beta2 -glycoprotein I (anti-beta2 {GPI}) positivity and the association of these antibodies, and a subgroup that bind specifically to domain {IV}/V of beta2 {GPI}, with clinical manifestations of the antiphospholipid syndrome ({APS}) in 3 patient groups and to evaluate the pathogenicity of {IgA} anti-beta2 {GPI} in a mouse model of thrombosis. {METHODS}: Patients with systemic lupus erythematosus ({SLE}) from a multiethnic, multicenter cohort ({LUpus} in {MInorities}, {NAture} versus nurture [{LUMINA}]) (n = 558), patients with {SLE} from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory ({APLS}) (n = 5,098) were evaluated. {IgA} anti-beta2 {GPI} titers and binding to domain {IV}/V of beta2 {GPI} were examined by enzyme-linked immunosorbent assay ({ELISA}). {CD}1 mice were inoculated with purified {IgA} anti-beta2 {GPI} antibodies, and surgical procedures and {ELISAs} were performed to evaluate thrombus development and tissue factor ({TF}) activity. {RESULTS}: A total of 198 patients were found to be positive for {IgA} anti-beta2 {GPI} isotype, and 57 patients were positive exclusively for {IgA} anti-beta2 {GPI} antibodies. Of these, 13 of 23 patients (56.5\%) in the {LUMINA} cohort, 17 of 17 patients (100\%) in the Hopkins cohort, and 10 of 17 patients (58.9\%) referred to {APLS} had at least one {APS}-related clinical manifestation. Fifty-four percent of all the {IgA} anti-beta2 {GPI}-positive serum samples reacted with domain {IV}/V of anti-beta2 {GPI}, and 77\% of those had clinical features of {APS}. Isolated {IgA} anti-beta2 {GPI} positivity was associated with an increased risk of arterial thrombosis (P {\textbackslash}textless 0.001), venous thrombosis (P = 0.015), and all thrombosis (P {\textbackslash}textless 0.001). The association between isolated {IgA} anti-beta2 {GPI} and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that {IgA} anti-beta2 {GPI} antibodies induced significantly larger thrombi and higher {TF} levels compared to controls. {CONCLUSION}: Isolated {IgA} anti-beta2 {GPI}-positive titers may identify additional patients with clinical features of {APS}. Testing for these antibodies when other antiphospholipid tests are negative and {APS} is suspected is recommended. {IgA} anti-beta2 {GPI} antibodies directed to domain {IV}/V of beta2 {GPI} represent an important subgroup of clinically relevant antiphospholipids.},
	pages = {3186--3193},
	number = {12},
	journaltitle = {Arthritis Rheum},
	author = {Murthy, V and Willis, R and Romay-Penabad, Z and Ruiz-Limon, P and Martinez-Martinez, L A and Jatwani, S and Jajoria, P and Seif, A and Alarcon, G S and Papalardo, E and Liu, J and Vila, L M and {McGwin} Jr., G and {McNearney}, T A and Maganti, R and Sunkureddi, P and Parekh, T and Tarantino, M and Akhter, E and Fang, H and Gonzalez, E B and Binder, W R and Norman, G L and Shums, Z and Teodorescu, M and Reveille, J D and Petri, M and Pierangeli, S S},
	date = {2013},
	pmid = {23983008},
	keywords = {Animals, Humans, Mice, Anti-Idiotypic/*blood, Antibodies, Antiphospholipid Syndrome/blood/*diagnosis/immunol, Autoantibodies/*blood, beta 2-Glycoprotein I/*immunology, Immunoglobulin A/*blood, Longitudinal Studies, Prevalence, Thrombosis/diagnosis/immunology}
}

@article{gorospe_tumor_1993,
	title = {Tumor necrosis factor increases stability of interleukin-1 {mRNA} by activating protein kinase C},
	volume = {268},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7681061},
	abstract = {The {mRNAs} coding for interleukin-1 alpha ({IL}-1 alpha) and {IL}-1 beta are constitutively transcribed but do not accumulate in human diploid fibroblasts and in fibrosarcoma cells. Treatment of these cells with tumor necrosis factor ({TNF}) induces accumulation of {IL}-1 {mRNA} by an unknown mechanism. This induction of {IL}-1 {mRNA} was investigated in {HT}-1080 cells. The induction was quite fast, with maximum levels of {IL}-1 alpha and beta {mRNA} reached 4 h after addition of {TNF}. Nuclear run-off experiment showed that {TNF} did not increase the rate of transcription of {IL}-1 {mRNA}. This {mRNA} was apparently unstable in untreated cells, but it accumulated in cycloheximide-treated cells. Phorbol esters induced {IL}-1 {mRNA}, suggesting that activation of protein kinase C was responsible for the accumulation of this {mRNA}. This hypothesis was confirmed by experiments with the {PKC} inhibitors staurosporine and calphostin C, which prevented the induction of {IL}-1 {mRNA} by {TNF} and accelerated the decay of this {mRNA} in cells pretreated with {TNF}. Both {IL}-1 alpha and {IL}-1 beta were detected in {TNF}-treated cells by Western blot analysis and enzyme-linked immunosorbent assay. These results indicate that the {TNF}-mediated induction of {IL}-1 can be entirely accounted for by stabilization of this {mRNA}.},
	pages = {6214--6220},
	number = {9},
	journaltitle = {J Biol Chem},
	author = {Gorospe, M and Kumar, S and Baglioni, C},
	date = {1993},
	pmid = {7681061},
	keywords = {Humans, {RNA}, Cultured, *Naphthalenes, Alkaloids/pharmacology, Blotting, Cycloheximide/pharmacology, Enzyme Activation, Interleukin-1/*genetics/metabolism, Kinetics, Messenger/*metabolism, Polycyclic Compounds/pharmacology, Protein Kinase C/antagonists \& inhibitors/*metabol, Staurosporine, Tetradecanoylphorbol Acetate/pharmacology, Tumor Cells, Tumor Necrosis Factor-alpha/*pharmacology, Western}
}

@article{atasoy_regulation_2003,
	title = {Regulation of eotaxin gene expression by {TNF}-alpha and {IL}-4 through {mRNA} stabilization: involvement of the {RNA}-binding protein {HuR}},
	volume = {171},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14530362},
	abstract = {During inflammatory responses, a major posttranscriptional regulation of early response and inflammatory gene expression occurs through modulation of {mRNA} turnover. We report that two potent inducers of the {CC} chemokine eotaxin, {TNF}-alpha and {IL}-4, regulate its production in airway epithelial cells by increasing eotaxin {mRNA} stability. In experiments using the transcriptional inhibitor actinomycin D, eotaxin {mRNA} half-life was significantly prolonged by cell stimulation with {TNF}-alpha or {IL}-4, with the combination of the two cytokines being the most effective in extending the {mRNA} half-life. Involvement of the eotaxin 3' untranslated region in the {mRNA}-stabilizing effect was tested by transient transfection of a construct expressing a chimeric transcript carrying a serum-inducible beta-globin reporter linked to the eotaxin 3' untranslated region. The half-life of the chimeric {mRNA} was markedly increased in cells stimulated with {TNF}-alpha and {IL}-4. Evidence that the {mRNA}-stabilizing protein {HuR} participated in the cytokine effect was obtained: first, {HuR} presence in the cytoplasm, believed to be required for {HuR}-mediated {mRNA} stabilization, increased in both transformed ({BEAS}-2B cell line) and primary bronchial epithelial cells following treatment with {TNF}-alpha and {IL}-4. Second, endogenous eotaxin {mRNA} was found to bind to {HuR} in vivo, as detected by immunoprecipitation of {HuR}-containing messenger ribonucleoprotein complexes followed by real-time {RT}-{PCR} analysis; such association increased after cell treatment with {TNF}-alpha and {IL}-4. Third, overexpression of {HuR} in {BEAS}-2B cells significantly increased the expression of eotaxin {mRNA} and protein. Our findings implicate {mRNA} stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for {HuR} in this effect.},
	pages = {4369--4378},
	number = {8},
	journaltitle = {J Immunol},
	author = {Atasoy, U and Curry, S L and Lopez de Silanes, I and Shyu, A B and Casolaro, V and Gorospe, M and Stellato, C},
	date = {2003},
	pmid = {14530362},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA}, *Antigens, 3' Untranslated Regions/physiology, Bronchi, {CC}/*biosynthesis/genetics, Cell Line, Chemokine {CCL}11, Chemokines, Drug Combinations, Gene Expression Regulation/*immunology, Hu Paraneoplastic Encephalomyelitis Antigens, Interleukin-4/*physiology, Messenger/*metabolism/physiology, Molecular Sequence Data, {NIH} 3T3 Cells, Respiratory Mucosa/immunology/metabolism, {RNA} Stability/genetics/*immunology, {RNA}-Binding Proteins/*physiology, Surface, Transformed, Tumor Necrosis Factor-alpha/*physiology, Up-Regulation/genetics/immunology}
}

@article{goecks_galaxy:_2010,
	title = {Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20738864},
	doi = {10.1186/gb-2010-11-8-r86},
	abstract = {Increased reliance on computational approaches in the life sciences has revealed grave concerns about how accessible and reproducible computation-reliant results truly are. Galaxy http://usegalaxy.org, an open web-based platform for genomic research, addresses these problems. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Pages are interactive, web-based documents that provide users with a medium to communicate a complete computational analysis.},
	pages = {R86},
	number = {8},
	journaltitle = {Genome Biol},
	author = {Goecks, J and Nekrutenko, A and Taylor, J},
	date = {2010},
	pmid = {20738864},
	keywords = {Animals, Humans, Databases, Nucleic Acid, Algorithms, *Internet, Computational Biology/*methods, Genomics/methods}
}

@article{liu_use_2014,
	title = {Use model-based Analysis of {ChIP}-Seq ({MACS}) to analyze short reads generated by sequencing protein-{DNA} interactions in embryonic stem cells},
	volume = {1150},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24743991},
	doi = {10.1007/978-1-4939-0512-6_4},
	abstract = {Model-based Analysis of {ChIP}-Seq ({MACS}) is a computational algorithm for identifying genome-wide protein-{DNA} interaction from {ChIP}-Seq data. {MACS} combines multiple modules to process aligned {ChIP}-Seq reads for either transcription factor or histone modification by removing redundant reads, estimating fragment length, building signal profile, calculating peak enrichment, and refining and reporting peak calls. In this protocol, we provide a detailed demonstration of how to apply {MACS} to analyze {ChIP}-Seq datasets related to protein-{DNA} interactions in embryonic stem cells ({ES} cells). Instruction on how to interpret and visualize the results is also provided. {MACS} is an open-source and is available from http://github.com/taoliu/{MACS}.},
	pages = {81--95},
	journaltitle = {Methods Mol Biol},
	author = {Liu, T},
	date = {2014},
	pmid = {24743991},
	keywords = {{DNA}, Genomics/*methods, Sequence Analysis, Humans, Protein Binding, Transcription Factors/metabolism, Algorithms, Software, *High-Throughput Nucleotide Sequencing, Cell Line, Chromatin Immunoprecipitation/*methods, {DNA}-Binding Proteins/*metabolism, {DNA}/*genetics/*metabolism, Embryonic Stem Cells/*metabolism, Histones/metabolism}
}

@article{zu_non-atg-initiated_2011,
	title = {Non-{ATG}-initiated translation directed by microsatellite expansions},
	volume = {108},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21173221},
	doi = {10.1073/pnas.1013343108},
	abstract = {Trinucleotide expansions cause disease by both protein- and {RNA}-mediated mechanisms. Unexpectedly, we discovered that {CAG} expansion constructs express homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence of an {ATG} start codon. This repeat-associated non-{ATG} translation ({RAN} translation) occurs across long, hairpin-forming repeats in transfected cells or when expansion constructs are integrated into the genome in lentiviral-transduced cells and brains. Additionally, we show that {RAN} translation across human spinocerebellar ataxia type 8 ({SCA}8) and myotonic dystrophy type 1 ({DM}1) {CAG} expansion transcripts results in the accumulation of {SCA}8 polyalanine and {DM}1 polyglutamine expansion proteins in previously established {SCA}8 and {DM}1 mouse models and human tissue. These results have implications for understanding fundamental mechanisms of gene expression. Moreover, these toxic, unexpected, homopolymeric proteins now should be considered in pathogenic models of microsatellite disorders.},
	pages = {260--265},
	number = {1},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Zu, T and Gibbens, B and Doty, N S and Gomes-Pereira, M and Huguet, A and Stone, M D and Margolis, J and Peterson, M and Markowski, T W and Ingram, M A and Nan, Z and Forster, C and Low, W C and Schoser, B and Somia, N V and Clark, H B and Schmechel, S and Bitterman, P B and Gourdon, G and Swanson, M S and Moseley, M and Ranum, L P},
	date = {2011},
	pmid = {21173221},
	keywords = {Humans, Amino Acid Sequence, Blotting, Cell Line, Cloning, Codon, {DNA} Primers/genetics, Fluorescent Antibody Technique, Genetic Vectors, Immunoblotting, Immunohistochemistry, Immunoprecipitation, Initiator/genetics, Lentivirus, Mass Spectrometry, Molecular, Molecular Sequence Data, Mutagenesis, Myotonic Dystrophy/genetics, Northern, Peptides/genetics/metabolism, Protein Biosynthesis/*genetics/physiology, Reverse Transcriptase Polymerase Chain Reaction, Spinocerebellar Ataxias/*genetics, Trinucleotide Repeat Expansion/*genetics}
}

@article{guo_novel_2013,
	title = {Novel {MicroRNA} Reporter Uncovers Repression of Let-7 by {GSK}-3beta},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23840442},
	doi = {10.1371/journal.pone.0066330},
	abstract = {Several members of the let-7 {microRNA} family are downregulated in ovarian and other cancers. They are thought to act as tumor suppressors by lowering growth-promoting and anti-apoptotic proteins. In order to measure cellular let-7 levels systematically, we have developed a highly sensitive let-7 reporter assay system based on the expression of a chimeric {mRNA} that contains the luciferase coding region and a 3'-untranslated region ({UTR}) bearing two let-7-binding sites. In cells expressing the reporter construct, termed {pmirGLO}-let7, luciferase activity was high when let-7 was absent, while luciferase activity was low when let-7 levels were elevated. The ovarian cancer cell lines {BG}-1 and {UCI}-101 were transfected with the let-7 reporter and surveyed with a library of kinase inhibitors in order to identify pathways affecting let-7 activity. Among the inhibitors causing changes in endogenous let-7 abundance, the lowering of glycogen synthase kinase 3 ({GSK}-3)beta function specifically increased let-7 levels and lowered luciferase activity. Similarly, silencing {GSK}-3beta increased both mature and primary-let-7 levels in {BG}-1 cells, and decreased {BG}-1 cell survival. Further studies identified p53 as a downstream effector of the {GSK}-3beta-mediated repression of let-7 biosynthesis. Our studies highlight {GSK}-3beta as a novel therapeutic target in ovarian tumorigenesis.},
	pages = {e66330},
	number = {6},
	journaltitle = {{PLoS} One},
	author = {Guo, R and Abdelmohsen, K and Morin, P J and Gorospe, M},
	date = {2013},
	pmid = {23840442}
}

@article{sunku_insights_2013,
	title = {Insights into the photoprotective switch of the major light-harvesting complex {II} ({LHCII}): a preserved core of arginine-glutamate interlocked helices complemented by adjustable loops},
	volume = {288},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23629658},
	doi = {10.1074/jbc.M113.456111},
	abstract = {Light-harvesting antennae of the {LHC} family form transmembrane three-helix bundles of which two helices are interlocked by conserved arginine-glutamate (Arg-Glu) ion pairs that form ligation sites for chlorophylls. The antenna proteins of photosystem {II} have an intriguing dual function. In excess light, they can switch their conformation from a light-harvesting into a photoprotective state, in which the excess and harmful excitation energies are safely dissipated as heat. Here we applied magic angle spinning {NMR} and selective Arg isotope enrichment as a noninvasive method to analyze the Arg structures of the major light-harvesting complex {II} ({LHCII}). The conformations of the Arg residues that interlock helix A and B appear to be preserved in the light-harvesting and photoprotective state. Several Arg residues have very downfield-shifted proton {NMR} responses, indicating that they stabilize the complex by strong hydrogen bonds. For the Arg Calpha chemical shifts, differences are observed between {LHCII} in the active, light-harvesting and in the photoprotective, quenched state. These differences are attributed to a conformational change of the Arg residue in the stromal loop region. We conclude that the interlocked helices of {LHCII} form a rigid core. Consequently, the {LHCII} conformational switch does not involve changes in A/B helix tilting but likely involves rearrangements of the loops and helical segments close to the stromal and lumenal ends.},
	pages = {19796--19804},
	number = {27},
	journaltitle = {J Biol Chem},
	author = {Sunku, K and de Groot, H J and Pandit, A},
	date = {2013},
	pmid = {23629658},
	keywords = {Arginine/*chemistry/metabolism, Biomolecular, Chlamydomonas reinhardtii/*enzymology, Glutamic Acid/*chemistry/metabolism, Light-Harvesting Protein Complexes/*chemistry/meta, Nuclear Magnetic Resonance, Protein Structure, Quaternary, Secondary}
}

@article{wang_novo_2013,
	title = {De novo prediction of {RNA}-protein interactions from sequence information},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23138266},
	doi = {10.1039/c2mb25292a},
	abstract = {Protein-{RNA} interactions are fundamentally important in understanding cellular processes. In particular, non-coding {RNA}-protein interactions play an important role to facilitate biological functions in signalling, transcriptional regulation, and even the progression of complex diseases. However, experimental determination of protein-{RNA} interactions remains time-consuming and labour-intensive. Here, we develop a novel extended naive-Bayes-classifier for de novo prediction of protein-{RNA} interactions, only using protein and {RNA} sequence information. Specifically, we first collect a set of known protein-{RNA} interactions as gold-standard positives and extract sequence-based features to represent each protein-{RNA} pair. To fill the gap between high dimensional features and scarcity of gold-standard positives, we select effective features by cutting a likelihood ratio score, which not only reduces the computational complexity but also allows transparent feature integration during prediction. An extended naive Bayes classifier is then constructed using these effective features to train a protein-{RNA} interaction prediction model. Numerical experiments show that our method can achieve the prediction accuracy of 0.77 even though only a small number of protein-{RNA} interaction data are available. In particular, we demonstrate that the extended naive-Bayes-classifier is superior to the naive-Bayes-classifier by fully considering the dependences among features. Importantly, we conduct {ncRNA} pull-down experiments to validate the predicted novel protein-{RNA} interactions and identify the interacting proteins of {sbRNA} {CeN}72 in C. elegans, which further demonstrates the effectiveness of our method.},
	pages = {133--142},
	number = {1},
	journaltitle = {Mol Biosyst},
	author = {Wang, Y and Chen, X and Liu, Z P and Huang, Q and Xu, D and Zhang, X S and Chen, R and Chen, L},
	date = {2013},
	pmid = {23138266},
	keywords = {Sequence Analysis, Animals, Protein Binding, Reproducibility of Results, Databases, *Bayes Theorem, Biological, Caenorhabditis elegans Proteins/chemistry/genetics, Caenorhabditis elegans/chemistry/genetics/metaboli, Computational Biology/*methods, Models, Protein, Protein/*methods, {RNA}-Binding Proteins/chemistry/*metabolism, {RNA}/chemistry/genetics/*metabolism, {ROC} Curve}
}

@article{park_staufen-mediated_2013,
	title = {Staufen-mediated {mRNA} decay},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23681777},
	doi = {10.1002/wrna.1168},
	abstract = {Staufen1 ({STAU}1)-mediated {mRNA} decay ({SMD}) is an {mRNA} degradation process in mammalian cells that is mediated by the binding of {STAU}1 to a {STAU}1-binding site ({SBS}) within the 3'-untranslated region (3'-{UTR}) of target {mRNAs}. During {SMD}, {STAU}1, a double-stranded (ds) {RNA}-binding protein, recognizes {dsRNA} structures formed either by intramolecular base pairing of 3'-{UTR} sequences or by intermolecular base pairing of 3'-{UTR} sequences with a long-noncoding {RNA} ({lncRNA}) via partially complementary Alu elements. Recently, {STAU}2, a paralog of {STAU}1, has also been reported to mediate {SMD}. Both {STAU}1 and {STAU}2 interact directly with the {ATP}-dependent {RNA} helicase {UPF}1, a key {SMD} factor, enhancing its helicase activity to promote effective {SMD}. Moreover, {STAU}1 and {STAU}2 form homodimeric and heterodimeric interactions via domain-swapping. Because both {SMD} and the mechanistically related nonsense-mediated {mRNA} decay ({NMD}) employ {UPF}1; {SMD} and {NMD} are competitive pathways. Competition contributes to cellular differentiation processes, such as myogenesis and adipogenesis, placing {SMD} at the heart of various physiologically important mechanisms.},
	pages = {423--435},
	number = {4},
	journaltitle = {Wiley Interdiscip Rev {RNA}},
	author = {Park, E and Maquat, L E},
	date = {2013},
	pmid = {23681777}
}

@article{yan_comprehensive_2015,
	title = {Comprehensive Genomic Characterization of Long Non-coding {RNAs} across Human Cancers},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26461095},
	doi = {10.1016/j.ccell.2015.09.006},
	abstract = {The discovery of long non-coding {RNA} ({lncRNA}) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of {lncRNA} alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atlas. Our results suggest that the expression and dysregulation of {lncRNAs} are highly cancer type specific compared with protein-coding genes. Using the integrative data generated by this analysis, we present a clinically guided small interfering {RNA} screening strategy and a co-expression analysis approach to identify cancer driver {lncRNAs} and predict their functions. This provides a resource for investigating {lncRNAs} in cancer and lays the groundwork for the development of new diagnostics and treatments.},
	pages = {529--540},
	number = {4},
	journaltitle = {Cancer Cell},
	author = {Yan, X and Hu, Z and Feng, Y and Hu, X and Yuan, J and Zhao, S D and Zhang, Y and Yang, L and Shan, W and He, Q and Fan, L and Kandalaft, L E and Tanyi, J L and Li, C and Yuan, C X and Zhang, D and Yuan, H and Hua, K and Lu, Y and Katsaros, D and Huang, Q and Montone, K and Fan, Y and Coukos, G and Boyd, J and Sood, A K and Rebbeck, T and Mills, G B and Dang, C V and Zhang, L},
	date = {2015},
	pmid = {26461095},
	keywords = {Human, Genetic, Genome, Humans, {RNA}, Transcription, Long Noncoding/*genetics, Gene Expression Profiling, *Gene Expression Regulation, *Genetic Variation, Cell Line, Computational Biology/methods, Epigenesis, Neoplasms/*genetics, Neoplastic, Tumor}
}

@article{fan_global_2002,
	title = {Global analysis of stress-regulated {mRNA} turnover by using {cDNA} arrays},
	volume = {99},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12149460},
	doi = {10.1073/pnas.162212399},
	abstract = {{cDNA} array technology has proven to be a powerful way to monitor global changes in gene expression patterns. Here, we present an approach that extends the current utility of {cDNA} arrays to allow the evaluation of the relative roles of transcription and {mRNA} turnover in governing gene expression on a global basis, compared with current individual gene-by-gene analyses. This method, which involves comparison of large-scale hybridization patterns generated with steady-state {mRNA} versus newly transcribed (nuclear run-on) {RNA}, was used to demonstrate the importance of {mRNA} turnover in regulating gene expression following several conditions of stress.},
	pages = {10611--10616},
	number = {16},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Fan, J and Yang, X and Wang, W and Wood 3rd, W H and Becker, K G and Gorospe, M},
	date = {2002},
	pmid = {12149460},
	keywords = {Humans, Messenger, Oligonucleotide Array Sequence Analysis, Cultured, *Gene Expression, *{RNA}, Carcinoma, Heat-Shock Response, Lung Neoplasms, Non-Small-Cell Lung, Physiological/*genetics, Prostaglandins A/pharmacology, Stress, Tumor Cells, Ultraviolet Rays}
}

@article{wu_large-scale_2002,
	title = {Large-scale prediction of Saccharomyces cerevisiae gene function using overlapping transcriptional clusters},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12089522},
	doi = {10.1038/ng906},
	abstract = {Genome sequencing has led to the discovery of tens of thousands of potential new genes. Six years after the sequencing of the well-studied yeast Saccharomyces cerevisiae and the discovery that its genome encodes approximately 6,000 predicted proteins, more than 2,000 have not yet been characterized experimentally, and determining their functions seems far from a trivial task. One crucial constraint is the generation of useful hypotheses about protein function. Using a new approach to interpret microarray data, we assign likely cellular functions with confidence values to these new yeast proteins. We perform extensive genome-wide validations of our predictions and offer visualization methods for exploration of the large numbers of functional predictions. We identify potential new members of many existing functional categories including 285 candidate proteins involved in transcription, processing and transport of non-coding {RNA} molecules. We present experimental validation confirming the involvement of several of these proteins in ribosomal {RNA} processing. Our methodology can be applied to a variety of genomics data types and organisms.},
	pages = {255--265},
	number = {3},
	journaltitle = {Nat Genet},
	author = {Wu, L F and Hughes, T R and Davierwala, A P and Robinson, M D and Stoughton, R and Altschuler, S J},
	date = {2002},
	pmid = {12089522},
	keywords = {Genetic, Genome, {RNA}, Transcription, Gene Expression Regulation, Oligonucleotide Array Sequence Analysis, Reproducibility of Results, Databases, Algorithms, Cluster Analysis, Confidence Intervals, Fungal, Fungal Proteins/genetics/metabolism/*physiology, Genetic/*genetics, Mathematics, Open Reading Frames/genetics, Phenotype, Post-Translational/genetics, Predictive Value of Tests, Probability, Protein Processing, Recombinant Fusion Proteins/metabolism, Ribosomal/genetics/metabolism, Saccharomyces cerevisiae/*genetics}
}

@article{shaaban_native_2014,
	title = {The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. {RM}-14-6},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24237421},
	doi = {10.1080/14786419.2013.855932},
	abstract = {We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species {RM}-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, this study highlights the first native bacterial production of isopterocarpolone and the first full characterisation of isopterocarpolone using 1D and 2D {NMR} spectroscopy and {HR}-{ESI} mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery.},
	pages = {337--339},
	number = {5},
	journaltitle = {Nat Prod Res},
	author = {Shaaban, K A and Singh, S and Elshahawi, S I and Wang, X and Ponomareva, L V and Sunkara, M and Copley, G C and Hower, J C and Morris, A J and Kharel, M K and Thorson, J S},
	date = {2014},
	pmid = {24237421}
}

@article{ulitsky_average_2006,
	title = {The average common substring approach to phylogenomic reconstruction},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16597244},
	doi = {10.1089/cmb.2006.13.336},
	abstract = {We describe a novel method for efficient reconstruction of phylogenetic trees, based on sequences of whole genomes or proteomes, whose lengths may greatly vary. The core of our method is a new measure of pairwise distances between sequences. This measure is based on computing the average lengths of maximum common substrings, which is intrinsically related to information theoretic tools (Kullback-Leibler relative entropy). We present an algorithm for efficiently computing these distances. In principle, the distance of two l long sequences can be calculated in O(l) time. We implemented the algorithm using suffix arrays our implementation is fast enough to enable the construction of the proteome phylogenomic tree for hundreds of species and the genome phylogenomic forest for almost two thousand viruses. An initial analysis of the results exhibits a remarkable agreement with "acceptable phylogenetic and taxonomic truth." To assess our approach, our results were compared to the traditional (single-gene or protein-based) maximum likelihood method. The obtained trees were compared to implementations of a number of alternative approaches, including two that were previously published in the literature, and to the published results of a third approach. Comparing their outcome and running time to ours, using a "traditional" trees and a standard tree comparison method, our algorithm improved upon the "competition" by a substantial margin. The simplicity and speed of our method allows for a whole genome analysis with the greatest scope attempted so far. We describe here five different applications of the method, which not only show the validity of the method, but also suggest a number of novel phylogenetic insights.},
	pages = {336--350},
	number = {2},
	journaltitle = {J Comput Biol},
	author = {Ulitsky, I and Burstein, D and Tuller, T and Chor, B},
	date = {2006},
	pmid = {16597244},
	keywords = {{DNA}, Sequence Analysis, *Algorithms, *Evolution, *Phylogeny, Mitochondrial/chemistry/classification/*genet, Molecular, Protein, Proteins/chemistry/classification/*genetics, Sequence Alignment/*methods, Viruses/chemistry/classification/*genetics}
}

@article{marsh_how_2010,
	title = {How do proteins gain new domains?},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20630117},
	doi = {10.1186/gb-2010-11-7-126},
	abstract = {A study of the contributions of different mechanisms of domain gain in animal proteins suggests that gene fusion is likely to be most frequent.},
	pages = {126},
	number = {7},
	journaltitle = {Genome Biol},
	author = {Marsh, J A and Teichmann, S A},
	date = {2010},
	pmid = {20630117},
	keywords = {Animals, Humans, Exons/genetics, *Protein Structure, Evolution, Introns/genetics, Models, Molecular, Proteins/*chemistry, Tertiary}
}

@article{stauber_crystal_2006,
	title = {Crystal structure of the {IL}-2 signaling complex: paradigm for a heterotrimeric cytokine receptor},
	volume = {103},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16477002},
	doi = {10.1073/pnas.0511161103},
	abstract = {{IL}-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits {IL}-2R alpha, {IL}-2R beta, and gamma(c). Here, we describe the crystal structure of the trimeric assembly of the human {IL}-2 receptor ectodomains in complex with {IL}-2 at 3.0 A resolution. The quaternary structure is consistent with a stepwise assembly from {IL}-2/{IL}-2R alpha to {IL}-2/{IL}-2R alpha/{IL}-2R beta to {IL}-2/{IL}-2R alpha/{IL}-2R beta/gamma(c). The {IL}-2R alpha subunit forms the largest of the three {IL}-2/{IL}-2R interfaces, which, together with the high abundance of charge-charge interactions, correlates well with the rapid association rate and high-affinity interaction of {IL}-2R alpha with {IL}-2 at the cell surface. Surprisingly, {IL}-2R alpha makes no contacts with {IL}-2R beta or gamma(c), and only minor changes are observed in the {IL}-2 structure in response to receptor binding. These findings support the principal role of {IL}-2R alpha to deliver {IL}-2 to the signaling complex and act as regulator of signal transduction. Cooperativity in assembly of the final quaternary complex is easily explained by the extraordinarily extensive set of interfaces found within the fully assembled {IL}-2 signaling complex, which nearly span the entire length of the {IL}-2R beta and gamma(c) subunits. Helix A of {IL}-2 wedges tightly between {IL}-2R beta and gamma(c) to form a three-way junction that coalesces into a composite binding site for the final gamma(c) recruitment. The {IL}-2/gamma(c) interface itself exhibits the smallest buried surface and the fewest hydrogen bonds in the complex, which is consistent with its promiscuous use in other cytokine receptor complexes.},
	pages = {2788--2793},
	number = {8},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Stauber, D J and Debler, E W and Horton, P A and Smith, K A and Wilson, I A},
	date = {2006},
	pmid = {16477002},
	keywords = {Humans, Crystallography, Interleukin-2/*chemistry, Protein Structure, Quaternary, Receptors, Signal Transduction}
}

@article{kundrapu_more_2014,
	title = {More cleaning, less screening: evaluation of the time required for monitoring versus performing environmental cleaning},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24442088},
	doi = {10.1086/674852},
	pages = {202--204},
	number = {2},
	journaltitle = {Infect Control Hosp Epidemiol},
	author = {Kundrapu, S and Sunkesula, V and Sitzlar, B M and Fertelli, D and Deshpande, A and Donskey, C J},
	date = {2014},
	pmid = {24442088}
}

@article{schroeder_oncodriverole_2014,
	title = {{OncodriveROLE} classifies cancer driver genes in loss of function and activating mode of action},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25161246},
	doi = {10.1093/bioinformatics/btu467},
	abstract = {{MOTIVATION}: Several computational methods have been developed to identify cancer drivers genes-genes responsible for cancer development upon specific alterations. These alterations can cause the loss of function ({LoF}) of the gene product, for instance, in tumor suppressors, or increase or change its activity or function, if it is an oncogene. Distinguishing between these two classes is important to understand tumorigenesis in patients and has implications for therapy decision making. Here, we assess the capacity of multiple gene features related to the pattern of genomic alterations across tumors to distinguish between activating and {LoF} cancer genes, and we present an automated approach to aid the classification of novel cancer drivers according to their role. {RESULT}: {OncodriveROLE} is a machine learning-based approach that classifies driver genes according to their role, using several properties related to the pattern of alterations across tumors. The method shows an accuracy of 0.93 and Matthew's correlation coefficient of 0.84 classifying genes in the Cancer Gene Census. The {OncodriveROLE} classifier, its results when applied to two lists of predicted cancer drivers and {TCGA}-derived mutation and copy number features used by the classifier are available at http://bg.upf.edu/oncodrive-role. {AVAILABILITY} {AND} {IMPLEMENTATION}: The R implementation of the {OncodriveROLE} classifier is available at http://bg.upf.edu/oncodrive-role. {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at Bioinformatics online.},
	pages = {i549--55},
	number = {17},
	journaltitle = {Bioinformatics},
	author = {Schroeder, M P and Rubio-Perez, C and Tamborero, D and Gonzalez-Perez, A and Lopez-Bigas, N},
	date = {2014},
	pmid = {25161246},
	keywords = {Humans, Algorithms, Software, *Artificial Intelligence, *Genes, *Oncogenes, Genomics/methods, Mutation, Neoplasms/genetics, Tumor Suppressor}
}

@article{gubin_conditional_2014,
	title = {Conditional knockout of the {RNA}-binding protein {HuR} in {CD}4+ T cells reveals a gene dosage effect on cytokine production},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24477678},
	doi = {10.2119/molmed.2013.00127},
	abstract = {The posttranscriptional mechanisms by which {RNA} binding proteins ({RBPs}) regulate T cell differentiation and cytokine production in vivo remain unclear. The {RBP} {HuR} binds to labile {mRNAs} usually leading to increases in {mRNA} stability and/or translation. Previous work demonstrated that {HuR} binds to the {mRNAs} encoding the Th2 transcription factor {GATA}-3 and Th2 cytokines {IL}-4 and {IL}-13, thereby regulating their expression. Using a novel conditional {HuR} knockout ({KO}) mouse in which {HuR} is deleted in activated T cells we show that Th2-polarized cells from heterozygous {HuR} conditional ({OX}40-Cre {HuRfl}/+) {KO} mice had decreased steady-state levels of {GATA}3, {IL}4 and {IL}13 {mRNAs} with little changes at the protein level. Surprisingly, Th2-polarized cells from homozygous {HuR} conditional ({OX}40-Cre {HuRfl}/fl) {KO} mice showed increased {IL}2, {IL}4 and {IL}13 {mRNA} and protein via different mechanisms. Specifically, {IL}4 was transcriptionally up regulated in {HuR} {KO} T cells, whereas {IL}2 and {IL}13 {mRNA} stabilities increased. Additionally, when using the standard ovalbumin model of allergic airway inflammation, {HuR} conditional {KO} mice mounted a robust inflammatory response similar to mice with wild-type {HuR} levels. These results reveal a complex differential posttranscriptional regulation of cytokines by {HuR} in which gene dosage plays an important role. These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection.},
	journaltitle = {Mol Med},
	author = {Gubin, M M and Techasintana, P and Magee, J D and Dahm, G M and Calaluce, R and Martindale, J L and Whitney, M S and Franklin, C L and Besch-Williford, C and Hollingsworth, J W and Abdelmohsen, K and Gorospe, M and Atasoy, U},
	date = {2014},
	pmid = {24477678}
}

@article{cohen_chromatin_2005,
	title = {Chromatin modifications on the inactive X chromosome},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15881892},
	abstract = {In female mammals, one X chromosome is transcriptionally silenced to achieve dosage compensation between {XX} females and {XY} males. This process, known as X-inactivation, occurs early in development, such that one X chromosome is silenced in every cell. Once X-inactivation has occurred, the inactive X chromosome is marked by a unique set of epigenetic features that distinguishes it from the active X chromosome and autosomes. These modifications appear sequentially during the transition from a transcriptionally active to an inactive state and, once established, act redundantly to maintain transcriptional silencing. In this review, we survey the unique epigenetic features that characterize the inactive X chromosome, describe the mechanisms by which these marks are established and maintained, and discuss how each contributes to silencing the inactive X chromosome.},
	pages = {91--122},
	journaltitle = {Prog Mol Subcell Biol},
	author = {Cohen, H R and Royce-Tolland, M E and Worringer, K A and Panning, B},
	date = {2005},
	pmid = {15881892},
	keywords = {Animals, Genetic, Humans, {RNA}, Untranslated/genetics/metabolism, *Dosage Compensation, Chromatin/genetics/*metabolism, {DNA} Replication, {DNA}/chemistry/metabolism, Female, Histones/metabolism, Long Untranslated, Male, Methylation, Stem Cells/physiology, X Chromosome/*genetics/*metabolism}
}

@article{sunkara_cyclic_2014,
	title = {Cyclic {AMP} synergizes with butyrate in promoting beta-defensin 9 expression in chickens},
	volume = {57},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24141182},
	doi = {10.1016/j.molimm.2013.09.003},
	abstract = {Host defense peptides ({HDP}) have both microbicidal and immunomodulatory properties. Specific induction of endogenous {HDP} synthesis has emerged as a novel approach to antimicrobial therapy. Cyclic adenosine monophosphate ({cAMP}) and butyrate have been implicated in {HDP} induction in humans. However, the role of {cAMP} signaling and the possible interactions between {cAMP} and butyrate in regulating {HDP} expression in other species remain unknown. Here we report that activation of {cAMP} signaling induces {HDP} gene expression in chickens as exemplified by beta-defensin 9 ({AvBD}9). We further showed that, albeit being weak inducers, {cAMP} agonists synergize strongly with butyrate or butyrate analogs in {AvBD}9 induction in macrophages and primary jejunal explants. Additionally, oral supplementation of forskolin, an adenylyl cyclase agonist in the form of a Coleus forskohlii extract, was found to induce {AvBD}9 expression in the crop of chickens. Furthermore, feeding with both forskolin and butyrate showed an obvious synergy in triggering {AvBD}9 expression in the crop and jejunum of chickens. Surprisingly, inhibition of the {MEK}-{ERK} mitogen-activated protein kinase ({MAPK}) pathway augmented the butyrate-{FSK} synergy, whereas blocking {JNK} or p38 {MAPK} pathway significantly diminished {AvBD}9 induction in chicken macrophages and jejunal explants in response to butyrate and {FSK} individually or in combination. Collectively, these results suggest the potential for concomitant use of butyrate and {cAMP} signaling activators in enhancing {HDP} expression, innate immunity, and disease resistance in both animals and humans.},
	pages = {171--180},
	number = {2},
	journaltitle = {Mol Immunol},
	author = {Sunkara, L T and Zeng, X and Curtis, A R and Zhang, G},
	date = {2014},
	pmid = {24141182},
	keywords = {Animals, Cells, Cultured, Antimicrobial Cationic Peptides/biosynthesis, beta-Defensins/*biosynthesis, Butyrates/*metabolism, Chickens, Coleus, Colforsin/administration \& dosage/metabolism, Cyclic {AMP}/*metabolism, Extracellular Signal-Regulated {MAP} Kinases/antagon, Immunity, Innate/*drug effects, Jejunum, {JNK} Mitogen-Activated Protein Kinases/antagonists, Macrophages, {MAP} Kinase Kinase Kinases/antagonists \& inhibitors, {MAP} Kinase Signaling System, p38 Mitogen-Activated Protein Kinases/antagonists, Plant Extracts/administration \& dosage/metabolism, Signal Transduction}
}

@article{chen_s100a14:_2013,
	title = {S100A14: novel modulator of terminal differentiation in esophageal cancer},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24107296},
	doi = {10.1158/1541-7786.MCR-13-0317},
	abstract = {Aberrant keratinocyte differentiation is a key mechanism in the initiation of cancer. Because activities regulating differentiation exhibit altered or reduced capacity in esophageal cancer cells, it is vital to pinpoint those genes that control epidermal proliferation and terminal differentiation to better understand esophageal carcinogenesis. S100A14 is a member of the S100 calcium-binding protein family and has been suggested to be involved in cell proliferation, apoptosis, and invasion. The present study used immunohistochemistry analysis of S100A14 in clinical specimens of esophageal squamous cell carcinoma ({ESCC}) to show that decreased S100A14 is strongly correlated with poor differentiation. Furthermore, both {mRNA} and protein expression of S100A14 was drastically increased upon 12-O-tetra-decanoylphorbol-13-acetate ({TPA}) and calcium-induced esophageal cancer cell differentiation. Overexpression of S100A14 resulted in a G1-phase cell cycle arrest and promoted calcium-inhibited cell growth. Conversely, decreasing S100A14 expression significantly promoted G1-S transition and prevented the morphologic changes associated with calcium-induced cell differentiation. Molecular investigation demonstrated that S100A14 altered the calcium-induced expression of late markers of differentiation, with the most prominent effect on involucrin ({IVL}) and filaggrin ({FLG}). Finally, it was determined that S100A14 is transcriptionally regulated by {JunB} and that S100A14 and {JunB} status significantly correlated in {ESCC} tissue. In summary, these data demonstrate that S100A14 is transcriptionally regulated by {JunB} and involved in {ESCC} cell differentiation. {IMPLICATIONS}: This study further differentiates the molecular mechanism controlling the development and progression of esophageal cancer.},
	pages = {1542--1553},
	number = {12},
	journaltitle = {Mol Cancer Res},
	author = {Chen, H and Ma, J and Sunkel, B and Luo, A and Ding, F and Li, Y and He, H and Zhang, S and Xu, C and Jin, Q and Wang, Q and Liu, Z},
	date = {2013},
	pmid = {24107296}
}

@article{pollard_detection_2010,
	title = {Detection of nonneutral substitution rates on mammalian phylogenies},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19858363},
	doi = {10.1101/gr.097857.109},
	abstract = {Methods for detecting nucleotide substitution rates that are faster or slower than expected under neutral drift are widely used to identify candidate functional elements in genomic sequences. However, most existing methods consider either reductions (conservation) or increases (acceleration) in rate but not both, or assume that selection acts uniformly across the branches of a phylogeny. Here we examine the more general problem of detecting departures from the neutral rate of substitution in either direction, possibly in a clade-specific manner. We consider four statistical, phylogenetic tests for addressing this problem: a likelihood ratio test, a score test, a test based on exact distributions of numbers of substitutions, and the genomic evolutionary rate profiling ({GERP}) test. All four tests have been implemented in a freely available program called {phyloP}. Based on extensive simulation experiments, these tests are remarkably similar in statistical power. With 36 mammalian species, they all appear to be capable of fairly good sensitivity with low false-positive rates in detecting strong selection at individual nucleotides, moderate selection in 3-bp elements, and weaker or clade-specific selection in longer elements. By applying {phyloP} to mammalian multiple alignments from the {ENCODE} project, we shed light on patterns of conservation/acceleration in known and predicted functional elements, approximate fractions of sites subject to constraint, and differences in clade-specific selection in the primate and glires clades. We also describe new "Conservation" tracks in the {UCSC} Genome Browser that display both {phyloP} and {phastCons} scores for genome-wide alignments of 44 vertebrate species.},
	pages = {110--121},
	number = {1},
	journaltitle = {Genome Research},
	author = {Pollard, K S and Hubisz, M J and Rosenbloom, K R and Siepel, A},
	date = {2010},
	pmid = {19858363},
	keywords = {Animals, Base Sequence, Conserved Sequence, Genetic, Humans, Software, *Base Sequence, *Evolution, *Phylogeny, *Selection, Computer Simulation, Likelihood Functions, Mammals, Mammals/classification/*genetics, Models, Molecular, Phylogeny, Primates, Primates/genetics, Sequence Alignment, Species Specificity, Statistical, Evolution, Molecular, Selection, Genetic, Models, Genetic, Models, Statistical},
	file = {Full Text:/home/jlagarde/Zotero/storage/34FJLL5H/Pollard et al. - 2010 - Detection of nonneutral substitution rates on mamm.pdf:application/pdf}
}

@article{li_new_1985,
	title = {A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3916709},
	abstract = {A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of {DNA} evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.},
	pages = {150--174},
	number = {2},
	journaltitle = {Mol Biol Evol},
	author = {Li, W H and Wu, C I and Luo, C C},
	date = {1985},
	pmid = {3916709},
	keywords = {Animals, Base Sequence, Humans, *Biological Evolution, *Genetic Techniques, Amino Acid Sequence, Biometry, Codon/genetics, {DNA}/genetics}
}

@article{chkhotua_first_2013,
	title = {The first kidney transplant in {HIV} infected patient in Georgia},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24323956},
	abstract = {Highly active antiretroviral therapy ({HAART}) has significantly improved the life expectancy of patients with {HIV}. As a result, kidney transplantation is considered an viable treatment option for {HIV} infected patients with end stage renal disease. The first living-related kidney transplant in Georgia has been performed between non-identical twin sisters in July 2013. In this paper we give the detailed case report and short overview of the existing literature. This is the first report of the successful kidney transplant in {HIV} infected patient in East Europe and former Soviet Union Countries including the Central Asia.},
	pages = {7--11},
	number = {224},
	journaltitle = {Georgian Med News},
	author = {Chkhotua, A and Gabunia, P and Tataradze, A and Nibladze, N and Tsertsvadze, T and Managadze, L},
	date = {2013},
	pmid = {24323956},
	keywords = {Humans, *Antiretroviral Therapy, *Kidney Transplantation, Adult, Chronic/*therapy, Female, Georgia (Republic), Highly Active, {HIV} Infections/pathology/*therapy/virology, {HIV}/pathogenicity, Immunosuppressive Agents/therapeutic use, Kidney Failure, Male}
}

@article{mele_human_2015,
	title = {The human transcriptome across tissues and individuals},
	volume = {348},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25954002},
	doi = {10.1126/science.aaa0355},
	abstract = {Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used {RNA} sequence data generated by Genotype-Tissue Expression ({GTEx}) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes-which is most clearly seen in blood-though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.},
	pages = {660--665},
	number = {6235},
	journaltitle = {Science},
	author = {Mele, M and Ferreira, P G and Reverter, F and {DeLuca}, D S and Monlong, J and Sammeth, M and Young, T R and Goldmann, J M and Pervouchine, D D and Sullivan, T J and Johnson, R and Segre, A V and Djebali, S and Niarchou, A and Wright, F A and Lappalainen, T and Calvo, M and Getz, G and Dermitzakis, E T and Ardlie, K G and Guigo, R},
	date = {2015},
	pmid = {25954002},
	keywords = {Sequence Analysis, Genome, Humans, {RNA}, Gene Expression Profiling, *Gene Expression Regulation, *Transcriptome, Alternative Splicing, Female, Human/*genetics, Male, Organ Specificity/genetics, Phenotype, Polymorphism, Sex Factors, Single Nucleotide},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/6QKM22DX/Melé et al. - 2015 - The human transcriptome across tissues and individ.pdf:application/pdf;The human transcriptome across tissues and individuals:/home/jlagarde/Zotero/storage/5PF9AX8D/mele2015.pdf:application/pdf}
}

@article{miller_expression_2005,
	title = {An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival},
	volume = {102},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16141321},
	doi = {10.1073/pnas.0506230102},
	abstract = {Perturbations of the p53 pathway are associated with more aggressive and therapeutically refractory tumors. However, molecular assessment of p53 status, by using sequence analysis and immunohistochemistry, are incomplete assessors of p53 functional effects. We posited that the transcriptional fingerprint is a more definitive downstream indicator of p53 function. Herein, we analyzed transcript profiles of 251 p53-sequenced primary breast tumors and identified a clinically embedded 32-gene expression signature that distinguishes p53-mutant and wild-type tumors of different histologies and outperforms sequence-based assessments of p53 in predicting prognosis and therapeutic response. Moreover, the p53 signature identified a subset of aggressive tumors absent of sequence mutations in p53 yet exhibiting expression characteristics consistent with p53 deficiency because of attenuated p53 transcript levels. Our results show the primary importance of p53 functional status in predicting clinical breast cancer behavior.},
	pages = {13550--13555},
	number = {38},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Miller, L D and Smeds, J and George, J and Vega, V B and Vergara, L and Ploner, A and Pawitan, Y and Hall, P and Klaar, S and Liu, E T and Bergh, J},
	date = {2005},
	pmid = {16141321},
	keywords = {Genetic, Humans, *Transcription, *Gene Expression Profiling/methods, *Gene Expression Regulation, *Mutation, Breast Neoplasms/*genetics/metabolism/mortality, Female, Neoplastic, Oligonucleotide Array Sequence Analysis/methods, Predictive Value of Tests, Prognosis, Tumor Suppressor Protein p53/biosynthesis/*genetic}
}

@article{laneve_interplay_2007,
	title = {The interplay between {microRNAs} and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells},
	volume = {104},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17483472},
	doi = {10.1073/pnas.0700071104},
	abstract = {{MicroRNAs} ({miRNAs}) are tiny noncoding {RNAs} whose function as modulators of gene expression is crucial for the proper control of cell growth and differentiation. Although the profile of {miRNA} expression has been defined for many different cellular systems, the elucidation of the regulatory networks in which they are involved is only just emerging. In this work, we identify a crucial role for three neuronal {miRNAs} (9, 125a, and 125b) in controlling human neuroblastoma cell proliferation. We show that these molecules act in an additive manner by repressing a common target, the truncated isoform of the neurotrophin receptor tropomyosin-related kinase C, and we demonstrate that the down-regulation of this isoform is critical for regulating neuroblastoma cell growth. Consistently with their function, these {miRNAs} were found to be down-modulated in primary neuroblastoma tumors.},
	pages = {7957--7962},
	number = {19},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Laneve, P and Di Marcotullio, L and Gioia, U and Fiori, M E and Ferretti, E and Gulino, A and Bozzoni, I and Caffarelli, E},
	date = {2007},
	pmid = {17483472},
	keywords = {Humans, Cell Line, Cell Proliferation, {MicroRNAs}/analysis/*physiology, Neuroblastoma/*pathology, Receptor, {trkC}/*physiology, Tumor}
}

@article{kraus_making_2013,
	title = {Making sense of Dlx1 antisense {RNA}},
	volume = {376},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23415800},
	doi = {10.1016/j.ydbio.2013.01.035},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) have been recently recognized as a major class of regulators in mammalian systems. {LncRNAs} function by diverse and heterogeneous mechanisms in gene regulation, and are key contributors to development, neurological disorders, and cancer. This emerging importance of {lncRNAs}, along with recent reports of a functional {lncRNA} encoded by the mouse Dlx5-Dlx6 locus, led us to interrogate the biological significance of another distal-less antisense {lncRNA}, the previously uncharacterized Dlx1 antisense (Dlx1as) transcript. We have functionally ablated this antisense {RNA} via a highly customized gene targeting approach in vivo. Mice devoid of Dlx1as {RNA} are viable and fertile, and display a mild skeletal and neurological phenotype reminiscent of a Dlx1 gain-of function phenotype, suggesting a role for this non-coding antisense {RNA} in modulating Dlx1 transcript levels and stability. The reciprocal relationship between Dlx1as and Dlx1 places this sense-antisense pair into a growing class of mammalian {lncRNA}-{mRNA} pairs characterized by inverse regulation.},
	pages = {224--235},
	number = {2},
	journaltitle = {Dev Biol},
	author = {Kraus, P and Sivakamasundari, V and Lim, S L and Xing, X and Lipovich, L and Lufkin, T},
	date = {2013},
	pmid = {23415800},
	keywords = {Animals, Genetic, Mice, {RNA}, *Gene Expression Regulation, Antisense/*genetics, Antisense/genetics, Crosses, Developmental, {DNA} Primers/genetics, Epigenesis, Gene Regulatory Networks, Gene Targeting, Homeodomain Proteins/*genetics/*physiology, Long Untranslated/metabolism, Messenger/metabolism, Models, Oligonucleotides, Phenotype, Time Factors, Transcription Factors/*genetics/*physiology}
}

@article{morlando_coupling_2004,
	title = {Coupling between {snoRNP} assembly and 3' processing controls box C/D {snoRNA} biosynthesis in yeast},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15167896},
	doi = {10.1038/sj.emboj.7600254},
	abstract = {{RNA} polymerase {II} transcribes genes encoding proteins and a large number of small stable {RNAs}. While pre-{mRNA} 3'-end formation requires a machinery ensuring tight coupling between cleavage and polyadenylation, small {RNAs} utilize polyadenylation-independent pathways. In yeast, specific factors required for {snRNA} and {snoRNA} 3'-end formation were characterized as components of the {APT} complex that is associated with the core complex of the cleavage/polyadenylation machinery (core-{CPF}). Other essential factors were identified as independent components: Nrd1p, Nab3p and Sen1p. Here we report that mutations in the conserved box D of {snoRNAs} and in the {snoRNP}-specific factor Nop1p interfere with transcription and 3'-end formation of box C/D {snoRNAs}. We demonstrate that Nop1p is associated with box C/D {snoRNA} genes and that it interacts with {APT} components. These data suggest a mechanism of quality control in which efficient transcription and 3'-end formation occur only when nascent {snoRNAs} are successfully assembled into functional particles.},
	pages = {2392--2401},
	number = {12},
	journaltitle = {{EMBO} J},
	author = {Morlando, M and Ballarino, M and Greco, P and Caffarelli, E and Dichtl, B and Bozzoni, I},
	date = {2004},
	pmid = {15167896},
	keywords = {Base Sequence, {DNA} Primers, Mutation, Plasmids, Ribonucleoproteins, Saccharomyces cerevisiae/*metabolism, Small Nucleolar/*metabolism}
}

@article{bassik_systematic_2013,
	title = {A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility},
	volume = {152},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23394947},
	doi = {10.1016/j.cell.2013.01.030},
	abstract = {Genetic interaction ({GI}) maps, comprising pairwise measures of how strongly the function of one gene depends on the presence of a second, have enabled the systematic exploration of gene function in microorganisms. Here, we present a two-stage strategy to construct high-density {GI} maps in mammalian cells. First, we use ultracomplex pooled {shRNA} libraries (25 {shRNAs}/gene) to identify high-confidence hit genes for a given phenotype and effective {shRNAs}. We then construct double-{shRNA} libraries from these to systematically measure {GIs} between hits. A {GI} map focused on ricin susceptibility broadly recapitulates known pathways and provides many unexpected insights. These include a noncanonical role for {COPI}, a previously uncharacterized protein complex affecting toxin clearance, a specialized role for the ribosomal protein {RPS}25, and functionally distinct mammalian {TRAPP} complexes. The ability to rapidly generate mammalian {GI} maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.},
	pages = {909--922},
	number = {4},
	journaltitle = {Cell},
	author = {Bassik, M C and Kampmann, M and Lebbink, R J and Wang, S and Hein, M Y and Poser, I and Weibezahn, J and Horlbeck, M A and Chen, S and Mann, M and Hyman, A A and Leproust, E M and {McManus}, M T and Weissman, J S},
	date = {2013},
	pmid = {23394947},
	keywords = {Genetic, Humans, {RNA}, *Biological Transport, *Epistasis, Carrier Proteins/metabolism, Cell Line, Coat Protein Complex I/metabolism, Endoplasmic Reticulum/metabolism, Heptanoic Acids/pharmacology, Membrane Proteins/metabolism, Proto-Oncogene Proteins/metabolism, Pyrroles/pharmacology, Ribosomal Proteins/metabolism, Ricin/*toxicity, Small Interfering, Tumor, Vesicular Transport Proteins/metabolism}
}

@article{groff_vivo_2016,
	title = {In Vivo Characterization of Linc-p21 Reveals Functional cis-Regulatory {DNA} Elements},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27524623},
	doi = {10.1016/j.celrep.2016.07.050},
	abstract = {The Linc-p21 locus, encoding a long non-coding {RNA}, plays an important role in p53 signaling, cell-cycle regulation, and tumor suppression. However, despite extensive study, confusion exists regarding its mechanism of action: is activity driven by the transcript acting in trans, in cis, or by an underlying functional enhancer? Here, using a knockout mouse model and a massively parallel enhancer assay, we delineate the functional elements at this locus. We observe that, even in tissues with no detectable Linc-p21 transcript, deletion of the locus significantly affects local gene expression, including of the cell-cycle regulator Cdkn1a. To characterize this {RNA}-independent regulatory effect, we systematically interrogated the underlying {DNA} sequence for enhancer activity at nucleotide resolution and confirmed the existence of multiple enhancer elements. Together, these data suggest that, in vivo, the cis-regulatory effects mediated by Linc-p21, in the presence or absence of transcription, are due to {DNA} enhancer elements.},
	pages = {2178--2186},
	number = {8},
	journaltitle = {Cell Rep},
	author = {Groff, A F and Sanchez-Gomez, D B and Soruco, M M and Gerhardinger, C and Barutcu, A R and Li, E and Elcavage, L and Plana, O and Sanchez, L V and Lee, J C and Sauvageau, M and Rinn, J L},
	date = {2016},
	pmid = {27524623}
}

@article{rinaldi_stress_2010,
	title = {Stress induces region specific alterations in {microRNAs} expression in mice},
	volume = {208},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19913057},
	doi = {10.1016/j.bbr.2009.11.012},
	abstract = {Several studies have demonstrated that exposure to both acute and chronic aversive stimuli can affect neural activity in different brain areas. In particular it has been shown that stressful events can induce not only short-term changes in neural transmission and gene regulation, but also long-term changes that can lead to structural modification. In this study we investigated, in {CD}1 mice, the effects of single or repeated exposures to restraint stress (2h for 1 or 5 consecutive days) in the frontal cortex on a crucial class of gene expression regulators, the {microRNAs} ({miRs}).First we performed a microarray profiling on {RNA} extracted from the frontal cortex of mice exposed to acute or repeated restraint stress. The results indicated a prominent increase in the expression levels of different {miRs} after acute stress while only minor changes were observed after repeated restraint. The Northern blot analysis on selected {miRs} confirmed an increase after acute restraint for let-7a, {miR}-9 and {miR} 26-a/b. Finally, Northern blot analysis of the selected {miRs} on {RNA} extracted from the hippocampus of stressed mice demonstrated that such changes were region specific, as no differences were observed in the hippocampus. These data suggest that control of {mRNA} translation through {miRs} is an additional mechanism by which stressful events regulates protein expression in the frontal cortex.},
	pages = {265--269},
	number = {1},
	journaltitle = {Behav Brain Res},
	author = {Rinaldi, A and Vincenti, S and De Vito, F and Bozzoni, I and Oliverio, A and Presutti, C and Fragapane, P and Mele, A},
	date = {2010},
	pmid = {19913057},
	keywords = {Animals, Mice, Gene Expression Profiling/methods, Gene Expression Regulation/*physiology, Hippocampus/metabolism, Male, {MicroRNAs}/classification/genetics/*metabolism, Oligonucleotide Array Sequence Analysis/methods, Psychological/*metabolism/pathology, Stress, Time Factors}
}

@article{salameh_prune2_2015,
	title = {{PRUNE}2 is a human prostate cancer suppressor regulated by the intronic long noncoding {RNA} {PCA}3},
	volume = {112},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26080435},
	doi = {10.1073/pnas.1507882112},
	abstract = {Prostate cancer antigen 3 ({PCA}3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify {PRUNE}2, a target protein-coding gene variant, which harbors the {PCA}3 locus, thereby classifying {PCA}3 as an antisense intronic long noncoding (lnc){RNA}. We show that {PCA}3 controls {PRUNE}2 levels via a unique regulatory mechanism involving formation of a {PRUNE}2/{PCA}3 double-stranded {RNA} that undergoes adenosine deaminase acting on {RNA} ({ADAR})-dependent adenosine-to-inosine {RNA} editing. {PRUNE}2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, {PRUNE}2 and {PCA}3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and {RNA} editing of {PRUNE}2 and {PCA}3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish {PCA}3 as a dominant-negative oncogene and {PRUNE}2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.},
	pages = {8403--8408},
	number = {27},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Salameh, A and Lee, A K and Cardo-Vila, M and Nunes, D N and Efstathiou, E and Staquicini, F I and Dobroff, A S and Marchio, S and Navone, N M and Hosoya, H and Lauer, R C and Wen, S and Salmeron, C C and Hoang, A and Newsham, I and Lima, L A and Carraro, D M and Oliviero, S and Kolonin, M G and Sidman, R L and Do, K A and Troncoso, P and Logothetis, C J and Brentani, R R and Calin, G A and Cavenee, W K and Dias-Neto, E and Pasqualini, R and Arap, W},
	date = {2015},
	pmid = {26080435}
}

@article{blagosklonny_impact_2010,
	title = {Impact papers on aging in 2009},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20351400},
	abstract = {The Editorial Board of Aging reviews research papers published in 2009, which they believe have or will have significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, {DNA} damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacological interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically.},
	pages = {111--121},
	number = {3},
	journaltitle = {Aging (Albany {NY})},
	author = {Blagosklonny, M V and Campisi, J and Sinclair, D A and Bartke, A and Blasco, M A and Bonner, W M and Bohr, V A and Brosh Jr., R M and Brunet, A and Depinho, R A and Donehower, L A and Finch, C E and Finkel, T and Gorospe, M and Gudkov, A V and Hall, M N and Hekimi, S and Helfand, S L and Karlseder, J and Kenyon, C and Kroemer, G and Longo, V and Nussenzweig, A and Osiewacz, H D and Peeper, D S and Rando, T A and Rudolph, K L and Sassone-Corsi, P and Serrano, M and Sharpless, N E and Skulachev, V P and Tilly, J L and Tower, J and Verdin, E and Vijg, J},
	date = {2010},
	pmid = {20351400},
	keywords = {Animals, Humans, Adult Stem Cells/physiology, Aging/drug effects/*physiology, Autophagy, Caloric Restriction, Circadian Rhythm, {DNA} Damage, Mitochondria/metabolism, Neoplasms/metabolism, Nuclear Reprogramming, Oxidative Stress, Post-Transcriptional, {RNA} Processing, Telomere/physiology}
}

@article{pierandrei-amaldi_expression_1982,
	title = {Expression of ribosomal-protein genes in Xenopus laevis development},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/6889922},
	abstract = {Using probes to Xenopus laevis ribosomal-protein (r-protein) {mRNAs}, we have found that in the oocyte the accumulation of r-protein {mRNAs} proceeds to a maximum level, which is attained at the onset of vitellogenesis and remains stable thereafter. In the embryo, r-protein {mRNA} sequences are present at low levels in the cytoplasm during early cleavage (stages 2-5), become undetectable until gastrulation (stage 10) and accumulate progressively afterwards. Normalization of the amount of {mRNA} to cell number suggests an activation of r-protein genes around stage 10; however, a variation in {mRNA} turnover cannot be excluded. Newly synthesized ribosomal proteins cannot be found from early cleavage up to stage 26, with the exception of S3, L17 and L31, which are constantly made, and protein L5, which starts to be synthesized around stage 7. A complete set of ribosomal proteins is actively produced only in tailbud embryos (stages 28-32), several hours after the appearance of their {mRNAs}. Before stage 26 these {mRNA} sequences are found on subpolysomal fractions, whereas more than 50\% of them are associated with polysomes at stage 31. Anucleolate mutants do not synthesize ribosomal proteins at the time when normal embryos do it very actively; nevertheless, they accumulate r-protein {mRNAs}.},
	pages = {163--171},
	number = {1},
	journaltitle = {Cell},
	author = {Pierandrei-Amaldi, P and Campioni, N and Beccari, E and Bozzoni, I and Amaldi, F},
	date = {1982},
	pmid = {6889922},
	keywords = {Animals, {RNA}, *Gene Expression Regulation, *Oogenesis, Cell Nucleolus, Cytoplasm/metabolism, Embryo, Female, Messenger/*metabolism, Mutation, Nonmammalian/*metabolism, Oocytes/metabolism, Polyribosomes/metabolism, Ribosomal Proteins/biosynthesis/*genetics, Ribosomal/biosynthesis, Xenopus laevis}
}

@article{guttman_ab_2010,
	title = {Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of {lincRNAs}},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20436462},
	doi = {10.1038/nbt.1633},
	abstract = {Massively parallel {cDNA} sequencing ({RNA}-Seq) provides an unbiased way to study a transcriptome, including both coding and noncoding genes. Until now, most {RNA}-Seq studies have depended crucially on existing annotations and thus focused on expression levels and variation in known transcripts. Here, we present Scripture, a method to reconstruct the transcriptome of a mammalian cell using only {RNA}-Seq reads and the genome sequence. We applied it to mouse embryonic stem cells, neuronal precursor cells and lung fibroblasts to accurately reconstruct the full-length gene structures for most known expressed genes. We identified substantial variation in protein coding genes, including thousands of novel 5' start sites, 3' ends and internal coding exons. We then determined the gene structures of more than a thousand large intergenic noncoding {RNA} ({lincRNA}) and antisense loci. Our results open the way to direct experimental manipulation of thousands of noncoding {RNAs} and demonstrate the power of ab initio reconstruction to render a comprehensive picture of mammalian transcriptomes.},
	pages = {503--510},
	number = {5},
	journaltitle = {Nat Biotechnol},
	author = {Guttman, M and Garber, M and Levin, J Z and Donaghey, J and Robinson, J and Adiconis, X and Fan, L and Koziol, M J and Gnirke, A and Nusbaum, C and Rinn, J L and Lander, E S and Regev, A},
	date = {2010},
	pmid = {20436462},
	keywords = {{DNA}, Gene Expression Profiling/*methods, Sequence Analysis, Animals, Genetic, Mice, {RNA}, Transcription, Computational Biology, Gene Expression Profiling, Cell Line, Computational Biology/*methods, Embryonic Stem Cells, Gene Library, Intergenic/*genetics, Messenger/*genetics, Models, {RNA}/*methods, {RNA}, Messenger, Transcription, Genetic, Models, Genetic, Sequence Analysis, {RNA}, {DNA}, Intergenic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/9TPY3HKA/Guttman et al. - 2010 - Ab initio reconstruction of cell type-specific tra.pdf:application/pdf}
}

@article{trapnell_differential_2013,
	title = {Differential analysis of gene regulation at transcript resolution with {RNA}-seq},
	volume = {31},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23222703},
	doi = {10.1038/nbt.2450},
	abstract = {Differential analysis of gene and transcript expression using high-throughput {RNA} sequencing ({RNA}-seq) is complicated by several sources of measurement variability and poses numerous statistical challenges. We present Cuffdiff 2, an algorithm that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries. Cuffdiff 2 robustly identifies differentially expressed transcripts and genes and reveals differential splicing and promoter-preference changes. We demonstrate the accuracy of our approach through differential analysis of lung fibroblasts in response to loss of the developmental transcription factor {HOXA}1, which we show is required for lung fibroblast and {HeLa} cell cycle progression. Loss of {HOXA}1 results in significant expression level changes in thousands of individual transcripts, along with isoform switching events in key regulators of the cell cycle. Cuffdiff 2 performs robust differential analysis in {RNA}-seq experiments at transcript resolution, revealing a layer of regulation not readily observable with other high-throughput technologies.},
	pages = {46--53},
	number = {1},
	journaltitle = {Nat Biotechnol},
	author = {Trapnell, C and Hendrickson, D G and Sauvageau, M and Goff, L and Rinn, J L and Pachter, L},
	date = {2013},
	pmid = {23222703},
	keywords = {Sequence Analysis, Humans, {RNA}, *Gene Expression Regulation, Fibroblasts/cytology, {HeLa} Cells, Homeodomain Proteins/genetics, Lung/cytology/metabolism, Messenger/*genetics, {RNA}/*methods, Transcription Factors/genetics}
}

@article{brody_rna-binding_2009,
	title = {The '{RNA}-binding ome': future implications for chemotherapeutic efficacy},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19903059},
	doi = {10.2217/fon.09.114},
	pages = {1317--1319},
	number = {9},
	journaltitle = {Future Oncol},
	author = {Brody, J R and Witkiewicz, A K and Yeo, C J and Gorospe, M and Keen, J C},
	date = {2009},
	pmid = {19903059},
	keywords = {Animals, Humans, *Genome, Antineoplastic Agents/*therapeutic use, Neoplasms/*drug therapy/*genetics, {RNA}-Binding Proteins/*genetics, {RNA}/*metabolism}
}

@article{letunic_smart_2004,
	title = {{SMART} 4.0: towards genomic data integration},
	volume = {32},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14681379},
	doi = {10.1093/nar/gkh088},
	abstract = {{SMART} (Simple Modular Architecture Research Tool) is a web tool (http://smart.embl.de/) for the identification and annotation of protein domains, and provides a platform for the comparative study of complex domain architectures in genes and proteins. The January 2004 release of {SMART} contains 685 protein domains. New developments in {SMART} are centred on the integration of data from completed metazoan genomes. {SMART} now uses predicted proteins from complete genomes in its source sequence databases, and integrates these with predictions of orthology. New visualization tools have been developed to allow analysis of gene intron-exon structure within the context of protein domain structure, and to align these displays to provide schematic comparisons of orthologous genes, or multiple transcripts from the same gene. Other improvements include the ability to query {SMART} by Gene Ontology terms, improved structure database searching and batch retrieval of multiple entries.},
	pages = {D142--4},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Letunic, I and Copley, R R and Schmidt, S and Ciccarelli, F D and Doerks, T and Schultz, J and Ponting, C P and Bork, P},
	date = {2004},
	pmid = {14681379},
	keywords = {*Software, Genomics/*methods, Animals, Genome, Humans, Algorithms, *Databases, Computational Biology/*methods, Internet, Introns/genetics, Protein, Protein Structure, Proteins/*chemistry, Proteome, Proteomics, Sequence Alignment, Tertiary}
}

@article{alexandrov_signatures_2013,
	title = {Signatures of mutational processes in human cancer},
	volume = {500},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23945592},
	doi = {10.1038/nature12477},
	abstract = {All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the {APOBEC} family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in {DNA} maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.},
	pages = {415--421},
	number = {7463},
	journaltitle = {Nature},
	author = {Alexandrov, L B and Nik-Zainal, S and Wedge, D C and Aparicio, S A and Behjati, S and Biankin, A V and Bignell, G R and Bolli, N and Borg, A and Borresen-Dale, A L and Boyault, S and Burkhardt, B and Butler, A P and Caldas, C and Davies, H R and Desmedt, C and Eils, R and Eyfjord, J E and Foekens, J A and Greaves, M and Hosoda, F and Hutter, B and Ilicic, T and Imbeaud, S and Imielinski, M and Jager, N and Jones, D T and Jones, D and Knappskog, S and Kool, M and Lakhani, S R and Lopez-Otin, C and Martin, S and Munshi, N C and Nakamura, H and Northcott, P A and Pajic, M and Papaemmanuil, E and Paradiso, A and Pearson, J V and Puente, X S and Raine, K and Ramakrishna, M and Richardson, A L and Richter, J and Rosenstiel, P and Schlesner, M and Schumacher, T N and Span, P N and Teague, J W and Totoki, Y and Tutt, A N and Valdes-Mas, R and van Buuren, M M and van 't Veer, L and Vincent-Salomon, A and Waddell, N and Yates, L R and Zucman-Rossi, J and Futreal, P A and {McDermott}, U and Lichter, P and Meyerson, M and Grimmond, S M and Siebert, R and Campo, E and Shibata, T and Pfister, S M and Campbell, P J and Stratton, M R},
	date = {2013},
	pmid = {23945592},
	keywords = {Genetic, Humans, Transcription, Organ Specificity, Genetic/genetics, Reproducibility of Results, Algorithms, Aging/genetics, Cell Transformation, Cytidine Deaminase/genetics, {DNA} Mutational Analysis, {DNA}/genetics/metabolism, Insertional/genetics, Models, Mutagenesis, Mutagenesis/*genetics, Mutagens/pharmacology, Mutation/*genetics, Neoplasms/enzymology/*genetics/pathology, Neoplastic/*genetics/patholog, Sequence Deletion/genetics}
}

@article{quail_tale_2012,
	title = {A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina {MiSeq} sequencers},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22827831},
	doi = {10.1186/1471-2164-13-341},
	abstract = {{BACKGROUND}: Next generation sequencing ({NGS}) technology has revolutionized genomic and genetic research. The pace of change in this area is rapid with three major new sequencing platforms having been released in 2011: Ion Torrent's {PGM}, Pacific Biosciences' {RS} and the Illumina {MiSeq}. Here we compare the results obtained with those platforms to the performance of the Illumina {HiSeq}, the current market leader. In order to compare these platforms, and get sufficient coverage depth to allow meaningful analysis, we have sequenced a set of 4 microbial genomes with mean {GC} content ranging from 19.3 to 67.7\%. Together, these represent a comprehensive range of genome content. Here we report our analysis of that sequence data in terms of coverage distribution, bias, {GC} distribution, variant detection and accuracy. {RESULTS}: Sequence generated by Ion Torrent, {MiSeq} and Pacific Biosciences technologies displays near perfect coverage behaviour on {GC}-rich, neutral and moderately {AT}-rich genomes, but a profound bias was observed upon sequencing the extremely {AT}-rich genome of Plasmodium falciparum on the {PGM}, resulting in no coverage for approximately 30\% of the genome. We analysed the ability to call variants from each platform and found that we could call slightly more variants from Ion Torrent data compared to {MiSeq} data, but at the expense of a higher false positive rate. Variant calling from Pacific Biosciences data was possible but higher coverage depth was required. Context specific errors were observed in both {PGM} and {MiSeq} data, but not in that from the Pacific Biosciences platform. {CONCLUSIONS}: All three fast turnaround sequencers evaluated here were able to generate usable sequence. However there are key differences between the quality of that data and the applications it will support.},
	pages = {341},
	journaltitle = {{BMC} Genomics},
	author = {Quail, M A and Smith, M and Coupland, P and Otto, T D and Harris, S R and Connor, T R and Bertoni, A and Swerdlow, H P and Gu, Y},
	date = {2012},
	pmid = {22827831},
	keywords = {Sequence Analysis, Base Sequence, Genetic, Genome, Databases, Bacterial/genetics, Base Composition/genetics, Bordetella pertussis/genetics, {DNA}/*instrumentation/*methods, Gene Library, Nucleotide Motifs/genetics, Plasmodium falciparum/genetics, Polymorphism, Protozoan/genetics, Single Nucleotide/genetics, Staphylococcus aureus/genetics}
}

@article{yu_novel_2007,
	title = {A novel set of {DNA} methylation markers in urine sediments for sensitive/specific detection of bladder cancer},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18094410},
	doi = {10.1158/1078-0432.CCR-07-0861},
	abstract = {{PURPOSE}: This study aims to provide a better set of {DNA} methylation markers in urine sediments for sensitive and specific detection of bladder cancer. {EXPERIMENTAL} {DESIGN}: Fifty-nine tumor-associated genes were profiled in three bladder cancer cell lines, a small cohort of cancer biopsies and urine sediments by methylation-specific {PCR}. Twenty-one candidate genes were then profiled in urine sediments from 132 bladder cancer patients (8 cases for stage 0a; 68 cases for stage I; 50 cases for stage {II}; 4 cases for stages {III}; and 2 cases for stage {IV}), 23 age-matched patients with noncancerous urinary lesions, 6 neurologic diseases, and 7 healthy volunteers. {RESULTS}: Despite six incidences of four genes reported in 3 of 23 noncancerous urinary lesion patients analyzed, cancer-specific hypermethylation in urine sediments were reported for 15 genes (P {\textbackslash}textless 0.05). Methylation assessment of an 11-gene set ({SALL}3, {CFTR}, {ABCC}6, {HPR}1, {RASSF}1A, {MT}1A, {RUNX}3, {ITGA}4, {BCL}2, {ALX}4, {MYOD}1, {DRM}, {CDH}13, {BMP}3B, {CCNA}1, {RPRM}, {MINT}1, and {BRCA}1) confirmed the existing diagnosis of 121 among 132 bladder cancer cases (sensitivity, 91.7\%) with 87\% accuracy. Significantly, more than 75\% of stage 0a and 88\% of stage I disease were detected, indicating its value in the early diagnosis of bladder cancer. Interestingly, the cluster of reported methylation markers used in the U.S. bladder cancers is distinctly different from that identified in this study, suggesting a possible epigenetic disparity between the American and Chinese cases. {CONCLUSIONS}: Methylation profiling of an 11-gene set in urine sediments provides a sensitive and specific detection of bladder cancer.},
	pages = {7296--7304},
	number = {24},
	journaltitle = {Clin Cancer Res},
	author = {Yu, J and Zhu, T and Wang, Z and Zhang, H and Qian, Z and Xu, H and Gao, B and Wang, W and Gu, L and Meng, J and Wang, J and Feng, X and Li, Y and Yao, X and Zhu, J},
	date = {2007},
	pmid = {18094410},
	keywords = {Base Sequence, Humans, *{DNA} Methylation, 80 and over, Adult, Aged, Biological/genetics/*urine, Female, Male, Middle Aged, Molecular Sequence Data, Polymerase Chain Reaction, {ROC} Curve, Sensitivity and Specificity, Tumor Markers, Urinary Bladder Neoplasms/*diagnosis/*genetics/*ur}
}

@article{du_integrative_2013,
	title = {Integrative genomic analyses reveal clinically relevant long noncoding {RNAs} in human cancer},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23728290},
	doi = {10.1038/nsmb.2591},
	abstract = {Despite growing appreciation of the importance of long noncoding {RNAs} ({lncRNAs}) in normal physiology and disease, our knowledge of cancer-related {lncRNAs} remains limited. By repurposing microarray probes, we constructed expression profiles of 10,207 {lncRNA} genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the {lncRNA} expression profiles with clinical outcome and somatic copy-number alterations, we identified {lncRNAs} that are associated with cancer subtypes and clinical prognosis and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two newly identified {lncRNAs}. Our analysis provides a resource of clinically relevant {lncRNAs} for the development of {lncRNA} biomarkers and the identification of {lncRNA} therapeutic targets. It also demonstrates the power of integrating publically available genomic data sets and clinical information for discovering disease-associated {lncRNAs}.},
	pages = {908--913},
	number = {7},
	journaltitle = {Nat Struct Mol Biol},
	author = {Du, Z and Fei, T and Verhaak, R G and Su, Z and Zhang, Y and Brown, M and Chen, Y and Liu, X S},
	date = {2013},
	pmid = {23728290},
	keywords = {{DNA}, Gene Expression Profiling/*methods, Conserved Sequence, Humans, {RNA}, Gene Expression Regulation, Exons, Intergenic, Oligonucleotide Array Sequence Analysis, Introns, Adenocarcinoma/genetics/pathology, Amino Acid, Amino Acid Sequence, Biological, Cell Line, {DNA} Probes, Gene Dosage, Genes, Kaplan-Meier Estimate, Long Noncoding/analysis/classification/*genet, Male, Models, Molecular, Molecular Sequence Data, Molecular Targeted Therapy, Neoplasm/analysis/*genetics, Neoplasms/classification/*genetics/mortality, Neoplastic/genetics, Overlapping, Prognosis, Prostatic Neoplasms/genetics/pathology, Protein Conformation, Sequence Alignment, Sequence Homology, Tumor Markers, Tumor/chemistry}
}

@article{loh_oct4_2006,
	title = {The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16518401},
	doi = {10.1038/ng1760},
	abstract = {Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem ({ES}) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse {ES} cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating {RNA} interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep {ES} cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.},
	pages = {431--440},
	number = {4},
	journaltitle = {Nat Genet},
	author = {Loh, Y H and Wu, Q and Chew, J L and Vega, V B and Zhang, W and Chen, X and Bourque, G and George, J and Leong, B and Liu, J and Wong, K Y and Sung, K W and Lee, C W and Zhao, X D and Chiu, K P and Lipovich, L and Kuznetsov, V A and Robson, P and Stanton, L W and Wei, C L and Ruan, Y and Lim, B and Ng, H H},
	date = {2006},
	pmid = {16518401},
	keywords = {Animals, Humans, Mice, Transcription, {DNA}-Binding Proteins/*physiology, Embryo, Gene Expression Regulation/physiology, Genetic/*physiology, Homeodomain Proteins/*physiology, Mammalian/*cytology/metabolism, Octamer Transcription Factor-3/*physiology, {RNA} Interference, Stem Cells/*cytology/metabolism}
}

@book{mardia_multivariate_1979,
	location = {London ; New York},
	title = {Multivariate analysis},
	isbn = {0124712509 0124712525 (pbk.)},
	url = {http://www.loc.gov/catdir/description/els031/79040922.html http://www.loc.gov/catdir/toc/els031/79040922.html},
	pagetotal = {xv, 521 p.},
	publisher = {Academic Press},
	author = {Mardia, K V and Kent, J T and Bibby, J M},
	date = {1979},
	pmid = {4646459},
	keywords = {Multivariate analysis.}
}

@article{la_marca_individualization_2014,
	title = {Individualization of controlled ovarian stimulation in {IVF} using ovarian reserve markers: from theory to practice},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24077980},
	doi = {10.1093/humupd/dmt037},
	abstract = {{BACKGROUND}: The main objective of individualization of treatment in {IVF} is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in {IVF} should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count ({AFC}) and anti-Mullerian hormone ({AMH}), and the therapeutic strategies that have been proposed in {IVF} after this prediction. {METHODS}: A systematic review of the existing literature was performed by searching Medline, {EMBASE}, Cochrane library and Web of Science for publications in the English language related to {AFC}, {AMH} and their incorporation into controlled ovarian stimulation ({COS}) protocols in {IVF}. Literature available to May 2013 was included. {RESULTS}: The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of {AMH} and {AFC} to predict response to {COS} were included in this review. The literature review demonstrated that {AFC} and {AMH}, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized {COS} protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the {GnRH} antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective {COS} and subsequent {IVF} outcomes. {CONCLUSION}: Personalized {IVF} offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of {GnRH} analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective {IVF} practice.},
	pages = {124--140},
	number = {1},
	journaltitle = {Hum Reprod Update},
	author = {La Marca, A and Sunkara, S K},
	date = {2014},
	pmid = {24077980}
}

@article{prislei_mechanisms_1992,
	title = {The mechanisms controlling ribosomal protein L1 pre-{mRNA} splicing are maintained in evolution and rely on conserved intron sequences},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1408749},
	abstract = {Sequences corresponding to the third intron of the X.laevis L1 ribosomal protein gene were isolated from the second copy of the X.laevis gene and from the single copy of X.tropicalis. Sequence comparison revealed that the three introns share an unusual sequence conservation which spans a region of 110 nucleotides. In addition, they have the same suboptimal 5' splice sites. The three introns show similar features upon oocyte microinjection: they have very low splicing efficiency and undergo the same site specific cleavages which lead to the accumulation of truncated molecules. Computer analysis and {RNAse} digestions have allowed to assign to the conserved region a specific secondary structure. Mutational analysis has shown that this structure is important for conferring the cleavage phenotype to these three introns. Competition experiments show that the cleavage phenotype can be prevented by coinjection of excess amounts of homologous sequences.},
	pages = {4473--4479},
	number = {17},
	journaltitle = {Nucleic Acids Res},
	author = {Prislei, S and Sperandio, S and Fragapane, P and Caffarelli, E and Presutti, C and Bozzoni, I},
	date = {1992},
	pmid = {1408749},
	keywords = {Animals, Base Sequence, Biological Evolution, Cloning, Introns/*genetics, Molecular, Molecular Sequence Data, Mutagenesis/genetics, Nucleic Acid Conformation, Ribosomal Proteins/*genetics/metabolism, {RNA} Precursors/genetics/*metabolism, {RNA} Splicing/genetics/*physiology, Xenopus laevis/*genetics/metabolism}
}

@article{singh_unique_2013,
	title = {A unique paradoxical reaction to tuberculosis therapy: case report and brief review of the literature},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21192247},
	doi = {10.1097/MJT.0b013e3181fa0dc0},
	abstract = {Extensive experience in the diagnosis and treatment of tuberculosis ({TB}) has led to treatment guidelines, which almost always result in progressive clinical improvement and cure in the compliant patient. Failure of a patient to respond as expected raises concerns of unexpected drug resistance, poor absorption, drug fever, or rarely an intense inflammatory reaction known as paradoxical reaction. Paradoxical reactions to anti-{TB} treatment are relatively rare in nonimmunocompromised individuals. Hepatic abscess is a very rare consequence of primary {TB} infection but has never been described as occurring as part of a paradoxical reaction. We present a case of a unique paradoxical reaction to initiation of {TB} treatment.},
	pages = {e706--9},
	number = {6},
	journaltitle = {Am J Ther},
	author = {Singh, B and Iqbal, F M and Sunkavalli, K K and Chawla, B},
	date = {2013},
	pmid = {21192247}
}

@article{yoon_tyrosine_2014,
	title = {Tyrosine phosphorylation of {HuR} by {JAK}3 triggers dissociation and degradation of {HuR} target {mRNAs}},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24106086},
	doi = {10.1093/nar/gkt903},
	abstract = {In response to stress conditions, many mammalian {mRNAs} accumulate in stress granules ({SGs}) together with numerous {RNA}-binding proteins that control {mRNA} turnover and translation. However, the signaling cascades that modulate the presence of ribonucleoprotein ({RNP}) complexes in {SGs} are poorly understood. Here, we investigated the localization of human antigen R ({HuR}), an {mRNA}-stabilizing {RNA}-binding protein, in {SGs} following exposure to the stress agent arsenite. Unexpectedly, the mobilization of {HuR} to {SGs} was prevented through the activation of Janus kinase 3 ({JAK}3) by the vitamin K3 analog menadione. {JAK}3 phosphorylated {HuR} at tyrosine 200, in turn inhibiting {HuR} localization in {SGs}, reducing {HuR} interaction with targets {SIRT}1 and {VHL} {mRNAs}, and accelerating target {mRNA} decay. Our findings indicate that {HuR} is tyrosine-phosphorylated by {JAK}3, and link this modification to {HuR} subcytoplasmic localization and to the fate of {HuR} target {mRNAs}.},
	pages = {1196--1208},
	number = {2},
	journaltitle = {Nucleic Acids Res},
	author = {Yoon, J H and Abdelmohsen, K and Srikantan, S and Guo, R and Yang, X and Martindale, J L and Gorospe, M},
	date = {2014},
	pmid = {24106086}
}

@article{gorospe_ribonucleoprotein_2009,
	title = {Ribonucleoprotein dynamics connects {mRNA} networks with drug mechanisms},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19638970},
	doi = {10.1038/msb.2009.48},
	pages = {289},
	journaltitle = {Mol Syst Biol},
	author = {Gorospe, M},
	date = {2009},
	pmid = {19638970},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Antigens, Hu Paraneoplastic Encephalomyelitis Antigens, Kinetics, Messenger/*metabolism, Pharmaceutical Preparations, Ribonucleoproteins/*metabolism, {RNA}-Binding Proteins, Surface}
}

@article{xu_let-7-repressesed_2014,
	title = {let-7-repressesed Shc translation delays replicative senescence},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24165399},
	doi = {10.1111/acel.12176},
	abstract = {The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the {microRNA} let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc {mRNA} levels. We identified 'seedless' let-7a interaction elements in the coding region of Shc {mRNA}; mutation of the 'seedless' interaction sites abolished the regulation of Shc by let-7a. Our results further revealed that repression of Shc expression by let-7a delays senescence of human diploid fibroblasts ({HDFs}). In sum, our findings link let-7a abundance to the expression of p66Shc, which in turn controls the replicative lifespan of {HDFs}.},
	pages = {185--192},
	number = {1},
	journaltitle = {Aging Cell},
	author = {Xu, F and Pang, L and Cai, X and Liu, X and Yuan, S and Fan, X and Jiang, B and Zhang, X and Dou, Y and Gorospe, M and Wang, W},
	date = {2014},
	pmid = {24165399}
}

@article{wilson_social_1975,
	title = {Social structuring of mammalian populations and rate of chromosomal evolution},
	volume = {72},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1061091},
	abstract = {To test the hypothesis that the evolution of organisms is dependent to a large degree on gene rearrangement, we devised a way of estimating rates of evolutionary change in karyotype. This non-biochemical method is based on consideration of chromosomal variability within taxonomic groups having a fossil record. The results show that chromosomal evolution has been faster in placental mammals than in other vertebrates or molluscs. This finding is consistent with published evidence that placentals have also been evolving unusually fast in anatomy and way of life. However, the structural genes of placentals seem not to have experienced accelerated evolution. Possibly, therefore, anatomical evolution may be facilitated by gene rearrangement. To explain how placentals achieved this rate of chromosomal evolution, we consider the process by which a new gene arrangement becomes fixed and spreads. The structure and dynamics of placental populations may be especially favorable for this process. The key factor involved seems to be the type of social behavior which produces small effective population sizes and inbreeding. As Bush points out elsewhere, such social structuring of populations may promote rapid fixation of gene rearrangements and rapid speciation.},
	pages = {5061--5065},
	number = {12},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Wilson, A C and Bush, G L and Case, S M and King, M C},
	date = {1975},
	pmid = {1061091},
	keywords = {Animals, *Biological Evolution, *Chromosomes, *Genetics, Karyotyping, Mammals, Mollusca, Population, Species Specificity, Time Factors, Vertebrates}
}

@article{robinson_integrative_2011,
	title = {Integrative genomics viewer},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21221095},
	doi = {10.1038/nbt.1754},
	pages = {24--26},
	number = {1},
	journaltitle = {Nat Biotechnol},
	author = {Robinson, J T and Thorvaldsdottir, H and Winckler, W and Guttman, M and Lander, E S and Getz, G and Mesirov, J P},
	date = {2011},
	pmid = {21221095},
	keywords = {*Software, Genomics/*methods, Humans, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, *Computer Graphics, *Online Systems, Chromosome Mapping/methods, Computational Biology/methods, Gene Dosage, Glioblastoma/genetics, Information Storage and Retrieval/methods, Internet, Neoplasms/genetics, Polymorphism, Single Nucleotide}
}

@article{sunk_histopathological_2013,
	title = {Histopathological correlation supports the use of x-rays in the diagnosis of hand osteoarthritis},
	volume = {72},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22580584},
	doi = {10.1136/annrheumdis-2011-200925},
	abstract = {{OBJECTIVE}: To correlate histopathological and radiographic features of distal and proximal interphalangeal ({DIP} and {PIP}) joints in order to test whether the use of an x-ray examination would be beneficial to the classification/diagnosis process of hand osteoarthritis ({OA}). {METHODS}: {DIP} and {PIP} joints were obtained from post mortem specimens (n=40). Plain x-rays of the {DIP} and {PIP} joints were taken and radiographic {OA} was determined by the Kellgren and Lawrence classification. Individual radiographic features were scored according to the method described by Altman. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. Spearman's correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups (bony swelling vs no bony swelling) were determined by Student t test. {RESULTS}: A highly significant correlation was found between histological (Mankin score) and radiographic (Kellgren/Lawrence score) changes in the investigated {DIP} (r(s)=0.87, p{\textbackslash}textless0.0001) and {PIP} (r(s)=0.79, p{\textbackslash}textless0.0001) joints. A subgroup of patients (37.5\% for {DIP} and 18.8\% for {PIP} joints) showed advanced radiographic changes (Kellgren/Lawrence score {\textbackslash}textgreater/=2) in joints without clinical bony swelling. Histologically, the mean Mankin scores accounted for 11+/-1.66 for {DIP} and 9.67+/-2.4 for {PIP} joints. {CONCLUSION}: On the basis of histopathological changes of {DIP} and {PIP} joints, this investigation demonstrates the validity of x-ray examinations and supports the use of plain radiography in the diagnosis of hand {OA} and in the classification of hand {OA} in clinical trials.},
	pages = {572--577},
	number = {4},
	journaltitle = {Ann Rheum Dis},
	author = {Sunk, I G and Amoyo-Minar, L and Niederreiter, B and Soleiman, A and Kainberger, F and Smolen, J S and Bobacz, K},
	date = {2013},
	pmid = {22580584},
	keywords = {Humans, Reproducibility of Results, 80 and over, Adult, Age Factors, Aged, Arthrography/*standards/statistics \& numerical dat, Cartilage/pathology/radiography, Cysts/epidemiology/pathology/radiography, Diagnosis, Differential, Edema/epidemiology/pathology/radiography, Female, Finger Joint/*pathology/*radiography, Hand/pathology/radiography, Male, Middle Aged, Osteoarthritis/epidemiology/*pathology/*radiograph, Osteophyte/epidemiology/pathology/radiography, Tissue Banks}
}

@article{gibson_creation_2010,
	title = {Creation of a bacterial cell controlled by a chemically synthesized genome},
	volume = {329},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20488990},
	doi = {10.1126/science.1190719},
	abstract = {We report the design, synthesis, and assembly of the 1.08-mega-base pair Mycoplasma mycoides {JCVI}-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new M. mycoides cells that are controlled only by the synthetic chromosome. The only {DNA} in the cells is the designed synthetic {DNA} sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.},
	pages = {52--56},
	number = {5987},
	journaltitle = {Science},
	author = {Gibson, D G and Glass, J I and Lartigue, C and Noskov, V N and Chuang, R Y and Algire, M A and Benders, G A and Montague, M G and Ma, L and Moodie, M M and Merryman, C and Vashee, S and Krishnakumar, R and Assad-Garcia, N and Andrews-Pfannkoch, C and Denisova, E A and Young, L and Qi, Z Q and Segall-Shapiro, T H and Calvey, C H and Parmar, P P and Hutchison 3rd, C A and Smith, H O and Venter, J C},
	date = {2010},
	pmid = {20488990},
	keywords = {{DNA}, Base Sequence, Genetic, *Genome, *Bioengineering, *Genetic Engineering, Bacterial, Bacterial Proteins/analysis, Bacterial/chemical synthesis/genetics, Cloning, Escherichia coli/genetics, Gene Deletion, Genes, Molecular, Molecular Sequence Data, Mycoplasma capricolum/*genetics, Mycoplasma mycoides/*genetics/growth \& development, Phenotype, Plasmids, Polymerase Chain Reaction, Polymorphism, Saccharomyces cerevisiae/genetics, Transformation}
}

@article{ng_gene_2005,
	title = {Gene identification signature ({GIS}) analysis for transcriptome characterization and genome annotation},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15782207},
	doi = {10.1038/nmeth733},
	abstract = {We have developed a {DNA} tag sequencing and mapping strategy called gene identification signature ({GIS}) analysis, in which 5' and 3' signatures of full-length {cDNAs} are accurately extracted into paired-end ditags ({PETs}) that are concatenated for efficient sequencing and mapped to genome sequences to demarcate the transcription boundaries of every gene. {GIS} analysis is potentially 30-fold more efficient than standard {cDNA} sequencing approaches for transcriptome characterization. We demonstrated this approach with 116,252 {PET} sequences derived from mouse embryonic stem cells. Initial analysis of this dataset identified hundreds of previously uncharacterized transcripts, including alternative transcripts of known genes. We also uncovered several intergenically spliced and unusual fusion transcripts, one of which was confirmed as a trans-splicing event and was differentially expressed. The concept of paired-end ditagging described here for transcriptome analysis can also be applied to whole-genome analysis of cis-regulatory and other {DNA} elements and represents an important technological advance for genome annotation.},
	pages = {105--111},
	number = {2},
	journaltitle = {Nat Methods},
	author = {Ng, P and Wei, C L and Sung, W K and Chiu, K P and Lipovich, L and Ang, C C and Gupta, S and Shahab, A and Ridwan, A and Wong, C H and Liu, E T and Ruan, Y},
	date = {2005},
	pmid = {15782207},
	keywords = {Gene Expression Profiling/*methods, Sequence Analysis, Animals, Mice, Reproducibility of Results, 5' Flanking Region/genetics, Cell Line, Chromosome Mapping/*methods, {DNA} Probes/*genetics, {DNA}/methods, Expressed Sequence Tags, Proteome/*genetics/*metabolism, Sensitivity and Specificity, Stem Cells/metabolism, Transcription Factors/*genetics/*metabolism}
}

@article{wang_factorbook.org:_2013,
	title = {Factorbook.org: a Wiki-based database for transcription factor-binding data generated by the {ENCODE} consortium},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23203885},
	doi = {10.1093/nar/gks1221},
	abstract = {The Encyclopedia of {DNA} Elements ({ENCODE}) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin states and {DNA} methylation patterns. The {ENCODE} project generates data utilizing a variety of techniques that can enrich for regulatory regions, such as chromatin immunoprecipitation ({ChIP}), micrococcal nuclease ({MNase}) digestion and {DNase} I digestion, followed by deeply sequencing the resulting {DNA}. As part of the {ENCODE} project, we have developed a Web-accessible repository accessible at http://factorbook.org. In Wiki format, factorbook is a transcription factor ({TF})-centric repository of all {ENCODE} {ChIP}-seq datasets on {TF}-binding regions, as well as the rich analysis results of these data. In the first release, factorbook contains 457 {ChIP}-seq datasets on 119 {TFs} in a number of human cell lines, the average profiles of histone modifications and nucleosome positioning around the {TF}-binding regions, sequence motifs enriched in the regions and the distance and orientation preferences between motif sites.},
	pages = {D171--6},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Wang, J and Zhuang, J and Iyer, S and Lin, X Y and Greven, M C and Kim, B H and Moore, J and Pierce, B G and Dong, X and Virgil, D and Birney, E and Hung, J H and Weng, Z},
	date = {2013},
	pmid = {23203885},
	keywords = {{DNA}, Sequence Analysis, Genetic, Humans, Binding Sites, *Databases, *Regulatory Elements, Cell Line, Chromatin Immunoprecipitation, High-Throughput Nucleotide Sequencing, Histones, Internet, Nucleosomes/metabolism, Nucleotide Motifs, Transcription Factors/*metabolism, Transcriptional}
}

@article{ooi_chromatin_2007,
	title = {Chromatin crosstalk in development and disease: lessons from {REST}},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17572692},
	doi = {10.1038/nrg2100},
	abstract = {Protein complexes that contain chromatin-modifying enzymes have an important role in regulating gene expression. Recent studies have shown that a single transcription factor, the repressor element 1-silencing transcription factor ({REST}), can act as a hub for the recruitment of multiple chromatin-modifying enzymes, uncovering interdependencies among individual enzymes that affect gene regulation. Research into the function of {REST} and its corepressors has provided novel insight into how chromatin-modifying proteins cooperate, and how alterations in this function cause disease. These mechanisms will be relevant to the combinatorial functioning of modular transcriptional regulators that work together to regulate a common promoter; they should also identify targets for potential therapies for a range of human diseases.},
	pages = {544--554},
	number = {7},
	journaltitle = {Nat Rev Genet},
	author = {Ooi, L and Wood, I C},
	date = {2007},
	pmid = {17572692},
	keywords = {Animals, Humans, {RNA}, Binding Sites, *Gene Expression Regulation, Chromatin/*physiology, Epilepsy/genetics, Gene Silencing, Genes, Histones/metabolism, Molecular Sequence Data, Regulon, Repressor Proteins/*physiology, Transcription Factors/*physiology, Tumor Suppressor, Untranslated/metabolism}
}

@article{fontes_projection_2011,
	title = {The projection score–an evaluation criterion for variable subset selection in {PCA} visualization},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21798031},
	doi = {10.1186/1471-2105-12-307},
	abstract = {{BACKGROUND}: In many scientific domains, it is becoming increasingly common to collect high-dimensional data sets, often with an exploratory aim, to generate new and relevant hypotheses. The exploratory perspective often makes statistically guided visualization methods, such as Principal Component Analysis ({PCA}), the methods of choice. However, the clarity of the obtained visualizations, and thereby the potential to use them to formulate relevant hypotheses, may be confounded by the presence of the many non-informative variables. For microarray data, more easily interpretable visualizations are often obtained by filtering the variable set, for example by removing the variables with the smallest variances or by only including the variables most highly related to a specific response. The resulting visualization may depend heavily on the inclusion criterion, that is, effectively the number of retained variables. To our knowledge, there exists no objective method for determining the optimal inclusion criterion in the context of visualization. {RESULTS}: We present the projection score, which is a straightforward, intuitively appealing measure of the informativeness of a variable subset with respect to {PCA} visualization. This measure can be universally applied to find suitable inclusion criteria for any type of variable filtering. We apply the presented measure to find optimal variable subsets for different filtering methods in both microarray data sets and synthetic data sets. We note also that the projection score can be applied in general contexts, to compare the informativeness of any variable subsets with respect to visualization by {PCA}. {CONCLUSIONS}: We conclude that the projection score provides an easily interpretable and universally applicable measure of the informativeness of a variable subset with respect to visualization by {PCA}, that can be used to systematically find the most interpretable {PCA} visualization in practical exploratory analysis.},
	pages = {307},
	journaltitle = {{BMC} Bioinformatics},
	author = {Fontes, M and Soneson, C},
	date = {2011},
	pmid = {21798031},
	keywords = {Humans, Algorithms, Software, *Gene Expression Profiling, *Oligonucleotide Array Sequence Analysis, *Principal Component Analysis, Leukemia/genetics, Lung Neoplasms/genetics}
}

@article{gifford_transposable_2013,
	title = {Transposable elements as genetic regulatory substrates in early development},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23411159},
	doi = {10.1016/j.tcb.2013.01.001},
	abstract = {The abundance and ancient origins of transposable elements ({TEs}) in eukaryotic genomes has spawned research into the potential symbiotic relationship between these elements and their hosts. In this review, we introduce the diversity of {TEs}, discuss how distinct classes are uniquely regulated in development, and describe how they appear to have been coopted for the purposes of gene regulation and the orchestration of a number of processes during early embryonic development. Although young, active {TEs} play an important role in somatic tissues and evolution, we focus mostly on the contributions of the older, fixed elements in mammalian genomes. We also discuss major challenges inherent in the study of {TEs} and contemplate future experimental approaches to further investigate how they coordinate developmental processes.},
	pages = {218--226},
	number = {5},
	journaltitle = {Trends Cell Biol},
	author = {Gifford, W D and Pfaff, S L and Macfarlan, T S},
	date = {2013},
	pmid = {23411159}
}

@article{shaaban_venturicidin_2013,
	title = {Venturicidin C, a new 20-membered macrolide produced by Streptomyces sp. {TS}-2-2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24252813},
	doi = {10.1038/ja.2013.113},
	abstract = {Venturicidin C (1), a new 20-membered macrolide along with the known venturicidins A (2) and B (3) were isolated from the crude extract of the Appalachian bacterial strain Streptomyces sp. {TS}-2-2. Additionally, nine other known compounds namely nocardamine, dehydroxynocardamine, desmethylenylnocardamine, ferrioxamine E, adenosine, riboflavin, cyclo(D)-trans-4-{OH}-Pro-(D)-Phe, cyclo(D)-Pro-(D)-Phe and N-(2-phenylethyl)-acetamide were also isolated and identified. The structure of the new macrolide 1 was elucidated by the cumulative analyses of {NMR} spectroscopy and {HR}-{MS} data. Complete {NMR} assignments for the known venturicidins A (2) and B (3) are also provided, for the first time, in this report. Venturicidins A-C did not inhibit the proliferation of A549 lung cancer cell line but all displayed potent antifungal activity.The Journal of Antibiotics advance online publication, 20 November 2013; doi:10.1038/ja.2013.113.},
	journaltitle = {J Antibiot (Tokyo)},
	author = {Shaaban, K A and Singh, S and Elshahawi, S I and Wang, X and Ponomareva, L V and Sunkara, M and Copley, G C and Hower, J C and Morris, A J and Kharel, M K and Thorson, J S},
	date = {2013},
	pmid = {24252813}
}

@article{love_moderated_2014,
	title = {Moderated estimation of fold change and dispersion for {RNA}-seq data with {DESeq}2},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25516281},
	doi = {10.1186/s13059-014-0550-8},
	abstract = {In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in {RNA}-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present {DESeq}2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The {DESeq}2 package is available at http://www.bioconductor.org/packages/release/bioc/html/{DESeq}2.html webcite.},
	pages = {550},
	number = {12},
	journaltitle = {Genome Biol},
	author = {Love, M I and Huber, W and Anders, S},
	date = {2014},
	pmid = {25516281}
}

@article{muotri_somatic_2005,
	title = {Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition},
	volume = {435},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15959507},
	doi = {10.1038/nature03663},
	abstract = {Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human {LINE}-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.},
	pages = {903--910},
	number = {7044},
	journaltitle = {Nature},
	author = {Muotri, A R and Chu, V T and Marchetto, M C and Deng, W and Moran, J V and Gage, F H},
	date = {2005},
	pmid = {15959507},
	keywords = {Animals, Humans, Mice, Promoter Regions, {RNA}, Transcription, Gene Expression Regulation, Cells, Cultured, Genetic/genetics, *Mosaicism, Brain/cytology/metabolism, Cell Differentiation, Cell Lineage, {DNA}-Binding Proteins/genetics, Genetic/*genetics, Green Fluorescent Proteins/genetics/metabolism, {HMGB} Proteins/genetics, Long Interspersed Nucleotide Elements/genetics, Messenger/genetics/metabolism, Molecular Sequence Data, Nerve Tissue Proteins/genetics/metabolism, Neurons/cytology/*metabolism, Rats, Recombination, Retroelements/*genetics, {SOXB}1 Transcription Factors, Stem Cells/cytology/*metabolism, Transcription Factors/genetics, Transgenic}
}

@article{grote_long_2013,
	title = {The long non-coding {RNA} Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24036695},
	abstract = {Epigenetic control mechanisms determine active and silenced regions of the genome. It is known that the Polycomb Repressive Complex 2 ({PRC}2) and the Trithorax group/Mixed lineage leukemia ({TrxG}/Mll) complex are able to set repressive and active histone marks, respectively. Long non-coding {RNAs} ({lncRNAs}) can interact with either of these complexes and guide them to regulatory elements, thereby modifying the expression levels of target genes. The {lncRNA} Fendrr is transiently expressed in lateral mesoderm of mid-gestational mouse embryos and was shown to interact with both {PRC}2 and {TrxG}/Mll complexes in vivo. Gene targeting revealed that loss of Fendrr results in impaired differentiation of tissues derived from lateral mesoderm, the heart and the body wall, ultimately leading to embryonic death. Molecular data suggests that Fendrr acts via {dsDNA}/{RNA} triplex formation at target regulatory elements, and directly increases {PRC}2 occupancy at these sites. This, in turn, modifies the ratio of repressive to active marks, adjusting the expression levels of Fendrr target genes in lateral mesoderm. We propose that Fendrr also mediates long-term epigenetic marks to define expression levels of its target genes within the descendants of lateral mesoderm cells. Here we discuss approaches for {lncRNA} gene knockouts in the mouse, and suggest a model how Fendrr and possibly other {lncRNAs} act during embryogenesis.},
	number = {10},
	journaltitle = {{RNA} Biol},
	author = {Grote, P and Herrmann, B G},
	date = {2013},
	pmid = {24036695}
}

@article{aparicio-prat_decko:_2015,
	title = {{DECKO}: Single-oligo, dual-{CRISPR} deletion of genomic elements including long non-coding {RNAs}},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26493208},
	doi = {10.1186/s12864-015-2086-z},
	abstract = {{BACKGROUND}: {CRISPR} genome-editing technology makes it possible to quickly and cheaply delete non-protein-coding regulatory elements. We present a vector system adapted for this purpose called {DECKO} (Double Excision {CRISPR} Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide {RNAs} ({gRNAs}) simultaneously. The key feature of {DECKO} is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both {gRNAs}, making it fully scalable from single-locus studies to complex library cloning. {RESULTS}: We apply {DECKO} to deleting the promoters of one protein-coding gene and two oncogenic {lncRNAs}, {UCA}1 and the highly-expressed {MALAT}1, focus of many previous studies employing {RNA} interference approaches. {DECKO} successfully deleted genomic fragments ranging in size from 100 to 3000 bp in four human cell lines. Using a clone-derivation workflow lasting approximately 20 days, we obtained 9 homozygous and 17 heterozygous promoter knockouts in three human cell lines. Frequent target region inversions were observed. These clones have reductions in steady-state {MALAT}1 {RNA} levels of up to 98 \% and display reduced proliferation rates. {CONCLUSIONS}: We present a dual {CRISPR} tool, {DECKO}, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to {CRISPR} knockout studies of non-coding genomic elements, including long non-coding {RNAs}.},
	pages = {846},
	number = {1},
	journaltitle = {{BMC} Genomics},
	author = {Aparicio-Prat, E and Arnan, C and Sala, I and Bosch, N and Guigo, R and Johnson, R},
	date = {2015},
	pmid = {26493208},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/U5DS25X2/Aparicio-Prat et al. - 2015 - DECKO Single-oligo, dual-CRISPR deletion of genom.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/IXE4ACAF/s12864-015-2086-z.html:text/html}
}

@article{da_rocha_jarid2_2014,
	title = {Jarid2 Is Implicated in the Initial Xist-Induced Targeting of {PRC}2 to the Inactive X Chromosome},
	volume = {53},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24462204},
	doi = {10.1016/j.molcel.2014.01.002},
	abstract = {During X chromosome inactivation ({XCI}), the Polycomb Repressive Complex 2 ({PRC}2) is thought to participate in the early maintenance of the inactive state. Although Xist {RNA} is essential for the recruitment of {PRC}2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate that the {PRC}2 cofactor Jarid2 is an important mediator of Xist-induced {PRC}2 targeting. The region containing the conserved B and F repeats of Xist is critical for Jarid2 recruitment via its unique N-terminal domain. Xist-induced Jarid2 recruitment occurs chromosome-wide independently of a functional {PRC}2 complex, unlike at other parts of the genome, such as {CG}-rich regions, where Jarid2 and {PRC}2 binding are interdependent. Conversely, we show that Jarid2 loss prevents efficient {PRC}2 and H3K27me3 enrichment to Xist-coated chromatin. Jarid2 thus represents an important intermediate between {PRC}2 and Xist {RNA} for the initial targeting of the {PRC}2 complex to the X chromosome during onset of {XCI}.},
	pages = {301--316},
	number = {2},
	journaltitle = {Mol Cell},
	author = {da Rocha, S T and Boeva, V and Escamilla-Del-Arenal, M and Ancelin, K and Granier, C and Matias, N R and Sanulli, S and Chow, J and Schulz, E and Picard, C and Kaneko, S and Helin, K and Reinberg, D and Stewart, A F and Wutz, A and Margueron, R and Heard, E},
	date = {2014},
	pmid = {24462204}
}

@article{kowdley_cancer_2012,
	title = {Cancer surgery in the elderly},
	volume = {2012},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22272172},
	doi = {10.1100/2012/303852},
	abstract = {The proportions both of elderly patients in the world and of elderly patients with cancer are both increasing. In the evaluation of these patients, physiologic age, and not chronologic age, should be carefully considered in the decision-making process prior to both cancer screening and cancer treatment in an effort to avoid ageism. Many tools exist to help the practitioner determine the physiologic age of the patient, which allows for more appropriate and more individualized risk stratification, both in the pre- and postoperative periods as patients are evaluated for surgical treatments and monitored for surgical complications, respectively. During and after operations in the oncogeriatric populations, physiologic changes occuring that accompany aging include impaired stress response, increased senescence, and decreased immunity, all three of which impact the risk/benefit ratio associated with cancer surgery in the elderly.},
	pages = {303852},
	journaltitle = {{ScientificWorldJournal}},
	author = {Kowdley, G C and Merchant, N and Richardson, J P and Somerville, J and Gorospe, M and Cunningham, S C},
	date = {2012},
	pmid = {22272172},
	keywords = {Humans, Age Factors, Aged, Aging/immunology/physiology, Breast Neoplasms/prevention \& control, Colorectal Neoplasms/prevention \& control, Decision Making, Female, Geriatric Assessment, Male, Middle Aged, Neoplasms/prevention \& control/*surgery, Prostatic Neoplasms/prevention \& control}
}

@article{engstrom_complex_2006,
	title = {Complex Loci in human and mouse genomes},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16683030},
	doi = {10.1371/journal.pgen.0020047},
	abstract = {Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units ({TUs}), along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human {TUs}. In both human and mouse, 25\% of {TUs} resided in cis-antisense pairs, only 17\% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40\% of all {TUs} might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.},
	pages = {e47},
	number = {4},
	journaltitle = {{PLoS} Genet},
	author = {Engstrom, P G and Suzuki, H and Ninomiya, N and Akalin, A and Sessa, L and Lavorgna, G and Brozzi, A and Luzi, L and Tan, S L and Yang, L and Kunarso, G and Ng, E L and Batalov, S and Wahlestedt, C and Kai, C and Kawai, J and Carninci, P and Hayashizaki, Y and Wells, C and Bajic, V B and Orlando, V and Reid, J F and Lenhard, B and Lipovich, L},
	date = {2006},
	pmid = {16683030},
	keywords = {Human, Animals, Genetic, Genome, Promoter Regions, *Genome, *Chromosome Mapping, Base Pairing, {DNA} Primers, Humans/*genetics, Mice/*genetics, Reverse Transcriptase Polymerase Chain Reaction}
}

@article{gorospe_rna-binding_2012,
	title = {{RNA}-binding proteins: post-transcriptional control of aging traits: an introduction to a series of review articles},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22999313},
	doi = {10.1016/j.arr.2012.09.001},
	pages = {421--422},
	number = {4},
	journaltitle = {Ageing Res Rev},
	author = {Gorospe, M},
	date = {2012},
	pmid = {22999313},
	keywords = {Animals, Humans, Aging/*genetics, Cell Aging/*genetics, {MicroRNAs}/genetics, Post-Transcriptional/*genetics, {RNA} Processing, {RNA}-Binding Proteins/*genetics}
}

@article{gorospe_protective_1996,
	title = {Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8943319},
	abstract = {Prostaglandin A2 ({PGA}2) suppresses tumor growth in vivo, is potently antiproliferative in vitro, and is a model drug for the study of the mammalian stress response. Our previous studies using breast carcinoma {MCF}-7 cells suggested that p21(Waf1/Cip1) induction enabled cells to survive {PGA}2 exposure. Indeed, the marked sensitivity of human colorectal carcinoma {RKO} cells to the cytotoxicity of {PGA}2 is known to be associated with a lack of a {PGA}2-mediated increase in p21(Waf1/Cip1) expression, inhibition of cyclin-dependent kinase activity, and growth arrest. To determine if cell death following exposure to {PGA}2 could be prevented by forcing the expression of p21(Waf1/Cip1) in {RKO} cells, we utilized an adenoviral vector-based expression system. We demonstrate that ectopic expression of p21(Waf1/Cip1) largely rescued {RKO} cells from {PGA}2-induced apoptotic cell death, directly implicating p21(Waf1/Cip1) as a determinant of the cellular outcome (survival versus death) following exposure to {PGA}2. To discern whether p21(Waf1/Cip1)-mediated protection operates through the implementation of cellular growth arrest, other growth-inhibitory treatments were studied for the ability to attenuate {PGA}2-induced cell death. Neither serum depletion nor suramin (a growth factor receptor antagonist) protected {RKO} cells against {PGA}2 cytotoxicity, and neither induced p21(Waf1/Cip1) expression. Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited {RKO} cell proliferation, and exerted marked protection against a subsequent {PGA}2 challenge. Taken together, our results directly demonstrate a protective role for p21(Waf1/Cip1) during {PGA}2 cellular stress and provide strong evidence that the implementation of cellular growth arrest contributes to this protective influence.},
	pages = {6654--6660},
	number = {12},
	journaltitle = {Mol Cell Biol},
	author = {Gorospe, M and Wang, X and Guyton, K Z and Holbrook, N J},
	date = {1996},
	pmid = {8943319},
	keywords = {Humans, Gene Expression Regulation, *Apoptosis/drug effects/genetics, Carcinoma/genetics/*pathology, Cell Division, Colorectal Neoplasms/genetics/*pathology, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/*genetics, Prostaglandins A/*pharmacology}
}

@article{gu_impact_2013,
	title = {Impact of the hypoxia-inducible factor-1 alpha ({HIF}1A) Pro582Ser polymorphism on diabetes nephropathy},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22991450},
	doi = {10.2337/dc12-1125},
	abstract = {{OBJECTIVE}: Hypoxia plays a major pathogenic role in diabetic nephropathy ({DN}). We have investigated in this study the effect of hypoxia-inducible factor 1 alpha subunit ({HIF}1A) genetic polymorphisms on the development of {DN}. {RESEARCH} {DESIGN} {AND} {METHODS}: In 1,165 American type 1 diabetic patients with and without {DN} selected from the Genetics of Kidneys in Diabetes ({GoKinD}) study, the {HIF}1A genetic polymorphisms were genotyped with {TaqMan} allelic discrimination. The regulation of {HIF}-1alpha in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect {HIF}1A Pro582Ser polymorphism on {HIF}-1alpha sensitivity to glucose was evaluated in vitro. {RESULTS}: We identified a protective association between {HIF}1A Pro582Ser polymorphism and {DN} in male subjects. We also provided mechanistic insights that {HIF}-1alpha is repressed in the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism confers less sensitivity to the inhibitory effect of glucose during a hypoxic challenge. {CONCLUSIONS}: The current study demonstrates for the first time that {HIF}1A Pro582Ser polymorphism has an effect on {DN}, possibly by conferring a relative resistance to the repressive effect of glucose on {HIF}-1alpha.},
	pages = {415--421},
	number = {2},
	journaltitle = {Diabetes Care},
	author = {Gu, H F and Zheng, X and Abu Seman, N and Gu, T and Botusan, I R and Sunkari, V G and Lokman, E F and Brismar, K and Catrina, S B},
	date = {2013},
	pmid = {22991450},
	keywords = {Humans, Adult, Cell Line, Diabetic Nephropathies/*genetics/*metabolism, Female, Genotype, Hypoxia-Inducible Factor 1/*genetics/*metabolism, Immunohistochemistry, Male, Middle Aged, Polymorphism, Single Nucleotide/*genetics}
}

@article{goodier_mapping_2013,
	title = {Mapping the {LINE}1 {ORF}1 protein interactome reveals associated inhibitors of human retrotransposition},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23749060},
	doi = {10.1093/nar/gkt512},
	abstract = {{LINE}1s occupy 17\% of the human genome and are its only active autonomous mobile {DNA}. L1s are also responsible for genomic insertion of processed pseudogenes and {\textbackslash}textgreater1 million non-autonomous retrotransposons (Alus and {SVAs}). These elements have significant effects on gene organization and expression. Despite the importance of retrotransposons for genome evolution, much about their biology remains unknown, including cellular factors involved in the complex processes of retrotransposition and forming and transporting L1 ribonucleoprotein particles. By co-immunoprecipitation of tagged L1 constructs and mass spectrometry, we identified proteins associated with the L1 {ORF}1 protein and its ribonucleoprotein. These include {RNA} transport proteins, gene expression regulators, post-translational modifiers, helicases and splicing factors. Many cellular proteins co-localize with L1 {ORF}1 protein in cytoplasmic granules. We also assayed the effects of these proteins on cell culture retrotransposition and found strong inhibiting proteins, including some that control {HIV} and other retroviruses. These data suggest candidate cofactors that interact with the L1 to modulate its activity and increase our understanding of the means by which the cell coexists with these genomic 'parasites'.},
	pages = {7401--7419},
	number = {15},
	journaltitle = {Nucleic Acids Res},
	author = {Goodier, J L and Cheung, L E and Kazazian Jr., H H},
	date = {2013},
	pmid = {23749060}
}

@article{sharma_clinical_2013,
	title = {Clinical genomicist workstation},
	volume = {2013},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24303327},
	abstract = {The use of {NextGen} Sequencing clinically necessitates the need for informatics tools that support the complete workflow from sample accessioning to data analysis and reporting. To address this need we have developed Clinical Genomicist Workstation ({CGW}). {CGW} is a secure, n-tiered application where web browser submits requests to application servers that persist the data in a relational database. {CGW} is used by Washington University Genomic and Pathology Services for clinical genomic testing of many cancers. {CGW} has been used to accession, analyze and sign out over 409 cases since November, 2011. There are 22 ordering oncologists and 7 clinical genomicists that use the {CGW}. In summary, {CGW} a 'soup-to-nuts' solution to track, analyze, interpret, and report clinical genomic diagnostic tests.},
	pages = {156--157},
	journaltitle = {{AMIA} Summits Transl Sci Proc},
	author = {Sharma, M K and Phillips, J and Agarwal, S and Wiggins, W S and Shrivastava, S and Koul, S B and Bhattacharjee, M and Houchins, C D and Kalakota, R R and George, B and Meyer, R R and Spencer, D H and Lockwood, C M and Nguyen, T T and Duncavage, E J and Al-Kateb, H and Cottrell, C E and Godala, S and Lokineni, R and Sawant, S M and Chatti, V and Surampudi, S and Sunkishala, R R and Darbha, R and Macharla, S and Milbrandt, J D and Virgin, H W and Mitra, R D and Head, R D and Kulkarni, S and Bredemeyer, A and Pfeifer, J D and Seibert, K and Nagarajan, R},
	date = {2013},
	pmid = {24303327}
}

@article{fatica_biosynthesis_1997,
	title = {Biosynthesis of U16 {snoRNA} in early development of X. laevis},
	volume = {241},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9425297},
	doi = {10.1006/bbrc.1997.7642},
	abstract = {The U16 and U18 {snoRNAs} are encoded in introns of the X.laevis L1 ribosomal protein gene and originate from processing of the pre-{mRNA}. These {snoRNAs} are newly synthesized around gastrula stage and progressively accumulate during embryogenesis. We show that the basic factors participating in U16 biosynthesis, such as the endonuclease involved in the cleavage reaction and the factors necessary for stabilization of mature {snoRNA} are present from very early stages. The use of anucleolate mutants has indicated that the synthesis and accumulation of U16 and U18 {snoRNAs} is not affected in the absence of ongoing {rRNA} transcription.},
	pages = {486--490},
	number = {2},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Fatica, A and Caffarelli, E and Beccari, E and Bozzoni, I},
	date = {1997},
	pmid = {9425297},
	keywords = {Animals, {RNA}, Cell Nucleolus, Gastrula, Messenger/metabolism, Post-Transcriptional, Ribosomal Proteins/genetics, Ribosomal/biosynthesis, {RNA} Precursors/metabolism, {RNA} Processing, Small Nuclear/*biosynthesis, Xenopus laevis/*embryology}
}

@article{morlando_primary_2008,
	title = {Primary {microRNA} transcripts are processed co-transcriptionally},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19172742},
	abstract = {{microRNAs} ({miRNAs}) are generated from long primary (pri-) {RNA} polymerase {II} (Pol {II})-derived transcripts by two {RNase} {III} processing reactions: Drosha cleavage of nuclear pri-{miRNAs} and Dicer cleavage of cytoplasmic pre-{miRNAs}. Here we show that Drosha cleavage occurs during transcription acting on both independently transcribed and intron-encoded {miRNAs}. We also show that both 5'-3' and 3'-5' exonucleases associate with the sites where co-transcriptional Drosha cleavage occurs, promoting intron degradation before splicing. We finally demonstrate that {miRNAs} can also derive from 3' flanking transcripts of Pol {II} genes. Our results demonstrate that multiple {miRNA}-containing transcripts are co-transcriptionally cleaved during their synthesis and suggest that exonucleolytic degradation from Drosha cleavage sites in pre-{mRNAs} may influence the splicing and maturation of numerous {mRNAs}.},
	pages = {902--909},
	number = {9},
	journaltitle = {Nat Struct Mol Biol},
	author = {Morlando, M and Ballarino, M and Gromak, N and Pagano, F and Bozzoni, I and Proudfoot, N J},
	date = {2008},
	pmid = {19172742},
	keywords = {Genetic, Humans, {RNA} Splicing, Transcription, Introns, beta-Globins/genetics, Chromatin Immunoprecipitation, Chromatin/genetics/metabolism, {HeLa} Cells, {MicroRNAs}/chemistry/*genetics/*metabolism, Microtubule-Associated Proteins/genetics, Nucleic Acid Conformation, Ribonuclease {III}/genetics/metabolism, {RNA} Polymerase {II}/genetics/metabolism}
}

@article{sunkin_allen_2013,
	title = {Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23193282},
	doi = {10.1093/nar/gks1042},
	abstract = {The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization ({ISH}) and supporting histology, microarray, {RNA} sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent {ISH} image viewers, graphical displays of {ISH}, microarray and {RNA} sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.},
	pages = {D996--D1008},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Sunkin, S M and Ng, L and Lau, C and Dolbeare, T and Gilbert, T L and Thompson, C L and Hawrylycz, M and Dang, C},
	date = {2013},
	pmid = {23193282},
	keywords = {Animals, Humans, Mice, Gene Expression Profiling, *Anatomy, *Atlases as Topic, *Databases, Adult, Artistic, Brain/*anatomy \& histology/embryology/growth \& dev, Computer Graphics, Factual, In Situ Hybridization, Internet, Primates}
}

@article{vazquez_down-regulation_2011,
	title = {Down-regulation of {EVI}1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia},
	volume = {96},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21750091},
	doi = {10.3324/haematol.2011.040535},
	abstract = {{BACKGROUND}: The {EVI}1 gene (3q26) codes for a zinc finger transcription factor with important roles in both mammalian development and leukemogenesis. Over-expression of {EVI}1 through either 3q26 rearrangements, {MLL} fusions, or other unknown mechanisms confers a poor prognosis in acute myeloid leukemia. {DESIGN} {AND} {METHODS}: We analyzed the prevalence and prognostic impact of {EVI}1 over-expression in a series of 476 patients with acute myeloid leukemia, and investigated the epigenetic modifications of the {EVI}1 locus which could be involved in the transcriptional regulation of this gene. {RESULTS}: Our data provide further evidence that {EVI}1 over-expression is a poor prognostic marker in acute myeloid leukemia patients less than 65 years old. Moreover, we found that patients with no basal expression of {EVI}1 had a better prognosis than patients with expression/over-expression (P=0.036). We also showed that cell lines with over-expression of {EVI}1 had no {DNA} methylation in the promoter region of the {EVI}1 locus, and had marks of active histone modifications: H3 and H4 acetylation, and trimethylation of histone H3 lysine 4. Conversely, cell lines with no expression of {EVI}1 have {DNA} hypermethylation and are marked by repressive trimethylation of histone H3 lysine 27 at the {EVI}1 promoter. {CONCLUSIONS}: Our results identify {EVI}1 over-expression as a poor prognostic marker in a large, independent cohort of acute myeloid leukemia patients less than 65 years old, and show that the total absence of {EVI}1 expression has a prognostic impact on the outcome of such patients. Furthermore, we demonstrated for the first time that an aberrant epigenetic pattern involving {DNA} methylation, H3 and H4 acetylation, and trimethylation of histone H3 lysine 4 and histone H3 lysine 27 might play a role in the transcriptional regulation of {EVI}1 in acute myeloid leukemia. This study opens new avenues for a better understanding of the regulation of {EVI}1 expression at a transcriptional level.},
	pages = {1448--1456},
	number = {10},
	journaltitle = {Haematologica},
	author = {Vazquez, I and Maicas, M and Cervera, J and Agirre, X and Marin-Bejar, O and Marcotegui, N and Vicente, C and Lahortiga, I and Gomez-Benito, M and Carranza, C and Valencia, A and Brunet, S and Lumbreras, E and Prosper, F and Gomez-Casares, M T and Hernandez-Rivas, J M and Calasanz, M J and Sanz, M A and Sierra, J and Odero, M D},
	date = {2011},
	pmid = {21750091},
	keywords = {Human, Genetic, Humans, Gene Expression Regulation, Gene Expression Profiling, *Epigenesis, 80 and over, Acute/*diagnosis/*genetics/mort, Aged, Alternative Splicing, Cell Line, Chromosomes, {DNA}-Binding Proteins/*genetics, Down-Regulation/*genetics, Female, Gene Rearrangement, Kaplan-Meier Estimate, Leukemia, Leukemic, Male, Middle Aged, Myeloid, Pair 3, Prognosis, Proto-Oncogenes/*genetics, Transcription Factors/*genetics, Tumor}
}

@article{kim_staufen1_2007,
	title = {Staufen1 regulates diverse classes of mammalian transcripts},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17510634},
	doi = {10.1038/sj.emboj.7601712},
	abstract = {It is currently unknown how extensively the double-stranded {RNA}-binding protein Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression. To date, Stau1 binding to the 3'-untranslated region (3'-{UTR}) of {ADP} ribosylation factor ({ARF})1 {mRNA} has been shown to target {ARF}1 {mRNA} for Stau1-mediated {mRNA} decay ({SMD}). {ARF}1 {SMD} depends on translation and recruitment of the nonsense-mediated {mRNA} decay factor Upf1 to the {ARF}1 3'-{UTR} by Stau1. Here, we demonstrate that Stau1 binds to a complex structure within the {ARF}1 3'-{UTR}. We also use microarrays to show that 1.1 and 1.0\% of the 11 569 {HeLa}-cell transcripts that were analyzed are upregulated and downregulated, respectively, at least two-fold upon Stau1 depletion in three independently performed experiments. We localize the Stau1 binding site to the 3'-{UTR} of four {mRNAs} that we define as natural {SMD} targets. Additionally, we provide evidence that the efficiency of {SMD} increases during the differentiation of C2C12 myoblasts to myotubes. We propose that Stau1 influences the expression of a wide variety of physiologic transcripts and metabolic pathways.},
	pages = {2670--2681},
	number = {11},
	journaltitle = {{EMBO} J},
	author = {Kim, Y K and Furic, L and Parisien, M and Major, F and {DesGroseillers}, L and Maquat, L E},
	date = {2007},
	pmid = {17510634},
	keywords = {Base Sequence, Humans, Protein Binding, Computational Biology, 3' Untranslated Regions/*metabolism, {ADP}-Ribosylation Factor 1/*metabolism, Base Pairing, Blotting, Confocal, Cytoskeletal Proteins/*metabolism, {DNA} Primers/genetics, Gene Expression Regulation/*genetics, {HeLa} Cells, Interleukin-7/metabolism, Microscopy, Molecular Sequence Data, Plasminogen Activator Inhibitor 1/metabolism, Protein Array Analysis, Proto-Oncogene Proteins c-jun/metabolism, Receptors, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Stability/genetics/*physiology, {RNA}-Binding Proteins/*metabolism, Western}
}

@article{nafissi_robust_2012,
	title = {Robust translation of the nucleoid protein Fis requires a remote upstream {AU} element and is enhanced by {RNA} secondary structure},
	volume = {194},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22389479},
	doi = {10.1128/JB.00053-12},
	abstract = {Synthesis of the Fis nucleoid protein rapidly increases in response to nutrient upshifts, and Fis is one of the most abundant {DNA} binding proteins in Escherichia coli under nutrient-rich growth conditions. Previous work has shown that control of Fis synthesis occurs at transcription initiation of the {dusB}-fis operon. We show here that while translation of the dihydrouridine synthase gene {dusB} is low, unusual mechanisms operate to enable robust translation of fis. At least two {RNA} sequence elements located within the {dusB} coding region are responsible for high fis translation. The most important is an {AU} element centered 35 nucleotides (nt) upstream of the fis {AUG}, which may function as a binding site for ribosomal protein S1. In addition, a 44-nt segment located upstream of the {AU} element and predicted to form a stem-loop secondary structure plays a prominent role in enhancing fis translation. On the other hand, mutations close to the {AUG}, including over a potential Shine-Dalgarno sequence, have little effect on Fis protein levels. The {AU} element and stem-loop regions are phylogenetically conserved within {dusB}-fis operons of representative enteric bacteria.},
	pages = {2458--2469},
	number = {10},
	journaltitle = {J Bacteriol},
	author = {Nafissi, M and Chau, J and Xu, J and Johnson, R C},
	date = {2012},
	pmid = {22389479},
	keywords = {Base Sequence, {RNA}, Gene Expression Regulation, Protein Binding, Bacterial/*physiology, Bacterial/genetics/*metabolism, Escherichia coli Proteins/genetics/*metabolism, Escherichia coli/genetics/*metabolism, Factor For Inversion Stimulation Protein/genetics/, Messenger/genetics/metabolism, Mutation, Nucleic Acid Conformation, Operon, Protein Biosynthesis, Reverse Transcriptase Polymerase Chain Reaction}
}

@article{salvatori_critical_2011,
	title = {Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of {miR}-26a and Histone Methyltransferase {EZH}2},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21901171},
	doi = {10.1177/1947601911416357},
	abstract = {Increased expression or aberrant activation of c-Myc plays an important role in leukemogenesis. Here, we show that in acute myeloid leukemia ({AML}), c-Myc directly controls the expression of {EZH}2, a component of the Polycomb repressive complex 2, and {miR}-26a. {miR}-26a is downregulated in primary blasts from {AML} patients and, during myeloid differentiation of {AML} cells, is induced together with a decrease in c-Myc and Ezh2 levels. Previously, {EZH}2 was shown to be regulated by {miR}-26a at the translational levels in lymphomas. However, we demonstrate that in {AML}, the variation of {EZH}2 mainly depends on c-Myc transcriptional control. We also show that enforced expression of {miR}-26a in {AML} cells is able to inhibit cell cycle progression by downregulating cyclin E2 expression. In addition, increased levels of {miR}-26a potentiate the antiproliferative effects of 1,25-dihydroxyvitamin D(3) ({VitD}) and stimulate myeloid differentiation. Our results identify new molecular targets of c-Myc in {AML} and highlight {miR}-26a attractiveness as a therapeutic target in leukemia.},
	pages = {585--592},
	number = {5},
	journaltitle = {Genes Cancer},
	author = {Salvatori, B and Iosue, I and Djodji Damas, N and Mangiavacchi, A and Chiaretti, S and Messina, M and Padula, F and Guarini, A and Bozzoni, I and Fazi, F and Fatica, A},
	date = {2011},
	pmid = {21901171}
}

@article{li_characterization_2013,
	title = {Characterization of small {RNAs} and their target genes in wheat seedlings using sequencing-based approaches},
	volume = {203-204},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23415324},
	doi = {10.1016/j.plantsci.2012.12.014},
	abstract = {Wheat is the most highly cultivated plant species for its grain production throughout the world. Because small {RNA}-dependent gene regulation is critical for successful completion of plant life cycle including its productivity, identification of not only {miRNAs} but also confirming their targets in wheat is important. To identify small {RNAs} including novel {miRNAs} as well as {miRNA} targets in wheat, we constructed small {RNA} and degradome libraries from wheat seedlings. Small {RNA} analysis resulted in identification of most conserved {miRNAs} including novel {miRNAs} that can be grouped into 32 {miRNA} families. The sequence analysis also led to the characterization of two abundantly expressed {rRNA}-derived small {RNAs}. To identify {miRNA} targets, degradome library was sequenced and the bioinformatic analysis confirmed 53 genes as targets for {miRNAs} and Tas3-{siRNAs}. Degradome analysis also confirmed a conserved fine-tuning mechanism of Tas3-{siRNA} abundance by {siRNA}-mediated silencing of {TAS}3 transcripts in diverse plant species. These findings added additional information to the small {RNA} knowledge-base in wheat.},
	pages = {17--24},
	journaltitle = {Plant Sci},
	author = {Li, Y F and Zheng, Y and Jagadeeswaran, G and Sunkar, R},
	date = {2013},
	pmid = {23415324},
	keywords = {{DNA}, Sequence Analysis, Base Sequence, {RNA}, Gene Expression Regulation, Computational Biology, Gene Expression Profiling, *Endoribonucleases, *Multienzyme Complexes, *Polyribonucleotide Nucleotidyltransferase, *{RNA} Helicases, Conserved Sequence/genetics, Gene Library, High-Throughput Nucleotide Sequencing/*methods, {MicroRNAs}/*genetics/isolation \& purification, Molecular Sequence Data, Plant, Plant Roots/genetics, Plant Shoots/genetics, Plant/*genetics/isolation \& purification, Ribosomal/genetics/isolation \& purification, {RNA} Cleavage, Seedling/*genetics, Sequence Alignment, Small Interfering/genetics/isolation \& purifi, Triticum/*genetics}
}

@article{maleki_estrogen_2013,
	title = {Estrogen, progesterone, and {HER}-2 receptor immunostaining in cytology: the effect of varied fixation on human breast cancer cells},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23447357},
	doi = {10.1002/dc.22973},
	abstract = {The {ASCO}/{CAP} Expert Panel recommends that all invasive breast carcinomas and breast cancer recurrences be tested for {ER}, {PR} and {HER}-2 expression. The guidelines for testing of surgical specimens by immunohistochemistry ({IHC}) are well defined, whereas they are lacking for cytological samples. We evaluated various fixation protocols for optimal receptor testing by immunohistochemistry and immunocytochemistry ({ICC}) of human breast cancer cell lines {MCF}-7 ({ER}/{PR} positive) and {SKBR}-3 (overexpressing {HER}-2). The cells were fixed in 10\% neutral buffered formalin or Saccomanno Fixative ({SF}) for various time points, and either embedded in paraffin as cell blocks or prepared as cytospins. {ER} and {PR} slides were assigned a proportion score ({PS}; 0-5), an intensity score ({IS}; 0-3) and a total score ({TS} = {PS} + {IS}). Standard {DAKO} scoring system ranging from 0 to 3+ was used for the evaluation of {HER}-2 staining. Human breast cancer cells stained successfully for {ER}, {PR} and {HER}-2 when fixed in formalin and prepared as cell blocks. The optimal fixation time for formalin-fixed cells ranged from 2 to 96 hours. Cells fixed in {SF} from 2 to 96 hours also stained well for {ER} and {PR}. However, {SF} produced variable results for {HER}-2 staining; particularly, {SF} fixation beyond 24 hours caused false negative results. The interpretation of {HER}-2 staining on cytospins was not feasible irrespective of the fixative and fixation time. In summary, formalin fixation from 2 to 96 hours and preparation of cells as cell blocks produces optimal results for {ER}, {PR}, and {HER}-2 testing in human breast cancer cells.},
	pages = {864--870},
	number = {10},
	journaltitle = {Diagn Cytopathol},
	author = {Maleki, S and Dorokhova, O and Sunkara, J and Schlesinger, K and Suhrland, M and Oktay, M H},
	date = {2013},
	pmid = {23447357}
}

@article{parlato_ifn-alpha_2013,
	title = {{IFN}-alpha regulates Blimp-1 expression via {miR}-23a and {miR}-125b in both monocytes-derived {DC} and {pDC}},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23977359},
	doi = {10.1371/journal.pone.0072833},
	abstract = {Type I interferon ({IFN}-I) have emerged as crucial mediators of cellular signals controlling {DC} differentiation and function. Human {DC} differentiated from monocytes in the presence of {IFN}-alpha ({IFN}-alpha {DC}) show a partially mature phenotype and a special capability of stimulating {CD}4+ T cell and cross-priming {CD}8+ T cells. Likewise, plasmacytoid {DC} ({pDC}) are blood {DC} highly specialized in the production of {IFN}-alpha in response to viruses and other danger signals, whose functional features may be shaped by {IFN}-I. Here, we investigated the molecular mechanisms stimulated by {IFN}-alpha in driving human monocyte-derived {DC} differentiation and performed parallel studies on peripheral unstimulated and {IFN}-alpha-treated {pDC}. A specific {miRNA} signature was induced in {IFN}-alpha {DC} and selected {miRNAs}, among which {miR}-23a and {miR}-125b, proved to be negatively associated with up-modulation of Blimp-1 occurring during {IFN}-alpha-driven {DC} differentiation. Of note, monocyte-derived {IFN}-alpha {DC} and in vitro {IFN}-alpha-treated {pDC} shared a restricted pattern of {miRNAs} regulating Blimp-1 expression as well as some similar phenotypic, molecular and functional hallmarks, supporting the existence of a potential relationship between these {DC} populations. On the whole, these data uncover a new role of Blimp-1 in human {DC} differentiation driven by {IFN}-alpha and identify Blimp-1 as an {IFN}-alpha-mediated key regulator potentially accounting for shared functional features between {IFN}-alpha {DC} and {pDC}.},
	pages = {e72833},
	number = {8},
	journaltitle = {{PLoS} One},
	author = {Parlato, S and Bruni, R and Fragapane, P and Salerno, D and Marcantonio, C and Borghi, P and Tataseo, P and Ciccaglione, A R and Presutti, C and Romagnoli, G and Bozzoni, I and Belardelli, F and Gabriele, L},
	date = {2013},
	pmid = {23977359}
}

@article{kim_regulation_2010,
	title = {Regulation of {HuR} by {DNA} Damage Response Kinases},
	volume = {2010},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20798862},
	doi = {10.4061/2010/981487},
	abstract = {As many {DNA}-damaging conditions repress transcription, posttranscriptional processes critically influence gene expression during the genotoxic stress response. The {RNA}-binding protein {HuR} robustly influences gene expression following {DNA} damage. {HuR} function is controlled in two principal ways: (1) by mobilizing {HuR} from the nucleus to the cytoplasm, where it modulates the stability and translation of target {mRNAs} and (2) by altering its association with target {mRNAs}. Here, we review evidence that two main effectors of ataxia-telangiectasia-mutated/{ATM}- and Rad3-related ({ATM}/{ATR}), the checkpoint kinases Chk1 and Chk2, jointly influence {HuR} function. Chk1 affects {HuR} localization by phosphorylating (hence inactivating) Cdk1, a kinase that phosphorylates {HuR} and thereby blocks {HuR}'s cytoplasmic export. Chk2 modulates {HuR} binding to target {mRNAs} by phosphorylating {HuR}'s {RNA}-recognition motifs ({RRM}1 and {RRM}2). We discuss how {HuR} phosphorylation by kinases including Chk1/Cdk1 and Chk2 impacts upon gene expression patterns, cell proliferation, and survival following genotoxic injury.},
	journaltitle = {J Nucleic Acids},
	author = {Kim, H H and Abdelmohsen, K and Gorospe, M},
	date = {2010},
	pmid = {20798862}
}

@article{rahrmann_forward_2013,
	title = {Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis},
	volume = {45},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23685747},
	doi = {10.1038/ng.2641},
	abstract = {Malignant peripheral nerve sheath tumors ({MPNSTs}) are sarcomas of Schwann cell lineage origin that occur sporadically or in association with the inherited syndrome neurofibromatosis type 1. To identify genetic drivers of {MPNST} development, we used the Sleeping Beauty ({SB}) transposon-based somatic mutagenesis system in mice with somatic loss of transformation-related protein p53 (Trp53) function and/or overexpression of human epidermal growth factor receptor ({EGFR}). Common insertion site ({CIS}) analysis of 269 neurofibromas and 106 {MPNSTs} identified 695 and 87 sites with a statistically significant number of recurrent transposon insertions, respectively. Comparison to human data sets identified new and known driver genes for {MPNST} formation at these sites. Pairwise co-occurrence analysis of {CIS}-associated genes identified many cooperating mutations that are enriched in Wnt/beta-catenin, {PI}3K-{AKT}-{mTOR} and growth factor receptor signaling pathways. Lastly, we identified several new proto-oncogenes, including Foxr2 (encoding forkhead box R2), which we functionally validated as a proto-oncogene involved in {MPNST} maintenance.},
	pages = {756--766},
	number = {7},
	journaltitle = {Nat Genet},
	author = {Rahrmann, E P and Watson, A L and Keng, V W and Choi, K and Moriarity, B S and Beckmann, D A and Wolf, N K and Sarver, A and Collins, M H and Moertel, C L and Wallace, M R and Gel, B and Serra, E and Ratner, N and Largaespada, D A},
	date = {2013},
	pmid = {23685747},
	keywords = {Animals, Humans, Mice, *Genes, Cell Line, Cell Transformation, {DNA} Mutational Analysis, {DNA} Transposable Elements/genetics, Genetic Association Studies, Genetic Testing/*methods, Mutation/physiology, Neoplasm/physiology, Neoplastic/*genetics, Nerve Sheath Neoplasms/*genetics, Neurofibroma/genetics, Signal Transduction/genetics, Transgenic, Tumor}
}

@article{schultz_smart:_2000,
	title = {{SMART}: a web-based tool for the study of genetically mobile domains},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10592234},
	abstract = {{SMART} (a Simple Modular Architecture Research Tool) allows the identification and annotation of genetically mobile domains and the analysis of domain architectures (http://{SMART}.embl-heidelberg.de ). More than 400 domain families found in signalling, extra-cellular and chromatin-associated proteins are detectable. These domains are extensively annotated with respect to phyletic distributions, functional class, tertiary structures and functionally important residues. Each domain found in a non-redundant protein database as well as search parameters and taxonomic information are stored in a relational database system. User interfaces to this database allow searches for proteins containing specific combinations of domains in defined taxa.},
	pages = {231--234},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Schultz, J and Copley, R R and Doerks, T and Ponting, C P and Bork, P},
	date = {2000},
	pmid = {10592234},
	keywords = {*Database Management Systems, *Internet, *Sequence Alignment, Information Storage and Retrieval, Proteins/chemistry}
}

@article{ingolia_genome-wide_2009,
	title = {Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling},
	volume = {324},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19213877},
	doi = {10.1126/science.1168978},
	abstract = {Techniques for systematically monitoring protein translation have lagged far behind methods for measuring messenger {RNA} ({mRNA}) levels. Here, we present a ribosome-profiling strategy that is based on the deep sequencing of ribosome-protected {mRNA} fragments and enables genome-wide investigation of translation with subcodon resolution. We used this technique to monitor translation in budding yeast under both rich and starvation conditions. These studies defined the protein sequences being translated and found extensive translational control in both determining absolute protein abundance and responding to environmental stress. We also observed distinct phases during translation that involve a large decrease in ribosome density going from early to late peptide elongation as well as widespread regulated initiation at non-adenine-uracil-guanine ({AUG}) codons. Ribosome profiling is readily adaptable to other organisms, making high-precision investigation of protein translation experimentally accessible.},
	pages = {218--223},
	number = {5924},
	journaltitle = {Science},
	author = {Ingolia, N T and Ghaemmaghami, S and Newman, J R and Weissman, J S},
	date = {2009},
	pmid = {19213877},
	keywords = {{DNA}, Sequence Analysis, {RNA}, *Genome, Introns, *Codon, *Protein Biosynthesis, 5' Untranslated Regions, Codon, Fungal, Fungal/*genetics/metabolism, Gene Library, Messenger/*genetics/metabolism, Peptide Chain Elongation, Peptide Chain Initiation, Protein Biosynthesis, Ribosomes/*metabolism, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins/*biosynthesis, Saccharomyces cerevisiae/*genetics/metabolism/phys, Translational, Ribosomes, {RNA}, Messenger, Sequence Analysis, {DNA}, Peptide Chain Initiation, Translational, Genome, Fungal, {RNA}, Fungal, Saccharomyces cerevisiae Proteins, Peptide Chain Elongation, Translational},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/5W6X3495/Ingolia et al. - 2009 - Genome-wide analysis in vivo of translation with n.pdf:application/pdf}
}

@article{leproust_synthesis_2010,
	title = {Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20308161},
	doi = {10.1093/nar/gkq163},
	abstract = {We have achieved the ability to synthesize thousands of unique, long oligonucleotides (150mers) in fmol amounts using parallel synthesis of {DNA} on microarrays. The sequence accuracy of the oligonucleotides in such large-scale syntheses has been limited by the yields and side reactions of the {DNA} synthesis process used. While there has been significant demand for libraries of long oligos (150mer and more), the yields in conventional {DNA} synthesis and the associated side reactions have previously limited the availability of oligonucleotide pools to lengths {\textbackslash}textless100 nt. Using novel array based depurination assays, we show that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies' {SurePrint} {DNA} microarray platform. We also demonstrate how depurination can be controlled and reduced by a novel detritylation process to enable the synthesis of high quality, long (150mer) oligonucleotide libraries and we report the characterization of synthesis efficiency for such libraries. Oligonucleotide libraries prepared with this method have changed the economics and availability of several existing applications (e.g. targeted resequencing, preparation of {shRNA} libraries, site-directed mutagenesis), and have the potential to enable even more novel applications (e.g. high-complexity synthetic biology).},
	pages = {2522--2540},
	number = {8},
	journaltitle = {Nucleic Acids Res},
	author = {{LeProust}, E M and Peck, B J and Spirin, K and {McCuen}, H B and Moore, B and Namsaraev, E and Caruthers, M H},
	date = {2010},
	pmid = {20308161},
	keywords = {Indicators and Reagents, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis/*methods, Oligonucleotides/*chemical synthesis/chemistry, Polymerase Chain Reaction, Purines/chemistry}
}

@article{aurlien_focal_2007,
	title = {Focal epileptiform activity described by a large computerised {EEG} database},
	volume = {118},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17452009},
	doi = {10.1016/j.clinph.2007.02.027},
	abstract = {{OBJECTIVE}: To study the age-related topographical tendency of expressing epileptiform activity, and the effect of focal epileptiform activity ({FEA}) on the general cortical brain activity. {METHODS}: 1647 consecutive routine {EEGs} containing {FEA} were visually assessed for {FEA} location and asymmetry. Background activity was compared with that in normal {EEGs} from 3268 drug-free outpatient controls. {RESULTS}: {FEA} localisation was age-related (p{\textbackslash}textless0.0005) except for the temporal region (p=0.22) where {FEA} was found equally often in the young and the old. The left hemisphere was more prone to {FEA} (p=0.018). The left-right asymmetry varied by age (p=0.013). {FEA} asymmetry occurred most frequently in {EEGs} from patients older than 80 years, and least frequent in the age-group 20-39 years. {FEA} was associated with lower alpha rhythm ({AR}) frequencies (p=0.0041) and higher {AR} amplitudes (p=0.0023), as well as higher general background activity ({GBA}) amplitude (p{\textbackslash}textless0.0005), while {GBA} frequencies were the same (p=0.96). {CONCLUSIONS}: Topographical localisation of {FEA} was age-dependent. There was an overall left dominance, but the side asymmetry was modest and varied by age. {FEA} was associated with changes in {AR} and {GBA}. {SIGNIFICANCE}: The results demonstrate that {FEA} is associated with cerebral cortical dysfunction also distant from the epileptic focus.},
	pages = {1369--1376},
	number = {6},
	journaltitle = {Clin Neurophysiol},
	author = {Aurlien, H and Aarseth, J H and Gjerde, I O and Karlsen, B and Skeidsvoll, H and Gilhus, N E},
	date = {2007},
	pmid = {17452009},
	keywords = {Humans, Databases, *Electroencephalography, 80 and over, Adult, Age Factors, Aged, Brain Mapping, Cerebral Cortex/*physiopathology, Computer-Assisted/*methods, Diagnosis, Epilepsy/epidemiology/pathology/*physiopathology, Factual/*statistics \& numerical data, Female, Male, Middle Aged}
}

@article{kudla_coding-sequence_2009,
	title = {Coding-sequence determinants of gene expression in Escherichia coli},
	volume = {324},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19359587},
	doi = {10.1126/science.1170160},
	abstract = {Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein ({GFP}). When expressed in Escherichia coli, {GFP} protein levels varied 250-fold across the library. {GFP} messenger {RNA} ({mRNA}) levels, {mRNA} degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of {mRNA} folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, {mRNA} folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.},
	pages = {255--258},
	number = {5924},
	journaltitle = {Science},
	author = {Kudla, G and Murray, A W and Tollervey, D and Plotkin, J B},
	date = {2009},
	pmid = {19359587},
	keywords = {{RNA}, *Codon, *Gene Expression, Amino Acid Substitution, Bacterial/chemistry/genetics/metabolism, Base Composition, Cloning, Escherichia coli/*genetics/growth \& development/me, Fluorescence, Gene Library, Genes, Green Fluorescent Proteins/*genetics/metabolism, Messenger/chemistry/*genetics/metabolism, Molecular, Mutation, Nucleic Acid Conformation, Protein Biosynthesis, {RNA} Stability, Spectrometry, Synthetic}
}

@article{spitale_rna_2011,
	title = {{RNA} templating the epigenome: long noncoding {RNAs} as molecular scaffolds},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21393997},
	abstract = {Cellular pathways must be synergized, controlled and organized to manage homeostasis. To achieve high selectivity within the crowded cellular milieu the cell utilizes scaffolding complexes whose role is to bring molecules in proximity thereby controlling and enhancing intermolecular interactions and signaling events. To date, scaffolds have been shown to be composed of proteinaceous units; however, recent evidence has supported the idea that non-coding {RNAs} may also play a similar role. In this point of view article we discuss recent data on {ncRNA} scaffolds, with particular focus on {ncRNA} {HOTAIR}. Using our current knowledge of signaling networks we discuss the role that {RNA} may play in writing and regulating histone modifications and the information needed for correct gene expression. Further, we speculate on additional, yet undiscovered roles that {ncRNAs} may be playing as molecular scaffolds.},
	pages = {539--543},
	number = {5},
	journaltitle = {Epigenetics},
	author = {Spitale, R C and Tsai, M C and Chang, H Y},
	date = {2011},
	pmid = {21393997},
	keywords = {Epigenomics, {RNA}, Gene Expression Regulation, Chromatin/*genetics, Histones/*genetics/*metabolism, Polycomb-Group Proteins, Repressor Proteins/genetics, {RNA}/*genetics/*metabolism, Signal Transduction/genetics, Untranslated/*genetics/*metabolism}
}

@article{zhuang_methylation_2012,
	title = {Methylation of p15INK4b and expression of {ANRIL} on chromosome 9p21 are associated with coronary artery disease},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23091611},
	doi = {10.1371/journal.pone.0047193},
	abstract = {{BACKGROUND}: Genome-wide association studies have identified that multiple single nucleiotide polymorphisms on chromosome 9p21 are tightly associated with coronary artery disease ({CAD}). However, the mechanism linking this risk locus to {CAD} remains unclear. {METHODOLOGY}/{PRINCIPAL} {FINDINGS}: The methylation status of six candidate genes ({BAX}, {BCL}-2, {TIMP}3, p14({ARF}), p15({INK}4b) and p16({INK}4a)) in 205 patients and controls who underwent coronary angiography were analyzed by quantitative {MethyLight} assay. Rs10757274 was genotyped and expression of {INK}4/{ARF} and antisense non-coding {RNA} in the {INK}4 locus ({ANRIL}) was determined by real-time {RT}-{PCR}. Compared with controls, {DNA} methylation levels at p15({INK}4b) significantly increased in {CAD} patients (p = 0.006). To validate and dissect the methylation percentage of each target {CpG} site at p15({INK}4b), pyrosequencing was performed, finding {CpG} +314 and +332 remarkably hypermethylated in {CAD} patients. Further investigation determined that p15({INK}4b) hypermethylation prevalently emerged in lymphocytes of {CAD} patients (p = 0.013). The rs10757274 genotype was significantly associated with {CAD} (p = 0.003) and {GG} genotype carriers had a higher level of {ANRIL} exon 1-5 expression compared among three genotypes (p = 0.009). There was a stepwise increase in p15({INK}4b) and p16({INK}4a) methylation as {ANRIL} exon 1-5 expression elevated (r = 0.23, p = 0.001 and r = 0.24, p = 0.001, respectively), although neither of two loci methylation was directly linked to rs10757274 genotype. {CONCLUSIONS}/{SIGNIFICANCE}: p15({INK}4b) methylation is associated with {CAD} and {ANRIL} expression. The epigenetic changes in p15({INK}4b) methylation and {ANRIL} expression may involve in the mechanisms of chromosome 9p21 on {CAD} development.},
	pages = {e47193},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Zhuang, J and Peng, W and Li, H and Wang, W and Wei, Y and Li, W and Xu, Y},
	date = {2012},
	pmid = {23091611},
	keywords = {Human, Genetic, Humans, {RNA}, Long Noncoding/*genetics, *Chromosomes, *{DNA} Methylation, *Gene Expression Regulation, *Genetic Predisposition to Disease, Aged, Coronary Artery Disease/*genetics, {CpG} Islands, Cyclin-Dependent Kinase Inhibitor p15/*genetics, Cyclin-Dependent Kinase Inhibitor p16/genetics, Epigenesis, Female, Gene Order, Genotype, Male, Middle Aged, Pair 9}
}

@article{mittal_characterization_2010,
	title = {Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20629487},
	doi = {10.1515/JPM.2010.097},
	abstract = {{AIMS}: to characterize the transcriptome of human myometrium during spontaneous labor at term. {METHODS}: myometrium was obtained from women with (n=19) and without labor (n=20). Illumina {HumanHT}-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction ({qRT}-{PCR}) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. {RESULTS}: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-{STAT} signaling; and c) complement and coagulation cascades; d) {NOD}-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) {qRT}-{PCR} confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor ({EGF})-like growth factor, chemokine C-C motif ligand 2 ({CCL}2/{MCP}1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin ({IL})-8, {IL}-6, chemokine C-X-C motif ligand 6 ({CXCL}6/{GCP}2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 ({SOCS}3) and decreased expression of {FK}506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) {IL}-6, {CXCL}6, {CCL}2 and {SOCS}3 protein expression was significantly higher in the term labor group compared to the term not in labor group. {CONCLUSIONS}: myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with {qRT}-{PCR} using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.},
	pages = {617--643},
	number = {6},
	journaltitle = {J Perinat Med},
	author = {Mittal, P and Romero, R and Tarca, A L and Gonzalez, J and Draghici, S and Xu, Y and Dong, Z and Nhan-Chang, C L and Chaiworapongsa, T and Lye, S and Kusanovic, J P and Lipovich, L and Mazaki-Tovi, S and Hassan, S S and Mesiano, S and Kim, C J},
	date = {2010},
	pmid = {20629487},
	keywords = {Gene Expression Profiling/*methods, Humans, Oligonucleotide Array Sequence Analysis, Adult, Blotting, Enzyme-Linked Immunosorbent Assay, Female, Labor, Myometrium/*physiology, Nonparametric, Obstetric/genetics/*physiology, Pregnancy, Reverse Transcriptase Polymerase Chain Reaction, {RNA}/chemistry/genetics, Statistics, Western, Young Adult}
}

@article{li_mageck_2014,
	title = {{MAGeCK} enables robust identification of essential genes from genome-scale {CRISPR}/Cas9 knockout screens},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25476604},
	doi = {10.1186/s13059-014-0554-4},
	abstract = {We propose the Model-based Analysis of Genome-wide {CRISPR}/Cas9 Knockout ({MAGeCK}) method for prioritizing single-guide {RNAs}, genes and pathways in genome-scale {CRISPR}/Cas9 knockout screens. {MAGeCK} demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, {MAGeCK} identified novel essential genes and pathways, including {EGFR} in vemurafenib-treated A375 cells harboring a {BRAF} mutation. {MAGeCK} also detected cell type-specific essential genes, including {BCR} and {ABL}1, in {KBM}7 cells bearing a {BCR}-{ABL} fusion, and {IGF}1R in {HL}-60 cells, which depends on the insulin signaling pathway for proliferation.},
	pages = {554},
	number = {12},
	journaltitle = {Genome Biol},
	author = {Li, W and Xu, H and Xiao, T and Cong, L and Love, M I and Zhang, F and Irizarry, R A and Liu, J S and Brown, M and Liu, X S},
	date = {2014},
	pmid = {25476604}
}

@article{ulitsky_e-maps_2008,
	title = {From E-{MAPs} to module maps: dissecting quantitative genetic interactions using physical interactions},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18628749},
	doi = {10.1038/msb.2008.42},
	abstract = {Recent technological breakthroughs allow the quantification of hundreds of thousands of genetic interactions ({GIs}) in Saccharomyces cerevisiae. The interpretation of these data is often difficult, but it can be improved by the joint analysis of {GIs} along with complementary data types. Here, we describe a novel methodology that integrates genetic and physical interaction data. We use our method to identify a collection of functional modules related to chromosomal biology and to investigate the relations among them. We show how the resulting map of modules provides clues for the elucidation of function both at the level of individual genes and at the level of functional modules.},
	pages = {209},
	journaltitle = {Mol Syst Biol},
	author = {Ulitsky, I and Shlomi, T and Kupiec, M and Shamir, R},
	date = {2008},
	pmid = {18628749},
	keywords = {Genetic, Protein Binding, *Epistasis, Cell Nucleus/metabolism, Mitosis, Phenotype, Porosity, Proteasome Endopeptidase Complex, Saccharomyces cerevisiae Proteins/*genetics/*metab, Saccharomyces cerevisiae/*genetics/*metabolism, Spindle Apparatus/metabolism}
}

@article{ohta_development_1996,
	title = {Development of Neutral and Nearly Neutral Theories},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8813019},
	abstract = {A short history of the major features of neutral theories of molecular evolution is presented. Emphasis is placed on the nearly neutral theory, as this version of the neutral theory has explained the widest range of phenomena. The shift of interest from protein to {DNA} evolution is chronicled, leading to the modern view that silent and replacement substitutions are responding to different evolutionary forces. However, the exact nature and magnitude of these forces remains controversial, as all current theoretical models suffer either from assumptions that are not quite realistic or from an inability to account readily for all phenomena. Although the gathering of sequence data has been the main effort of contemporary population genetics, further exploration of theoretical models of molecular evolution would provide a more coherent framework for data analysis.},
	pages = {128--142},
	number = {2},
	journaltitle = {Theor Popul Biol},
	author = {Ohta, T and Gillespie, J H},
	date = {1996},
	pmid = {8813019}
}

@article{pogue_fosfomycin_2013,
	title = {Fosfomycin activity versus carbapenem-resistant Enterobacteriaceae and vancomycin-resistant Enterococcus, Detroit, 2008-10},
	volume = {66},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23715037},
	doi = {10.1038/ja.2013.56},
	pages = {625--627},
	number = {10},
	journaltitle = {J Antibiot (Tokyo)},
	author = {Pogue, J M and Marchaim, D and Abreu-Lanfranco, O and Sunkara, B and Mynatt, R P and Zhao, J J and Bheemreddy, S and Hayakawa, K and Martin, E T and Dhar, S and Kaye, K S and Lephart, P R},
	date = {2013},
	pmid = {23715037},
	keywords = {Humans, *Drug Resistance, *Vancomycin Resistance, Anti-Bacterial Agents/*pharmacology, Bacterial, beta-Lactam Resistance, Carbapenems/*pharmacology, Enterobacteriaceae Infections/microbiology, Enterobacteriaceae/classification/*drug effects/is, Enterococcus/*drug effects/isolation \& purificatio, Fosfomycin/*pharmacology, Gram-Positive Bacterial Infections/microbiology, Michigan, Microbial Sensitivity Tests, Multiple, Urinary Tract Infections/drug therapy/microbiology}
}

@article{faulkner_regulated_2009,
	title = {The regulated retrotransposon transcriptome of mammalian cells},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19377475},
	doi = {10.1038/ng.368},
	abstract = {Although repetitive elements pervade mammalian genomes, their overall contribution to transcriptional activity is poorly defined. Here, as part of the {FANTOM}4 project, we report that 6-30\% of cap-selected mouse and human {RNA} transcripts initiate within repetitive elements. Analysis of approximately 250,000 retrotransposon-derived transcription start sites shows that the associated transcripts are generally tissue specific, coincide with gene-dense regions and form pronounced clusters when aligned to full-length retrotransposon sequences. Retrotransposons located immediately 5' of protein-coding loci frequently function as alternative promoters and/or express noncoding {RNAs}. More than a quarter of {RefSeqs} possess a retrotransposon in their 3' {UTR}, with strong evidence for the reduced expression of these transcripts relative to retrotransposon-free transcripts. Finally, a genome-wide screen identifies 23,000 candidate regulatory regions derived from retrotransposons, in addition to more than 2,000 examples of bidirectional transcription. We conclude that retrotransposon transcription has a key influence upon the transcriptional output of the mammalian genome.},
	pages = {563--571},
	number = {5},
	journaltitle = {Nat Genet},
	author = {Faulkner, G J and Kimura, Y and Daub, C O and Wani, S and Plessy, C and Irvine, K M and Schroder, K and Cloonan, N and Steptoe, A L and Lassmann, T and Waki, K and Hornig, N and Arakawa, T and Takahashi, H and Kawai, J and Forrest, A R and Suzuki, H and Hayashizaki, Y and Hume, D A and Orlando, V and Grimmond, S M and Carninci, P},
	date = {2009},
	pmid = {19377475},
	keywords = {3' Untranslated Regions, Animals, Genetic, Humans, Mice, Promoter Regions, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Messenger, Cells, Cultured, *Gene Expression Profiling, *Gene Expression Regulation, 3' Untranslated Regions/genetics/metabolism, Mammals, Mammals/genetics, Retroelements/*genetics, Untranslated/metabolism, {RNA}, Messenger, Cells, Cultured, Promoter Regions, Genetic, {RNA}, Untranslated, Retroelements}
}

@article{yi_reduced_2010,
	title = {Reduced nuclear export of {HuR} {mRNA} by {HuR} is linked to the loss of {HuR} in replicative senescence},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20007147},
	doi = {10.1093/nar/gkp1114},
	abstract = {The {RNA}-binding protein, {HuR}, associates with the {HuR} {mRNA}, but the consequences of this interaction are unknown. Here, we use human diploid fibroblasts ({HDFs}) and cervical carcinoma cells to study this regulatory paradigm. Ectopic overexpression of {HuR} potently enhanced the translation and cytoplasmic levels of endogenous {HuR}, but did not affect {HuR} {mRNA} levels. Inhibition of {CRM}1 function by Lemptomycin B or by knockdown of {CRM}1 greatly diminished the cytoplasmic levels of endogenous {HuR} {mRNA} and hence blocked the induction of endogenous {HuR} by exogenous {HuR}. Further studies showed that {HuR} interacted with the 3'-untranslated region ({UTR}) of {HuR} and that overexpression of {HuR} increased the cytoplasmic levels of a chimeric luciferase-{HuR} 3'-{UTR} reporter transcript, as well as luciferase activity; conversely, {HuR} knockdown reduced both parameters. Moreover, the loss of {HuR} in senescent, late-passage {HDFs} was accompanied by a reduced cytoplasmic presence of endogenous {HuR} {mRNA}, ectopic Luc-{HuR}-3'{UTR} reporter transcript, and luciferase activity relative to what was observed in young, early-passage cells. Our results reveal a positive feedback mechanism for the regulation of {HuR}, which may play an important role in the regulation of {HuR} during replicative senescence.},
	pages = {1547--1558},
	number = {5},
	journaltitle = {Nucleic Acids Res},
	author = {Yi, J and Chang, N and Liu, X and Guo, G and Xue, L and Tong, T and Gorospe, M and Wang, W},
	date = {2010},
	pmid = {20007147},
	keywords = {3' Untranslated Regions, Humans, {RNA}, Cells, Cultured, Cell Nucleus, *Cell Aging, *Gene Expression Regulation, Active Transport, Antigens, Cell Nucleus/*metabolism, Cytoplasm/metabolism, {DNA} Replication, Genes, {HeLa} Cells, Homeostasis, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/*metabolism, Protein Biosynthesis, Reporter, {RNA}-Binding Proteins/biosynthesis/*genetics/metabo, Surface/biosynthesis/*genetics/metabolis}
}

@article{marques_wrangling_2011,
	title = {Wrangling for {microRNAs} provokes much crosstalk},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22104690},
	doi = {10.1186/gb-2011-12-11-132},
	abstract = {Levels of transcripts sharing {microRNA} response elements are co-regulated. These {RNA}-{RNA} interactions imply that combinations of {microRNAs} modulate cell-specific transcript networks.},
	pages = {132},
	number = {11},
	journaltitle = {Genome Biol},
	author = {Marques, A C and Tan, J and Ponting, C P},
	date = {2011},
	pmid = {22104690},
	keywords = {Animals, Humans, {RNA}, *Genome, *Gene Expression Regulation, Binding, Cell Transformation, Competitive, Mammals, Messenger/*genetics, {MicroRNAs}/*genetics, Neoplastic, Protein Isoforms/genetics/metabolism, {PTEN} Phosphohydrolase/genetics/metabolism, Response Elements/*genetics, Retroelements/genetics}
}

@article{currat_comment_2006,
	title = {Comment on "Ongoing adaptive evolution of {ASPM}, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans"},
	volume = {313},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16840683},
	doi = {10.1126/science.1122712},
	abstract = {Mekel-Bobrov et al. and Evans et al. (Reports, 9 Sept. 2005, p. 1720 and p. 1717, respectively) examined sequence data from modern humans within two gene regions associated with brain development, {ASPM} and microcephalin, and concluded that selection of these genes must be ongoing. We show that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.},
	pages = {172; author reply 172},
	number = {5784},
	journaltitle = {Science},
	author = {Currat, M and Excoffier, L and Maddison, W and Otto, S P and Ray, N and Whitlock, M C and Yeaman, S},
	date = {2006},
	pmid = {16840683},
	keywords = {{DNA}, Genetic, Humans, *Haplotypes, *Population Growth, *Sequence Analysis, Adaptation, Biological, Biological Evolution, Brain, Demography, Founder Effect, Gene Frequency, Models, Nerve Tissue Proteins/*genetics, Organ Size, Population Density, Selection, Theoretical}
}

@article{margulies_initial_2005,
	title = {An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing},
	volume = {102},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15778292},
	doi = {10.1073/pnas.0409882102},
	abstract = {With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful approach for finding such elements by identifying sequences that have been highly conserved during evolution. Here, we propose an initial strategy for detecting such regions by generating low-redundancy sequence from a collection of 16 eutherian mammals, beyond the 7 for which genome sequence data are already available. We show that such sequence can be accurately aligned to the human genome and used to identify most of the highly conserved regions. Although not a long-term substitute for generating high-quality genomic sequences from many mammalian species, this strategy represents a practical initial approach for rapidly annotating the most evolutionarily conserved sequences in the human genome, providing a key resource for the systematic study of human genome function.},
	pages = {4795--4800},
	number = {13},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Margulies, E H and Vinson, J P and Miller, W and Jaffe, D B and Lindblad-Toh, K and Chang, J L and Green, E D and Lander, E S and Mullikin, J C and Clamp, M},
	date = {2005},
	pmid = {15778292},
	keywords = {Human, {DNA}/*methods, Genomics/*methods, Sequence Analysis, Animals, Base Sequence, Humans, *Genome, Computational Biology, Mammals/*genetics, Conserved Sequence/*genetics, Phylogeny, Sequence Alignment}
}

@article{dinger_evolution_2011,
	title = {The evolution of {RNAs} with multiple functions},
	volume = {93},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21802485},
	doi = {10.1016/j.biochi.2011.07.018},
	abstract = {Increasing numbers of transcripts have been reported to transmit both protein-coding and regulatory information. Apart from challenging our conception of the gene, this observation raises the question as to what extent this phenomenon occurs across the genome and how and why such dual encoding of function has evolved in the eukaryotic genome. To address this question, we consider the evolutionary path of genes in the earliest forms of life on Earth, where it is generally regarded that proteins evolved from a cellular machinery based entirely within {RNA}. This led to the domination of protein-coding genes in the genomes of microorganisms, although it is likely that {RNA} never lost its other capacities and functionalities, as evidenced by cis-acting riboswitches and {UTRs}. On the basis that the subsequent evolution of a more sophisticated regulatory architecture to provide higher levels of epigenetic control and accurate spatiotemporal expression in developmentally complex organisms is a complicated task, we hypothesize: (i) that {mRNAs} have been and remain subject to secondary selection to provide trans-acting regulatory capability in parallel with protein-coding functions; (ii) that some and perhaps many protein-coding loci, possibly as a consequence of gene duplication, have lost protein-coding functions en route to acquiring more sophisticated trans-regulatory functions; (iii) that many transcripts have become subject to secondary processing to release different products; and (iv) that novel proteins have emerged within loci that previously evolved functionality as regulatory {RNAs}. In support of the idea that there is a dynamic flux between different types of informational {RNAs} in both evolutionary and real time, we review recent observations that have arisen from transcriptomic surveys of complex eukaryotes and reconsider how these observations impact on the notion that apparently discrete loci may express transcripts with more than one function. In conclusion, we posit that many eukaryotic loci have evolved the capacity to transact a multitude of overlapping and potentially independent functions as both regulatory and protein-coding {RNAs}.},
	pages = {2013--2018},
	number = {11},
	journaltitle = {Biochimie},
	author = {Dinger, M E and Gascoigne, D K and Mattick, J S},
	date = {2011},
	pmid = {21802485},
	keywords = {Genome, Humans, {RNA}, Messenger/genetics, {RNA}/*genetics, Untranslated/*genetics, *Evolution, Alternative Splicing, Bacteria/genetics, Molecular, Open Reading Frames/*genetics, Riboswitch/genetics, {RNA} Splicing/genetics, Untranslated Regions/genetics}
}

@article{caffarelli_inefficient_1992,
	title = {Inefficient in vitro splicing of the regulatory intron of the L1 ribosomal protein gene of X.laevis depends on suboptimal splice site sequences},
	volume = {183},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1550574},
	abstract = {The splicing of the third intron of the L1 r-protein gene of X.laevis was studied in the heterologous in vitro {HeLa} nuclear system. Despite the evolutionary distance, the cis-elements responsible for the default process play a similar role in the two organisms. Analysis of the splicing of various mutant substrates showed that the 5' splice site is primarily responsible for the low efficiency of splicing of the third intron. The suboptimal 5' splice site sequence leads to the utilization of an upstream alternative site which corresponds to the one utilized in vivo. The accumulation of splicing intermediates in the in vitro system allowed the identification of the branch site and of the branch consensus sequence. In contrast, the in vivo regulatory mechanism involving cleavage of the pre-{mRNA} is not mimicked in the {HeLa} extract.},
	pages = {680--687},
	number = {2},
	journaltitle = {Biochem Biophys Res Commun},
	author = {Caffarelli, E and Fragapane, P and Bozzoni, I},
	date = {1992},
	pmid = {1550574},
	keywords = {Animals, Base Sequence, Humans, *Gene Expression Regulation, *Introns, *{RNA} Splicing, Cell Extracts/physiology, Cell Nucleus/metabolism, Consensus Sequence, {HeLa} Cells/metabolism, Molecular Sequence Data, Ribosomal Proteins/*genetics, Xenopus laevis/*genetics}
}

@article{zou_polyamine_2006,
	title = {Polyamine depletion increases cytoplasmic levels of {RNA}-binding protein {HuR} leading to stabilization of nucleophosmin and p53 {mRNAs}},
	volume = {281},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16690610},
	doi = {10.1074/jbc.M602344200},
	abstract = {Polyamines are essential for maintaining normal intestinal epithelial integrity, an effect that relies, at least in part, on their ability to keep low levels of nucleophosmin ({NPM}) and p53 {mRNAs}. The {RNA}-binding protein {HuR} associates with the p53 {mRNA}, as reported previously, and with the {NPM} {mRNA}, computationally predicted to be a target of {HuR}. Here, we show that {HuR} binds the {NPM} and p53 3'-untranslated regions and stabilizes these {mRNAs} in polyamine-depleted intestinal epithelial cells. Depletion of cellular polyamines by inhibiting ornithine decarboxylase with alpha-difluoromethylornithine dramatically enhanced the cytoplasmic abundance of {HuR}, whereas ectopic ornithine decarboxylase overexpression decreased cytoplasmic {HuR}; neither intervention changed whole-cell {HuR} levels. {HuR} was found to specifically bind the 3'-untranslated regions of {NPN} and p53 {mRNAs}. {HuR} silencing rendered the {NPM} and p53 {mRNAs} unstable and prevented increases in {NPM} and p53 {mRNA} and protein in polyamine-deficient cells. These results indicate that polyamines modulate cytoplasmic {HuR} levels in intestinal epithelial cells, in turn controlling the stability of the {NPM} and p53 {mRNAs} and influencing {NPM} and p53 protein levels.},
	pages = {19387--19394},
	number = {28},
	journaltitle = {J Biol Chem},
	author = {Zou, T and Mazan-Mamczarz, K and Rao, J N and Liu, L and Marasa, B S and Zhang, A H and Xiao, L and Pullmann, R and Gorospe, M and Wang, J Y},
	date = {2006},
	pmid = {16690610},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, Protein Binding, Antigens, Eflornithine/chemistry, Hu Paraneoplastic Encephalomyelitis Antigens, Molecular Sequence Data, Nuclear Proteins/*chemistry, Ornithine Decarboxylase/chemistry, Polyamines/*chemistry, Rats, {RNA}-Binding Proteins/*chemistry/physiology, Surface/*physiology, Tumor Suppressor Protein p53/metabolism/*physiolog}
}

@article{williams_pp32_2010,
	title = {pp32 ({ANP}32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting {HuR} binding to {mRNAs}},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21152064},
	doi = {10.1371/journal.pone.0015455},
	abstract = {The expression of protein phosphatase 32 ({PP}32, {ANP}32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of {HuR} ({ELAV}1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine ({ARA}-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of {HuR} with the {mRNA} encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase ({dCK}), causing a significant reduction in {dCK} protein levels. Similarly, ectopic pp32 expression caused a reduction in {HuR} binding of {mRNAs} encoding tumor-promoting proteins (e.g., {VEGF} and {HuR}), while silencing pp32 dramatically enhanced the binding of these {mRNA} targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic {HuR} status, nuclear pp32 levels and cytoplasmic {HuR} levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt {HuR} binding to target {mRNAs} encoding key proteins for cancer cell survival and drug efficacy.},
	pages = {e15455},
	number = {11},
	journaltitle = {{PLoS} One},
	author = {Williams, T K and Costantino, C L and Bildzukewicz, N A and Richards, N G and Rittenhouse, D W and Einstein, L and Cozzitorto, J A and Keen, J C and Dasgupta, A and Gorospe, M and Gonye, G E and Yeo, C J and Witkiewicz, A K and Brody, J R},
	date = {2010},
	pmid = {21152064},
	keywords = {Humans, {RNA}, Protein Binding, *Cell Proliferation, Antigens, Antimetabolites, Antineoplastic/pharmacology, Blotting, Cell Line, Deoxycytidine Kinase/genetics/metabolism, Deoxycytidine/*analogs \& derivatives/pharmacology, Drug Resistance/genetics, {HEK}293 Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/genetics/*metabolism, Pancreatic Neoplasms/genetics/metabolism/pathology, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism, Tumor, Western}
}

@article{brennan_mrna-destabilizing_2009,
	title = {The {mRNA}-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis},
	volume = {69},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19491267},
	doi = {10.1158/0008-5472.CAN-08-4238},
	abstract = {{AU}-rich element-binding proteins ({ARE}-{BP}) regulate the stability and/or translational efficiency of {mRNAs} containing cognate binding sites. Many targeted transcripts encode factors that control processes such as cell division, apoptosis, and angiogenesis, suggesting that dysregulated {ARE}-{BP} expression could dramatically influence oncogenic phenotypes. Using several approaches, we evaluated the expression of four well-characterized {ARE}-{BPs} across a variety of human neoplastic syndromes. {AUF}1, {TIA}-1, and {HuR} {mRNAs} were not systematically dysregulated in cancers; however, tristetraprolin {mRNA} levels were significantly decreased across many tumor types, including advanced cancers of the breast and prostate. Restoring tristetraprolin expression in an aggressive tumor cell line suppressed three key tumorgenic phenotypes: cell proliferation, resistance to proapoptotic stimuli, and expression of vascular endothelial growth factor {mRNA}. However, the cellular consequences of tristetraprolin expression varied across different cell models. Analyses of gene array data sets revealed that suppression of tristetraprolin expression is a negative prognostic indicator in breast cancer, because patients with low tumor tristetraprolin {mRNA} levels were more likely to present increased pathologic tumor grade, vascular endothelial growth factor expression, and mortality from recurrent disease. Collectively, these data establish that tristetraprolin expression is frequently suppressed in human cancers, which in turn can alter tumorigenic phenotypes that influence patient outcomes.},
	pages = {5168--5176},
	number = {12},
	journaltitle = {Cancer Res},
	author = {Brennan, S E and Kuwano, Y and Alkharouf, N and Blackshear, P J and Gorospe, M and Wilson, G M},
	date = {2009},
	pmid = {19491267},
	keywords = {{DNA}, Complementary, Humans, {RNA}, Gene Expression Profiling, Apoptosis, Cell Proliferation, {HeLa} Cells, Messenger/*genetics, Neoplasms/*metabolism/pathology, Phenotype, Prognosis, Tristetraprolin/*antagonists \& inhibitors, Vascular Endothelial Growth Factor A/genetics}
}

@article{sharma_aluminium_2013,
	title = {Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of {PGC}-1alpha expression},
	volume = {273},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24084166},
	doi = {10.1016/j.taap.2013.09.012},
	abstract = {The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1alpha ({PGC}-1alpha) and its downstream targets i.e. Nuclear respiratory factor-1({NRF}-1), Nuclear respiratory factor-2({NRF}-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in {ROS} levels, mitochondrial {DNA} oxidation and decrease in citrate synthase activity in the Hippocampus ({HC}) and Corpus striatum ({CS}) regions of rat brain. On the other hand, there was a decrease in the {mRNA} levels of the mitochondrial encoded subunits-{NADH} dehydrogenase ({ND}) subunits i.e. {ND}1, {ND}2, {ND}3, Cytochrome b (Cytb), Cytochrome oxidase ({COX}) subunits i.e. {COX}1, {COX}3, {ATP} synthase ({ATPase}) subunit 6 along with reduced expression of nuclear encoded subunits {COX}4, {COX}5A, {COX}5B of Electron transport chain ({ETC}). Besides, a decrease in mitochondrial {DNA} copy number and mitochondrial content in both regions of rat brain was observed. The {PGC}-1alpha was down-regulated in aluminium treated rats along with {NRF}-1, {NRF}-2 and Tfam, which act downstream from {PGC}-1alpha in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, {PGC}-1alpha seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases.},
	pages = {365--380},
	number = {2},
	journaltitle = {Toxicol Appl Pharmacol},
	author = {Sharma, D R and Sunkaria, A and Wani, W Y and Sharma, R K and Kandimalla, R J and Bal, A and Gill, K D},
	date = {2013},
	pmid = {24084166},
	keywords = {Animals, *Gene Expression Regulation/drug effects, Aluminum/*toxicity, Male, Mitochondrial Turnover/drug effects/*physiology, Neurodegenerative Diseases/metabolism/pathology/ph, Oxidative Stress/drug effects/*physiology, Rats, Transcription Factors/biosynthesis/*metabolism, Wistar}
}

@article{buckley_new_2011,
	title = {New insights into non-coding {RNA} networks in Huntington's disease},
	volume = {231},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21821026},
	doi = {10.1016/j.expneurol.2011.07.005},
	pages = {191--194},
	number = {2},
	journaltitle = {Exp Neurol},
	author = {Buckley, N J and Johnson, R},
	date = {2011},
	pmid = {21821026},
	keywords = {Animals, Down-Regulation/*physiology, Huntington Disease/*genetics/*metabolism/*physiopa, {MicroRNAs}/*metabolism}
}

@article{wheeler_human_2013,
	title = {From human genome to cancer genome: the first decade},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23817046},
	doi = {10.1101/gr.157602.113},
	abstract = {The realization that cancer progression required the participation of cellular genes provided one of several key rationales, in 1986, for embarking on the human genome project. Only with a reference genome sequence could the full spectrum of somatic changes leading to cancer be understood. Since its completion in 2003, the human reference genome sequence has fulfilled its promise as a foundational tool to illuminate the pathogenesis of cancer. Herein, we review the key historical milestones in cancer genomics since the completion of the genome, and some of the novel discoveries that are shaping our current understanding of cancer.},
	pages = {1054--1062},
	number = {7},
	journaltitle = {Genome Res},
	author = {Wheeler, D A and Wang, L},
	date = {2013},
	pmid = {23817046},
	keywords = {Human, Animals, Humans, *Genome, Cell Transformation, Genes, Genetic Heterogeneity, Genomics/*trends, Mutation Rate, Neoplasm, Neoplasms/*genetics, Neoplastic/genetics}
}

@article{hornstra_multiple_1992,
	title = {Multiple in vivo footprints are specific to the active allele of the X-linked human hypoxanthine phosphoribosyltransferase gene 5' region: implications for X chromosome inactivation},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1448069},
	abstract = {Dosage compensation of X-linked genes in male and female mammals is accomplished by random inactivation of one X chromosome in each female somatic cell. As a result, a transcriptionally active allele and a transcriptionally inactive allele of most X-linked genes reside within each female nucleus. To examine the mechanism responsible for maintaining this unique system of differential gene expression, we have analyzed the differential binding of regulatory proteins to the 5' region of the human hypoxanthine phosphoribosyltransferase ({HPRT}) gene on the active and inactive X chromosomes. Studies of {DNA}-protein interactions associated with the transcriptionally active and inactive {HPRT} alleles were carried out in intact cultured cells by in vivo footprinting by using ligation-mediated polymerase chain reaction and dimethyl sulfate. Analysis of the active allele demonstrates at least six footprinted regions, whereas no footprints were detected on the inactive allele. Of the footprints on the active allele, at least four occur over canonical {GC} boxes or Sp1 consensus binding sites, one is associated with a potential {AP}-2 binding site, and another is associated with a {DNA} sequence not previously reported to interact with a sequence-specific {DNA}-binding factor. While no footprints were observed for the {HPRT} gene on the inactive X chromosome, reactivation of the inactive allele with 5-azacytidine treatment restored the in vivo footprint pattern found on the active allele. Results of these experiments, in conjunction with recent studies on the X-linked human {PGK}-1 gene, bear implications for models of X chromosome inactivation.},
	pages = {5345--5354},
	number = {12},
	journaltitle = {Mol Cell Biol},
	author = {Hornstra, I K and Yang, T P},
	date = {1992},
	pmid = {1448069},
	keywords = {Animals, Base Sequence, Genetic, Humans, Mice, *Dosage Compensation, *X Chromosome, Alleles, Cell Line, Cricetinae, Dna, Genetic Linkage, {HeLa} Cells, Hybrid Cells, Hypoxanthine Phosphoribosyltransferase/*genetics/m, Male, Molecular Sequence Data, Polymerase Chain Reaction}
}

@article{bianchi_synaptogenesis_2013,
	title = {Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans},
	volume = {110 Suppl},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23754422},
	doi = {10.1073/pnas.1301224110},
	abstract = {Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans approximately 25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3-5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages.},
	pages = {10395--10401},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Bianchi, S and Stimpson, C D and Duka, T and Larsen, M D and Janssen, W G and Collins, Z and Bauernfeind, A L and Schapiro, S J and Baze, W B and {McArthur}, M J and Hopkins, W D and Wildman, D E and Lipovich, L and Kuzawa, C W and Jacobs, B and Hof, P R and Sherwood, C C},
	date = {2013},
	pmid = {23754422},
	keywords = {Animals, Humans, *Dendrites/physiology, *Neocortex/cytology/physiology, *Pan troglodytes/anatomy \& histology/physiology, *Phylogeny, *Pyramidal Cells/cytology/physiology, Feedback, Female, Male, Sensory/physiology, Synapses/*physiology}
}

@article{matos_profile_2015,
	title = {The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26488476},
	doi = {10.1371/journal.pone.0141139},
	abstract = {{INTRODUCTION}: The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase ({HPSE}) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 ({HPSE}2) modulates {HPSE} activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions. {METHODS}: {HPSE} and {HPSE}2 expression by {qRT}-{PCR}, immunohistochemistry evaluation, western blot analysis and {HPSE} enzymatic activity were evaluated. {RESULTS}: The expression of heparanases by {qRT}-{PCR} showed an increase of {HPSE}2 in thyroid carcinoma (P = 0.001). {HPSE} activity was found to be higher in the malignant neoplasms than in the benign tumors (P{\textbackslash}textless0.0001). On Western blot analysis, {HPSE}2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P{\textbackslash}textless0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100\%, showing itself to be an accurate test for distinguishing between malignant and benign lesions. {CONCLUSIONS}: This study shows, for the first time, a distinct profile of {HPSE} expression in thyroid carcinoma suggesting its role in carcinogenesis.},
	pages = {e0141139},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Matos, L L and Suarez, E R and Theodoro, T R and Trufelli, D C and Melo, C M and Garcia, L F and Oliveira, O C and Matos, M G and Kanda, J L and Nader, H B and Martins, J R and Pinhal, M A},
	date = {2015},
	pmid = {26488476},
	keywords = {Humans, Diagnosis, Differential, Female, Glucuronidase/*metabolism, Immunohistochemistry/methods, Male, Middle Aged, Neoplasms/*metabolism/*pathology, Thyroid Gland/metabolism/pathology, Thyroid Neoplasms/*metabolism/*pathology}
}

@article{miller_prolonged_2012,
	title = {Prolonged myelination in human neocortical evolution},
	volume = {109},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23012402},
	doi = {10.1073/pnas.1117943109},
	abstract = {Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.},
	pages = {16480--16485},
	number = {41},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Miller, D J and Duka, T and Stimpson, C D and Schapiro, S J and Baze, W B and {McArthur}, M J and Fobbs, A J and Sousa, A M and Sestan, N and Wildman, D E and Lipovich, L and Kuzawa, C W and Hof, P R and Sherwood, C C},
	date = {2012},
	pmid = {23012402},
	keywords = {Animals, Humans, *Biological Evolution, Adolescent, Adult, Blotting, Child, Infant, Motor Cortex/growth \& development/metabolism, Myelin Proteins/*metabolism, Myelin Sheath/*metabolism, Myelin-Associated Glycoprotein/metabolism, Neocortex/growth \& development/*metabolism, Newborn, Pan troglodytes, Prefrontal Cortex/growth \& development/metabolism, Somatosensory Cortex/growth \& development/metaboli, Time Factors, Visual Cortex/growth \& development/metabolism, Western, Young Adult}
}

@article{gilbert_functional_2011,
	title = {Functional specialization of ribosomes?},
	volume = {36},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21242088},
	doi = {10.1016/j.tibs.2010.12.002},
	abstract = {Ribosomes are highly conserved macromolecular machines that are responsible for protein synthesis in all living organisms. Work published in the past year has shown that changes to the ribosome core can affect the mechanism of translation initiation that is favored in the cell, which potentially leads to specific changes in the relative efficiencies with which different proteins are made. Here, I examine recent data from expression and proteomic studies that suggest that cells make slightly different ribosomes under different growth conditions, and discuss genetic evidence that such differences are functional. In particular, I argue that eukaryotic cells probably produce ribosomes that lack one or more core ribosomal proteins ({RPs}) under some conditions, and that core {RPs} contribute differentially to translation of distinct subpopulations of {mRNAs}.},
	pages = {127--132},
	number = {3},
	journaltitle = {Trends Biochem Sci},
	author = {Gilbert, W V},
	date = {2011},
	pmid = {21242088},
	keywords = {Animals, Humans, {RNA}, Messenger/genetics, Eukaryotic Cells/metabolism, Ribosomal Proteins/genetics/metabolism, Ribosomes/genetics/*metabolism}
}

@article{villa_processing_1998,
	title = {Processing of the intron-encoded U18 small nucleolar {RNA} in the yeast Saccharomyces cerevisiae relies on both exo- and endonucleolytic activities},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9584178},
	abstract = {Many small nucleolar {RNAs} ({snoRNAs}) are encoded within introns of protein-encoding genes and are released by processing of their host pre-{mRNA}. We have investigated the mechanism of processing of the yeast U18 {snoRNA}, which is found in the intron of the gene coding for translational elongation factor {EF}-1beta. We have focused our analysis on the relationship between splicing of the {EF}-1beta pre-{mRNA} and production of the mature {snoRNA}. Mutations inhibiting splicing of the {EF}-1beta pre-{mRNA} have been shown to produce normal U18 {snoRNA} levels together with the accumulation of intermediates deriving from the pre-{mRNA}, thus indicating that the precursor is an efficient processing substrate. Inhibition of 5'–{\textbackslash}textgreater3' exonucleases obtained by insertion of G cassettes or by the use of a rat1-1 xrn1Delta mutant strain does not impair U18 release. In the Exo- strain, 3' cutoff products, diagnostic of an endonuclease-mediated processing pathway, were detected. Our data indicate that biosynthesis of the yeast U18 {snoRNA} relies on two different pathways, depending on both exonucleolytic and endonucleolytic activities: a major processing pathway based on conversion of the debranched intron and a minor one acting by endonucleolytic cleavage of the pre-{mRNA}.},
	pages = {3376--3383},
	number = {6},
	journaltitle = {Mol Cell Biol},
	author = {Villa, T and Ceradini, F and Presutti, C and Bozzoni, I},
	date = {1998},
	pmid = {9584178},
	keywords = {{RNA}, {RNA} Splicing, *Introns, *Saccharomyces cerevisiae Proteins, {DNA}-Binding Proteins/metabolism, Endodeoxyribonucleases/*metabolism, Exodeoxyribonuclease V, Exodeoxyribonucleases/*metabolism, Exoribonucleases/*metabolism, Fungal Proteins/genetics/metabolism, Peptide Elongation Factor 1, Peptide Elongation Factors/genetics/metabolism, Ribonucleoproteins/genetics/metabolism, {RNA} Precursors/metabolism, Saccharomyces cerevisiae/*genetics, Small Nuclear/*genetics}
}

@article{kurihara_genome-wide_2009,
	title = {Genome-wide suppression of aberrant {mRNA}-like noncoding {RNAs} by {NMD} in Arabidopsis},
	volume = {106},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19181858},
	doi = {10.1073/pnas.0808902106},
	abstract = {The nonsense-mediated {mRNA} decay ({NMD}) pathway is a well-known eukaryotic surveillance mechanism that eliminates aberrant {mRNAs} that contain a premature termination codon ({PTC}). The {UP}-Frameshift ({UPF}) proteins, {UPF}1, {UPF}2, and {UPF}3, are essential for normal {NMD} function. Several {NMD} substrates have been identified, but detailed information on {NMD} substrates is lacking. Here, we noticed that, in Arabidopsis, most of the {mRNA}-like nonprotein-coding {RNAs} ({ncRNAs}) have the features of an {NMD} substrate. We examined the expression profiles of 2 Arabidopsis mutants, upf1-1 and upf3-1, using a whole-genome tiling array. The results showed that expression of not only protein-coding transcripts but also many {mRNA}-like {ncRNAs} ({mlncRNAs}), including natural antisense transcript {RNAs} (nat-{RNAs}) transcribed from the opposite strands of the coding strands, were up-regulated in both mutants. The percentage of the up-regulated {mlncRNAs} to all expressed {mlncRNAs} was much higher than that of the up-regulated protein-coding transcripts to all expressed protein- coding transcripts. This finding demonstrates that one of the most important roles of {NMD} is the genome-wide suppression of the aberrant {mlncRNAs} including nat-{RNAs}.},
	pages = {2453--2458},
	number = {7},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Kurihara, Y and Matsui, A and Hanada, K and Kawashima, M and Ishida, J and Morosawa, T and Tanaka, M and Kaminuma, E and Mochizuki, Y and Matsushima, A and Toyoda, T and Shinozaki, K and Seki, M},
	date = {2009},
	pmid = {19181858},
	keywords = {Genetic, {RNA}, Gene Expression Regulation, *Genome, Exons, Untranslated/*genetics, Arabidopsis Proteins/metabolism, Arabidopsis/*genetics, Biological, Cycloheximide/pharmacology, Genes, Messenger/metabolism, Models, Mutation, Plant, Protein Synthesis Inhibitors/pharmacology, Reverse Transcriptase Polymerase Chain Reaction, {RNA}/metabolism}
}

@article{zeng_induction_2013,
	title = {Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24023657},
	doi = {10.1371/journal.pone.0072922},
	abstract = {Dietary modulation of the synthesis of endogenous host defense peptides ({HDPs}) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, {HDP} regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce {HDP} expression in pigs, we evaluated the expressions of a panel of porcine {HDPs} in {IPEC}-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time {PCR}. We revealed that butyrate is a potent inducer of multiple, but not all, {HDP} genes. Porcine beta-defensin 2 ({pBD}2), {pBD}3, epididymis protein 2 splicing variant C ({pEP}2C), and protegrins were induced markedly in response to butyrate, whereas {pBD}1 expression remained largely unaltered in any cell type. Additionally, a comparison of the {HDP}-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of {HDP} expression in {IPEC}-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in {HDP} induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce {HDP} gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.},
	pages = {e72922},
	number = {8},
	journaltitle = {{PLoS} One},
	author = {Zeng, X and Sunkara, L T and Jiang, W and Bible, M and Carter, S and Ma, X and Qiao, S and Zhang, G},
	date = {2013},
	pmid = {24023657}
}

@article{lipovich_primate-specific_2006,
	title = {Primate-specific endogenous cis-antisense transcription in the human 5q31 protocadherin gene cluster},
	volume = {62},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16341467},
	doi = {10.1007/s00239-005-0041-3},
	abstract = {Protocadherins ({PCDH}), localized to synaptic junctions, contribute to the formation of neuronal networks during brain development; thus, it is speculated that protocadherins may play a role in evolution of neuronal complexity. While protocadherin genes are highly conserved in vertebrates, {EST} evidence from the locus suggests apparently species-specific cis-antisense transcripts. Novel cis-antisense transcripts, which partially overlap the {PCDHalpha}12 variable exon, {PCDHbeta}3 single-exon gene, and {PCDHpsi}5 unprocessed pseudogene in the human 5q31 {PCDHalpha}/beta/gamma gene cluster and which are coexpressed with sense-strand transcripts in fetal and adult brain, were identified computationally and validated by gene-specific strand-specific reverse transcriptase {PCR} ({SSRTPCR}) and sequencing. Absence of antisense transcripts arising from equivalent genomic locations in mouse indicates that the antisense transcripts originated in the primates after the primate-rodent divergence. Furthermore, not all expected orthologues of human sense and antisense {PCDH} transcripts were detected in rhesus macaque brain, implying that protocadherin expression patterns differ between primate species. {RT} followed by quantitative real-time {PCR} ({QPCR}) analysis of the three genes in the brain of all three species, and of the {PCDHbeta}15 gene paralogous to {PCDHpsi}5 in human and rhesus, revealed that the presence of antisense transcripts was significantly associated with lower sense expression levels across all orthologues. This inverse relationship, along with the pattern of sense and antisense coexpression in the brain, is consistent with a regulatory role for the primate-specific {PCDH} cis-antisense transcripts, which may represent recent evolutionary inventions modulating the activity of this conserved gene cluster.},
	pages = {73--88},
	number = {1},
	journaltitle = {J Mol Evol},
	author = {Lipovich, L and Vanisri, R R and Kong, S L and Lin, C Y and Liu, E T},
	date = {2006},
	pmid = {16341467},
	keywords = {Human, {DNA}, Animals, Genetic, Humans, Transcription, *Chromosomes, *Multigene Family, *Primates, Antisense/*physiology, Cadherins/*genetics, Pair 5, Protein Precursors/*genetics, Regulatory Elements, Species Specificity, Transcriptional}
}

@article{rosenbloom_ucsc_2015,
	title = {The {UCSC} Genome Browser database: 2015 update},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25428374},
	doi = {10.1093/nar/gku1177},
	abstract = {Launched in 2001 to showcase the draft human genome assembly, the {UCSC} Genome Browser database (http://genome.ucsc.edu) and associated tools continue to grow, providing a comprehensive resource of genome assemblies and annotations to scientists and students worldwide. Highlights of the past year include the release of a browser for the first new human genome reference assembly in 4 years in December 2013 ({GRCh}38, {UCSC} hg38), a watershed comparative genomics annotation (100-species multiple alignment and conservation) and a novel distribution mechanism for the browser ({GBiB}: Genome Browser in a Box). We created browsers for new species (Chinese hamster, elephant shark, minke whale), 'mined the web' for {DNA} sequences and expanded the browser display with stacked color graphs and region highlighting. As our user community increasingly adopts the {UCSC} track hub and assembly hub representations for sharing large-scale genomic annotation data sets and genome sequencing projects, our menu of public data hubs has tripled.},
	pages = {D670--81},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Rosenbloom, K R and Armstrong, J and Barber, G P and Casper, J and Clawson, H and Diekhans, M and Dreszer, T R and Fujita, P A and Guruvadoo, L and Haeussler, M and Harte, R A and Heitner, S and Hickey, G and Hinrichs, A S and Hubley, R and Karolchik, D and Learned, K and Lee, B T and Li, C H and Miga, K H and Nguyen, N and Paten, B and Raney, B J and Smit, A F and Speir, M L and Zweig, A S and Haussler, D and Kuhn, R M and Kent, W J},
	date = {2015},
	pmid = {25428374}
}

@article{sunk_interphalangeal_2013,
	title = {Interphalangeal Osteoarthritis Radiographic Simplified ({iOARS}) score: a radiographic method to detect osteoarthritis of the interphalangeal finger joints based on its histopathological alterations},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23897771},
	doi = {10.1136/annrheumdis-2012-203117},
	abstract = {{OBJECTIVE}: To develop a radiographic score for assessment of hand osteoarthritis ({OA}) that is based on histopathological alterations of the distal ({DIP}) and proximal ({PIP}) interphalangeal joints. {METHODS}: {DIP} and {PIP} joints were obtained from corpses (n=40). Plain radiographies of these joints were taken. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. A 2x2 Fisher's exact test was applied to define those radiographic features most likely to be associated with histological alterations. Receiver operating characteristic curves were analysed to determine radiographic thresholds. Intraclass correlation coefficients ({ICC}) estimated intra- and inter-reader variability. Spearman's correlation was applied to examine the relationship between our score and histopathological changes. Differences between groups were determined by a Student's t test. {RESULTS}: The Interphalangeal Osteoarthritis Radiographic Simplified ({iOARS}) score is presented. The score is based on histopathological changes of {DIP} and {PIP} joints and follows a simple dichotomy whether {OA} is present or not. The {iOARS} score relies on three equally ranked radiographic features (osteophytes, joint space narrowing and subchondral sclerosis). For both {DIP} and {PIP} joints, the presence of one x-ray features reflects interphalangeal {OA}. Sensitivity and specificity for {DIP} joints were 92.3\% and 90.9\%, respectively, and 75\% and 100\% for {PIP} joints. All readers were able to reproduce their own readings in {DIP} and {PIP} joints after 4 weeks. The overall agreement between the three readers was good; {ICCs} ranged from 0.945 to 0.586. Additionally, outcomes of the {iOARS} score in a hand {OA} cohort revealed a higher prevalence of interphalangeal joint {OA} compared with the Kellgren and Lawrence score. {CONCLUSIONS}: The {iOARS} score is uniquely based on histopathological alterations of the interphalangeal joints in order to reliably determine {OA} of the {DIP} and {PIP} joints radiographically. Its high specificity and sensitivity together with the dichotomous approach renders the {iOARS} score reliable, fast to perform and easy to apply. This tool may not only be valuable in daily clinical practice but also in clinical and epidemiological trials.},
	journaltitle = {Ann Rheum Dis},
	author = {Sunk, I G and Amoyo-Minar, L and Stamm, T and Haider, S and Niederreiter, B and Supp, G and Soleiman, A and Kainberger, F and Smolen, J S and Bobacz, K},
	date = {2013},
	pmid = {23897771}
}

@article{arking_genetic_2014,
	title = {Genetic association study of {QT} interval highlights role for calcium signaling pathways in myocardial repolarization},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24952745},
	doi = {10.1038/ng.3014},
	abstract = {The {QT} interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. {QT} prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death ({SCD}) and could indicate the presence of the potentially lethal mendelian long-{QT} syndrome ({LQTS}). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with {QT} interval that collectively explain approximately 8-10\% of {QT}-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new {QT} interval-associated loci in 298 unrelated probands with {LQTS} identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, {LQTS} and {SCD}.},
	pages = {826--836},
	number = {8},
	journaltitle = {Nat Genet},
	author = {Arking, D E and Pulit, S L and Crotti, L and van der Harst, P and Munroe, P B and Koopmann, T T and Sotoodehnia, N and Rossin, E J and Morley, M and Wang, X and Johnson, A D and Lundby, A and Gudbjartsson, D F and Noseworthy, P A and Eijgelsheim, M and Bradford, Y and Tarasov, K V and Dorr, M and Muller-Nurasyid, M and Lahtinen, A M and Nolte, I M and Smith, A V and Bis, J C and Isaacs, A and Newhouse, S J and Evans, D S and Post, W S and Waggott, D and Lyytikainen, L P and Hicks, A A and Eisele, L and Ellinghaus, D and Hayward, C and Navarro, P and Ulivi, S and Tanaka, T and Tester, D J and Chatel, S and Gustafsson, S and Kumari, M and Morris, R W and Naluai, A T and Padmanabhan, S and Kluttig, A and Strohmer, B and Panayiotou, A G and Torres, M and Knoflach, M and Hubacek, J A and Slowikowski, K and Raychaudhuri, S and Kumar, R D and Harris, T B and Launer, L J and Shuldiner, A R and Alonso, A and Bader, J S and Ehret, G and Huang, H and Kao, W H and Strait, J B and Macfarlane, P W and Brown, M and Caulfield, M J and Samani, N J and Kronenberg, F and Willeit, J and Smith, J G and Greiser, K H and Meyer Zu Schwabedissen, H and Werdan, K and Carella, M and Zelante, L and Heckbert, S R and Psaty, B M and Rotter, J I and Kolcic, I and Polasek, O and Wright, A F and Griffin, M and Daly, M J and Arnar, D O and Holm, H and Thorsteinsdottir, U and Denny, J C and Roden, D M and Zuvich, R L and Emilsson, V and Plump, A S and Larson, M G and O'Donnell, C J and Yin, X and Bobbo, M and D'Adamo, A P and Iorio, A and Sinagra, G and Carracedo, A and Cummings, S R and Nalls, M A and Jula, A and Kontula, K K and Marjamaa, A and Oikarinen, L and Perola, M and Porthan, K and Erbel, R and Hoffmann, P and Jockel, K H and Kalsch, H and Nothen, M M and den Hoed, M and Loos, R J and Thelle, D S and Gieger, C and Meitinger, T and Perz, S and Peters, A and Prucha, H and Sinner, M F and Waldenberger, M and de Boer, R A and Franke, L and van der Vleuten, P A and Beckmann, B M and Martens, E and Bardai, A and Hofman, N and Wilde, A A and Behr, E R and Dalageorgou, C and Giudicessi, J R and Medeiros-Domingo, A and Barc, J and Kyndt, F and Probst, V and Ghidoni, A and Insolia, R and Hamilton, R M and Scherer, S W and Brandimarto, J and Margulies, K and Moravec, C E and del Greco, M F and Fuchsberger, C and O'Connell, J R and Lee, W K and Watt, G C and Campbell, H and Wild, S H and El Mokhtari, N E and Frey, N and Asselbergs, F W and Mateo Leach, I and Navis, G and van den Berg, M P and van Veldhuisen, D J and Kellis, M and Krijthe, B P and Franco, O H and Hofman, A and Kors, J A and Uitterlinden, A G and Witteman, J C and Kedenko, L and Lamina, C and Oostra, B A and Abecasis, G R and Lakatta, E G and Mulas, A and Orru, M and Schlessinger, D and Uda, M and Markus, M R and Volker, U and Snieder, H and Spector, T D and Arnlov, J and Lind, L and Sundstrom, J and Syvanen, A C and Kivimaki, M and Kahonen, M and Mononen, N and Raitakari, O T and Viikari, J S and Adamkova, V and Kiechl, S and Brion, M and Nicolaides, A N and Paulweber, B and Haerting, J and Dominiczak, A F and Nyberg, F and Whincup, P H and Hingorani, A D and Schott, J J and Bezzina, C R and Ingelsson, E and Ferrucci, L and Gasparini, P and Wilson, J F and Rudan, I and Franke, A and Muhleisen, T W and Pramstaller, P P and Lehtimaki, T J and Paterson, A D and Parsa, A and Liu, Y and van Duijn, C M and Siscovick, D S and Gudnason, V and Jamshidi, Y and Salomaa, V and Felix, S B and Sanna, S and Ritchie, M D and Stricker, B H and Stefansson, K and Boyer, L A and Cappola, T P and Olsen, J V and Lage, K and Schwartz, P J and Kaab, S and Chakravarti, A and Ackerman, M J and Pfeufer, A and de Bakker, P I and Newton-Cheh, C},
	date = {2014},
	pmid = {24952745},
	keywords = {Humans, Adult, Aged, Arrhythmias, Calcium Signaling/*genetics, Cardiac/etiology, Cardiac/genetics/metabolism, Death, Electrocardiography/methods, Female, Genetic Predisposition to Disease, Genome-Wide Association Study/methods, Genotype, Heart Ventricles/metabolism, Long {QT} Syndrome/*genetics/metabolism, Male, Middle Aged, Myocardium/metabolism, Polymorphism, Single Nucleotide, Sudden}
}

@article{figueroa_novel_2009,
	title = {Novel roles of hakai in cell proliferation and oncogenesis},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19535458},
	doi = {10.1091/mbc.E08-08-0845},
	abstract = {During tumor development, cells acquire multiple phenotypic changes upon misregulation of oncoproteins and tumor suppressor proteins. Hakai was originally identified as an E3 ubiquitin-ligase for the E-cadherin complex that regulates cell-cell contacts. Here, we present evidence that Hakai plays a crucial role in various cellular processes and tumorigenesis. Overexpression of Hakai affects not only cell-cell contacts but also proliferation in both epithelial and fibroblast cells. Furthermore, the knockdown of Hakai significantly suppresses proliferation of transformed epithelial cells. Expression of Hakai is correlated to the proliferation rate in human tissues and is highly up-regulated in human colon and gastric adenocarcinomas. Moreover, we identify {PTB}-associated splicing factor ({PSF}), an {RNA}-binding protein, as a novel Hakai-interacting protein. By using {cDNA} arrays, we have determined various specific {PSF}-associated {mRNAs} encoding proteins that are involved in several cancer-related processes. Hakai affects the ability of {PSF} to bind these {mRNAs}, and expression of {PSF} short hairpin {RNA} or a dominant-negative {PSF} mutant significantly suppresses proliferation of Hakai-overexpressing cells. Collectively, these results suggest that Hakai is an important regulator of cell proliferation and that Hakai may be an oncoprotein and a potential molecular target for cancer treatment.},
	pages = {3533--3542},
	number = {15},
	journaltitle = {Mol Biol Cell},
	author = {Figueroa, A and Kotani, H and Toda, Y and Mazan-Mamczarz, K and Mueller, E C and Otto, A and Disch, L and Norman, M and Ramdasi, R M and Keshtgar, M and Gorospe, M and Fujita, Y},
	date = {2009},
	pmid = {19535458},
	keywords = {Animals, Humans, Mice, {RNA}, Protein Binding, Oligonucleotide Array Sequence Analysis, *Cell Proliferation, Blotting, Cadherins/genetics/metabolism, Cell Adhesion, Cell Line, Endometrium/*metabolism, Female, Flow Cytometry, Fluorescent Antibody Technique, Immunohistochemistry, Lymph Nodes/*metabolism, Messenger/genetics/metabolism, Mutation, Neoplasms/genetics/metabolism/pathology, {NIH} 3T3 Cells, {RNA} Interference, {RNA}-Binding Proteins/genetics/metabolism, Tumor, Ubiquitin-Protein Ligases/genetics/*metabolism, Western}
}

@article{jinek_programmable_2012,
	title = {A programmable dual-{RNA}-guided {DNA} endonuclease in adaptive bacterial immunity},
	volume = {337},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22745249},
	doi = {10.1126/science.1225829},
	abstract = {Clustered regularly interspaced short palindromic repeats ({CRISPR})/{CRISPR}-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using {CRISPR} {RNAs} ({crRNAs}) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature {crRNA} that is base-paired to trans-activating {crRNA} ({tracrRNA}) forms a two-{RNA} structure that directs the {CRISPR}-associated protein Cas9 to introduce double-stranded (ds) breaks in target {DNA}. At sites complementary to the {crRNA}-guide sequence, the Cas9 {HNH} nuclease domain cleaves the complementary strand, whereas the Cas9 {RuvC}-like domain cleaves the noncomplementary strand. The dual-{tracrRNA}:{crRNA}, when engineered as a single {RNA} chimera, also directs sequence-specific Cas9 {dsDNA} cleavage. Our study reveals a family of endonucleases that use dual-{RNAs} for site-specific {DNA} cleavage and highlights the potential to exploit the system for {RNA}-programmable genome editing.},
	pages = {816--821},
	number = {6096},
	journaltitle = {Science},
	author = {Jinek, M and Chylinski, K and Fonfara, I and Hauer, M and Doudna, J A and Charpentier, E},
	date = {2012},
	pmid = {22745249},
	keywords = {Base Sequence, *{DNA} Breaks, *{DNA} Cleavage, *Inverted Repeat Sequences, Bacteriophages/*immunology, Deoxyribonucleases, Double-Stranded, Molecular Sequence Data, Nucleic Acid Conformation, Plasmids/metabolism, {RNA}/chemistry/*metabolism, Streptococcus pyogenes/*enzymology/physiology, Type {II} Site-Specific/chemistr}
}

@article{sorrells_intersecting_2015,
	title = {Intersecting transcription networks constrain gene regulatory evolution},
	volume = {523},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26153861},
	doi = {10.1038/nature14613},
	abstract = {Epistasis-the non-additive interactions between different genetic loci-constrains evolutionary pathways, blocking some and permitting others. For biological networks such as transcription circuits, the nature of these constraints and their consequences are largely unknown. Here we describe the evolutionary pathways of a transcription network that controls the response to mating pheromone in yeast. A component of this network, the transcription regulator Ste12, has evolved two different modes of binding to a set of its target genes. In one group of species, Ste12 binds to specific {DNA} binding sites, while in another lineage it occupies {DNA} indirectly, relying on a second transcription regulator to recognize {DNA}. We show, through the construction of various possible evolutionary intermediates, that evolution of the direct mode of {DNA} binding was not directly accessible to the ancestor. Instead, it was contingent on a lineage-specific change to an overlapping transcription network with a different function, the specification of cell type. These results show that analysing and predicting the evolution of cis-regulatory regions requires an understanding of their positions in overlapping networks, as this placement constrains the available evolutionary pathways.},
	pages = {361--365},
	number = {7560},
	journaltitle = {Nature},
	author = {Sorrells, T R and Booth, L N and Tuch, B B and Johnson, A D},
	date = {2015},
	pmid = {26153861}
}

@article{haerty_no_2014,
	title = {No gene in the genome makes sense except in the light of evolution},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24773316},
	doi = {10.1146/annurev-genom-090413-025621},
	abstract = {Evolutionary conservation has been an accurate predictor of functional elements across the first decade of metazoan genomics. More recently, there has been a move to define functional elements instead from biochemical annotations. Evolutionary methods are, however, more comprehensive than biochemical approaches can be and can assess quantitatively, especially for subtle effects, how biologically important–how injurious after mutation–different types of elements are. Evolutionary methods are thus critical for understanding the large fraction (up to 10\%) of the human genome that does not encode proteins and yet might convey function. These methods can also capture the ephemeral nature of much noncoding functional sequence, with large numbers of functional elements having been gained and lost rapidly along each mammalian lineage. Here, we review how different strengths of purifying selection have impacted on protein-coding and non-protein-coding loci and on transcription factor binding sites in mammalian and fruit fly genomes.},
	pages = {71--92},
	journaltitle = {Annu Rev Genomics Hum Genet},
	author = {Haerty, W and Ponting, C P},
	date = {2014},
	pmid = {24773316}
}

@article{mcdonald_adaptive_1991,
	title = {Adaptive protein evolution at the Adh locus in Drosophila},
	volume = {351},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/1904993},
	doi = {10.1038/351652a0},
	abstract = {Proteins often differ in amino-acid sequence across species. This difference has evolved by the accumulation of neutral mutations by random drift, the fixation of adaptive mutations by selection, or a mixture of the two. Here we propose a simple statistical test of the neutral protein evolution hypothesis based on a comparison of the number of amino-acid replacement substitutions to synonymous substitutions in the coding region of a locus. If the observed substitutions are neutral, the ratio of replacement to synonymous fixed differences between species should be the same as the ratio of replacement to synonymous polymorphisms within species. {DNA} sequence data on the Adh locus (encoding alcohol dehydrogenase, {EC} 1.1.1.1) in three species in the Drosophila melanogaster species subgroup do not fit this expectation; instead, there are more fixed replacement differences between species than expected. We suggest that these excess replacement substitutions result from adaptive fixation of selectively advantageous mutations.},
	pages = {652--654},
	number = {6328},
	journaltitle = {Nature},
	author = {{McDonald}, J H and Kreitman, M},
	date = {1991},
	pmid = {1904993},
	keywords = {Animals, Base Sequence, Genetic, Nucleic Acid, *Biological Evolution, Alcohol Dehydrogenase/*genetics, {DNA}/genetics, Drosophila melanogaster/enzymology/*genetics, Drosophila/enzymology/*genetics, Molecular Sequence Data, Polymorphism, Sequence Homology}
}

@article{cummins_iron_2013,
	title = {Iron sulfide ({FeS}) nanotubes using sulfurization of hematite nanowires},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23668724},
	doi = {10.1021/nl400325s},
	abstract = {We report the phase transformation of hematite (alpha-Fe2O3) single crystal nanowires to crystalline {FeS} nanotubes using sulfurization with H2S gas at relatively low temperatures. Characterization indicates that phase pure hexagonal {FeS} nanotubes were formed. Time-series sulfurization experiments suggest epitaxial growth of {FeS} as a shell layer on hematite. This is the first report of hollow, crystalline {FeS} nanotubes with {NiAs} structure and also on the Kirkendall effect in solid-gas reactions with nanowires involving sulfurization.},
	pages = {2423--2430},
	number = {6},
	journaltitle = {Nano Lett},
	author = {Cummins, D R and Russell, H B and Jasinski, J B and Menon, M and Sunkara, M K},
	date = {2013},
	pmid = {23668724}
}

@article{hung_long_2010,
	title = {Long noncoding {RNA} in genome regulation: prospects and mechanisms},
	volume = {7},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20930520},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are pervasively transcribed and critical regulators of the epigenome[1, 2]. These long, polyadenylated {RNAs} do not code for proteins, but function directly as {RNAs}, recruiting chromatin modifiers to mediate transcriptional changes in processes ranging from X-inactivation ({XIST}) to imprinting (H19)[3]. The recent discovery that {lncRNA} {HOTAIR} can link chromatin changes to cancer metastasis[4] furthers the relevance of {lncRNAs} to human disease. Here, we discuss {lncRNAs} as regulatory modules and explore the implications for disease pathogenesis. Although large-scale analyses of mammalian transcriptomes have revealed that more than 50\% of transcripts have no protein coding potential[2, 5, 6], the functions of these putative transcripts are largely unknown. A subset of these noncoding transcripts are termed long noncoding {RNAs} ({lncRNAs}), based on an arbitrary minimum length of 200 nucleotides. {LncRNAs} are roughly classified based on their position relative to protein-coding genes: intergenic (between genes), intragenic/intronic (within genes), and antisense[2]. Initial efforts to characterize these molecules demonstrated that they function in cis, regulating their immediate genomic neighbors. Examples include {AIR}, {XIST}, and Kcnq1ot (reviewed in [1, 7, 8]), which recruit chromatin modifying complexes to silence adjacent sites. The scope of {lncRNAs} in gene regulation was advanced with the finding that {lncRNA} {HOTAIR} exhibited trans regulatory capacities. {HOTAIR} is transcribed at the intersection of opposing chromatin domains in the {HOXC} locus, but targets Polycomb Repressive Complex 2 ({PRC}2) to silence 40 kilobases of {HOXD}[9], a locus involved in developmental patterning. A subsequent study revealed that {HOTAIR} is overexpressed in approximately one quarter of human breast cancers, directing {PRC}2 to approximately 800 ectopic sites in the genome, which leads to histone H3 lysine 27 trimethylation and changes in gene expression[4]. The impacts of {lncRNA}-mediated chromatin changes are noteworthy: not only did {HOTAIR} drive metastasis in a mouse model, but {HOTAIR} expression in human breast cancer was found to be an independent prognostic marker for death and metastasis[4]. The fact that {HOTAIR} drives chromatin reprogramming genome-wide suggests that long-range regulation by {lncRNAs} may be a widespread mechanism. This is supported by a study showing that {\textbackslash}textgreater 20\% of tested {lncRNAs} are bound by {PRC}2 and other chromatin modifiers[10]. Furthermore, this is an underestimate of the total {RNAs} involved in chromatin modification, as {PRC}2 target genes also transcribe smaller 50-200 nt {RNAs} that interact with {SUZ}12 to mediate gene repression[11]. These findings provoke questions regarding the initial triggers for {HOTAIR} overexpression and whether understanding of {lncRNA} mechanics may have clinical relevance.},
	pages = {582--585},
	number = {5},
	journaltitle = {{RNA} Biol},
	author = {Hung, T and Chang, H Y},
	date = {2010},
	pmid = {20930520},
	keywords = {Animals, Humans, {RNA}, *Gene Expression Regulation, Chromatin Assembly and Disassembly, Disease/genetics, Untranslated/*metabolism}
}

@article{figueroa_role_2003,
	title = {Role of {HuR} in skeletal myogenesis through coordinate regulation of muscle differentiation genes},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12832484},
	abstract = {In this report, we investigate the role of the {RNA}-binding protein {HuR} during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, {HuR} cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. {mRNAs} encoding key regulators of myogenesis-specific transcription (myogenin and {MyoD}) and cell cycle withdrawal (p21), bearing {AU}-rich regions, were found to be targets of {HuR} in a differentiation-dependent manner. Accordingly, {mRNA} half-lives were highest during differentiation, declining when differentiation was completed. Importantly, {HuR}-overexpressing C2C12 cells displayed increased target {mRNA} expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for {HuR} during skeletal myogenesis linked to {HuR}'s coordinate regulation of muscle differentiation genes.},
	pages = {4991--5004},
	number = {14},
	journaltitle = {Mol Cell Biol},
	author = {Figueroa, A and Cuadrado, A and Fan, J and Atasoy, U and Muscat, G E and Munoz-Canoves, P and Gorospe, M and Munoz, A},
	date = {2003},
	pmid = {12832484},
	keywords = {3' Untranslated Regions, Animals, Base Sequence, Mice, {RNA}, Cells, Cultured, *Antigens, *Gene Expression Regulation, Cell Differentiation/drug effects/genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/genetics, Cytoplasm/drug effects/genetics/metabolism, Developmental, Half-Life, Hu Paraneoplastic Encephalomyelitis Antigens, Inbred C57BL, Insulin/pharmacology, Messenger/metabolism, Molecular Sequence Data, Muscle, Muscle Development/*physiology, Myoblasts/physiology, {MyoD} Protein/genetics, Myogenin/genetics, Regeneration/genetics, {RNA}-Binding Proteins/*physiology, Selenium/pharmacology, Skeletal/cytology/*physiology, Surface, Transferrin/pharmacology}
}

@article{tsai_long_2010,
	title = {Long noncoding {RNA} as modular scaffold of histone modification complexes},
	volume = {329},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20616235},
	doi = {10.1126/science.1192002},
	abstract = {Long intergenic noncoding {RNAs} ({lincRNAs}) regulate chromatin states and epigenetic inheritance. Here, we show that the {lincRNA} {HOTAIR} serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of {HOTAIR} binds polycomb repressive complex 2 ({PRC}2), whereas a 3' domain of {HOTAIR} binds the {LSD}1/{CoREST}/{REST} complex. The ability to tether two distinct complexes enables {RNA}-mediated assembly of {PRC}2 and {LSD}1 and coordinates targeting of {PRC}2 and {LSD}1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that {lincRNAs} may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.},
	pages = {689--693},
	number = {5992},
	journaltitle = {Science},
	author = {Tsai, M C and Manor, O and Wan, Y and Mosammaparast, N and Wang, J K and Lan, F and Shi, Y and Segal, E and Chang, H Y},
	date = {2010},
	pmid = {20616235},
	keywords = {Genetic, Humans, Promoter Regions, {RNA}, Transcription, Binding Sites, Protein Binding, Cells, Cultured, Carrier Proteins/metabolism, Cell Line, Chromatin, Chromatin Immunoprecipitation, Chromatin/*metabolism, Co-Repressor Proteins, {DNA}-Binding Proteins, {DNA}-Binding Proteins/*metabolism, {HeLa} Cells, Histone Demethylases/*metabolism, Histones, Histones/*metabolism, Methylation, Mutation, Nerve Tissue Proteins/metabolism, Nuclear Proteins/metabolism, Nucleic Acid Conformation, Polycomb Repressive Complex 2, Polycomb-Group Proteins, Repressor Proteins/*metabolism, {RNA} Interference, Transcription Factors, Transcription Factors/*metabolism, Untranslated/chemistry/*metabolism, Nuclear Proteins, Repressor Proteins, Transcription, Genetic, Cells, Cultured, Promoter Regions, Genetic, {RNA}, Untranslated, Nerve Tissue Proteins, Carrier Proteins, Enhancer of Zeste Homolog 2 Protein, Histone Demethylases},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/JE2SG26J/Tsai et al. - 2010 - Long noncoding RNA as modular scaffold of histone .pdf:application/pdf}
}

@article{calin_ultraconserved_2007,
	title = {Ultraconserved regions encoding {ncRNAs} are altered in human leukemias and carcinomas},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17785203},
	doi = {10.1016/j.ccr.2007.07.027},
	abstract = {Noncoding {RNA} ({ncRNA}) transcripts are thought to be involved in human tumorigenesis. We report that a large fraction of genomic ultraconserved regions ({UCRs}) encode a particular set of {ncRNAs} whose expression is altered in human cancers. Genome-wide profiling revealed that {UCRs} have distinct signatures in human leukemias and carcinomas. {UCRs} are frequently located at fragile sites and genomic regions involved in cancers. We identified certain {UCRs} whose expression may be regulated by {microRNAs} abnormally expressed in human chronic lymphocytic leukemia, and we proved that the inhibition of an overexpressed {UCR} induces apoptosis in colon cancer cells. Our findings argue that {ncRNAs} and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.},
	pages = {215--229},
	number = {3},
	journaltitle = {Cancer Cell},
	author = {Calin, G A and Liu, C G and Ferracin, M and Hyslop, T and Spizzo, R and Sevignani, C and Fabbri, M and Cimmino, A and Lee, E J and Wojcik, S E and Shimizu, M and Tili, E and Rossi, S and Taccioli, C and Pichiorri, F and Liu, X and Zupo, S and Herlea, V and Gramantieri, L and Lanza, G and Alder, H and Rassenti, L and Volinia, S and Schmittgen, T D and Kipps, T J and Negrini, M and Croce, C M},
	date = {2007},
	pmid = {17785203},
	keywords = {Sequence Analysis, Base Sequence, Conserved Sequence, Humans, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Carcinoma, Carcinoma/*genetics, Cluster Analysis, Leukemia, Leukemia/*genetics, {MicroRNAs}, {MicroRNAs}/physiology, Molecular Sequence Data, Neoplastic, Oncogenes/physiology, Untranslated/*chemistry, {RNA}, Untranslated, Sequence Analysis, {RNA}, Gene Expression Regulation, Neoplastic, Oncogenes}
}

@article{managadze_vast_2013,
	title = {The vast, conserved mammalian {lincRNome}},
	volume = {9},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23468607},
	doi = {10.1371/journal.pcbi.1002917},
	abstract = {We compare the sets of experimentally validated long intergenic non-coding (linc){RNAs} from human and mouse and apply a maximum likelihood approach to estimate the total number of {lincRNA} genes as well as the size of the conserved part of the {lincRNome}. Under the assumption that the sets of experimentally validated {lincRNAs} are random samples of the {lincRNomes} of the corresponding species, we estimate the total {lincRNome} size at approximately 40,000 to 50,000 species, at least twice the number of protein-coding genes. We further estimate that the fraction of the human and mouse euchromatic genomes encoding {lincRNAs} is more than twofold greater than the fraction of protein-coding sequences. Although the sequences of most {lincRNAs} are much less strongly conserved than protein sequences, the extent of orthology between the {lincRNomes} is unexpectedly high, with 60 to 70\% of the {lincRNA} genes shared between human and mouse. The orthologous mammalian {lincRNAs} can be predicted to perform equivalent functions; accordingly, it appears likely that thousands of evolutionarily conserved functional roles of {lincRNAs} remain to be characterized.},
	pages = {e1002917},
	number = {2},
	journaltitle = {{PLoS} Comput Biol},
	author = {Managadze, D and Lobkovsky, A E and Wolf, Y I and Shabalina, S A and Rogozin, I B and Koonin, E V},
	date = {2013},
	pmid = {23468607},
	keywords = {Genomics, Animals, Genetic, Humans, Mice, {RNA}, Long Noncoding/*genetics, *Genome, Databases, *Genome Size}
}

@article{lu_inhibition_2011,
	title = {Inhibition of cyclin-dependent kinase phosphorylation of {FOXO}1 and prostate cancer cell growth by a peptide derived from {FOXO}1},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21969818},
	abstract = {Increasing evidence suggests that {FOXO}1 possesses a tumor suppressor function. Inactivation of {FOXO}1 has been documented in many types of human cancer, and restoring the activity of {FOXO}1 holds promise for cancer treatment. In this study, we identified a {FOXO}1-derived peptide termed {FO}1-6nls that inhibits cyclin-dependent kinases 1 and 2 ({CDK}1/2)-mediated phosphorylation of {FOXO}1 at the serine 249 residue in vitro and in vivo. Overexpression of {FO}1-6nls in prostate cancer ({PCa}) cells not only blocked {CDK}1-induced cytoplasmic localization of {FOXO}1 but also augmented {FOXO}1's transcriptional activity. This effect of {FO}1-6nls requires its binding to {CDK}1 and {CDK}2. Moreover, the ectopic expression of {FO}1-6nls inhibited the growth of {PTEN}-positive {DU}145 {PCa} cells. Importantly, the growth-inhibitory function of {FO}1-6nls is dependent on {FOXO}1. Finally, the ectopic expression of {FO}1-6nls overcame {CDK}1-mediated inhibition of {FOXO}1-induced apoptosis of {PCa} cells. These results indicate that the {FOXO}1-derived peptide {FO}1-6nls can restore {FOXO}1's tumor suppressor function by specifically opposing {CDK}1/2-mediated phosphorylation and inhibition of {FOXO}1 and hence may have a therapeutic potential for the treatment of {PCa}.},
	pages = {854--863},
	number = {9},
	journaltitle = {Neoplasia},
	author = {Lu, H and Liu, P and Pan, Y and Huang, H},
	date = {2011},
	pmid = {21969818},
	keywords = {Genetic, Humans, Transcription, {CDC}2 Protein Kinase/*metabolism, Cell Line, Cell Proliferation, Cyclin-Dependent Kinase 2/antagonists \& inhibitors, Forkhead Transcription Factors/chemistry/*metaboli, Male, Peptide Fragments/genetics/*metabolism, Phosphorylation, Prostatic Neoplasms/*metabolism/*pathology, Signal Transduction, Tumor}
}

@article{villa_identification_2000,
	title = {Identification of a novel element required for processing of intron-encoded box C/D small nucleolar {RNAs} in Saccharomyces cerevisiae},
	volume = {20},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10648617},
	abstract = {Processing of intron-encoded box C/D small nucleolar {RNAs} ({snoRNAs}) in metazoans through both the splicing-dependent and -independent pathways requires the conserved core motif formed by boxes C and D and the adjoining 5'-3'-terminal stem. By comparative analysis, we found that five out of six intron-encoded box C/D {snoRNAs} in yeast do not possess a canonical terminal stem. Instead, complementary regions within the flanking host intron sequences have been identified in all these cases. Here we show that these sequences are essential for processing of U18 and {snR}38 {snoRNAs} and that they compensate for the lack of a canonical terminal stem. We also show that the Rnt1p endonuclease, previously shown to be required for the processing of many {snoRNAs} encoded by monocistronic or polycistronic transcriptional units, is not required for U18 processing. Our results suggest a role of the complementary sequences in the early recognition of intronic {snoRNA} substrates and point out the importance of base pairing in favoring the communication between boxes C and D at the level of pre-{snoRNA} molecules for efficient assembly with {snoRNP}-specific factors.},
	pages = {1311--1320},
	number = {4},
	journaltitle = {Mol Cell Biol},
	author = {Villa, T and Ceradini, F and Bozzoni, I},
	date = {2000},
	pmid = {10648617},
	keywords = {Animals, Base Sequence, {RNA}, {RNA} Splicing, Introns, *Saccharomyces cerevisiae Proteins, Biological, {DNA} Primers/genetics, Endoribonucleases/metabolism, Exoribonucleases/antagonists \& inhibitors/metaboli, Fungal/chemistry/*genetics/*metabolism, Genetic Complementation Test, Models, Molecular Sequence Data, Nucleic Acid Conformation, Post-Transcriptional, Ribonuclease {III}, {RNA} Processing, Saccharomyces cerevisiae/*genetics/*metabolism, Small Nucleolar/chemistry/*genetics/*metaboli}
}

@article{murray_studies_1967,
	title = {Studies on composition and leakage of proteins and esterases of normal rat liver and Morris Hepatoma 5123 t.c},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/4289509},
	pages = {403--411},
	number = {2},
	journaltitle = {Cancer Res},
	author = {Murray, R K and Kalant, H and Guttman, M and Morris, H P},
	date = {1967},
	pmid = {4289509},
	keywords = {Animals, Carcinoma, Edetic Acid/*pharmacology, Electrophoresis, Esterases/analysis/blood, Experimental, Hepatocellular/*metabolism, Liver Neoplasms, Liver/*drug effects/*enzymology/*metabolism, Neoplasm Proteins/metabolism, Neoplasms, Proteins/*metabolism, Rats}
}

@article{mazan-mamczarz_rna-binding_2003,
	title = {{RNA}-binding protein {HuR} enhances p53 translation in response to ultraviolet light irradiation},
	volume = {100},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12821781},
	doi = {10.1073/pnas.1432104100},
	abstract = {Exposure to short-wavelength {UV} light ({UVC}) strongly induces p53 expression. In human {RKO} colorectal carcinoma cells, this increase was not due to elevated p53 {mRNA} abundance, cytoplasmic export of p53 {mRNA}, or {UVC}-triggered stabilization of the p53 protein. Instead, p53 translation was potently enhanced after {UVC} irradiation. The 3' {UTR} of p53 was found to be a target of the {RNA}-binding protein {HuR} in a {UVC}-dependent manner in vitro and in vivo. {HuR}-overexpressing {RKO} cells displayed elevated p53 levels, whereas cells expressing reduced {HuR} showed markedly diminished p53 abundance and p53 translation. Our results demonstrate a role for {HuR} in binding to the p53 {mRNA} and enhancing its translation.},
	pages = {8354--8359},
	number = {14},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Mazan-Mamczarz, K and Galban, S and Lopez de Silanes, I and Martindale, J L and Atasoy, U and Keene, J D and Gorospe, M},
	date = {2003},
	pmid = {12821781},
	keywords = {{DNA}, Humans, {RNA}, Gene Expression Regulation, Protein Binding, Cultured, *Antigens, *Ultraviolet Rays, 3' Untranslated Regions/*genetics, Biotinylation, Carcinoma/pathology, Colorectal Neoplasms/pathology, Complementary/genetics, Electrophoretic Mobility Shift Assay, Genes, Hu Paraneoplastic Encephalomyelitis Antigens, Messenger/genetics/*metabolism, Neoplasm Proteins/biosynthesis/genetics/physiology, Neoplasm/genetics/metabolism, Neoplastic/radiation e, p53, Precipitin Tests, Protein Biosynthesis/*radiation effects, Protein Interaction Mapping, {RNA}-Binding Proteins/physiology, Small Interfering/metabolism, Surface, Transfection, Tumor Cells, Tumor Suppressor Protein p53/*biosynthesis}
}

@article{frenkel-morgenstern_chimeras_2012,
	title = {Chimeras taking shape: potential functions of proteins encoded by chimeric {RNA} transcripts},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22588898},
	doi = {10.1101/gr.130062.111},
	abstract = {Chimeric {RNAs} comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the {ESTs} isolated from several organisms and using high throughput {RNA} sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput {RNA} sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric {RNAs}. We confirmed the expression of 175 chimeric {RNAs} in 16 human tissues, with an abundance varying from 0.06 to 17 {RPKM} (Reads Per Kilobase per Million mapped reads). We show that these chimeric {RNAs} are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric {RNAs}, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric {RNAs} are translated into potentially functional proteins in humans.},
	pages = {1231--1242},
	number = {7},
	journaltitle = {Genome Res},
	author = {Frenkel-Morgenstern, M and Lacroix, V and Ezkurdia, I and Levin, Y and Gabashvili, A and Prilusky, J and Del Pozo, A and Tress, M and Johnson, R and Guigo, R and Valencia, A},
	date = {2012},
	pmid = {22588898},
	keywords = {Human, Sequence Analysis, Humans, {RNA}, Gene Expression Regulation, *Genome, Exons, Organ Specificity, Databases, Nucleic Acid, *Protein Biosynthesis, Amino Acid Sequence, Cell Membrane/genetics/metabolism, High-Throughput Nucleotide Sequencing, Mass Spectrometry/methods, Messenger/genetics/metabolism, Molecular Sequence Annotation, Molecular Sequence Data, Mutant Chimeric Proteins/*genetics/metabolism, Protein Sorting Signals, Protein Structure, Proteomics/methods, {RNA}/methods, Secondary, Structure-Activity Relationship, Tertiary}
}

@article{xu_top3beta_2013,
	title = {Top3beta is an {RNA} topoisomerase that works with fragile X syndrome protein to promote synapse formation},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23912945},
	doi = {10.1038/nn.3479},
	abstract = {Topoisomerases are crucial for solving {DNA} topological problems, but they have not been linked to {RNA} metabolism. Here we show that human topoisomerase 3beta (Top3beta) is an {RNA} topoisomerase that biochemically and genetically interacts with {FMRP}, a protein that is deficient in fragile X syndrome and is known to regulate the translation of {mRNAs} that are important for neuronal function, abnormalities of which are linked to autism. Notably, the {FMRP}-Top3beta interaction is abolished by a disease-associated mutation of {FMRP}, suggesting that Top3beta may contribute to the pathogenesis of mental disorders. Top3beta binds multiple {mRNAs} encoded by genes with neuronal functions linked to schizophrenia and autism. Expression of one such gene, that encoding protein tyrosine kinase 2 (ptk2, also known as focal adhesion kinase or {FAK}), is reduced in the neuromuscular junctions of Top3beta mutant flies. Synapse formation is defective in Top3beta mutant flies and mice, as well as in {FMRP} mutant flies and mice. Our findings suggest that Top3beta acts as an {RNA} topoisomerase and works with {FMRP} to promote the expression of {mRNAs} that are crucial for neurodevelopment and mental health.},
	pages = {1238--1247},
	number = {9},
	journaltitle = {Nat Neurosci},
	author = {Xu, D and Shen, W and Guo, R and Xue, Y and Peng, W and Sima, J and Yang, J and Sharov, A and Srikantan, S and Fox 3rd, D and Qian, Y and Martindale, J L and Piao, Y and Machamer, J and Joshi, S R and Mohanty, S and Shaw, A C and Lloyd, T E and Brown, G W and Ko, M S and Gorospe, M and Zou, S and Wang, W},
	date = {2013},
	pmid = {23912945},
	keywords = {Animals, Humans, Mice, Cells, Cultured, Chickens, {DNA} Topoisomerases, Drosophila, Drosophila Proteins/genetics, Embryo, Eye/cytology/metabolism, Fragile X Mental Retardation Protein/genetics/*met, Gene Expression Regulation/genetics, Genetically Modified, Inbred C57BL, Mammalian, Nerve Tissue Proteins/metabolism, Neurogenesis/genetics, Neuromuscular Junction/*genetics, Neurons/physiology, {RNA}-Binding Proteins/metabolism, Transfection, Type I/deficiency/genetics/*me}
}

@article{raval_real-time_2005,
	title = {Real-time magnetic resonance imaging-guided stenting of aortic coarctation with commercially available catheter devices in Swine},
	volume = {112},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16043639},
	doi = {10.1161/CIRCULATIONAHA.105.542647},
	abstract = {{BACKGROUND}: Real-time {MR} imaging ({rtMRI}) is now technically capable of guiding catheter-based cardiovascular interventions. Compared with x-ray, {rtMRI} offers superior tissue imaging in any orientation without ionizing radiation. Translation to clinical trials has awaited the availability of clinical-grade catheter devices that are both {MRI} visible and safe. We report a preclinical safety and feasibility study of {rtMRI}-guided stenting in a porcine model of aortic coarctation using only commercially available catheter devices. {METHOD} {AND} {RESULTS}: Coarctation stenting was performed wholly under {rtMRI} guidance in 13 swine. {rtMRI} permitted procedure planning, device tracking, and accurate stent deployment. "Active" guidewires, incorporating {MRI} antennas, improved device visualization compared with unmodified "passive" nitinol guidewires and shortened procedure time (26+/-11 versus 106+/-42 minutes; P=0.008). Follow-up catheterization and necropsy showed accurate stent deployment, durable gradient reduction, and appropriate neointimal formation. {MRI} immediately identified aortic rupture when oversized devices were tested. {CONCLUSIONS}: This experience demonstrates preclinical safety and feasibility of {rtMRI}-guided aortic coarctation stenting using commercially available catheter devices. Patients may benefit from {rtMRI} in the future because of combined device and tissue imaging, freedom from ionizing radiation, and the ability to identify serious complications promptly.},
	pages = {699--706},
	number = {5},
	journaltitle = {Circulation},
	author = {Raval, A N and Telep, J D and Guttman, M A and Ozturk, C and Jones, M and Thompson, R B and Wright, V J and Schenke, W H and {DeSilva}, R and Aviles, R J and Raman, V K and Slack, M C and Lederman, R J},
	date = {2005},
	pmid = {16043639},
	keywords = {Animals, *Stents, Animal, Aortic Coarctation/radiography/*surgery, Catheterization, Computer Systems, Equipment Design, Magnetic Resonance Imaging/*methods, Models, Swine}
}

@article{sunke_vinylic_2013,
	title = {Vinylic amino group activation: a new and general strategy leading to functionalized fused heteroaromatics},
	volume = {49},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23525274},
	doi = {10.1039/c3cc41337c},
	abstract = {A conceptually new and general strategy has been developed for the construction of a benzimidazole or a benzoxazole ring fused with isoquinolinone affording a diverse and unique class of small molecules as potential and novel inhibitors of {PDE}4.},
	pages = {3570--3572},
	number = {34},
	journaltitle = {Chem Commun (Camb)},
	author = {Sunke, R and Adepu, R and Kapavarapu, R and Chintala, S and Meda, C L and Parsa, K V and Pal, M},
	date = {2013},
	pmid = {23525274},
	keywords = {Benzimidazoles/*chemistry, Benzoxazoles/*chemistry, Cyclization, Ion Exchange Resins/chemistry, Isoquinolines/*chemistry, Phosphodiesterase 4 Inhibitors/*chemistry, Styrenes/chemistry}
}

@article{jagadeeswaran_cloning_2013,
	title = {Cloning of small {RNAs} for the discovery of novel {microRNAs} in plants},
	volume = {956},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23135848},
	doi = {10.1007/978-1-62703-194-3_9},
	abstract = {Endogenous small {RNAs} can be grouped into several distinct classes of 21-nt-long {microRNAs} ({miRNAs}), short interfering {RNAs} ({siRNAs}), trans-acting {siRNAs} ({tasiRNAs}), and 24-nt long heterochromatic {siRNAs}. {miRNAs} are increasingly being recognized as significant effectors of gene regulation in a wide range of organisms. These molecules are typically approximately 21-nt long and are amenable for cloning by streamlined protocols. Here we detail the methodology for cloning small {RNAs} in rice to identify novel {miRNAs} and other important small {RNAs}. Briefly, small {RNA} molecules are size fractionated, attached to adaptors, and subsequently converted into {cDNA} and {PCR} amplified. Current high-throughput sequencing technologies allow sequencing of the {PCR} products directly.},
	pages = {109--118},
	journaltitle = {Methods Mol Biol},
	author = {Jagadeeswaran, G and Sunkar, R},
	date = {2013},
	pmid = {23135848},
	keywords = {{RNA}, Cloning, {MicroRNAs}/*genetics, Molecular/*methods, Plant/genetics/isolation \& purification, Plants/*genetics, Quality Control, Small Untranslated/*genetics}
}

@article{li_global_2013,
	title = {Global identification of small {RNA} targets in plants by sequencing sliced ends of messenger {RNAs}},
	volume = {956},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23135849},
	doi = {10.1007/978-1-62703-194-3_10},
	abstract = {Small {RNAs} ({microRNAs} and other classes of endogenous small interfering {RNAs}) play important roles in a wide variety of biological processes. However, integration of small {RNAs} in diverse biological networks relies on the confirmation of their {RNA} targets. In plants, {miRNAs} negatively regulate {mRNA} targets by guiding a cleavage in the complementary site that leaves a 3' polyadenylated {RNA} possessing monophosphate at its 5' end. This chapter describes a detailed step-by-step protocol for cloning such sliced 3' products in order to identify small {RNA} targets. Using this protocol, we have identified more than 150 small {RNA} targets in rice; some are conserved and others are non-conserved targets for rice small {RNAs}.},
	pages = {119--129},
	journaltitle = {Methods Mol Biol},
	author = {Li, Y F and Sunkar, R},
	date = {2013},
	pmid = {23135849},
	keywords = {Sequence Analysis, {RNA}, Cloning, {DNA}/methods, Gene Library, Messenger/*genetics/isolation \& purification, Molecular/*methods, Plant/*genetics/isolation \& purification, Plants/*genetics, Polymerase Chain Reaction/methods, Quality Control, Small Untranslated/*genetics/isolation \& puri}
}

@article{jiang_differential_2013,
	title = {Differential regulation of human cathelicidin {LL}-37 by free fatty acids and their analogs},
	volume = {50},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24140860},
	doi = {10.1016/j.peptides.2013.10.008},
	abstract = {{LL}-37 is the single cathelicidin host defense peptide in humans with direct antimicrobial and immunomodulatory activities. Specific regulation of {LL}-37 synthesis has emerged as a novel non-antibiotic approach to disease control and prevention. Short-chain fatty acids, and butyrate in particular, were found recently to be strong inducers of {LL}-37 gene expression without causing inflammation. Here, we further evaluated the {LL}-37-inducing efficiency of a broad range of saturated free fatty acids and their derivatives in human {HT}-29 colonic epithelial cells and U-937 monocytic cells by real-time {RT}-{PCR}. Surprisingly, we revealed that valerate, hexanoate, and heptanoate with 5-7 carbons are more potent than 4-carbon butyrate in promoting {LL}-37 gene expression in both cell types. Free fatty acids with longer than 7 or shorter than 4 carbons showed only a marginal effect on {LL}-37 expression. Studies with a series of fatty acid derivatives with modifications in the aliphatic chain or carboxylic acid group yielded several analogs such as benzyl butyrate, trans-cinnamyl butyrate, glyceryl tributyrate, and phenethyl butyrate with a comparable {LL}-37-inducing activity to sodium butyrate. On the other hand, although reactive, the anhydride derivatives of short- and medium-chain fatty acids are as potent as their corresponding free acid forms in {LL}-37 induction. Thus, these newly identified free fatty acids and their analogs with a strong capacity to augment {LL}-37 synthesis may hold promise as immune boosting dietary supplements for antimicrobial therapy.},
	pages = {129--138},
	journaltitle = {Peptides},
	author = {Jiang, W and Sunkara, L T and Zeng, X and Deng, Z and Myers, S M and Zhang, G},
	date = {2013},
	pmid = {24140860}
}

@article{galban_rna-binding_2008,
	title = {{RNA}-binding proteins {HuR} and {PTB} promote the translation of hypoxia-inducible factor 1alpha},
	volume = {28},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17967866},
	doi = {10.1128/MCB.00973-07},
	abstract = {The levels of hypoxia-inducible factor 1alpha ({HIF}-1alpha) are tightly controlled. Here, we investigated the posttranscriptional regulation of {HIF}-1alpha expression in human cervical carcinoma {HeLa} cells responding to the hypoxia mimetic {CoCl}(2). Undetectable in untreated cells, {HIF}-1alpha levels increased dramatically in {CoCl}(2)-treated cells, while {HIF}-1alpha {mRNA} levels were unchanged. {HIF}-1alpha translation was potently elevated by {CoCl}(2) treatment, as determined by de novo translation analysis and by monitoring the polysomal association of {HIF}-1alpha {mRNA}. An internal ribosome entry site in the {HIF}-1alpha 5' untranslated region ({UTR}) was found to enhance translation constitutively, but it did not further induce translation in response to {CoCl}(2) treatment. Instead, we postulated that {RNA}-binding proteins {HuR} and {PTB}, previously shown to bind {HIF}-1alpha {mRNA}, participated in its translational upregulation after {CoCl}(2) treatment. Indeed, both {RNA}-binding proteins were found to bind {HIF}-1alpha {mRNA} in a {CoCl}(2)-inducible manner as assessed by immunoprecipitation of endogenous ribonucleoprotein complexes. Using a chimeric reporter, polypyrimidine tract-binding protein ({PTB}) was found to bind the {HIF}-1alpha 3'{UTR}, while {HuR} associated principally with the 5'{UTR}. Lowering {PTB} expression or {HuR} expression using {RNA} interference reduced {HIF}-1alpha translation and expression levels but not {HIF}-1alpha {mRNA} abundance. Conversely, {HIF}-1alpha expression and translation in response to {CoCl}(2) were markedly elevated after {HuR} overexpression. We propose that {HuR} and {PTB} jointly upregulate {HIF}-1alpha translation in response to {CoCl}(2).},
	pages = {93--107},
	number = {1},
	journaltitle = {Mol Cell Biol},
	author = {Galban, S and Kuwano, Y and Pullmann Jr., R and Martindale, J L and Kim, H H and Lal, A and Abdelmohsen, K and Yang, X and Dang, Y and Liu, J O and Lewis, S M and Holcik, M and Gorospe, M},
	date = {2008},
	pmid = {17967866},
	keywords = {Humans, {RNA}, Transcription, Messenger/genetics, Protein Binding, Genetic/genetics, alpha Subunit/genetics, Antigens, Cell Hypoxia/drug effects, Cell Line, Cobalt/pharmacology, Gene Expression Regulation/drug effects, Hu Paraneoplastic Encephalomyelitis Antigens, Hypoxia-Inducible Factor 1, Polypyrimidine Tract-Binding Protein/genetics/*met, Protein Biosynthesis/drug effects, Protein Transport, Ribosomes/genetics/metabolism, {RNA} Interference, {RNA}-Binding Proteins/genetics/*metabolism, Surface/genetics/*metabolism, Tumor}
}

@article{paulsen_detection_2008,
	title = {Detection of Huntington's disease decades before diagnosis: the Predict-{HD} study},
	volume = {79},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18096682},
	doi = {10.1136/jnnp.2007.128728},
	abstract = {{OBJECTIVE}: The objective of the Predict-{HD} study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington's disease ({HD}), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of {HD} relative to the time of eventual diagnosis. {METHODS}: We studied 438 participants who were positive for the {HD} gene mutation, but did not yet meet the diagnostic criteria for {HD} and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on {CAG} repeat length and current age) as the predictor. {RESULTS}: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. {CONCLUSIONS}: These findings from the Predict-{HD} study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive {HD} trials.},
	pages = {874--880},
	number = {8},
	journaltitle = {J Neurol Neurosurg Psychiatry},
	author = {Paulsen, J S and Langbehn, D R and Stout, J C and Aylward, E and Ross, C A and Nance, M and Guttman, M and Johnson, S and {MacDonald}, M and Beglinger, L J and Duff, K and Kayson, E and Biglan, K and Shoulson, I and Oakes, D and Hayden, M},
	date = {2008},
	pmid = {18096682},
	keywords = {Human, Humans, *Genetic Testing, *Magnetic Resonance Imaging, *Neurologic Examination, *Neuropsychological Tests, Adult, Aged, Attention, Caudate Nucleus/pathology, Chromosomes, Early Diagnosis, Female, Huntington Disease/*diagnosis/genetics, Longitudinal Studies, Male, Mental Recall, Middle Aged, Nerve Tissue Proteins/*genetics, Nuclear Proteins/*genetics, Olfaction Disorders/diagnosis/genetics, Pair 4/genetics, Predictive Value of Tests, Probability, Putamen/pathology, Reaction Time, Trinucleotide Repeats, Verbal Learning}
}

@article{pollard_rna_2006,
	title = {An {RNA} gene expressed during cortical development evolved rapidly in humans},
	volume = {443},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16915236},
	doi = {10.1038/nature05113},
	abstract = {The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', {HAR}1, is part of a novel {RNA} gene ({HAR}1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. {HAR}1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. {HAR}1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.},
	pages = {167--172},
	number = {7108},
	journaltitle = {Nature},
	author = {Pollard, K S and Salama, S R and Lambert, N and Lambot, M A and Coppens, S and Pedersen, J S and Katzman, S and King, B and Onodera, C and Siepel, A and Kern, A D and Dehay, C and Igel, H and Ares Jr., M and Vanderhaeghen, P and Haussler, D},
	date = {2006},
	pmid = {16915236},
	keywords = {Animals, Base Sequence, Humans, {RNA}, Gene Expression Profiling, Organ Specificity, *Evolution, *Gene Expression Regulation, Aging/genetics, Cell Adhesion Molecules, Cerebral Cortex/anatomy \& histology/*embryology/*m, Developmental, Extracellular Matrix Proteins/genetics, Macaca, Macaca/genetics, Molecular, Molecular Sequence Data, Mutation, Mutation/genetics, Neocortex/anatomy \& histology/embryology/metabolis, Nerve Tissue Proteins/genetics, Neuronal/genetics, Nucleic Acid Conformation, {RNA} Stability, Serine Endopeptidases/genetics, Time Factors, Untranslated/chemistry/*genetics/metabolism, Evolution, Molecular, {RNA}, Untranslated, Nerve Tissue Proteins, Gene Expression Regulation, Developmental, Aging, Cell Adhesion Molecules, Neuronal, Cerebral Cortex, Extracellular Matrix Proteins, Neocortex, Serine Endopeptidases}
}

@article{khazina_trimeric_2011,
	title = {Trimeric structure and flexibility of the L1ORF1 protein in human L1 retrotransposition},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21822284},
	doi = {10.1038/nsmb.2097},
	abstract = {The {LINE}-1 (L1) retrotransposon emerges as a major source of human interindividual genetic variation, with important implications for evolution and disease. L1 retrotransposition is poorly understood at the molecular level, and the mechanistic details and evolutionary origin of the L1-encoded L1ORF1 protein (L1ORF1p) are particularly obscure. Here three crystal structures of trimeric L1ORF1p and {NMR} solution structures of individual domains reveal a sophisticated and highly structured, yet remarkably flexible, {RNA}-packaging protein. It trimerizes via an N-terminal, ion-containing coiled coil that serves as scaffold for the flexible attachment of the central {RRM} and the C-terminal {CTD} domains. The structures explain the specificity for single-stranded {RNA} substrates, and a mutational analysis indicates that the precise control of domain flexibility is critical for retrotransposition. Although the evolutionary origin of L1ORF1p remains unclear, our data reveal previously undetected structural and functional parallels to viral proteins.},
	pages = {1006--1014},
	number = {9},
	journaltitle = {Nat Struct Mol Biol},
	author = {Khazina, E and Truffault, V and Buttner, R and Schmidt, S and Coles, M and Weichenrieder, O},
	date = {2011},
	pmid = {21822284},
	keywords = {Humans, *Long Interspersed Nucleotide Elements, Biomolecular, Crystallography, Models, Molecular, Nuclear Magnetic Resonance, Protein Structure, Proteins/*chemistry, Substrate Specificity, Tertiary, X-Ray}
}

@article{letunic_smart:_2015,
	title = {{SMART}: recent updates, new developments and status in 2015},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25300481},
	doi = {10.1093/nar/gku949},
	abstract = {{SMART} (Simple Modular Architecture Research Tool) is a web resource (http://smart.embl.de/) providing simple identification and extensive annotation of protein domains and the exploration of protein domain architectures. In the current version, {SMART} contains manually curated models for more than 1200 protein domains, with approximately 200 new models since our last update article. The underlying protein databases were synchronized with {UniProt}, Ensembl and {STRING}, bringing the total number of annotated domains and other protein features above 100 million. {SMART}'s 'Genomic' mode, which annotates proteins from completely sequenced genomes was greatly expanded and now includes 2031 species, compared to 1133 in the previous release. {SMART} analysis results pages have been completely redesigned and include links to several new information sources. A new, vector-based display engine has been developed for protein schematics in {SMART}, which can also be exported as high-resolution bitmap images for easy inclusion into other documents. Taxonomic tree displays in {SMART} have been significantly improved, and can be easily navigated using the integrated search engine.},
	pages = {D257--60},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Letunic, I and Doerks, T and Bork, P},
	date = {2015},
	pmid = {25300481},
	keywords = {*Databases, *Protein Structure, Data Curation, Protein, Protein Interaction Mapping, Tertiary/genetics}
}

@article{koszelak-rosenblum_his-311_2008,
	title = {His-311 and Arg-559 are key residues involved in fatty acid oxygenation in pathogen-inducible oxygenase},
	volume = {283},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18596034},
	doi = {10.1074/jbc.M804358200},
	abstract = {Pathogen-inducible oxygenase ({PIOX}) oxygenates fatty acids into 2R-hydroperoxides. {PIOX} belongs to the fatty acid alpha-dioxygenase family, which exhibits homology to cyclooxygenase enzymes ({COX}-1 and {COX}-2). Although these enzymes share common catalytic features, including the use of a tyrosine radical during catalysis, little is known about other residues involved in the dioxygenase reaction of {PIOX}. We generated a model of linoleic acid ({LA}) bound to {PIOX} based on computational sequence alignment and secondary structure predictions with {COX}-1 and experimental observations that governed the placement of carbon-2 of {LA} below the catalytic Tyr-379. Examination of the model identified His-311, Arg-558, and Arg-559 as potential molecular determinants of the dioxygenase reaction. Substitutions at His-311 and Arg-559 resulted in mutant constructs that retained virtually no oxygenase activity, whereas substitutions of Arg-558 caused only moderate decreases in activity. Arg-559 mutant constructs exhibited increases of greater than 140-fold in Km, whereas no substantial change in Km was observed for His-311 or Arg-558 mutant constructs. Thermal shift assays used to measure ligand binding affinity show that the binding of {LA} is significantly reduced in a Y379F/R559A mutant construct compared with that observed for Y379F/R558A construct. Although Oryza sativa {PIOX} exhibited oxygenase activity against a variety of 14-20-carbon fatty acids, the enzyme did not oxygenate substrates containing modifications at the carboxylate, carbon-1, or carbon-2. Taken together, these data suggest that Arg-559 is required for high affinity binding of substrates to {PIOX}, whereas His-311 is involved in optimally aligning carbon-2 below Tyr-379 for catalysis.},
	pages = {24962--24971},
	number = {36},
	journaltitle = {J Biol Chem},
	author = {Koszelak-Rosenblum, M and Krol, A C and Simmons, D M and Goulah, C C and Wroblewski, L and Malkowski, M G},
	date = {2008},
	pmid = {18596034},
	keywords = {*Models, Amino Acid, Amino Acid Substitution, Binding Sites/physiology, Catalytic Domain/physiology, Cyclooxygenase 1/chemistry/genetics/metabolism, Cyclooxygenase 2/chemistry/genetics/metabolism, Dioxygenases/*chemistry/genetics/metabolism, Ligands, Linoleic Acid/*chemistry/genetics/metabolism, Missense, Molecular, Mutation, Oryza sativa/*enzymology, Oxidation-Reduction, Plant Proteins/*chemistry/genetics/metabolism, Protein Structure, Secondary/physiology, Sequence Homology, Substrate Specificity/physiology}
}

@article{chen_transcriptional_2014,
	title = {Transcriptional diversity during lineage commitment of human blood progenitors},
	volume = {345},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25258084},
	doi = {10.1126/science.1251033},
	abstract = {Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced {RNA} from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B ({NFIB}) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.},
	pages = {1251033},
	number = {6204},
	journaltitle = {Science},
	author = {Chen, L and Kostadima, M and Martens, J H and Canu, G and Garcia, S P and Turro, E and Downes, K and Macaulay, I C and Bielczyk-Maczynska, E and Coe, S and Farrow, S and Poudel, P and Burden, F and Jansen, S B and Astle, W J and Attwood, A and Bariana, T and de Bono, B and Breschi, A and Chambers, J C and Choudry, F A and Clarke, L and Coupland, P and van der Ent, M and Erber, W N and Jansen, J H and Favier, R and Fenech, M E and Foad, N and Freson, K and van Geet, C and Gomez, K and Guigo, R and Hampshire, D and Kelly, A M and Kerstens, H H and Kooner, J S and Laffan, M and Lentaigne, C and Labalette, C and Martin, T and Meacham, S and Mumford, A and Nurnberg, S and Palumbo, E and van der Reijden, B A and Richardson, D and Sammut, S J and Slodkowicz, G and Tamuri, A U and Vasquez, L and Voss, K and Watt, S and Westbury, S and Flicek, P and Loos, R and Goldman, N and Bertone, P and Read, R J and Richardson, S and Cvejic, A and Soranzo, N and Ouwehand, W H and Stunnenberg, H G and Frontini, M and Rendon, A},
	date = {2014},
	pmid = {25258084},
	keywords = {Transcriptome, Humans, *Alternative Splicing, Cell Lineage/*genetics, Genetic Variation, Hematopoiesis/*genetics, Hematopoietic Stem Cells/*cytology/metabolism, {NFI} Transcription Factors/genetics/metabolism, {RNA}-Binding Proteins/metabolism, Thrombopoiesis/genetics}
}

@article{lopez_de_silanes_identification_2005,
	title = {Identification and functional outcome of {mRNAs} associated with {RNA}-binding protein {TIA}-1},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16227602},
	doi = {10.1128/MCB.25.21.9520-9531.2005},
	abstract = {The {RNA}-binding protein {TIA}-1 (T-cell intracellular antigen 1) functions as a posttranscriptional regulator of gene expression and aggregates to form stress granules following cellular damage. {TIA}-1 was previously shown to bind {mRNAs} encoding tumor necrosis factor alpha ({TNF}-alpha) and cyclooxygenase 2 ({COX}-2), but {TIA}-1 target {mRNAs} have not been systematically identified. Here, immunoprecipitation ({IP}) of {TIA}-1-{RNA} complexes, followed by microarray-based identification and computational analysis of bound transcripts, was used to elucidate a common motif present among {TIA}-1 target {mRNAs}. The predicted {TIA}-1 motif was a U-rich, 30- to 37-nucleotide (nt)-long bipartite element forming loops of variable size and a bent stem. The {TIA}-1 motif was found in the {TNF}-alpha and {COX}-2 {mRNAs} and in 3,019 additional {UniGene} transcripts (approximately 3\% of the {UniGene} database), localizing preferentially to the 3' untranslated region. The interactions between {TIA}-1 and target transcripts were validated by {IP} of endogenous {mRNAs}, followed by reverse transcription and {PCR}-mediated detection, and by pulldown of biotinylated {RNAs}, followed by Western blotting. Further studies using {RNA} interference revealed that {TIA}-1 repressed the translation of bound {mRNAs}. In summary, we report a signature motif present in {mRNAs} that associate with {TIA}-1 and provide support to the notion that {TIA}-1 represses the translation of target transcripts.},
	pages = {9520--9531},
	number = {21},
	journaltitle = {Mol Cell Biol},
	author = {Lopez de Silanes, I and Galban, S and Martindale, J L and Yang, X and Mazan-Mamczarz, K and Indig, F E and Falco, G and Zhan, M and Gorospe, M},
	date = {2005},
	pmid = {16227602},
	keywords = {Base Sequence, Humans, {RNA}, Computational Biology, Oligonucleotide Array Sequence Analysis, Cell Line, Cyclooxygenase 2/genetics, Immunoprecipitation, Messenger/*genetics/metabolism, {RNA}-Binding Proteins/*genetics/metabolism, Small Interfering/metabolism, Tumor, Tumor Necrosis Factor-alpha/genetics}
}

@article{yepes_clustering_2015,
	title = {Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26355846},
	doi = {10.1371/journal.pone.0137132},
	abstract = {Although the identification of inherent structure in chronic lymphocytic leukemia ({CLL}) gene expression data using class discovery approaches has not been extensively explored, the natural clustering of patient samples can reveal molecular subdivisions that have biological and clinical implications. To explore this, we preprocessed raw gene expression data from two published studies, combined the data to increase the statistical power, and performed unsupervised clustering analysis. The clustering analysis was replicated in 4 independent cohorts. To assess the biological significance of the resultant clusters, we evaluated their prognostic value and identified cluster-specific markers. The clustering analysis revealed two robust and stable subgroups of {CLL} patients in the pooled dataset. The subgroups were confirmed by different methodological approaches (non-negative matrix factorization {NMF} clustering and hierarchical clustering) and validated in different cohorts. The subdivisions were related with differential clinical outcomes and markers associated with the microenvironment and the {MAPK} and {BCR} signaling pathways. It was also found that the cluster markers were independent of the immunoglobulin heavy chain variable ({IGVH}) genes mutational status. These findings suggest that the microenvironment can influence the clinical behavior of {CLL}, contributing to prognostic differences. The workflow followed here provides a new perspective on differences in prognosis and highlights new markers that should be explored in this context.},
	pages = {e0137132},
	number = {9},
	journaltitle = {{PLoS} One},
	author = {Yepes, S and Torres, M M and Andrade, R E},
	date = {2015},
	pmid = {26355846}
}

@article{pelczar_host_1998,
	title = {The host gene for intronic U17 small nucleolar {RNAs} in mammals has no protein-coding potential and is a member of the 5'-terminal oligopyrimidine gene family},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9671460},
	abstract = {Intron-encoded U17a and U17b {RNAs} are members of the H/{ACA}-box class of small nucleolar {RNAs} ({snoRNAs}) participating in {rRNA} processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the three-exon transcription unit, named U17HG, positioned approximately 9 kb upstream of the {RCC}1 locus. Comparison of the human and mouse U17HG genes has revealed that {snoRNA}-encoding intron sequences but not exon sequences are conserved between the two species and that neither human nor mouse spliced U17HG poly(A)+ {RNAs} have the potential to code for proteins. Analyses of polysome profiles and effects of translation inhibitors on the abundance of U17HG {RNA} in {HeLa} cells indicated that despite its cytoplasmic localization, little if any U17HG {RNA} is associated with polysomes. This distinguishes U17HG {RNA} from another non-protein-coding {snoRNA} host gene product, {UHG} {RNA}, described previously (K. T. Tycowski, M. D. Shu, and J. A. Steitz, Nature 379:464-466, 1996). Determination of the 5' terminus of the U17HG {RNA} revealed that transcription of the U17HG gene starts with a C residue followed by a polypyrimidine tract, making this gene a member of the 5'-terminal oligopyrimidine (5'{TOP}) family, which includes genes encoding ribosomal proteins and some translation factors. Interestingly, other known {snoRNA} host genes, including the {UHG} gene (Tycowski et al., op. cit.), have features of the 5'{TOP} genes. Similar characteristics of the transcription start site regions in {snoRNA} host and ribosomal protein genes raise the possibility that expression of components of ribosome biogenesis and translational machineries is coregulated.},
	pages = {4509--4518},
	number = {8},
	journaltitle = {Mol Cell Biol},
	author = {Pelczar, P and Filipowicz, W},
	date = {1998},
	pmid = {9671460},
	keywords = {{DNA}, Animals, Base Sequence, Complementary, Genetic, Humans, Mice, Promoter Regions, {RNA}, Transcription, *Cell Cycle Proteins, *Guanine Nucleotide Exchange Factors, *Introns, *Nuclear Proteins, *Pyrimidines, 3T3 Cells, Centrifugation, Cycloheximide/pharmacology, Density Gradient, {DNA}-Binding Proteins/genetics, Gene Expression, {HeLa} Cells, Molecular Sequence Data, Multigene Family, Pactamycin/pharmacology, Poly A/metabolism, Protein Biosynthesis, Protein Synthesis Inhibitors/pharmacology, Puromycin/pharmacology, Rna, Small Nuclear/*genetics, Sucrose}
}

@article{tomashevski_cyclin-c-dependent_2010,
	title = {Cyclin-C-dependent cell-cycle entry is required for activation of non-homologous end joining {DNA} repair in postmitotic neurons},
	volume = {17},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20111042},
	doi = {10.1038/cdd.2009.221},
	abstract = {It is commonly believed that neurons remain in G(0) phase of the cell cycle indefinitely. Cell-cycle re-entry, however, is known to contribute to neuronal apoptosis. Moreover, recent evidence demonstrates the expression of cell-cycle proteins in differentiated neurons under physiological conditions. The functional roles of such expression remain unclear. Since {DNA} repair is generally attenuated by differentiation in most cell types, the cell-cycle-associated events in postmitotic cells may reflect the need to re-enter the cell cycle to activate {DNA} repair. We show that cyclin-C-directed, {pRb}-dependent G(0) exit activates the non-homologous end joining pathway of {DNA} repair ({NHEJ}) in postmitotic neurons. Using {RNA} interference, we found that abrogation of cyclin-C-mediated exit from G(0) compromised {DNA} repair but did not initiate apoptosis. Forced G(1) entry combined with prevention of G(1) –{\textbackslash}textgreater S progression triggered {NHEJ} activation even in the absence of {DNA} lesions, but did not induce apoptosis in contrast to unrestricted progression through G(1) –{\textbackslash}textgreater S. We conclude that G(0) –{\textbackslash}textgreater G(1) transition is functionally significant for {NHEJ} repair in postmitotic neurons. These findings reveal the importance of cell-cycle activation for controlling both {DNA} repair and apoptosis in postmitotic neurons, and underline the particular role of G(1) –{\textbackslash}textgreater S progression in apoptotic signaling, providing new insights into the mechanisms of {DNA} damage response ({DDR}) in postmitotic neurons.},
	pages = {1189--1198},
	number = {7},
	journaltitle = {Cell Death Differ},
	author = {Tomashevski, A and Webster, D R and Grammas, P and Gorospe, M and {Kruman II}},
	date = {2010},
	pmid = {20111042},
	keywords = {{RNA}, *Cell Cycle, *{DNA} Repair, Apoptosis, Cyclin C/*metabolism, Cyclin-Dependent Kinase Inhibitor p21/genetics/met, G0 Phase, G1 Phase, Hydrogen Peroxide/pharmacology, Neurons/cytology/*metabolism, Phosphorylation, Retinoblastoma Protein/metabolism, {RNA} Interference, Small Interfering/metabolism}
}

@article{kawai_global_2004,
	title = {Global {mRNA} stabilization preferentially linked to translational repression during the endoplasmic reticulum stress response},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15254244},
	doi = {10.1128/MCB.24.15.6773-6787.2004},
	abstract = {The stability of {mRNAs} undergoing translation has long been a controversial question. Here, we systematically investigate links between {mRNA} turnover and translation during the endoplasmic reticulum ({ER}) stress response, a process during which protein synthesis is potently regulated. {cDNA} array-based approaches to assess the stability and translational status of each {mRNA} were devised. First, {ER} stress-triggered changes in {mRNA} stability were studied by comparing differences in steady-state {mRNA} levels with differences in gene transcription. Second, changes in translational status were monitored by studying {ER} stress-induced shifts in the relative distribution of each {mRNA} along sucrose gradients. Together, the array-derived data reveal complex links between {mRNA} stability and translation, with all regulatory groups represented: both stabilized and destabilized {mRNAs} were found among translationally induced as well as translationally suppressed {mRNA} collections. Remarkably, however, the subset of stabilized {mRNAs} was prominently enriched in translationally suppressed transcripts, suggesting that {ER} stress was capable of causing the stabilization of {mRNAs} associated with a global reduction in protein synthesis. The {cDNA} array-based approach described here can be applied to global analyses of {mRNA} turnover and translation and can serve to investigate subsets of {mRNAs} subject to joint posttranscriptional control.},
	pages = {6773--6787},
	number = {15},
	journaltitle = {Mol Cell Biol},
	author = {Kawai, T and Fan, J and Mazan-Mamczarz, K and Gorospe, M},
	date = {2004},
	pmid = {15254244},
	keywords = {{DNA}, Humans, {RNA}, Oligonucleotide Array Sequence Analysis, *Protein Biosynthesis, Blotting, Cell Line, Centrifugation, Complementary/metabolism, Dactinomycin/pharmacology, Density Gradient, Dose-Response Relationship, Drug, Endoplasmic Reticulum/*metabolism, {HeLa} Cells, Messenger/*metabolism, Northern, Nucleic Acid Conformation, Physiological, Polyribosomes/metabolism, Post-Transcriptional, {RNA} Processing, Stress, Sucrose/pharmacology, Time Factors, Tumor, Western}
}

@article{sun_stratified_2006,
	title = {Stratified false discovery control for large-scale hypothesis testing with application to genome-wide association studies},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16800000},
	doi = {10.1002/gepi.20164},
	abstract = {The multiplicity problem has become increasingly important in genetic studies as the capacity for high-throughput genotyping has increased. The control of False Discovery Rate ({FDR}) (Benjamini and Hochberg. [1995] J. R. Stat. Soc. Ser. B 57:289-300) has been adopted to address the problems of false positive control and low power inherent in high-volume genome-wide linkage and association studies. In many genetic studies, there is often a natural stratification of the m hypotheses to be tested. Given the {FDR} framework and the presence of such stratification, we investigate the performance of a stratified false discovery control approach (i.e. control or estimate {FDR} separately for each stratum) and compare it to the aggregated method (i.e. consider all hypotheses in a single stratum). Under the fixed rejection region framework (i.e. reject all hypotheses with unadjusted p-values less than a pre-specified level and then estimate {FDR}), we demonstrate that the aggregated {FDR} is a weighted average of the stratum-specific {FDRs}. Under the fixed {FDR} framework (i.e. reject as many hypotheses as possible and meanwhile control {FDR} at a pre-specified level), we specify a condition necessary for the expected total number of true positives under the stratified {FDR} method to be equal to or greater than that obtained from the aggregated {FDR} method. Application to a recent Genome-Wide Association ({GWA}) study by Maraganore et al. ([2005] Am. J. Hum. Genet. 77:685-693) illustrates the potential advantages of control or estimation of {FDR} by stratum. Our analyses also show that controlling {FDR} at a low rate, e.g. 5\% or 10\%, may not be feasible for some {GWA} studies.},
	pages = {519--530},
	number = {6},
	journaltitle = {Genet Epidemiol},
	author = {Sun, L and Craiu, R V and Paterson, A D and Bull, S B},
	date = {2006},
	pmid = {16800000},
	keywords = {Human, Genetic, Humans, *Genome, *Models, *Polymorphism, Chromosome Mapping, Data Interpretation, Diabetes Mellitus, False Positive Reactions, Genetic Predisposition to Disease/*genetics, Heritable, Phenotype, Quantitative Trait, Single Nucleotide, Statistical, Type 1/diagnosis/*genetics}
}

@article{yu_comment_2007,
	title = {Comment on "Ongoing adaptive evolution of {ASPM}, a brain size determinant in Homo sapiens"},
	volume = {316},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17446375},
	doi = {10.1126/science.1137568},
	abstract = {Mekel-Bobrov et al. (Reports, 9 September 2005, p. 1720) suggested that {ASPM}, a gene associated with microcephaly, underwent natural selection within the last 500 to 14,100 years. Their analyses based on comparison with computer simulations indicated that {ASPM} had an unusual pattern of variation. However, when we compare {ASPM} empirically to a large number of other loci, its variation is not unusual and does not support selection.},
	pages = {370},
	number = {5823},
	journaltitle = {Science},
	author = {Yu, F and Hill, R S and Schaffner, S F and Sabeti, P C and Wang, E T and Mignault, A A and Ferland, R J and Moyzis, R K and Walsh, C A and Reich, D},
	date = {2007},
	pmid = {17446375},
	keywords = {{DNA}, Sequence Analysis, Genetic, Humans, *Polymorphism, *Selection, Adaptation, African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Biological, Biological Evolution, Brain/anatomy \& histology, European Continental Ancestry Group/genetics, Gene Frequency, Haplotypes, Nerve Tissue Proteins/*genetics, Recombination, Single Nucleotide, Time}
}

@article{pullmann_jr._analysis_2007,
	title = {Analysis of turnover and translation regulatory {RNA}-binding protein expression through binding to cognate {mRNAs}},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17620417},
	doi = {10.1128/MCB.00500-07},
	abstract = {{RNA}-binding proteins ({RBPs}) that associate with specific {mRNA} sequences and function as {mRNA} turnover and translation regulatory ({TTR}) {RBPs} are emerging as pivotal posttranscriptional regulators of gene expression. However, little is known about the mechanisms that govern the expression of {TTR}-{RBPs}. Here, we employed human cervical carcinoma {HeLa} cells to test the hypothesis that {TTR}-{RBP} expression is influenced posttranscriptionally by {TTR}-{RBPs} themselves. Systematic testing of the {TTR}-{RBPs} {AUF}1, {HuR}, {KSRP}, {NF}90, {TIA}-1, and {TIAR} led to three key discoveries. First, each {TTR}-{RBP} was found to associate with its cognate {mRNA} and with several other {TTR}-{RBP}-encoding {mRNAs}, as determined by testing both endogenous and biotinylated transcripts. Second, silencing of individual {TTR}-{RBPs} influenced the expression of other {TTR}-{RBPs} at the {mRNA} and/or protein level. Third, further analysis of two specific ribonucleoprotein ({RNP}) complexes revealed that {TIA}-1 expression was controlled via {HuR}-enhanced {mRNA} stabilization and {TIAR}-repressed translation. Together, our findings underscore the notion that {TTR}-{RBP} expression is controlled, at least in part, at the posttranscriptional level through a complex circuitry of self- and cross-regulatory {RNP} interactions.},
	pages = {6265--6278},
	number = {18},
	journaltitle = {Mol Cell Biol},
	author = {Pullmann Jr., R and Kim, H H and Abdelmohsen, K and Lal, A and Martindale, J L and Yang, X and Gorospe, M},
	date = {2007},
	pmid = {17620417},
	keywords = {3' Untranslated Regions, Humans, {RNA}, *Gene Expression Regulation, *Protein Biosynthesis, Biotinylation, Blotting, Genes, Green Fluorescent Proteins/metabolism, {HeLa} Cells, Messenger/*analysis/metabolism, Poly(A)-Binding Proteins/metabolism, Post-Translational, Precipitin Tests, Protein Processing, Reporter, {RNA} Interference, {RNA}-Binding Proteins/*analysis/genetics/metabolism, Small Interfering, Transfection, Western}
}

@article{wei_5_2004,
	title = {5' Long serial analysis of gene expression ({LongSAGE}) and 3' {LongSAGE} for transcriptome characterization and genome annotation},
	volume = {101},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15272081},
	doi = {10.1073/pnas.0403514101},
	abstract = {Complete genome annotation relies on precise identification of transcription units bounded by a transcription initiation site ({TIS}) and a polyadenylation site ({PAS}). To facilitate this process, we developed a set of two complementary methods, 5' Long serial analysis of gene expression ({LS}) and 3'{LS}. These analyses are based on the original {SAGE} and {LS} methods coupled with full-length {cDNA} cloning, and enable the high-throughput extraction of the first and the last 20 bp of each transcript. We demonstrate that the mapping of 5'{LS} and 3'{LS} tags to the genome allows the localization of {TIS} and {PAS}. By using 537 tag pairs mapping to the region of known genes, we confirmed that {\textbackslash}textgreater90\% of the tag pairs appropriately assigned to the first and last exons. Moreover, by using tag sequences as primers for {RT}-{PCRs}, we were able to recover putative full-length transcripts in 81\% of the attempts. This large-scale generation of transcript terminal tags is at least 20-40 times more efficient than full-length {cDNA} cloning and sequencing in the identification of complete transcription units. The apparent precision and deep coverage makes 5'{LS} and 3'{LS} an advanced approach for genome annotation through whole-transcriptome characterization.},
	pages = {11701--11706},
	number = {32},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Wei, C L and Ng, P and Chiu, K P and Wong, C H and Ang, C C and Lipovich, L and Liu, E T and Ruan, Y},
	date = {2004},
	pmid = {15272081},
	keywords = {{DNA}, Genomics/*methods, Animals, Complementary, Mice, {RNA}, Transcription Initiation Site, Cells, Cultured, Chromosome Mapping/methods, {DNA} Primers, Embryo, Mammalian/cytology, Messenger/*genetics, Polyadenylation, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells/cytology}
}

@article{fredriksson_systematic_2014,
	title = {Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25383969},
	doi = {10.1038/ng.3141},
	abstract = {Somatic mutations in noncoding sequences are poorly explored in cancer, a rare exception being the recent identification of activating mutations in {TERT} regulatory {DNA}. Although this finding is suggestive of a general mechanism for oncogene activation, this hypothesis remains untested. Here we map somatic mutations in 505 tumor genomes across 14 cancer types and systematically screen for associations between mutations in regulatory regions and {RNA}-level changes. We identify recurrent promoter mutations in several genes but find that {TERT} mutations are exceptional in showing a strong and genome-wide significant association with increased expression. Detailed analysis of {TERT} across cancers shows that the strength of this association is highly variable and is strongest in copy number-stable cancers such as thyroid carcinoma. We additionally propose that {TERT} promoter mutations control expression of the nearby gene {CLPTM}1L. Our analysis provides a detailed pan-cancer view of {TERT} transcriptional activation but finds no clear evidence for frequent oncogenic promoter mutations beyond {TERT}.},
	pages = {1258--1263},
	number = {12},
	journaltitle = {Nat Genet},
	author = {Fredriksson, N J and Ny, L and Nilsson, J A and Larsson, E},
	date = {2014},
	pmid = {25383969},
	keywords = {Genetic, Humans, Promoter Regions, *Gene Expression Profiling, *Gene Expression Regulation, *Mutation, Carrier Proteins/genetics, Cell Transformation, {DNA} Mutational Analysis, Neoplasms/*genetics/metabolism, Neoplastic, Telomerase/genetics}
}

@article{zou_polyamines_2008,
	title = {Polyamines modulate the subcellular localization of {RNA}-binding protein {HuR} through {AMP}-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1},
	volume = {409},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17919121},
	doi = {10.1042/BJ20070860},
	abstract = {Polyamines are required for maintenance of intestinal epithelial integrity, and a decrease in cellular polyamines increases the cytoplasmic levels of {RNA}-binding protein {HuR} stabilizing p53 and nucleophosmin {mRNAs}, thus inhibiting {IEC} (intestinal epithelial cell) proliferation. The {AMPK} ({AMP}-activated protein kinase), an enzyme involved in responding to metabolic stress, was recently found to be implicated in regulating the nuclear import of {HuR}. Here, we provide evidence showing that polyamines modulate subcellular localization of {HuR} through {AMPK}-regulated phosphorylation and acetylation of Impalpha1 (importin alpha1) in {IECs}. Decreased levels of cellular polyamines as a result of inhibiting {ODC} (ornithine decarboxylase) with {DFMO} (D,L-alpha-difluoromethylornithine) repressed {AMPK} activity and reduced Impalpha1 levels, whereas increased levels of polyamines as a result of {ODC} overexpression induced both {AMPK} and Impalpha1 levels. {AMPK} activation by overexpression of the {AMPK} gene increased Impalpha1 but reduced the cytoplasmic levels of {HuR} in control and polyamine-deficient cells. {IECs} overexpressing wild-type Impalpha1 exhibited a decrease in cytoplasmic {HuR} abundance, while cells overexpressing Impalpha1 proteins bearing K22R (lacking acetylation site), S105A (lacking phosphorylation site) or K22R/S105A (lacking both sites) mutations displayed increased levels of cytoplasmic {HuR}. Ectopic expression of these Impalpha1 mutants also prevented the increased levels of cytoplasmic {HuR} following polyamine depletion. These results indicate that polyamine-mediated {AMPK} activation triggers {HuR} nuclear import through phosphorylation and acetylation of Impalpha1 in {IECs} and that polyamine depletion increases cytoplasmic levels of {HuR} as a result of inactivation of the {AMPK}-driven Impalpha1 pathway.},
	pages = {389--398},
	number = {2},
	journaltitle = {Biochem J},
	author = {Zou, T and Liu, L and Rao, J N and Marasa, B S and Chen, J and Xiao, L and Zhou, H and Gorospe, M and Wang, J Y},
	date = {2008},
	pmid = {17919121},
	keywords = {Animals, Humans, Cells, Cultured, Acetylation, alpha Karyopherins/*metabolism, {AMP}-Activated Protein Kinases, Antigens, Biological, Cell Nucleus/*metabolism, Cytoplasm/metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Models, Multienzyme Complexes/*metabolism, Phosphorylation, Polyamines/*metabolism, Protein-Serine-Threonine Kinases/*metabolism, Rats, {RNA}-Binding Proteins/*analysis/*metabolism, Signal Transduction, Surface/*analysis/*metabolism}
}

@article{huntley_comprehensive_2006,
	title = {A comprehensive catalog of human {KRAB}-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16606702},
	doi = {10.1101/gr.4842106},
	abstract = {Kruppel-type zinc finger ({ZNF}) motifs are prevalent components of transcription factor proteins in all eukaryotes. {KRAB}-{ZNF} proteins, in which a potent repressor domain is attached to a tandem array of {DNA}-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of {ZNF} proteins in mammals. To define the full repertoire of human {KRAB}-{ZNF} proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 {KRAB}-{ZNF} protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and {ZNF} loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 {KRAB}-{ZNF} genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 {KRAB}-{ZNF} coding genes are primate specific, including many recent duplicates. {KRAB}-{ZNF} genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets.},
	pages = {669--677},
	number = {5},
	journaltitle = {Genome Res},
	author = {Huntley, S and Baggott, D M and Hamilton, A T and Tran-Gyamfi, M and Yang, S and Kim, J and Gordon, L and Branscomb, E and Stubbs, L},
	date = {2006},
	pmid = {16606702},
	keywords = {Human, Genetic, Genome, Humans, Computational Biology, Gene Expression Profiling, *Databases, *Evolution, Database Management Systems, Gene Expression, Internet, Kruppel-Like Transcription Factors/*genetics, Molecular, Multigene Family, Phylogeny, Protein Structure, Repressor Proteins/chemistry/*genetics, Tertiary, Zinc Fingers/*genetics}
}

@article{fatica_yeast_2000,
	title = {Yeast {snoRNA} accumulation relies on a cleavage-dependent/polyadenylation-independent 3'-processing apparatus},
	volume = {19},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11080167},
	doi = {10.1093/emboj/19.22.6218},
	abstract = {In Saccharomyces cerevisiae, {snoRNAs} are encoded by independent genes and within introns. Despite this heterogenous organization, {snoRNA} biosynthesis relies on a common theme: entry sites for 5'-3' and 3'-5' exonucleases are created on precursor molecules allowing the release of mature {snoRNAs}. In independently transcribed {snoRNAs}, such entry sites are often produced by the Rnt1p endonuclease. In many cases, cleavage sites are absent in the 3' portion of the pre-{snoRNAs}, suggesting that processing starts from the 3' end of the primary transcript. Here we show that cleavage/polyadenylation sites driving efficient polyadenylation, such as {CYC}1, prevent production of mature and functional {snoRNPs}. With these sites, {snoRNA} accumulation is restored only if polyadenylation activity is inhibited. Analysis of sequences downstream of {snoRNA}-coding units and the use of strains carrying mutations in {RNA} polymerase {II} ({polII}) cleavage/polyadenylation activities allowed us to establish that formation of {snoRNA} mature 3' ends requires only the cleavage activity of the {polII} 3'-processing machinery. These data indicate that, in vivo, uncoupling of cleavage and polyadenylation is necessary for an essential cellular biosynthesis.},
	pages = {6218--6229},
	number = {22},
	journaltitle = {{EMBO} J},
	author = {Fatica, A and Morlando, M and Bozzoni, I},
	date = {2000},
	pmid = {11080167},
	keywords = {Base Sequence, Genetic, {RNA}, Transcription, Binding Sites, {DNA} Polymerase {II}/genetics/metabolism, Fungal/chemistry/genetics/*metabolism, Mutation, Nucleic Acid Conformation, Oligodeoxyribonucleotides/genetics, Poly A/metabolism, Post-Transcriptional, {RNA} Processing, Saccharomyces cerevisiae/genetics/*metabolism, Small Nucleolar/chemistry/genetics/*metabolis}
}

@article{sanchez_genome-wide_2014,
	title = {Genome-wide analysis of the human p53 transcriptional network unveils a {lncRNA} tumour suppressor signature},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25524025},
	doi = {10.1038/ncomms6812},
	abstract = {Despite the inarguable relevance of p53 in cancer, genome-wide studies relating endogenous p53 activity to the expression of {lncRNAs} in human cells are still missing. Here, by integrating {RNA}-seq with p53 {ChIP}-seq analyses of a human cancer cell line under {DNA} damage, we define a high-confidence set of 18 {lncRNAs} that are p53 transcriptional targets. We demonstrate that two of the p53-regulated {lncRNAs} are required for the efficient binding of p53 to some of its target genes, modulating the p53 transcriptional network and contributing to apoptosis induction by {DNA} damage. We also show that the expression of p53-{lncRNAs} is lowered in colorectal cancer samples, constituting a tumour suppressor signature with high diagnostic power. Thus, p53-regulated {lncRNAs} establish a positive regulatory feedback loop that enhances p53 tumour suppressor activity. Furthermore, the signature defined by p53-regulated {lncRNAs} supports their potential use in the clinic as biomarkers and therapeutic targets.},
	pages = {5812},
	journaltitle = {Nat Commun},
	author = {Sanchez, Y and Segura, V and Marin-Bejar, O and Athie, A and Marchese, F P and Gonzalez, J and Bujanda, L and Guo, S and Matheu, A and Huarte, M},
	date = {2014},
	pmid = {25524025}
}

@article{young_noncoding_2005,
	title = {The noncoding {RNA} taurine upregulated gene 1 is required for differentiation of the murine retina},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15797018},
	doi = {10.1016/j.cub.2005.02.027},
	abstract = {{BACKGROUND}: With the advent of genome-wide analyses, it is becoming evident that a large number of noncoding {RNAs} ({ncRNAs}) are expressed in vertebrates. However, of the thousands of {ncRNAs} identified, the functions of relatively few have been established. {RESULTS}: In a screen for genes upregulated by taurine in developing retinal cells, we identified a gene that appears to be a {ncRNA}. Taurine Upregulated Gene 1 ({TUG}1) is a spliced, polyadenylated {RNA} that does not encode any open reading frame greater than 82 amino acids in its full-length, 6.7 kilobase (kb) {RNA} sequence. Analyses of Northern blots and in situ hybridization revealed that {TUG}1 is expressed in the developing retina and brain, as well as in adult tissues. In the newborn retina, knockdown of {TUG}1 with {RNA} interference ({RNAi}) resulted in malformed or nonexistent outer segments of transfected photoreceptors. Immunofluorescent staining and microarray analyses suggested that this loss of proper photoreceptor differentiation is a result of the disregulation of photoreceptor gene expression. {CONCLUSIONS}: A function for a newly identified {ncRNA}, {TUG}1, has been established. {TUG}1 is necessary for the proper formation of photoreceptors in the developing rodent retina.},
	pages = {501--512},
	number = {6},
	journaltitle = {Curr Biol},
	author = {Young, T L and Matsuda, T and Cepko, C L},
	date = {2005},
	pmid = {15797018},
	keywords = {{DNA}, Sequence Analysis, Animals, Base Sequence, Mice, {RNA}, *Gene Expression Regulation, Amino Acid Sequence, Blotting, Cloning, Complementary/genetics, Electroporation, Eye Proteins/genetics/*metabolism, Female, Fluorescent Antibody Technique, In Situ Hybridization, In Situ Nick-End Labeling, Microarray Analysis, Molecular, Molecular Sequence Data, Northern, Open Reading Frames/genetics, Pregnancy, Rats, Retina/embryology/*metabolism, {RNA} Interference, Sprague-Dawley, Taurine/*metabolism, Untranslated/*metabolism}
}

@article{rosati_coding_1999,
	title = {Coding region intron/exon organization, alternative splicing, and X-chromosome inactivation of the {KRAB}/{FPB}-domain-containing human zinc finger gene {ZNF}41},
	volume = {85},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10449920},
	doi = {15315},
	abstract = {{ZNF}41 belongs to a cluster of human zinc finger genes residing within a gene-rich region at Xp11.23. {ZNF}41 encodes a {KRAB}/{FPB} (Kruppel-associated/finger preceding box) domain, a potent transcription repression motif present in hundreds of vertebrate zinc finger protein genes, composed of two protein modules, A and B. Three introns, placed at identical positions in paralogous genes, interrupt four exons encoding the {ZNF}41 N-terminal amino acids, the {KRAB}/{FPB}-A and {KRAB}/{FPB}-B modules, and the remaining coding region adjoined to the C-terminal zinc finger domain. Since the {KRAB}/{FPB}-A and {KRAB}/{FPB}-B modules are encoded by dedicated exons in {ZNF}41 and paralogous genes, exon skipping may lead to differential usage of these modules in alternative gene products. {RT}-{PCR} analysis of {ZNF}41 {mRNAs} showed that, while skipping of the {KRAB}/{FPB}-A and/or {KRAB}/{FPB}-B exons was not detected, the use of alternative donor/acceptor sites upstream of the {KRAB}/{FPB}-A exon generates multiple {ZNF}41 transcripts potentially encoding polypeptides differing in the N-terminal region and expressed in different tissues. The expression pattern in cell hybrids containing either active or inactive X chromosomes indicates that {ZNF}41, which resides within a region of the X chromosome that includes genes that are both subject to and escape X-inactivation, is susceptible to X-chromosome inactivation.},
	pages = {291--296},
	number = {3},
	journaltitle = {Cytogenet Cell Genet},
	author = {Rosati, M and Franze, A and Matarazzo, M R and Grimaldi, G},
	date = {1999},
	pmid = {10449920},
	keywords = {Base Sequence, Genetic, Humans, {RNA}, *Dosage Compensation, Alternative Splicing/*genetics, Amino Acid, Amino Acid Sequence, {DNA}-Binding Proteins/*genetics, Gene Expression, Hybrid Cells, Kruppel-Like Transcription Factors, Messenger/biosynthesis, Molecular Sequence Data, Protein Structure, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Tertiary, X Chromosome/genetics, Zinc Fingers/*genetics}
}

@article{halvorsen_disease-associated_2010,
	title = {Disease-associated mutations that alter the {RNA} structural ensemble},
	volume = {6},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20808897},
	doi = {10.1371/journal.pgen.1001074},
	abstract = {Genome-wide association studies ({GWAS}) often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the {RNA} transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms ({SNPs}) from the Human Gene Mutation Database ({HGMD}) that map to the untranslated regions ({UTRs}) of a gene. Rather than using minimum free energy approaches (e.g. {mFold}), we use a partition function calculation that takes into consideration the ensemble of possible {RNA} conformations for a given sequence. We identified in the human genome disease-associated {SNPs} that significantly alter the global conformation of the {UTR} to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease ({COPD}), and Hypertension), we identified multiple {SNPs} in {UTRs} that alter the {mRNA} structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal {RNA} structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5' {UTRs} of {FTL} and {RB}1) {SNP}-induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the {UTR} and {SNP} combinations we identify constitute a "{RiboSNitch}," that is a regulatory {RNA} in which a specific {SNP} has a structural consequence that results in a disease phenotype. Our {SNPfold} algorithm can help identify {RiboSNitches} by leveraging {GWAS} data and an analysis of the {mRNA} structural ensemble.},
	pages = {e1001074},
	number = {8},
	journaltitle = {{PLoS} Genet},
	author = {Halvorsen, M and Martin, J S and Broadaway, S and Laederach, A},
	date = {2010},
	pmid = {20808897},
	keywords = {Human, Genome, Humans, Disease/*genetics, *Mutation, Genome-Wide Association Study, Nucleic Acid Conformation, Polymorphism, {RNA}/*chemistry/genetics, Single Nucleotide, Untranslated Regions}
}

@article{gracheva_molecular_2010,
	title = {Molecular basis of infrared detection by snakes},
	volume = {464},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20228791},
	doi = {10.1038/nature08943},
	abstract = {Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a 'thermal image' of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibres of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify {TRPA}1 channels as infrared receptors on sensory nerve fibres that innervate the pit organ. {TRPA}1 orthologues from pit-bearing snakes (vipers, pythons and boas) are the most heat-sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of transient receptor potential ({TRP}) channels as thermosensors in the vertebrate nervous system.},
	pages = {1006--1011},
	number = {7291},
	journaltitle = {Nature},
	author = {Gracheva, E O and Ingolia, N T and Kelly, Y M and Cordero-Morales, J F and Hollopeter, G and Chesler, A T and Sanchez, E E and Perez, J C and Weissman, J S and Julius, D},
	date = {2010},
	pmid = {20228791},
	keywords = {Animals, *Hot Temperature, *Infrared Rays, Boidae/genetics/metabolism, Chickens, Cloning, Crotalus/anatomy \& histology/genetics/metabolism/*, Light Signal Transduction/*physiology/*radiation e, Molecular, Molecular Sequence Data, Predatory Behavior/physiology/radiation effects, Rats, Sensory Receptor Cells/metabolism, Transient Receptor Potential Channels/genetics/*me, Trigeminal Ganglion/cytology/metabolism}
}

@article{hirosawa-takamori_novel_2009,
	title = {A novel stem loop control element-dependent {UGA} read-through system without translational selenocysteine incorporation in Drosophila},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18772345},
	doi = {10.1096/fj.08-116640},
	abstract = {Translational read-through of the {UGA} stop codon is an evolutionarily conserved feature that most prominently represents the basis of selenoprotein biosynthesis. It requires a specific cis-acting stem loop control element, termed {SECIS}, which is located in the 3'-untranslated region of eukaryotic selenoprotein {mRNAs}. In a search for novel factors underlying the {SECIS}-directed {UGA} read-through process, we identified an evolutionary conserved {GTPase}-activating protein, termed {GAPsec}. We show that the activity of the Drosophila {GAPsec} ({dGAPsec}) is necessary to support {SECIS}-dependent {UGA} read-through activity in flies and the mouse homolog {mGAPsec} in mice tissue culture cells. However, selenoprotein biosynthesis is not impaired in flies that lack {dGAPsec} activity. The results indicate that {GAPsec} is part of a novel {SECIS}-dependent translational read-through system that does not involve selenocysteine incorporation.},
	pages = {107--113},
	number = {1},
	journaltitle = {{FASEB} J},
	author = {Hirosawa-Takamori, M and Ossipov, D and Novoselov, S V and Turanov, A A and Zhang, Y and Gladyshev, V N and Krol, A and Vorbruggen, G and Jackle, H},
	date = {2009},
	pmid = {18772345},
	keywords = {Animals, Mice, Gene Expression Profiling, Amino Acid Sequence, Codon, Drosophila Proteins/chemistry/genetics/metabolism, Drosophila/*metabolism, Gene Expression Regulation/*physiology, Genetically Modified, {GTPase}-Activating Proteins/chemistry/genetics/meta, Inverted Repeat Sequences/*physiology, Molecular Sequence Data, {NIH} 3T3 Cells, Organisms, Selenocysteine/*metabolism, Terminator/*metabolism, Two-Hybrid System Techniques}
}

@article{fujimoto_whole-genome_2016,
	title = {Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer},
	volume = {48},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27064257},
	doi = {10.1038/ng.3547},
	abstract = {Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations ({STVs}), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding {RNA} genes ({NEAT}1 and {MALAT}1), promoters, {CTCF}-binding sites, and regulatory regions. {STV} analysis found a significant association with replication timing and identified known ({CDKN}2A, {CCND}1, {APC}, and {TERT}) and new ({ASH}1L, {NCOR}1, and {MACROD}2) cancer-related genes that were recurrently affected by {STVs}, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to {STVs} and noncoding mutations.},
	pages = {500--509},
	number = {5},
	journaltitle = {Nat Genet},
	author = {Fujimoto, A and Furuta, M and Totoki, Y and Tsunoda, T and Kato, M and Shiraishi, Y and Tanaka, H and Taniguchi, H and Kawakami, Y and Ueno, M and Gotoh, K and Ariizumi, S and Wardell, C P and Hayami, S and Nakamura, T and Aikata, H and Arihiro, K and Boroevich, K A and Abe, T and Nakano, K and Maejima, K and Sasaki-Oku, A and Ohsawa, A and Shibuya, T and Nakamura, H and Hama, N and Hosoda, F and Arai, Y and Ohashi, S and Urushidate, T and Nagae, G and Yamamoto, S and Ueda, H and Tatsuno, K and Ojima, H and Hiraoka, N and Okusaka, T and Kubo, M and Marubashi, S and Yamada, T and Hirano, S and Yamamoto, M and Ohdan, H and Shimada, K and Ishikawa, O and Yamaue, H and Chayama, K and Miyano, S and Aburatani, H and Shibata, T and Nakagawa, H},
	date = {2016},
	pmid = {27064257}
}

@article{morais-de-sa_connecting_2013,
	title = {Connecting polarized cytokinesis to epithelial architecture},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24189532},
	doi = {10.4161/cc.26910},
	pages = {3583--3584},
	number = {23},
	journaltitle = {Cell Cycle},
	author = {Morais-de-Sa, E and Sunkel, C E},
	date = {2013},
	pmid = {24189532}
}

@article{gorospe_p53-dependent_1998,
	title = {p53-dependent elevation of p21Waf1 expression by {UV} light is mediated through {mRNA} stabilization and involves a vanadate-sensitive regulatory system},
	volume = {18},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9488455},
	abstract = {Exposure of mammalian cells to adverse stimuli triggers the expression of numerous stress response genes, many of which are presumed to enhance cell survival. In this study, we examined the mechanisms contributing to the induction of p21Waf1 by stress and its influence on the survival of cells subjected to short-wavelength {UVC} irradiation. {UVC} was found to elevate p21Waf1 {mRNA} expression in mouse embryonal fibroblasts ({MEFs}) and human colorectal carcinoma ({RKO}) cells in a p53-dependent manner. The lack of p21Waf1 induction in p53-deficient {MEFs} and {RKO} cells correlated with diminished cell survival following {UVC} irradiation. Unexpectedly, {UVC} treatment was also found to block the induction of p21Waf1 by various stress-inducing agents such as mimosine in the p53-deficient cells. Additional studies indicated that induction of p21Waf1 by {UVC} occurs primarily through enhanced {mRNA} stability rather than increased transcription; in p53-/- {MEFs}, failure to elevate p21Waf1 after treatment with {UVC} appears to be due to their inability to stabilize the p21Waf1 transcripts. Treatment of the p53-/- {MEFs} with the protein tyrosine phosphatase inhibitor vanadate reversed the {UVC}-induced block on p21Waf1 induction and resulted in their enhanced survival following irradiation. Thus, in cells bearing normal p53, {UVC} augments p21Waf1 expression by increasing the half-life of p21Waf1 {mRNA}; without p53, p21Waf1 {mRNA} remains unstable after {UVC}, apparently due to a pathway involving tyrosine phosphatase activity.},
	pages = {1400--1407},
	number = {3},
	journaltitle = {Mol Cell Biol},
	author = {Gorospe, M and Wang, X and Holbrook, N J},
	date = {1998},
	pmid = {9488455},
	keywords = {Animals, Humans, Mice, {RNA}, Messenger, Cultured, Cell Line, Cell Survival/radiation effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclins/*biosynthesis/genetics/metabolism, Gene Expression Regulation/drug effects/*radiation, Post-Transcriptional, {RNA} Processing, Tumor Cells, Tumor Suppressor Protein p53/genetics/*metabolism, Ultraviolet Rays, Vanadates/*metabolism/pharmacology}
}

@article{sunkaria_dichlorvos-induced_2013,
	title = {Dichlorvos-induced cell cycle arrest and {DNA} damage repair activation in primary rat microglial cells},
	volume = {91},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23280485},
	doi = {10.1002/jnr.23173},
	abstract = {Dichlorvos, an organophosphate ({OP}), is known to cause oxidative stress in the central nervous system ({CNS}). Previously we have shown that dichlorvos treatment promoted the levels of proinflammatory molecules and ultimately induced apoptotic cell death in primary microglial cells. Here we studied the effect of dichlorvos on crucial cell cycle regulatory proteins and the {DNA} damage sensor ataxia-telangiectasia mutated ({ATM}). We found a significant increase in p53 and its downstream target, p21, levels in dichlorvos-treated microglial cells compared with control cells. Moreover, dichlorvos exposure promoted the levels of different cell cycle regulatory proteins. These results along with flow cytometry results suggested that primary microglial cells were arrested at G1 and G2/M phase after dichlorvos exposure. We have shown in a previous study that dichlorvos can induce {DNA} damage in microglia; here we found that microglial cells also tried to repair this damage by inducing a {DNA} repair enzyme, i.e., {ATM}. We observed a significant increase in the levels of {ATM} after dichlorvos treatment compared with control.},
	pages = {444--452},
	number = {3},
	journaltitle = {J Neurosci Res},
	author = {Sunkaria, A and Wani, W Y and Sharma, D R and Gill, K D},
	date = {2013},
	pmid = {23280485},
	keywords = {Animals, Cells, Cultured, *Primary Cell Culture, Cell Cycle Checkpoints/*drug effects/genetics, Dichlorvos/*toxicity, {DNA} Damage/*drug effects/genetics, {DNA} Repair/*drug effects/genetics, Microglia/*drug effects/metabolism, Newborn, Organophosphates/toxicity, Rats, Wistar}
}

@article{kozomara_mirbase:_2014,
	title = {{miRBase}: annotating high confidence {microRNAs} using deep sequencing data},
	volume = {42},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24275495},
	doi = {10.1093/nar/gkt1181},
	abstract = {We describe an update of the {miRBase} database (http://www.mirbase.org/), the primary {microRNA} sequence repository. The latest {miRBase} release (v20, June 2013) contains 24 521 {microRNA} loci from 206 species, processed to produce 30 424 mature {microRNA} products. The rate of deposition of novel {microRNAs} and the number of researchers involved in their discovery continue to increase, driven largely by small {RNA} deep sequencing experiments. In the face of these increases, and a range of {microRNA} annotation methods and criteria, maintaining the quality of the {microRNA} sequence data set is a significant challenge. Here, we describe recent developments of the {miRBase} database to address this issue. In particular, we describe the collation and use of deep sequencing data sets to assign levels of confidence to {miRBase} entries. We now provide a high confidence subset of {miRBase} entries, based on the pattern of mapped reads. The high confidence {microRNA} data set is available alongside the complete {microRNA} collection at http://www.mirbase.org/. We also describe embedding {microRNA}-specific Wikipedia pages on the {miRBase} website to encourage the {microRNA} community to contribute and share textual and functional information.},
	pages = {D68--73},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Kozomara, A and Griffiths-Jones, S},
	date = {2014},
	pmid = {24275495},
	keywords = {Animals, Humans, Mice, {RNA}, Nucleic Acid, *Databases, *High-Throughput Nucleotide Sequencing, *Molecular Sequence Annotation, *Sequence Analysis, Internet, {MicroRNAs}/*chemistry}
}

@article{komili_functional_2007,
	title = {Functional specificity among ribosomal proteins regulates gene expression},
	volume = {131},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17981122},
	doi = {10.1016/j.cell.2007.08.037},
	abstract = {Duplicated genes escape gene loss by conferring a dosage benefit or evolving diverged functions. The yeast Saccharomyces cerevisiae contains many duplicated genes encoding ribosomal proteins. Prior studies have suggested that these duplicated proteins are functionally redundant and affect cellular processes in proportion to their expression. In contrast, through studies of {ASH}1 {mRNA} in yeast, we demonstrate paralog-specific requirements for the translation of localized {mRNAs}. Intriguingly, these paralog-specific effects are limited to a distinct subset of duplicated ribosomal proteins. Moreover, transcriptional and phenotypic profiling of cells lacking specific ribosomal proteins reveals differences between the functional roles of ribosomal protein paralogs that extend beyond effects on {mRNA} localization. Finally, we show that ribosomal protein paralogs exhibit differential requirements for assembly and localization. Together, our data indicate complex specialization of ribosomal proteins for specific cellular processes and support the existence of a ribosomal code.},
	pages = {557--571},
	number = {3},
	journaltitle = {Cell},
	author = {Komili, S and Farny, N G and Roth, F P and Silver, P A},
	date = {2007},
	pmid = {17981122},
	keywords = {Genetic, {RNA}, Transcription, Gene Expression Profiling, *Gene Expression Regulation, Amino Acid, {DNA}-Binding Proteins/biosynthesis/genetics, Duplicate, Fungal, Genes, Messenger/genetics/metabolism, Nuclear Proteins/metabolism, Phenotype, Protein Biosynthesis, Reporter, Repressor Proteins/biosynthesis/genetics, Ribosomal Proteins/genetics/*metabolism, {RNA} Transport, {RNA}-Binding Proteins/metabolism, Saccharomyces cerevisiae Proteins/biosynthesis/gen, Saccharomyces cerevisiae/cytology/*genetics, Sequence Homology}
}

@article{auyeung_beyond_2013,
	title = {Beyond secondary structure: primary-sequence determinants license pri-{miRNA} hairpins for processing},
	volume = {152},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23415231},
	doi = {10.1016/j.cell.2013.01.031},
	abstract = {To use {microRNAs} to downregulate {mRNA} targets, cells must first process these ∼22 nt {RNAs} from primary transcripts (pri-{miRNAs}). These transcripts form {RNA} hairpins important for processing, but additional determinants must distinguish pri-{miRNAs} from the many other hairpin-containing transcripts expressed in each cell. Illustrating the complexity of this recognition, we show that most Caenorhabditis elegans pri-{miRNAs} lack determinants required for processing in human cells. To find these determinants, we generated many variants of four human pri-{miRNAs}, sequenced millions that retained function, and compared them with the starting variants. Our results confirmed the importance of pairing in the stem and revealed three primary-sequence determinants, including an {SRp}20-binding motif ({CNNC}) found downstream of most pri-{miRNA} hairpins in bilaterian animals, but not in nematodes. Adding this and other determinants to C. elegans pri-{miRNAs} imparted efficient processing in human cells, thereby confirming the importance of primary-sequence determinants for distinguishing pri-{miRNAs} from other hairpin-containing transcripts.},
	pages = {844--858},
	number = {4},
	journaltitle = {Cell},
	author = {Auyeung, V C and Ulitsky, I and {McGeary}, S E and Bartel, D P},
	date = {2013},
	pmid = {23415231},
	keywords = {Animals, Humans, *Inverted Repeat Sequences, *Nucleotide Motifs, *{RNA} Processing, Caenorhabditis elegans/*genetics/metabolism, Cell Extracts/chemistry, {MicroRNAs}/*chemistry/genetics/*metabolism, Multiprotein Complexes/metabolism, Nucleic Acid Conformation, Post-Transcriptional, Ribonuclease {III}/metabolism, {RNA}-Binding Proteins/metabolism}
}

@article{michelhaugh_mining_2011,
	title = {Mining Affymetrix microarray data for long non-coding {RNAs}: altered expression in the nucleus accumbens of heroin abusers},
	volume = {116},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21128942},
	doi = {10.1111/j.1471-4159.2010.07126.x},
	abstract = {Although recent data suggest that some long non-coding {RNAs} ({lncRNAs}) exert widespread effects on gene expression and organelle formation, {lncRNAs} as a group constitute a sizable but poorly characterized fraction of the human transcriptome. We investigated whether some human {lncRNA} sequences were fortuitously represented on commonly used microarrays, then used this annotation to assess {lncRNA} expression in human brain. A computational and annotation pipeline was developed to identify {lncRNA} transcripts represented on Affymetrix U133 arrays. A previously published dataset derived from human nucleus accumbens was then examined for potential {lncRNA} expression. Twenty-three {lncRNAs} were determined to be represented on U133 arrays. Of these, dataset analysis revealed that five {lncRNAs} were consistently detected in samples of human nucleus accumbens. Strikingly, the abundance of these {lncRNAs} was up-regulated in human heroin abusers compared to matched drug-free control subjects, a finding confirmed by quantitative {PCR}. This study presents a paradigm for examining existing Affymetrix datasets for the detection and potential regulation of {lncRNA} expression, including changes associated with human disease. The finding that all detected {lncRNAs} were up-regulated in heroin abusers is consonant with the proposed role of {lncRNAs} as mediators of widespread changes in gene expression as occur in drug abuse.},
	pages = {459--466},
	number = {3},
	journaltitle = {J Neurochem},
	author = {Michelhaugh, S K and Lipovich, L and Blythe, J and Jia, H and Kapatos, G and Bannon, M J},
	date = {2011},
	pmid = {21128942},
	keywords = {Humans, {RNA}, Analgesics, Brain Chemistry/drug effects/*genetics, Data Mining/*methods, Gene Expression Regulation/drug effects/genetics, Genetic Markers/drug effects/physiology, Heroin Dependence/*genetics/metabolism, Heroin/adverse effects, Nucleus Accumbens/drug effects/*metabolism, Oligonucleotide Array Sequence Analysis/*methods, Opioid/adverse effects, Polymerase Chain Reaction/methods, Reward, Untranslated/*biosynthesis/drug effects/*gene, Up-Regulation/drug effects/genetics}
}

@article{zhuang_mir-195_2013,
	title = {{miR}-195 competes with {HuR} to modulate stim1 {mRNA} stability and regulate cell migration},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23804758},
	doi = {10.1093/nar/gkt565},
	abstract = {Stromal interaction molecule 1 (Stim1) functions as a sensor of Ca2+ within stores and plays an essential role in the activation of store-operated Ca2+ entry ({SOCE}). Although lowering Stim1 levels reduces store-operated Ca2+ entry and inhibits intestinal epithelial repair after wounding, the mechanisms that control Stim1 expression remain unknown. Here, we show that cellular Stim1 abundance is controlled posttranscriptionally via factors that associate with 3'-untranslated region (3'-{UTR}) of stim1 {mRNA}. {MicroRNA}-195 ({miR}-195) and the {RNA}-binding protein {HuR} competed for association with the stim1 3'-{UTR} and regulated stim1 {mRNA} decay in opposite directions. Interaction of {miR}-195 with the stim1 3'-{UTR} destabilized stim1 {mRNA}, whereas the stability of stim1 {mRNA} increased with {HuR} association. Interestingly, ectopic {miR}-195 overexpression enhanced stim1 {mRNA} association with argonaute-containing complexes and increased the colocalization of tagged stim1 {RNA} with processing bodies (P-bodies); the translocation of stim1 {mRNA} was abolished by {HuR} overexpression. Moreover, decreased levels of Stim1 by {miR}-195 overexpression inhibited cell migration over the denuded area after wounding but was rescued by increasing {HuR} levels. In sum, Stim1 expression is controlled by two factors competing for influence on stim1 {mRNA} stability: the {mRNA}-stabilizing protein {HuR} and the decay-promoting {miR}-195.},
	pages = {7905--7919},
	number = {16},
	journaltitle = {Nucleic Acids Res},
	author = {Zhuang, R and Rao, J N and Zou, T and Liu, L and Xiao, L and Cao, S and Hansraj, N Z and Gorospe, M and Wang, J Y},
	date = {2013},
	pmid = {23804758},
	keywords = {3' Untranslated Regions, Animals, {RNA}, *{RNA} Stability, Cell Line, Cell Movement/*genetics, Epithelial Cells/cytology/metabolism, Hu Paraneoplastic Encephalomyelitis Antigens/*meta, Membrane Glycoproteins/*genetics/metabolism, Messenger/*metabolism, {MicroRNAs}/*metabolism, Rats}
}

@article{jurka_repbase_2000,
	title = {Repbase update: a database and an electronic journal of repetitive elements},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10973072},
	pages = {418--420},
	number = {9},
	journaltitle = {Trends Genet},
	author = {Jurka, J},
	date = {2000},
	pmid = {10973072},
	keywords = {Nucleic Acid, *Database Management Systems, *Repetitive Sequences, Automation}
}

@article{johnson_long_2012,
	title = {Long non-coding {RNAs} in Huntington's disease neurodegeneration},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22202438},
	doi = {10.1016/j.nbd.2011.12.006},
	abstract = {Neurodegeneration in the brains of Huntington's disease patients is accompanied by widespread changes in gene regulatory networks. Recent studies have found that these changes are not restricted to protein-coding genes, but also include non-coding {RNAs} ({ncRNAs}). One particularly abundant but poorly understood class of {ncRNAs} is the long non-coding {RNAs} ({lncRNAs}), of which at least ten thousand have been identified in the human genome. Although we presently know little about their function, {lncRNAs} are widely expressed in the mammalian nervous system, and many are likely to play critical roles in neuronal development and activity. {LncRNAs} are now being implicated in neurodegenerative processes, including Alzheimer's ({AD}) and Huntington's disease ({HD}). In the present study, I discuss the potential significance of {lncRNAs} in {HD}. To support this, I have mined existing microarray data to discover seven new {lncRNAs} that are dysregulated in {HD} brains. Interestingly, several of these contain genomic binding sites for the transcriptional repressor {REST}, a key mediator of transcriptional changes in {HD}, including the known {REST} target {lncRNA}, {DGCR}5. Previously described {lncRNAs} {TUG}1 (necessary for retinal development) and {NEAT}1 (a structural component of nuclear paraspeckles) are upregulated in {HD} caudate, while the brain-specific tumour-suppressor {MEG}3 is downregulated. Three other {lncRNAs} of unknown function are also significantly changed in {HD} brains. Many {lncRNAs} regulate gene expression through formation of epigenetic ribonucleoprotein complexes, including {TUG}1 and {MEG}3. These findings lead me to propose that {lncRNA} expression changes in {HD} are widespread, that many of these result in altered epigenetic gene regulation in diseased neurons, and that contributes to neurodegeneration. Therefore, elucidating {lncRNA} network changes in {HD} may be important in understanding and treating this and other neurodegenerative processes.},
	pages = {245--254},
	number = {2},
	journaltitle = {Neurobiol Dis},
	author = {Johnson, R},
	date = {2012},
	pmid = {22202438},
	keywords = {Animals, Humans, {RNA}, Untranslated/*genetics, Brain/pathology/physiology, Huntington Disease/*genetics/pathology, Nerve Degeneration/*genetics/pathology, Protein Array Analysis/methods}
}

@article{vanderperre_direct_2013,
	title = {Direct detection of alternative open reading frames translation products in human significantly expands the proteome},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23950983},
	doi = {10.1371/journal.pone.0070698},
	abstract = {A fully mature {mRNA} is usually associated to a reference open reading frame encoding a single protein. Yet, mature {mRNAs} contain unconventional alternative open reading frames ({AltORFs}) located in untranslated regions ({UTRs}) or overlapping the reference {ORFs} ({RefORFs}) in non-canonical +2 and +3 reading frames. Although recent ribosome profiling and footprinting approaches have suggested the significant use of unconventional translation initiation sites in mammals, direct evidence of large-scale alternative protein expression at the proteome level is still lacking. To determine the contribution of alternative proteins to the human proteome, we generated a database of predicted human {AltORFs} revealing a new proteome mainly composed of small proteins with a median length of 57 amino acids, compared to 344 amino acids for the reference proteome. We experimentally detected a total of 1,259 alternative proteins by mass spectrometry analyses of human cell lines, tissues and fluids. In plasma and serum, alternative proteins represent up to 55\% of the proteome and may be a potential unsuspected new source for biomarkers. We observed constitutive co-expression of {RefORFs} and {AltORFs} from endogenous genes and from transfected {cDNAs}, including tumor suppressor p53, and provide evidence that out-of-frame clones representing {AltORFs} are mistakenly rejected as false positive in {cDNAs} screening assays. Functional importance of alternative proteins is strongly supported by significant evolutionary conservation in vertebrates, invertebrates, and yeast. Our results imply that coding of multiple proteins in a single gene by the use of {AltORFs} may be a common feature in eukaryotes, and confirm that translation of unconventional {ORFs} generates an as yet unexplored proteome.},
	pages = {e70698},
	number = {8},
	journaltitle = {{PLoS} One},
	author = {Vanderperre, B and Lucier, J F and Bissonnette, C and Motard, J and Tremblay, G and Vanderperre, S and Wisztorski, M and Salzet, M and Boisvert, F M and Roucou, X},
	date = {2013},
	pmid = {23950983},
	keywords = {Genetic, Humans, Protein Binding, Reproducibility of Results, Databases, *Alternative Splicing, *Open Reading Frames, *Protein Biosynthesis, *Proteome, *Proteomics/methods, Amino Acid Sequence, {BRCA}1 Protein/chemistry/genetics/metabolism, Cell Line, Computational Biology/methods, Gene Expression, Molecular Sequence Data, Peptide Chain Initiation, Sequence Alignment, Transfection, Translational}
}

@article{lim_genome-wide_2007,
	title = {Genome-wide mapping of {RELA}(p65) binding identifies E2F1 as a transcriptional activator recruited by {NF}-{kappaB} upon {TLR}4 activation},
	volume = {27},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17707233},
	doi = {10.1016/j.molcel.2007.06.038},
	abstract = {{NF}-{kappaB} is a key mediator of inflammation. Here, we mapped the genome-wide loci bound by the {RELA} subunit of {NF}-{kappaB} in lipopolysaccharide ({LPS})-stimulated human monocytic cells, and together with global gene expression profiling, found an overrepresentation of the E2F1-binding motif among {RELA}-bound loci associated with {NF}-{kappaB} target genes. Knockdown of endogenous E2F1 impaired the {LPS} inducibility of the proinflammatory cytokines {CCL}3({MIP}-1alpha), {IL}23A(p19), {TNF}-alpha, and {IL}1-beta. Upon {LPS} stimulation, E2F1 is rapidly recruited to the promoters of these genes along with p50/{RELA} heterodimer via a mechanism that is dependent on {NF}-{kappaB} activation. Together with the observation that E2F1 physically interacts with p50/{RELA} in {LPS}-stimulated cells, our findings suggest that {NF}-{kappaB} recruits E2F1 to fully activate the transcription of {NF}-{kappaB} target genes. Global gene expression profiling subsequently revealed a spectrum of {NF}-{kappaB} target genes that are positively regulated by E2F1, further demonstrating the critical role of E2F1 in the Toll-like receptor 4 pathway.},
	pages = {622--635},
	number = {4},
	journaltitle = {Mol Cell},
	author = {Lim, C A and Yao, F and Wong, J J and George, J and Xu, H and Chiu, K P and Sung, W K and Lipovich, L and Vega, V B and Chen, J and Shahab, A and Zhao, X D and Hibberd, M and Wei, C L and Lim, B and Ng, H H and Ruan, Y and Chin, K C},
	date = {2007},
	pmid = {17707233},
	keywords = {Base Sequence, Genome, Humans, Binding Sites, Amino Acid Motifs, Cell Line, Cell Nucleus/drug effects/metabolism, Consensus Sequence, Cytokines/metabolism, E2F1 Transcription Factor/*metabolism, Gene Expression Regulation/drug effects, Human/*genetics, Inflammation Mediators/metabolism, Lipopolysaccharides/pharmacology, Molecular Sequence Data, Protein Binding/drug effects, Protein Transport/drug effects, Retinoblastoma Protein/metabolism, Toll-Like Receptor 4/*metabolism, Trans-Activators/*metabolism, Transcription Factor {RelA}/*metabolism}
}

@article{odonnell_multimodality_2010,
	title = {Multimodality cardiovascular molecular imaging technology},
	volume = {51 Suppl 1},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20457794},
	doi = {10.2967/jnumed.109.068155},
	abstract = {Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.},
	pages = {38S--50S},
	journaltitle = {J Nucl Med},
	author = {O'Donnell, M and {McVeigh}, E R and Strauss, H W and Tanaka, A and Bouma, B E and Tearney, G J and Guttman, M A and Garcia, E V},
	date = {2010},
	pmid = {20457794},
	keywords = {Animals, Humans, Acoustics, Biological, Cardiovascular Diseases/*diagnosis/pathology, Cardiovascular System/*pathology, Computer Graphics, Computer-Assisted, Contrast Media/pharmacology, Diagnostic Imaging/methods, Image Processing, Magnetic Resonance Imaging/methods, Models, Optical/methods, Tomography, Ultrasonography/methods, User-Computer Interface}
}

@article{song_impact_2011,
	title = {Impact of pyrrolidine dithiocarbamate and interleukin-6 on mammalian target of rapamycin complex 1 regulation and global protein translation},
	volume = {339},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21917559},
	doi = {10.1124/jpet.111.185678},
	abstract = {Interleukin-6 ({IL}-6) is a proinflammatory cytokine that exerts a wide range of cellular, physiological, and pathophysiological responses. Pyrrolidine dithiocarbamate ({PDTC}) antagonizes the cellular responsiveness to {IL}-6 through impairment in signal transducer and activator of transcription-3 activation and downstream signaling. To further elucidate the biological properties of {PDTC}, global gene expression profiling of human {HepG}2 hepatocellular carcinoma cells was carried out after treatment with {PDTC} or {IL}-6 for up to 8 h. Through an unbiased pathway analysis method, gene array analysis showed dramatic and temporal differences in expression changes in response to {PDTC} versus {IL}-6. A significant number of genes associated with metabolic pathways, inflammation, translation, and mitochondrial function were changed, with ribosomal protein genes and {DNA} damage-inducible transcript 4 protein ({DDIT}4) primarily up-regulated with {PDTC} but down-regulated with {IL}-6. Quantitative polymerase chain reaction and Western blot analyses validated the microarray data and showed the reciprocal expression pattern of the mammalian target of rapamycin ({mTOR})-negative regulator {DDIT}4 in response to {PDTC} versus {IL}-6. Cell treatment with {PDTC} resulted in a rapid and sustained activation of Akt and subsequently blocked the {IL}-6-mediated increase in {mTOR} complex 1 function through up-regulation in {DDIT}4 expression. Conversely, down-regulation of {DDIT}4 with small interfering {RNA} dampened the capacity of {PDTC} to block {IL}-6-dependent {mTOR} activation. The overall protein biosynthetic capacity of the cells was severely blunted by {IL}-6 but increased in a rapamycin-independent pathway by {PDTC}. These results demonstrate a critical effect of {PDTC} on {mTOR} complex 1 function and provide evidence that {PDTC} can reverse {IL}-6-related signaling via induction of {DDIT}4.},
	pages = {905--913},
	number = {3},
	journaltitle = {J Pharmacol Exp Ther},
	author = {Song, S and Abdelmohsen, K and Zhang, Y and Becker, K G and Gorospe, M and Bernier, M},
	date = {2011},
	pmid = {21917559},
	keywords = {Humans, {RNA}, Gene Expression Profiling, Antioxidants/*pharmacology, Cytokines/*pharmacology, Down-Regulation/drug effects, Hep G2 Cells, Interleukin-6/*pharmacology, Multiprotein Complexes, {NF}-kappa B/*antagonists \& inhibitors, Protein Biosynthesis/drug effects, Proteins/genetics/*metabolism, Pyrrolidines/*pharmacology, Signal Transduction/drug effects, Small Interfering/metabolism, Thiocarbamates/*pharmacology, {TOR} Serine-Threonine Kinases, Transcription Factors/*metabolism, Transcriptional Activation/drug effects, Up-Regulation/drug effects}
}

@article{kundrapu_randomized_2014,
	title = {A randomized trial of soap and water hand wash versus alcohol hand rub for removal of Clostridium difficile spores from hands of patients},
	volume = {35},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24442089},
	doi = {10.1086/674859},
	pages = {204--206},
	number = {2},
	journaltitle = {Infect Control Hosp Epidemiol},
	author = {Kundrapu, S and Sunkesula, V and Jury, I and Deshpande, A and Donskey, C J},
	date = {2014},
	pmid = {24442089}
}

@article{flockhart_brafv600e_2012,
	title = {{BRAFV}600E remodels the melanocyte transcriptome and induces {BANCR} to regulate melanoma cell migration},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22581800},
	doi = {10.1101/gr.140061.112},
	abstract = {Aberrations of protein-coding genes are a focus of cancer genomics; however, the impact of oncogenes on expression of the ∼50\% of transcripts without protein-coding potential, including long noncoding {RNAs} ({lncRNAs}), has been largely uncharacterized. Activating mutations in the {BRAF} oncogene are present in {\textbackslash}textgreater70\% of melanomas, 90\% of which produce active mutant {BRAF}(V600E) protein. To define the impacts of oncogenic {BRAF} on the melanocyte transcriptome, massively parallel {cDNA} sequencing ({RNA}-seq) was performed on genetically matched normal human melanocytes with and without {BRAF}(V600E) expression. To enhance potential disease relevance by verifying expression of altered genes in {BRAF}-driven cancer tissue, parallel {RNA}-seq was also undertaken of two {BRAF}(V600E)-mutant human melanomas. {BRAF}(V600E) regulated expression of 1027 protein-coding transcripts and 39 annotated {lncRNAs}, as well as 70 unannotated, potentially novel, intergenic transcripts. These transcripts display both tissue-specific and multi-tissue expression profiles and harbor distinctive regulatory chromatin marks and transcription factor binding sites indicative of active transcription. Coding potential analysis of the 70 unannotated transcripts suggested that most may represent newly identified {lncRNAs}. {BRAF}-regulated {lncRNA} 1 ({BANCR}) was identified as a recurrently overexpressed, previously unannotated 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. {BANCR} knockdown reduced melanoma cell migration, and this could be rescued by the chemokine {CXCL}11. Combining {RNA}-seq of oncogene-expressing normal cells with {RNA}-seq of their corresponding human cancers may represent a useful approach to discover new oncogene-regulated {RNA} transcripts of potential clinical relevance in cancer.},
	pages = {1006--1014},
	number = {6},
	journaltitle = {Genome Res},
	author = {Flockhart, R J and Webster, D E and Qu, K and Mascarenhas, N and Kovalski, J and Kretz, M and Khavari, P A},
	date = {2012},
	pmid = {22581800},
	keywords = {Human, Humans, {RNA}, Untranslated, Gene Expression Regulation, *Transcriptome, Cell Movement/genetics, Chemokine {CXCL}11/genetics/metabolism, Chromosomes, Gene Knockdown Techniques, Melanocytes/pathology/*physiology, Melanoma/*genetics/metabolism/*pathology, Mutation, Neoplastic, Pair 9, Proto-Oncogene Proteins B-raf/*genetics/metabolism, Transcription Factors/genetics/metabolism}
}

@article{lowe_thousands_2007,
	title = {Thousands of human mobile element fragments undergo strong purifying selection near developmental genes},
	volume = {104},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17463089},
	doi = {10.1073/pnas.0611223104},
	abstract = {At least 5\% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2\% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Recent work has highlighted a handful of cases where mobile element insertions have resulted in the introduction of novel conserved nonexonic elements. Here, we present a genome-wide survey of 10,402 constrained nonexonic elements in the human genome that have all been deposited by characterized mobile elements. These repeat instances have been under strong purifying selection since at least the boreoeutherian ancestor (100 Mya). They are most often located in gene deserts and show a strong preference for residing closest to genes involved in development and transcription regulation. In particular, constrained nonexonic elements with clear repetitive origins are located near genes involved in cell adhesion, including all characterized cellular members of the reelin-signaling pathway. Overall, we find that mobile elements have contributed at least 5.5\% of all constrained nonexonic elements unique to mammals, suggesting that mobile elements may have played a larger role than previously recognized in shaping and specializing the landscape of gene regulation during mammalian evolution.},
	pages = {8005--8010},
	number = {19},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Lowe, C B and Bejerano, G and Haussler, D},
	date = {2007},
	pmid = {17463089},
	keywords = {Genetic, Humans, *{DNA} Transposable Elements, *Genes, *Selection, Cell Adhesion Molecules, Developmental, Extracellular Matrix Proteins/physiology, Genes, Multigene Family, Nerve Tissue Proteins/physiology, Neuronal/physiology, Regulator, Serine Endopeptidases/physiology, Signal Transduction}
}

@article{prensner_long_2013,
	title = {The long noncoding {RNA} {SChLAP}1 promotes aggressive prostate cancer and antagonizes the {SWI}/{SNF} complex},
	volume = {45},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24076601},
	doi = {10.1038/ng.2771},
	abstract = {Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding {RNA} termed {SChLAP}1 (second chromosome locus associated with prostate-1; also called {LINC}00913) that is overexpressed in a subset of prostate cancers. {SChLAP}1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that {SChLAP}1 is critical for cancer cell invasiveness and metastasis. Mechanistically, {SChLAP}1 antagonizes the genome-wide localization and regulatory functions of the {SWI}/{SNF} chromatin-modifying complex. These results suggest that {SChLAP}1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the {SWI}/{SNF} complex.},
	pages = {1392--1398},
	number = {11},
	journaltitle = {Nat Genet},
	author = {Prensner, J R and Iyer, M K and Sahu, A and Asangani, I A and Cao, Q and Patel, L and Vergara, I A and Davicioni, E and Erho, N and Ghadessi, M and Jenkins, R B and Triche, T J and Malik, R and Bedenis, R and {McGregor}, N and Ma, T and Chen, W and Han, S and Jing, X and Cao, X and Wang, X and Chandler, B and Yan, W and Siddiqui, J and Kunju, L P and Dhanasekaran, S M and Pienta, K J and Feng, F Y and Chinnaiyan, A M},
	date = {2013},
	pmid = {24076601},
	keywords = {Animals, Genetic, Humans, Mice, Promoter Regions, {RNA}, Long Noncoding/*genetics, Gene Expression Profiling, Cell Line, Cell Proliferation, Chromosomal Proteins, {DNA}-Binding Proteins/*genetics, Female, Male, Molecular Sequence Data, Neoplasm Invasiveness/genetics, Neoplasm Metastasis/genetics, Non-Histone/*genetics/*metab, Prostatic Neoplasms/*genetics, {RNA} Interference, Small Interfering, Transcription Factors/*genetics/*metabolism, Tumor}
}

@article{lee_minireview:_2010,
	title = {Minireview: posttranscriptional regulation of the insulin and insulin-like growth factor systems},
	volume = {151},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20032049},
	doi = {10.1210/en.2009-1123},
	abstract = {Insulin and {IGFs} share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of {mRNAs} encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by {IGFs} and {IGF} receptors, whose expression is likewise subject to changes in the stability and translation of the encoding {mRNAs}. The control of {mRNA} half-life and translation is governed by {RNA}-binding proteins and {microRNAs} that interact with target transcripts at the 3' and 5' untranslated regions. In this review, we describe the {RNA}-binding proteins and {microRNAs} that target the {mRNAs} encoding insulin, {IGFs}, and their receptors. We discuss how these {mRNA}-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and {IGF} function, thereby effecting critical control of energy metabolism.},
	pages = {1403--1408},
	number = {4},
	journaltitle = {Endocrinology},
	author = {Lee, E K and Gorospe, M},
	date = {2010},
	pmid = {20032049},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation/genetics, Insulin-Like Growth Factor I/*genetics/metabolism, Insulin/*genetics/metabolism, Messenger/*genetics/metabolism, {MicroRNAs}/genetics/metabolism, Post-Transcriptional/genetics, {RNA} Processing}
}

@article{yoon_posttranscriptional_2013,
	title = {Posttranscriptional gene regulation by long noncoding {RNA}},
	volume = {425},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23178169},
	doi = {10.1016/j.jmb.2012.11.024},
	abstract = {Eukaryotic cells transcribe a vast number of noncoding {RNA} species. Among them, long noncoding {RNAs} ({lncRNAs}) have been widely implicated in the regulation of gene transcription. However, examples of posttranscriptional gene regulation by {lncRNAs} are emerging. Through extended base-pairing, {lncRNAs} can stabilize or promote the translation of target {mRNAs}, while partial base-pairing facilitates {mRNA} decay or inhibits target {mRNA} translation. In the absence of complementarity, {lncRNAs} can suppress precursor {mRNA} splicing and translation by acting as decoys of {RNA}-binding proteins or {microRNAs} and can compete for {microRNA}-mediated inhibition leading to increased expression of the {mRNA}. Through these regulatory mechanisms, {lncRNAs} can elicit differentiation, proliferation, and cytoprotective programs, underscoring the rising recognition of {lncRNA} roles in human disease. In this review, we summarize the mechanisms of posttranscriptional gene regulation by {lncRNAs} identified until now.},
	pages = {3723--3730},
	number = {19},
	journaltitle = {J Mol Biol},
	author = {Yoon, J H and Abdelmohsen, K and Gorospe, M},
	date = {2013},
	pmid = {23178169},
	keywords = {Humans, {RNA}, {RNA} Splicing, Long Noncoding, *{RNA}, *{RNA} Processing, Cell Line, Messenger/genetics/metabolism, {MicroRNAs}/genetics/metabolism, Post-Transcriptional, {RNA} Stability, {RNA}-Binding Proteins/genetics/metabolism, Tumor}
}

@article{tanaka_esg1_2006,
	title = {Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative {RNA}-binding protein with broad {RNA} targets},
	volume = {48},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16872451},
	doi = {10.1111/j.1440-169X.2006.00875.x},
	abstract = {In our earlier attempt to identify genes involved in the maintenance of cellular pluripotency, we found that {KH}-domain protein Embryonal stem cell-specific gene 1 (Esg1) showed similar expression patterns to those of Oct3/4 (Pou5f1), whereas the forced repression of Oct3/4 in mouse embryonic stem cells immediately downregulated the expression of Esg1. Here we further confirm this overlap by in situ hybridization and immunohistochemical analyses. Both Esg1 transcript and protein exist in the egg and preimplantation embryos. At embryonic day 3.5, blastocyst stage, however, {ESG}1 protein was more abundant in the inner cell mass ({ICM}) than in trophectoderm ({TE}), whereas Esg1 transcript was detected in both the {ICM} and the {TE}, particularly in the polar trophectoderm. The presence of an {RNA}-binding {KH}-domain in {ESG}1 led us to search for and identify 902 target transcripts by microarray analysis of immunoprecipitated {ESG}1 complex. Interaction of 20 target {mRNA} with {ESG}1, including Cdc25a, Cdc42, Ezh2, Nfyc and Nr5a2, was further validated by reverse transcriptase-polymerase chain reaction of the immunoprecipitation material, supporting the notion that {ESG}1 is an {RNA}-binding protein which associates with specific target transcripts.},
	pages = {381--390},
	number = {6},
	journaltitle = {Dev Growth Differ},
	author = {Tanaka, T S and Lopez de Silanes, I and Sharova, L V and Akutsu, H and Yoshikawa, T and Amano, H and Yamanaka, S and Gorospe, M and Ko, M S},
	date = {2006},
	pmid = {16872451},
	keywords = {Animals, Mice, Gene Expression Regulation, Gene Expression Profiling, Basic Helix-Loop-Helix Transcription Factors/analy, Biological, Blastocyst/chemistry/*metabolism, Blotting, Cell Proliferation, Developmental/genetics, Female, Immunoblotting, Immunohistochemistry, In Situ Hybridization/methods, Inbred C57BL, Inbred Strains, Male, Models, Morula/chemistry/cytology/metabolism, Northern, Octamer Transcription Factor-3/analysis/genetics, Oligonucleotide Array Sequence Analysis/methods, {RNA}-Binding Proteins/analysis/*genetics/metabolism, {RNA}/genetics/*metabolism, Stem Cells/*metabolism, Transcription Factors/analysis/genetics/metabolism}
}

@article{hwang_microrna-146a_2012,
	title = {{MicroRNA}-146a suppresses metastatic activity in brain metastasis},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22949171},
	doi = {10.1007/s10059-012-0171-6},
	abstract = {Primary lung tumors, breast tumors, and melanoma metastasize mainly in the brain where therapy is limited to surgery and radiation. To investigate the molecular basis of brain metastases, we isolated brain-trophic metastatic {MDA}-{MB}-435-{LvBr}2 ({LvBr}2) cells via left ventricle ({LV}) injection of {MDA}-{MB}-435 cells into immunodeficiency ({NOD}/{SCID}) mice. Whereas parent {MDA}-{MB}-435 cells displayed an elongated morphology, {LvBr}2 cells were round and displayed an aggregated distribution. {LvBr}2 cells expressed lower beta-catenin levels and higher heterogeneous nuclear ribonucleoprotein C1/C2 ({hnRNPC}) levels than parental cells. Since {microRNAs} are known to play an important role in cancer progression including metastasis, we screened {microRNAs} expressed specifically in brain metastases. {MicroRNA}-146a was almost undetectable in {LvBr}2 cells and highly expressed in the parental cells. Overexpression of {miR}-146a increased beta-catenin expression and suppressed the migratory and invasive activity of {LvBr}2 cells. The {miR}-146a-elicited decrease in {hnRNPC} in turn lowered the expression of {MMP}-1, {uPA}, and {uPAR} and inhibited the migratory and invasive activity of {LvBr}2 cells. Taken together, our findings indicate that {miR}-146a is virtually absent from brain metastases and can suppress their metastatic potential including their migratory and invasive activities associated with upregulation of beta-catenin and downregulation of {hnRNPC}.},
	pages = {329--334},
	number = {3},
	journaltitle = {Mol Cells},
	author = {Hwang, S J and Seol, H J and Park, Y M and Kim, K H and Gorospe, M and Nam, D H and Kim, H H},
	date = {2012},
	pmid = {22949171},
	keywords = {Animals, Mice, *Gene Expression Regulation, beta Catenin/genetics/metabolism, Brain Neoplasms/*genetics/pathology/*secondary, Cell Line, Heterogeneous-Nuclear Ribonucleoprotein Group C/ge, Matrix Metalloproteinase 1/genetics, {MicroRNAs}/*genetics, Neoplastic, Tumor, Urokinase-Type Plasminogen Activator/genetics, Xenograft Model Antitumor Assays}
}

@article{srinivasan_detection_2013,
	title = {Detection of respiratory viruses in asymptomatic children undergoing allogeneic hematopoietic cell transplantation},
	volume = {60},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22987475},
	doi = {10.1002/pbc.24314},
	abstract = {Detection of respiratory viruses by molecular methods, in children without respiratory symptoms undergoing hematopoietic cell transplantation ({HCT}), has not been well described. A prospective study of 33 asymptomatic children detected respiratory viruses in 8 of 33 (24\%) patients before {HCT}. Human rhinovirus ({HRV}) was detected in five patients, and human adenovirus ({hADV}) in three patients. Two additional patients shed {HRV}, and one shed human coronavirus ({hCoV}), post-{HCT}. Two patients had co-infections. Of the 11 asymptomatic patients where respiratory virus was detected, 3 (27\%) later developed an upper respiratory tract infection, from the same virus.},
	pages = {149--151},
	number = {1},
	journaltitle = {Pediatr Blood Cancer},
	author = {Srinivasan, A and Flynn, P and Gu, Z and Hartford, C and Lovins, R and Sunkara, A and Srivastava, D K and Leung, W and Hayden, R T},
	date = {2013},
	pmid = {22987475},
	keywords = {Humans, *Hematopoietic Stem Cell Transplantation, Adenoviruses, Adolescent, Child, Cohort Studies, Coronavirus/*isolation \& purification, Female, Homologous, Human/*isolation \& purification, Infant, Male, Preschool, Prospective Studies, Rhinovirus/*isolation \& purification, Transplantation}
}

@article{kuwano_nf90_2010,
	title = {{NF}90 selectively represses the translation of target {mRNAs} bearing an {AU}-rich signature motif},
	volume = {38},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19850717},
	doi = {10.1093/nar/gkp861},
	abstract = {The {RNA}-binding protein nuclear factor 90 ({NF}90) has been implicated in the stabilization, transport and translational control of several target {mRNAs}. However, a systematic analysis of {NF}90 target {mRNAs} has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of {NF}90-associated {mRNAs}. Comparison of the 3'-untranslated regions ({UTRs}) of these {mRNAs} led to the elucidation of a 25- to 30-nucleotide, {RNA} signature motif rich in adenines and uracils. Insertion of the {AU}-rich {NF}90 motif ('{NF}90m') in the 3'{UTR} of an {EGFP} heterologous reporter did not affect the steady-state level of the chimeric {EGFP}-{NF}90m {mRNA} or its cytosolic abundance. Instead, the translation of {EGFP}-{NF}90m {mRNA} was specifically repressed in an {NF}90-dependent manner, as determined by analysing nascent {EGFP} translation, the distribution of chimeric {mRNAs} on polysome gradients and the steady-state levels of expressed {EGFP} protein. The interaction of endogenous {NF}90 with target {mRNAs} was validated after testing both endogenous {mRNAs} and recombinant biotinylated transcripts containing {NF}90 motif hits. Further analysis showed that the stability of endogenous {NF}90 target {mRNAs} was not significantly influenced by {NF}90 abundance, while their translation increased when {NF}90 levels were reduced. In summary, we have identified an {AU}-rich {RNA} motif present in {NF}90 target {mRNAs} and have obtained evidence that {NF}90 represses the translation of this subset of {mRNAs}.},
	pages = {225--238},
	number = {1},
	journaltitle = {Nucleic Acids Res},
	author = {Kuwano, Y and Pullmann Jr., R and Marasa, B S and Abdelmohsen, K and Lee, E K and Yang, X and Martindale, J L and Zhan, M and Gorospe, M},
	date = {2010},
	pmid = {19850717},
	keywords = {Sequence Analysis, Humans, {RNA}, Oligonucleotide Array Sequence Analysis, *3' Untranslated Regions, *Protein Biosynthesis, Adenine/analysis, {HeLa} Cells, Messenger/metabolism, Nuclear Factor 90 Proteins/antagonists \& inhibitor, {RNA} Interference, Uracil/analysis}
}

@article{georgakilas_microtss:_2014,
	title = {{microTSS}: accurate {microRNA} transcription start site identification reveals a significant number of divergent pri-{miRNAs}},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25492647},
	doi = {10.1038/ncomms6700},
	abstract = {A large fraction of {microRNAs} ({miRNAs}) are derived from intergenic non-coding loci and the identification of their promoters remains 'elusive'. Here, we present {microTSS}, a machine-learning algorithm that provides highly accurate, single-nucleotide resolution predictions for intergenic {miRNA} transcription start sites ({TSSs}). {MicroTSS} integrates high-resolution {RNA}-sequencing data with active transcription marks derived from chromatin immunoprecipitation and {DNase}-sequencing to enable the characterization of tissue-specific promoters. {MicroTSS} is validated with a specifically designed Drosha-null/conditional-null mouse model, generated using the conditional by inversion ({COIN}) methodology. Analyses of global run-on sequencing data revealed numerous pri-{miRNAs} in human and mouse either originating from divergent transcription at promoters of active genes or partially overlapping with annotated long non-coding {RNAs}. {MicroTSS} is readily applicable to any cell or tissue samples and constitutes the missing part towards integrating the regulation of {miRNA} transcription into the modelling of tissue-specific regulatory networks.},
	pages = {5700},
	journaltitle = {Nat Commun},
	author = {Georgakilas, G and Vlachos, I S and Paraskevopoulou, M D and Yang, P and Zhang, Y and Economides, A N and Hatzigeorgiou, A G},
	date = {2014},
	pmid = {25492647},
	keywords = {Sequence Analysis, Animals, Genetic, Humans, Mice, Promoter Regions, {RNA}, Computational Biology, Algorithms, *Transcription Initiation Site, Antisense/genetics, Chromatin Immunoprecipitation, Cluster Analysis, Embryonic Stem Cells/cytology, Messenger/metabolism, {MicroRNAs}/*genetics, Models, Oligonucleotides, Ribonuclease {III}/genetics, {RNA} Polymerase {II}/metabolism, Support Vector Machine, Transgenic, Untranslated/metabolism}
}

@article{noguchi_interleukin-2_1993,
	title = {Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans},
	volume = {73},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8462096},
	abstract = {The interleukin-2 ({IL}-2) receptor gamma chain ({IL}-2R gamma) is a component of high and intermediate affinity {IL}-2 receptors that is required to achieve full ligand binding affinity and internalization. We have localized the {IL}-2R gamma gene to human chromosome Xq13. Genetic linkage analysis indicates that the {IL}-2R gamma gene and the locus for X-linked severe combined immunodeficiency ({XSCID}) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with {XSCID} has a different mutation in his {IL}-2R gamma gene resulting in a different premature stop codon and predicted C-terminal truncation. These data establish that {XSCID} is associated with mutations of the {IL}-2R gamma gene product. Since {XSCID} is characterized by absent or markedly reduced numbers of T cells, our findings imply that {IL}-2R gamma plays a vital role in thymic maturation of T cells. These results also have important implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for {XSCID}.},
	pages = {147--157},
	number = {1},
	journaltitle = {Cell},
	author = {Noguchi, M and Yi, H and Rosenblatt, H M and Filipovich, A H and Adelstein, S and Modi, W S and {McBride}, O W and Leonard, W J},
	date = {1993},
	pmid = {8462096},
	keywords = {Base Sequence, Humans, Chromosome Mapping, Genetic Linkage, Interleukin-2/*genetics, Male, Molecular Sequence Data, Mutation, Pedigree, Receptors, Severe Combined Immunodeficiency/*genetics, X Chromosome}
}

@article{chiaretti_gene_2010,
	title = {Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia with myeloid-like gene features and over-expression of {miR}-223},
	volume = {95},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20418243},
	doi = {10.3324/haematol.2009.015099},
	abstract = {{BACKGROUND}: Until recently, few molecular aberrations were recognized in acute lymphoblastic leukemia of T-cell origin; novel lesions have recently been identified and a certain degree of overlap between acute myeloid leukemia and T-cell acute lymphoblastic leukemia has been suggested. To identify novel T-cell acute lymphoblastic leukemia entities, gene expression profiling was performed and clinico-biological features were studied. {DESIGN} {AND} {METHODS}: Sixty-nine untreated adults with T-cell acute lymphoblastic leukemia were evaluated by oligonucleotide arrays: unsupervised and supervised analyses were performed. The up-regulation of myeloid genes and {miR}-223 expression were validated by quantitative polymerase chain reaction analysis. {RESULTS}: Using unsupervised clustering, we identified five subgroups. Of these, one branch included seven patients whose gene expression profile resembled that of acute myeloid leukemia. These cases were characterized by over-expression of a large set of myeloid-related genes for surface antigens, transcription factors and granule proteins. Real-time quantitative polymerase chain reaction analysis confirmed over-expression of {MPO}, {CEBPA}, {CEBPB}, {GRN} and {IL}8. We, therefore, evaluated the expression levels of {miR}-223, involved in myeloid differentiation: these cases had significantly higher levels of {miR}-223 than had the other cases of T-cell acute lymphoblastic leukemia, with values comparable to those observed in acute myeloid leukemia. Finally, these patients appear to have an unfavorable clinical course. {CONCLUSIONS}: Using gene profiling we identified a subset of adult T-cell acute lymphoblastic leukemia, accounting for 10\% of the cases analyzed, which displays myeloid features. These cases were not recognized by standard approaches, underlining the importance of gene profiling in identifying novel acute leukemia subsets. The recognition of this subgroup may have clinical, prognostic and therapeutic implications.},
	pages = {1114--1121},
	number = {7},
	journaltitle = {Haematologica},
	author = {Chiaretti, S and Messina, M and Tavolaro, S and Zardo, G and Elia, L and Vitale, A and Fatica, A and Gorello, P and Piciocchi, A and Scappucci, G and Bozzoni, I and Fozza, C and Candoni, A and Guarini, A and Foa, R},
	date = {2010},
	pmid = {20418243},
	keywords = {Humans, *Gene Expression Profiling, *Gene Expression Regulation, Acute/*genetics, Adult, Adult T-Cell/*genetics/patholog, Leukemia, Leukemia-Lymphoma, {MicroRNAs}/*genetics, Myeloid, Neoplastic}
}

@article{singh_structural_2013,
	title = {Structural and Functional Characterization of {CalS}11, a {TDP}-Rhamnose 3'-O-Methyltransferase Involved in Calicheamicin Biosynthesis},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23662776},
	doi = {10.1021/cb400068k},
	abstract = {Sugar methyltransferases ({MTs}) are an important class of tailoring enzymes that catalyze the transfer of a methyl group from S-adenosyl-l-methionine to sugar-based N-, C- and O-nucleophiles. While sugar N- and C-{MTs} involved in natural product biosynthesis have been found to act on sugar nucleotide substrates prior to a subsequent glycosyltransferase reaction, corresponding sugar O-methylation reactions studied thus far occur after the glycosyltransfer reaction. Herein we report the first in vitro characterization using (1)H-(13)C-{gHSQC} with isotopically labeled substrates and the X-ray structure determination at 1.55 A resolution of the {TDP}-3'-O-rhamnose-methyltransferase {CalS}11 from Micromonospora echinospora. This study highlights a unique {NMR}-based methyltransferase assay, implicates {CalS}11 to be a metal- and general acid/base-dependent O-methyltransferase, and as a first crystal structure for a {TDP}-hexose-O-methyltransferase, presents a new template for mechanistic studies and/or engineering.},
	pages = {1632--1639},
	number = {7},
	journaltitle = {{ACS} Chem Biol},
	author = {Singh, S and Chang, A and Helmich, K E and Bingman, C A and Wrobel, R L and Beebe, E T and Makino, S and Aceti, D J and Dyer, K and Hura, G L and Sunkara, M and Morris, A J and Phillips Jr., G N and Thorson, J S},
	date = {2013},
	pmid = {23662776}
}

@article{renzi_large-scale_2006,
	title = {Large-scale purification and crystallization of the endoribonuclease {XendoU}: troubleshooting with His-tagged proteins},
	volume = {62},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16511328},
	doi = {10.1107/S1744309106006373},
	abstract = {{XendoU} is the first endoribonuclease described in higher eukaryotes as being involved in the endonucleolytic processing of intron-encoded small nucleolar {RNAs}. It is conserved among eukaryotes and its viral homologue is essential in {SARS} replication and transcription. The large-scale purification and crystallization of recombinant {XendoU} are reported. The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents ({EDTA}, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Purified monodisperse {XendoU} crystallized in two different space groups: trigonal P3(1)21, diffracting to low resolution, and monoclinic C2, diffracting to higher resolution.},
	pages = {298--301},
	issue = {Pt 3},
	journaltitle = {Acta Crystallogr Sect F Struct Biol Cryst Commun},
	author = {Renzi, F and Panetta, G and Vallone, B and Brunori, M and Arceci, M and Bozzoni, I and Laneve, P and Caffarelli, E},
	date = {2006},
	pmid = {16511328},
	keywords = {Animals, Crystallization/methods, Edetic Acid/chemistry, Endoribonucleases/*chemistry/*isolation \& purifica, Escherichia coli/metabolism, Histidine/*genetics, Oligopeptides/*genetics, Recombinant Fusion Proteins/chemistry/isolation \&, Xenopus laevis, Xenopus Proteins/*chemistry/*isolation \& purificat}
}

@article{stern-ginossar_decoding_2012,
	title = {Decoding human cytomegalovirus},
	volume = {338},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23180859},
	doi = {10.1126/science.1227919},
	abstract = {The human cytomegalovirus ({HCMV}) genome was sequenced 20 years ago. However, like those of other complex viruses, our understanding of its protein coding potential is far from complete. We used ribosome profiling and transcript analysis to experimentally define the {HCMV} translation products and follow their temporal expression. We identified hundreds of previously unidentified open reading frames and confirmed a fraction by means of mass spectrometry. We found that regulated use of alternative transcript start sites plays a broad role in enabling tight temporal control of {HCMV} protein expression and allowing multiple distinct polypeptides to be generated from a single genomic locus. Our results reveal an unanticipated complexity to the {HCMV} coding capacity and illustrate the role of regulated changes in transcript start sites in generating this complexity.},
	pages = {1088--1093},
	number = {6110},
	journaltitle = {Science},
	author = {Stern-Ginossar, N and Weisburd, B and Michalski, A and Le, V T and Hein, M Y and Huang, S X and Ma, M and Shen, B and Qian, S B and Hengel, H and Mann, M and Ingolia, N T and Weissman, J S},
	date = {2012},
	pmid = {23180859},
	keywords = {{DNA}, Sequence Analysis, Genetic, Humans, Transcription, *Genome, *Open Reading Frames, Alternative Splicing, Cytomegalovirus Infections/*virology, Cytomegalovirus/*genetics, Genetic Variation, Protein Biosynthesis/genetics, Proteome/genetics, Viral}
}

@article{pandey_risk-associated_2014,
	title = {The risk-associated long noncoding {RNA} {NBAT}-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25517750},
	doi = {10.1016/j.ccell.2014.09.014},
	abstract = {Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding {RNAs} ({lncRNAs}). We identified a {lncRNA} neuroblastoma associated transcript-1 ({NBAT}-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. {CpG} methylation and a high-risk neuroblastoma associated {SNP} on chromosome 6p22 functionally contribute to {NBAT}-1 differential expression. Loss of {NBAT}-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. {NBAT}-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor {NRSF}/{REST}. Thus, loss of {NBAT}-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.},
	pages = {722--737},
	number = {5},
	journaltitle = {Cancer Cell},
	author = {Pandey, G K and Mitra, S and Subhash, S and Hertwig, F and Kanduri, M and Mishra, K and Fransson, S and Ganeshram, A and Mondal, T and Bandaru, S and Ostensson, M and Akyurek, L M and Abrahamsson, J and Pfeifer, S and Larsson, E and Shi, L and Peng, Z and Fischer, M and Martinsson, T and Hedborg, F and Kogner, P and Kanduri, C},
	date = {2014},
	pmid = {25517750},
	keywords = {Transcriptome, Animals, Humans, Mice, {RNA}, *Cell Proliferation, Biological/*physiology, Cell Line, Disease Progression, Long Noncoding/*physiology, Neoplasm Transplantation, Neural Stem Cells/physiology, Neuroblastoma/genetics/*metabolism/pathology, Neurogenesis, Polymorphism, Repressor Proteins/metabolism, Risk, Single Nucleotide, Tumor, Tumor Markers}
}

@article{bassett_considerations_2014,
	title = {Considerations when investigating {lncRNA} function in vivo},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25124674},
	doi = {10.7554/eLife.03058},
	abstract = {Although a small number of the vast array of animal long non-coding {RNAs} ({lncRNAs}) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the {lncRNA} per se or to the associated loss of other overlapping {DNA} regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of {lncRNAs} in the light of different models of {lncRNA} molecular mechanism, and reflect on the design of experiments to mutate {lncRNA} loci. These considerations should assist in the further investigation of these transcriptional products of the genome.{DOI}: http://dx.doi.org/10.7554/{eLife}.03058.001.},
	pages = {e03058},
	journaltitle = {Elife},
	author = {Bassett, A R and Akhtar, A and Barlow, D P and Bird, A P and Brockdorff, N and Duboule, D and Ephrussi, A and Ferguson-Smith, A C and Gingeras, T R and Haerty, W and Higgs, D R and Miska, E A and Ponting, C P},
	date = {2014},
	pmid = {25124674}
}

@article{xu_induction_1997,
	title = {Induction of mitogen-activated protein kinase phosphatase-1 during acute hypertension},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9231829},
	abstract = {Recently, we demonstrated that elevated blood pressure activates mitogen-activated protein ({MAP}) kinases in rat aorta. Here we provide evidence that the vascular response to acute hypertension also includes induction of {MAP} kinase phosphatase-1 ({MKP}-1), which has been shown to function in the dephosphorylation and inactivation of {MAP} kinases. Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of {MKP}-1 {mRNA} followed by elevated {MKP}-1 protein expression in rat aorta. That the induction of {MKP}-1 by restraint was due to the rise in blood pressure was supported by the finding that several different hypertensive agents (phenylephrine, vasopressin, and angiotensin {II}) were likewise capable of eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent that prevented the acute rise in blood pressure in response to the hypertensive agents, abrogated {MKP}-1 {mRNA} induction. The in vivo effects could not be mimicked by treatment of cultured aortic smooth muscle cells with similar doses of the hypertensive agents. These findings support a role for {MKP}-1 in the in vivo regulation of {MAP} kinase activity during hemodynamic stress.},
	pages = {106--111},
	number = {1},
	journaltitle = {Hypertension},
	author = {Xu, Q and Fawcett, T W and Gorospe, M and Guyton, K Z and Liu, Y and Holbrook, N J},
	date = {1997},
	pmid = {9231829},
	keywords = {Animals, Cells, Cultured, *Gene Expression Regulation, Acute Disease, Angiotensin {II}/pharmacology, Antihypertensive Agents/pharmacology, Blood Pressure/drug effects, Blotting, Cardiovascular System/enzymology/physiopathology, Data Interpretation, Enzyme Activation, Enzymologic, Hypertension/*enzymology/etiology/physiopathology, Male, Mitogens/pharmacology, Muscle, Nitroprusside/pharmacology, Phenylephrine/pharmacology, Phosphoprotein Phosphatases/*genetics/*metabolism, Physical, Physiological/complications, Protein Kinases/*genetics/*metabolism, Protein Phosphatase 1, Rats, Restraint, {RNA}/analysis, Smooth, Statistical, Stress, Vascular/cytology/enzymology/metab, Vasoconstrictor Agents/pharmacology, Vasodilator Agents/pharmacology, Vasopressins/pharmacology, Western, Wistar}
}

@article{horvath_midterm_2010,
	title = {Midterm results of transapical aortic valve replacement via real-time magnetic resonance imaging guidance},
	volume = {139},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19969312},
	doi = {10.1016/j.jtcvs.2009.08.005},
	abstract = {{OBJECTIVE}: Percutaneous valve replacements are presently being evaluated in clinical trials. As delivery of the valve is catheter based, the safety and efficacy of these procedures may be influenced by the imaging used. To assist the surgeon and improve the success of the operation, we have performed transapical aortic valve replacements using real-time magnetic resonance imaging guidance. {METHODS}: Twenty-eight swine underwent aortic valve replacement by real-time magnetic resonance imaging on the beating heart. Stentless bioprostheses mounted on balloon-expandable stents were used. Magnetic resonance imaging (1.5 T) was used to identify the critical anatomic landmarks. In addition to anatomic confirmation of adequate placement of the prosthesis, functional assessment of the valve and left ventricle and perfusion were also obtained with magnetic resonance imaging. A series of short-term feasibility experiments were conducted (n = 18) in which the animals were humanely killed after valve placement and assessment by magnetic resonance imaging. Ten additional animals were allowed to survive and had follow-up magnetic resonance imaging scans and confirmatory echocardiography at 1, 3, and 6 months postoperatively. {RESULTS}: Real-time magnetic resonance imaging provided superior visualization of the landmarks needed. The time to implantation after apical access was 74 +/- 18 seconds. Perfusion scanning demonstrated adequate coronary flow and functional imaging documented preservation of ventricular contractility in all animals after successful deployment. Phase contrast imaging revealed minimal intravalvular or paravalvular leaks. Longer term results demonstrated stability of the implants with preservation of myocardial perfusion and function over time. {CONCLUSIONS}: Real-time magnetic resonance imaging provides excellent visualization for intraoperative guidance of aortic valve replacement on the beating heart. Additionally, it allows assessment of tissue perfusion and organ function that is not obtainable by conventional imaging alone.},
	pages = {424--430},
	number = {2},
	journaltitle = {J Thorac Cardiovasc Surg},
	author = {Horvath, K A and Mazilu, D and Guttman, M and Zetts, A and Hunt, T and Li, M},
	date = {2010},
	pmid = {19969312},
	keywords = {Animals, *Magnetic Resonance Imaging, Aortic Valve/*surgery, Bioprosthesis, Catheterization, Cine, Computer-Assisted/*methods, Heart Valve Prosthesis, Heart Valve Prosthesis Implantation/*methods, Magnetic Resonance Imaging, Surgery, Swine, Treatment Outcome}
}

@article{liu_impairments_1998,
	title = {Impairments in both p70 S6 kinase and extracellular signal-regulated kinase signaling pathways contribute to the decline in proliferative capacity of aged hepatocytes},
	volume = {240},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9570919},
	doi = {10.1006/excr.1997.3931},
	abstract = {Treatment of primary cultured hepatocytes from adult (6-month-old) rats with epidermal growth factor ({EGF}) results in a marked elevation in {DNA} synthesis, a response that is markedly attenuated in cells of aged (24-month-old) animals. Recently we demonstrated that this age-related attenuation is associated with reduced activation of extracellular signal-regulated kinase ({ERK}) in response to {EGF} treatment. In order to gain further insight into the mechanisms responsible for the age-related decline in this proliferative response, we investigated the expression and/or activities of several other regulatory molecules important for G1 to S phase progression in {EGF}-stimulated young and aged hepatocytes. Induction of cyclin D1 and activation of cyclin-dependent kinase 2 ({CDK}2) by {EGF} were found to be diminished in the aged cells. In young cells, prior treatment with rapamycin inhibited the induction of {DNA} synthesis and activation of {CDK}2 to levels similar to those seen in aged cells without inhibiting {ERK} activity and cyclin D1 expression. This suggested that a distinct, {ERK}-independent, rapamycin-sensitive pathway might also contribute to the proliferative response in hepatocytes and be subject to age-related alterations. Further studies demonstrated that activation of p70 S6 kinase (p70S6k), a rapamycin-sensitive event, following {EGF} treatment was 40\% lower in aged hepatocytes relative to young cells, although the kinetics of activation did not differ in the two age groups. Western blot analysis for p70S6k expression revealed similar levels of proteins in young and aged cells. From these findings, we conclude that deficiencies in both the {ERK} and p70S6k signaling pathways contribute to the age-related decline in the proliferative response of hepatocytes.},
	pages = {40--48},
	number = {1},
	journaltitle = {Exp Cell Res},
	author = {Liu, Y and Gorospe, M and Kokkonen, G C and Boluyt, M O and Younes, A and Mock, Y D and Wang, X and Roth, G S and Holbrook, N J},
	date = {1998},
	pmid = {9570919},
	keywords = {Animals, Cells, Cultured, *{CDC}2-{CDC}28 Kinases, Cell Aging/physiology, Cell Cycle/physiology, Cell Division/physiology, Cyclin D1/metabolism, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases/metabolism, Cysteine Proteinase Inhibitors/pharmacology, {DNA}/biosynthesis, Liver/*cytology/*enzymology, Male, Mitogen-Activated Protein Kinases/*metabolism, Nerve Tissue Proteins/*metabolism, Polyenes/pharmacology, Protein-Serine-Threonine Kinases/metabolism, Rats, Ribosomal Protein S6 Kinases/*metabolism, Signal Transduction/drug effects/*physiology, Sirolimus, Wistar}
}

@article{hutchison_evidence_2013,
	title = {Evidence for {miR}-181 involvement in neuroinflammatory responses of astrocytes},
	volume = {61},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23650073},
	doi = {10.1002/glia.22483},
	abstract = {Inflammation is a common component of acute injuries of the central nervous system ({CNS}) such as ischemia, and degenerative disorders such as Alzheimer's disease. Glial cells play important roles in local {CNS} inflammation, and an understanding of the roles for {microRNAs} in glial reactivity in injury and disease settings may therefore lead to the development of novel therapeutic interventions. Here, we show that the {miR}-181 family is developmentally regulated and present in high amounts in astrocytes compared to neurons. Overexpression of {miR}-181c in cultured astrocytes results in increased cell death when exposed to lipopolysaccharide ({LPS}). We show that {miR}-181 expression is altered by exposure to {LPS}, a model of inflammation, in both wild-type and transgenic mice lacking both receptors for the inflammatory cytokine {TNF}-alpha. Knockdown of {miR}-181 enhanced {LPS}-induced production of pro-inflammatory cytokines ({TNF}-alpha, {IL}-6, {IL}-1beta, {IL}-8) and {HMGB}1, while overexpression of {miR}-181 resulted in a significant increase in the expression of the anti-inflammatory cytokine {IL}-10. To assess the effects of {miR}-181 on the astrocyte transcriptome, we performed gene array and pathway analysis on astrocytes with reduced levels of {miR}-181b/c. To examine the pool of potential {miR}-181 targets, we employed a biotin pull-down of {miR}-181c and gene array analysis. We validated the {mRNAs} encoding {MeCP}2 and X-linked inhibitor of apoptosis as targets of {miR}-181. These findings suggest that {miR}-181 plays important roles in the molecular responses of astrocytes in inflammatory settings. Further understanding of the role of {miR}-181 in inflammatory events and {CNS} injury could lead to novel approaches for the treatment of {CNS} disorders with an inflammatory component.},
	pages = {1018--1028},
	number = {7},
	journaltitle = {Glia},
	author = {Hutchison, E R and Kawamoto, E M and Taub, D D and Lal, A and Abdelmohsen, K and Zhang, Y and Wood 3rd, W H and Lehrmann, E and Camandola, S and Becker, K G and Gorospe, M and Mattson, M P},
	date = {2013},
	pmid = {23650073},
	keywords = {Animals, Mice, Cells, Cultured, Astrocytes/drug effects/*metabolism, Biotinylation, Brain-Derived Neurotrophic Factor/pharmacology, Cerebral Cortex/cytology, Cytokines/metabolism, Knockout, L-Lactate Dehydrogenase/metabolism, Lipopolysaccharides/pharmacology, Male, Methyl-{CpG}-Binding Protein 2/genetics/metabolism, {MicroRNAs}/*metabolism, Neuroimmunomodulation/drug effects/*immunology, Neurons/drug effects/metabolism, Receptors, Transfection, Tumor Necrosis Factor, Type I/deficienc, Type {II}/deficien, X-Linked Inhibitor of Apoptosis Protein/genetics}
}

@article{galban_factors_2009,
	title = {Factors interacting with {HIF}-1alpha {mRNA}: novel therapeutic targets},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19671045},
	abstract = {The heterodimeric transcription factor {HIF}-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The {HIF}-1beta subunit is constitutively expressed, but the levels of the {HIF}-1alpha subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of {HIF}-1alpha production and degradation. While the regulation of {HIF}-1alpha degradation is understood in significant detail, much less is known about the regulation of {HIF}-1alpha biosynthesis. Here, we review recent evidence that {HIF}-1alpha production is effectively controlled by post-transcriptional mechanisms. We focus on the {RNA}-binding proteins ({RBPs}) and the non-coding {RNAs} that interact with the {HIF}-1alpha {mRNA} and influence its half-life and translation rate. {HIF}-1alpha {mRNA}-binding factors are emerging as promising pharmacological targets to control {HIF}-1alpha production selectively and efficiently.},
	pages = {3853--3860},
	number = {33},
	journaltitle = {Curr Pharm Des},
	author = {Galban, S and Gorospe, M},
	date = {2009},
	pmid = {19671045},
	keywords = {Animals, Humans, {RNA}, Gene Expression Regulation, *Drug Delivery Systems, alpha Subunit/*genetic, Aryl Hydrocarbon Receptor Nuclear Translocator/gen, Half-Life, Hypoxia-Inducible Factor 1, Messenger/*metabolism, Neoplasms/drug therapy/physiopathology, Neovascularization, Pathologic/drug therapy/physio, Post-Transcriptional/physiology, {RNA} Processing}
}

@article{su_interferon-gamma_2015,
	title = {Interferon-gamma regulates cellular metabolism and {mRNA} translation to potentiate macrophage activation},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26147685},
	doi = {10.1038/ni.3205},
	abstract = {Interferon-gamma ({IFN}-gamma) primes macrophages for enhanced microbial killing and inflammatory activation by Toll-like receptors ({TLRs}), but little is known about the regulation of cell metabolism or {mRNA} translation during this priming. We found that {IFN}-gamma regulated the metabolism and {mRNA} translation of human macrophages by targeting the kinases {mTORC}1 and {MNK}, both of which converge on the selective regulator of translation initiation {eIF}4E. Physiological downregulation of {mTORC}1 by {IFN}-gamma was associated with autophagy and translational suppression of repressors of inflammation such as {HES}1. Genome-wide ribosome profiling in {TLR}2-stimulated macrophages showed that {IFN}-gamma selectively modulated the macrophage translatome to promote inflammation, further reprogram metabolic pathways and modulate protein synthesis. These results show that {IFN}-gamma-mediated metabolic reprogramming and translational regulation are key components of classical inflammatory macrophage activation.},
	pages = {838--849},
	number = {8},
	journaltitle = {Nat Immunol},
	author = {Su, X and Yu, Y and Zhong, Y and Giannopoulou, E G and Hu, X and Liu, H and Cross, J R and Ratsch, G and Rice, C M and Ivashkiv, L B},
	date = {2015},
	pmid = {26147685},
	keywords = {Base Sequence, Humans, {RNA}, Gene Expression Profiling, Cells, Cultured, Basic Helix-Loop-Helix Transcription Factors/genet, Blotting, Eukaryotic Initiation Factor-4E/genetics/immunolog, Fluorescence, Homeodomain Proteins/genetics/immunology/metabolis, Interferon-gamma/*immunology/pharmacology, Intracellular Signaling Peptides and Proteins/gene, Macrophage Activation/drug effects/genetics/*immun, Macrophages/drug effects/*immunology/metabolism, Messenger/genetics/*immunology, {MicroRNAs}/genetics, Microscopy, Multiprotein Complexes/genetics/immunology/metabol, Protein Biosynthesis/drug effects/genetics/*immuno, Protein-Serine-Threonine Kinases/genetics/immunolo, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, Signal Transduction/drug effects/genetics/immunolo, Toll-Like Receptor 2/genetics/immunology/metabolis, {TOR} Serine-Threonine Kinases/genetics/immunology/m, Western}
}

@article{ule_clip_2003,
	title = {{CLIP} identifies Nova-regulated {RNA} networks in the brain},
	volume = {302},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14615540},
	doi = {10.1126/science.1090095},
	abstract = {Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia ({POMA}), an autoimmune neurologic disease characterized by abnormal motor inhibition. Nova proteins regulate neuronal pre-messenger {RNA} splicing by directly binding to {RNA}. To identify Nova {RNA} targets, we developed a method to purify protein-{RNA} complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation ({CLIP}).Thirty-four transcripts were identified multiple times by Nova {CLIP}.Three-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibition.Splicing targets confirmed in Nova-/- mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory gamma-aminobutyric acid and glycine receptors, two previously identified Nova splicing targets.Thus, {CLIP} reveals that Nova coordinately regulates a biologically coherent set of {RNAs} encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in {POMA}.},
	pages = {1212--1215},
	number = {5648},
	journaltitle = {Science},
	author = {Ule, J and Jensen, K B and Ruggiu, M and Mele, A and Ule, A and Darnell, R B},
	date = {2003},
	pmid = {14615540},
	keywords = {3' Untranslated Regions, Animals, Mice, {RNA}, Exons, Introns, *Antigens, Alternative Splicing, Brain/*metabolism, Carrier Proteins/genetics/metabolism, Membrane Proteins/genetics/metabolism, Messenger/genetics/*metabolism, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinases/genetics/metabol, Neoplasm, Nerve Tissue Proteins/*metabolism, Neural Inhibition, Neurons/*metabolism, Precipitin Tests, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Precursors/genetics/*metabolism, {RNA}-Binding Proteins/*metabolism, Ultraviolet Rays}
}

@article{lal_egad_2006,
	title = {Egad, more forms of gene regulation: the gadd45a story},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16775423},
	abstract = {Despite the historical hegemony of transcription, mounting evidence supports the importance of posttranscriptional gene regulation via processes such as {mRNA} splicing, localization, turnover, and translation. However, each of these steps is still largely viewed as an exclusive proposition, whereby a particular gene under given circumstances is controlled by a single specific regulatory mechanism. Our recent investigation of gadd45a expression in response to genotoxic stress illustrates a more complex scenario, wherein transcriptional changes operate in concert with {mRNA} turnover and translational regulation. gadd45a thus joins a handful of reported genes whose levels are potently altered in response to cellular damage or mitogenic cues through the coordinated action of {DNA}- and {RNA}-binding proteins. Eliciting cellular responses that are strong, swift, and versatile, gene regulation by multiple factors acting on different levels is emerging as the norm, rather than the exception, for a growing collection of gene products which critically influence cellular homeostasis.},
	pages = {1422--1425},
	number = {13},
	journaltitle = {Cell Cycle},
	author = {Lal, A and Gorospe, M},
	date = {2006},
	pmid = {16775423},
	keywords = {Animals, Humans, Transcription, Protein Binding, Genetic/genetics, Cell Cycle Proteins/*genetics/*metabolism, Gene Expression Regulation/*genetics, Nuclear Proteins/*genetics/*metabolism}
}

@article{lopez_de_silanes_role_2003,
	title = {Role of the {RNA}-binding protein {HuR} in colon carcinogenesis},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14562043},
	doi = {10.1038/sj.onc.1206862},
	abstract = {Immunohistochemical analysis of paired tumor and normal tissue specimens revealed that the expression and cytoplasmic abundance of the {RNA}-binding protein {HuR} increased with malignancy, particularly in colon carcinomas. Interventions to modulate {HuR} expression in human {RKO} colon cancer cells altered gene expression profiles and identified beta-catenin {mRNA} as a novel {HuR} target. Subcutaneous injection of {HuR}-overexpressing {RKO} cells into nude mice produced significantly larger tumors than those arising from control populations; conversely, {RKO} cells expressing reduced {HuR} through small interference {RNA}- or antisense {HuR}-based approaches developed significantly more slowly. We propose that {HuR}-regulated target {mRNA} expression contributes to colon cancer growth. Our results suggest a pivotal function for {HuR} in colon carcinogenesis.},
	pages = {7146--7154},
	number = {46},
	journaltitle = {Oncogene},
	author = {Lopez de Silanes, I and Fan, J and Yang, X and Zonderman, A B and Potapova, O and Pizer, E S and Gorospe, M},
	date = {2003},
	pmid = {14562043},
	keywords = {Animals, Base Sequence, Genetic, Humans, Mice, Transcription, Oligonucleotide Array Sequence Analysis, Cultured, *Antigens, *Gene Expression Regulation, Cell Nucleus/pathology/physiology, Cell Transformation, Colonic Neoplasms/*genetics/pathology, Cytoplasm/pathology/physiology, Heterologous, Hu Paraneoplastic Encephalomyelitis Antigens, Neoplastic, Neoplastic/genetics, Nude, {RNA}-Binding Proteins/*genetics, Surface, Templates, Transfection, Transplantation, Tumor Cells}
}

@article{mariner_human_2008,
	title = {Human Alu {RNA} is a modular transacting repressor of {mRNA} transcription during heat shock},
	volume = {29},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18313387},
	doi = {10.1016/j.molcel.2007.12.013},
	abstract = {Noncoding {RNAs} ({ncRNAs}) have recently been discovered to regulate {mRNA} transcription in trans, a role traditionally reserved for proteins. The breadth of {ncRNAs} as transacting transcriptional regulators and the diversity of signals to which they respond are only now becoming recognized. Here we show that human Alu {RNA}, transcribed from short interspersed elements ({SINEs}), is a transacting transcriptional repressor during the cellular heat shock response. Alu {RNA} blocks transcription by binding {RNA} polymerase {II} (Pol {II}) and entering complexes at promoters in vitro and in human cells. Transcriptional repression by Alu {RNA} involves two loosely structured domains that are modular, a property reminiscent of classical protein transcriptional regulators. Two other {SINE} {RNAs}, human {scAlu} {RNA} and mouse B1 {RNA}, also bind Pol {II} but do not repress transcription in vitro. These studies provide an explanation for why mouse cells harbor two major classes of {SINEs}, whereas human cells contain only one.},
	pages = {499--509},
	number = {4},
	journaltitle = {Mol Cell},
	author = {Mariner, P D and Walters, R D and Espinoza, C A and Drullinger, L F and Wagner, S D and Kugel, J F and Goodrich, J A},
	date = {2008},
	pmid = {18313387},
	keywords = {Animals, Genetic, Humans, Mice, Promoter Regions, {RNA}, *Transcription, *Gene Expression Regulation, *{RNA}, *Short Interspersed Nucleotide Elements, Alu Elements/*genetics, Antisense/genetics/metabolism, Cell Line, Heat-Shock Response/*genetics, Messenger/chemistry/genetics/*metabolism, Nucleic Acid Conformation, Oligonucleotides, {RNA} Polymerase {II}/antagonists \& inhibitors/metabol, Untranslated/chemistry/genetics/metabolism}
}

@article{gupta_long_2010,
	title = {Long non-coding {RNA} {HOTAIR} reprograms chromatin state to promote cancer metastasis},
	volume = {464},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20393566},
	doi = {10.1038/nature08975},
	abstract = {Large intervening non-coding {RNAs} ({lincRNAs}) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual {lincRNAs} can function as the interface between {DNA} and specific chromatin remodelling activities. Here we show that {lincRNAs} in the {HOX} loci become systematically dysregulated during breast cancer progression. The {lincRNA} termed {HOTAIR} is increased in expression in primary breast tumours and metastases, and {HOTAIR} expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of {HOTAIR} in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 ({PRC}2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on {PRC}2. Conversely, loss of {HOTAIR} can inhibit cancer invasiveness, particularly in cells that possess excessive {PRC}2 activity. These findings indicate that {lincRNAs} have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.},
	pages = {1071--1076},
	number = {7291},
	journaltitle = {Nature},
	author = {Gupta, R A and Shah, N and Wang, K C and Kim, J and Horlings, H M and Wong, D J and Tsai, M C and Hung, T and Argani, P and Rinn, J L and Wang, Y and Brzoska, P and Kong, B and Li, R and West, R B and van de Vijver, M J and Sukumar, S and Chang, H Y},
	date = {2010},
	pmid = {20393566},
	keywords = {Animals, Genetic, Genome, Humans, Mice, {RNA}, Gene Expression Regulation, Chromatin/*genetics, Breast Neoplasms/genetics/pathology, Cell Line, Cell Proliferation, Chromatin Assembly and Disassembly/*genetics, Disease Progression, Epigenesis, Female, Genes, Histones/metabolism, Homeobox/genetics, Human/genetics, Methylation, Middle Aged, Neoplasm Invasiveness, Neoplasm Metastasis/*genetics, Neoplasm Transplantation, Neoplastic, Nude, Polycomb-Group Proteins, Prognosis, Repressor Proteins/analysis/metabolism, {RNA} Interference, {SCID}, Survival Rate, Tumor, Untranslated/biosynthesis/*genetics}
}

@article{kim_nuclear_2008,
	title = {Nuclear {HuR} accumulation through phosphorylation by Cdk1},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18593881},
	doi = {10.1101/gad.1645808},
	abstract = {A predominantly nuclear {RNA}-binding protein, {HuR} translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target {mRNAs}. Here, we present evidence that {HuR} phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. {HuR} was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions. In keeping with the prominently cytoplasmic location of the nonphosphorylatable point mutant {HuR}(S202A), phospho-{HuR}(S202) was shown to be predominantly nuclear using a novel anti-phospho-{HuR}(S202) antibody. The enhanced cytoplasmic presence of unphosphorylated {HuR} was linked to its decreased association with 14-3-3 and to its heightened binding to target {mRNAs}. Our findings suggest that Cdk1 phosphorylates {HuR} during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence.},
	pages = {1804--1815},
	number = {13},
	journaltitle = {Genes Dev},
	author = {Kim, H H and Abdelmohsen, K and Lal, A and Pullmann Jr., R and Yang, X and Galban, S and Srikantan, S and Martindale, J L and Blethrow, J and Shokat, K M and Gorospe, M},
	date = {2008},
	pmid = {18593881},
	keywords = {Humans, Protein Binding, Cell Nucleus, 14-3-3 Proteins/metabolism, Active Transport, Antigens, {CDC}2 Protein Kinase/*metabolism, Cell Cycle/physiology, Cell Nucleus/*metabolism, Cytoplasm/metabolism, {HeLa} Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Phosphorylation, {RNA}-Binding Proteins/*metabolism, Surface/*metabolism}
}

@article{hauser_clinical_1997,
	title = {Clinical trials of add-on medications in Parkinson's disease: Efficacy versus usefulness},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18591048},
	abstract = {Clinical trials designed to evaluate the efficacy of new anti-parkinsonian agents often employ an 'add-on' protocol in which patients with motor fluctuations on levodopa are randomized to receive active medication or placebo. Levodopa doses may not be increased, but can be decreased in response to dopaminergic side-effects such as increasing dyskinesia or hallucinations. Although these trials can delineate efficacy, additional studies are necessary to evaluate the usefulness of these medications in the clinical setting. The most important questions to be answered by such studies are: (1) Is the benefit derived from addon medication greater than that which could be brought about by further levodopa titration alone?, and (2) Can 'off' time be decreased and motor function improved without a proportionate increase in unwanted dyskinesia? The short-term symptomatic usefulness of an add-on medication can be evaluated by comparing the effects of the addition of active medication plus levodopa titration to further levodopa titration alone. We discuss the limitations of current add-on protocols as well as protocols which may help address the issue of clinical usefulness.},
	pages = {1--6},
	number = {1},
	journaltitle = {Parkinsonism Relat Disord},
	author = {Hauser, R A and Zesiewicz, T A and Factor, S A and Guttman, M and Weiner, W J},
	date = {1997},
	pmid = {18591048}
}

@article{wang_comparison_2010,
	title = {Comparison of computational models for assessing conservation of gene expression across species},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20949029},
	doi = {10.1371/journal.pone.0013239},
	abstract = {Assessing conservation/divergence of gene expression across species is important for the understanding of gene regulation evolution. Although advances in microarray technology have provided massive high-dimensional gene expression data, the analysis of such data is still challenging. To date, assessing cross-species conservation of gene expression using microarray data has been mainly based on comparison of expression patterns across corresponding tissues, or comparison of co-expression of a gene with a reference set of genes. Because direct and reliable high-throughput experimental data on conservation of gene expression are often unavailable, the assessment of these two computational models is very challenging and has not been reported yet. In this study, we compared one corresponding tissue based method and three co-expression based methods for assessing conservation of gene expression, in terms of their pair-wise agreements, using a frequently used human-mouse tissue expression dataset. We find that 1) the co-expression based methods are only moderately correlated with the corresponding tissue based methods, 2) the reliability of co-expression based methods is affected by the size of the reference ortholog set, and 3) the corresponding tissue based methods may lose some information for assessing conservation of gene expression. We suggest that the use of either of these two computational models to study the evolution of a gene's expression may be subject to great uncertainty, and the investigation of changes in both gene expression patterns over corresponding tissues and co-expression of the gene with other genes is necessary.},
	pages = {e13239},
	number = {10},
	journaltitle = {{PLoS} One},
	author = {Wang, Y and Robbins, K R and Rekaya, R},
	date = {2010},
	pmid = {20949029},
	keywords = {Oligonucleotide Array Sequence Analysis, *Computer Simulation, *Gene Expression, Species Specificity}
}

@article{muller_regulatory_2008,
	title = {Regulatory networks define phenotypic classes of human stem cell lines},
	volume = {455},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18724358},
	doi = {10.1038/nature07213},
	abstract = {Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells-typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation-to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine has highlighted the need for a general, reproducible method for classification of these cells. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approximately 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein-protein network ({PluriNet}) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the {PluriNet} seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.},
	pages = {401--405},
	number = {7211},
	journaltitle = {Nature},
	author = {Muller, F J and Laurent, L C and Kostka, D and Ulitsky, I and Williams, R and Lu, C and Park, I H and Rao, M S and Shamir, R and Schwartz, P H and Schmidt, N O and Loring, J F},
	date = {2008},
	pmid = {18724358},
	keywords = {Animals, Humans, Mice, Protein Binding, Computational Biology, Oligonucleotide Array Sequence Analysis, Databases, Algorithms, *Gene Expression Profiling, Artificial Intelligence, Cell Differentiation, Cell Line, Embryonic Stem Cells/classification/metabolism, Factual, Multipotent Stem Cells/classification/metabolism, Oocytes/classification/metabolism, Phenotype, Pluripotent Stem Cells/classification/metabolism, Stem Cells/*classification/*metabolism}
}

@article{cacchiarelli_micrornas_2008,
	title = {{MicroRNAs} as prime players in a combinatorial view of evolution},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18698151},
	abstract = {{MicroRNA}-mediated gene regulation allows the establishment of complex circuitries acting in many different phases of development and differentiation. {MicroRNA} genes and their target sites are under Darwinian selection and the idea that {microRNAs} can act as prime players in determining species identity has been recently speculated. By studying the 3'-untranslated regions ({UTRs}) of orthologous neuronal genes, we found that, at variance with house-keeping genes, the density of {miRNA} target sites involved in complex cell networks increased from invertebrates to human, paralleling the increase in species complexity. This suggests that genes contributing to complex cellular functions had a selective advantage for acquiring and potentiate {miRNA}-mediated regulation.},
	pages = {120--122},
	number = {3},
	journaltitle = {{RNA} Biol},
	author = {Cacchiarelli, D and Santoni, D and Bozzoni, I},
	date = {2008},
	pmid = {18698151},
	keywords = {Animals, Humans, *Evolution, 3' Untranslated Regions/metabolism, Drosophila melanogaster/genetics, {MicroRNAs}/*metabolism, Molecular, Neurogenesis/genetics, Ribosomal Proteins/genetics/metabolism}
}

@article{belgard_transcriptomic_2011,
	title = {A transcriptomic atlas of mouse neocortical layers},
	volume = {71},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21867878},
	doi = {10.1016/j.neuron.2011.06.039},
	abstract = {In the mammalian cortex, neurons and glia form a patterned structure across six layers whose complex cytoarchitectonic arrangement is likely to contribute to cognition. We sequenced transcriptomes from layers 1-6b of different areas (primary and secondary) of the adult (postnatal day 56) mouse somatosensory cortex to understand the transcriptional levels and functional repertoires of coding and noncoding loci for cells constituting these layers. A total of 5,835 protein-coding genes and 66 noncoding {RNA} loci are differentially expressed ("patterned") across the layers, on the basis of a machine-learning model (naive Bayes) approach. Layers 2-6b are each associated with specific functional and disease annotations that provide insights into their biological roles. This new resource (http://genserv.anat.ox.ac.uk/layers) greatly extends currently available resources, such as the Allen Mouse Brain Atlas and microarray data sets, by providing quantitative expression levels, by being genome-wide, by including novel loci, and by identifying candidate alternatively spliced transcripts that are differentially expressed across layers.},
	pages = {605--616},
	number = {4},
	journaltitle = {Neuron},
	author = {Belgard, T G and Marques, A C and Oliver, P L and Abaan, H O and Sirey, T M and Hoerder-Suabedissen, A and Garcia-Moreno, F and Molnar, Z and Margulies, E H and Ponting, C P},
	date = {2011},
	pmid = {21867878},
	keywords = {Animals, Mice, {RNA}, *Gene Expression Profiling, Anatomy, Artistic, Atlases as Topic, Bayes Theorem, Gene Expression, Microarray Analysis, {RNA}/metabolism, Somatosensory Cortex/*anatomy \& histology/*chemist, Untranslated/metabolism}
}

@article{mekel-bobrov_ongoing_2005,
	title = {Ongoing adaptive evolution of {ASPM}, a brain size determinant in Homo sapiens},
	volume = {309},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16151010},
	doi = {10.1126/science.1116815},
	abstract = {The gene {ASPM} (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of {ASPM} in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.},
	pages = {1720--1722},
	number = {5741},
	journaltitle = {Science},
	author = {Mekel-Bobrov, N and Gilbert, S L and Evans, P D and Vallender, E J and Anderson, J R and Hudson, R R and Tishkoff, S A and Lahn, B T},
	date = {2005},
	pmid = {16151010},
	keywords = {{DNA}, Sequence Analysis, Animals, Genetic, Humans, *Biological Evolution, *Selection, Adaptation, African Continental Ancestry Group, Asian Continental Ancestry Group/genetics, Biological, Brain/*anatomy \& histology/physiology, European Continental Ancestry Group, Gene Conversion, Gene Frequency, Genotype, Haplotypes, Linkage Disequilibrium, Models, Nerve Tissue Proteins/*genetics, Organ Size, Pan troglodytes/genetics, Phylogeny, Polymorphism, Recombination, Time}
}

@article{twayana_biogenesis_2013,
	title = {Biogenesis and function of non-coding {RNAs} in muscle differentiation and in Duchenne muscular dystrophy},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23863142},
	doi = {10.1042/BST20120353},
	abstract = {It is now becoming largely accepted that the non-coding portion of the genome, rather than its coding counterpart, is likely to account for the greater complexity of higher eukaryotes. Moreover, non-coding {RNAs} have been demonstrated to participate in regulatory circuitries that are crucial for development and differentiation. Whereas the biogenesis and function of small non-coding {RNAs}, particularly {miRNAs} ({microRNAs}), has been extensively clarified in many eukaryotic systems, very little is known about the long non-coding counterpart of the transcriptome. In the present review, we revise the current knowledge of how small non-coding {RNAs} and {lncRNAs} (long non-coding {RNAs}) impinge on circuitries controlling proper muscle differentiation and homoeostasis and how their biogenesis is regulated. Moreover, we provide new insights into an additional mechanism of post-transcriptional regulation mediated by {lncRNAs}, which, acting as {miRNA} 'sponges', have an impact on the distribution of {miRNA} molecules on their targets with features similar to those described for {ceRNAs} (competing endogenous {RNAs}).},
	pages = {844--849},
	number = {4},
	journaltitle = {Biochem Soc Trans},
	author = {Twayana, S and Legnini, I and Cesana, M and Cacchiarelli, D and Morlando, M and Bozzoni, I},
	date = {2013},
	pmid = {23863142},
	keywords = {Humans, {RNA}, Untranslated/*genetics, Cell Differentiation/*genetics, Duchenne/*genetics/pathology, {MicroRNAs}/physiology, Muscle, Muscular Dystrophy, Skeletal/*pathology}
}

@article{ho_targeting_2015,
	title = {Targeting non-coding {RNAs} with the {CRISPR}/Cas9 system in human cell lines},
	volume = {43},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25414344},
	doi = {10.1093/nar/gku1198},
	abstract = {The {CRISPR}/Cas has been recently shown to be a powerful genome-editing tool in a variety of organisms. However, these studies are mainly focused on protein-coding genes. The present study aims to determine whether this technology can be applied to non-coding genes. One of the challenges for knockout of non-coding genes is that a small deletion or insertion generated by the standard {CRISPR}/Cas system may not necessarily lead to functional loss of a given non-coding gene because of lacking an open reading frame, especially in polyploidy human cell lines. To overcome this challenge, we adopt a selection system that allows for marker genes to integrate into the genome through homologous recombination ({HR}). Moreover, we construct a dual guide {RNA} vector that can make two cuts simultaneously at designated sites such that a large fragment can be deleted. With these approaches, we are able to successfully generate knockouts for {miR}-21, {miR}-29a, {lncRNA}-21A, {UCA}1 and {AK}023948 in various human cell lines. Finally, we show that the {HR}-mediated targeting efficiency can be further improved by suppression of the non-homologous end joining pathway. Together, these results demonstrate the feasibility of knockout for non-coding genes by the {CRISPR}/Cas system in human cell lines.},
	pages = {e17},
	number = {3},
	journaltitle = {Nucleic Acids Res},
	author = {Ho, T T and Zhou, N and Huang, J and Koirala, P and Xu, M and Fung, R and Wu, F and Mo, Y Y},
	date = {2015},
	pmid = {25414344},
	keywords = {Humans, {RNA}, Untranslated/*genetics, *Clustered Regularly Interspaced Short Palindromic, Base Pair Mismatch, Blotting, Cell Line, {MicroRNAs}/genetics, Reverse Transcriptase Polymerase Chain Reaction, Western}
}

@article{gorospe_gastric_2007,
	title = {Gastric mucosal calcinosis: clinicopathologic considerations},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17452819},
	doi = {10.1097/PAP.0b013e31805048ea},
	abstract = {Generally, gastric mucosal calcinosis ({GMC}) is only rarely encountered in routine biopsies. {GMC} may be classified as dystrophic, metastatic, or idiopathic. Metastatic calcification represents the most frequently encountered subtype, and refers to the deposition of calcium salts on largely normal tissues in the setting of an abnormal serum biochemical environment (hypercalcemia, hyperphosphatemia, and/or an elevated {CaxPO}4 product). In contrast, dystrophic calcification implies calcification in inflammed, fibrotic, or otherwise altered tissue in the setting of a normal biochemical environment. The gastric mucosa, along with the kidneys and lungs, are preferential sites for metastatic calcification, a finding that has been attributed to the relative intracellular alkalinity at these sites. In addition to the wide variety of hypercalcemia and/or hyperphosphatemia-causing clinical conditions, {GMC} has also been associated with atrophic gastritis, hypervitaminosis A, organ transplantation, gastric neoplasia, uremia with eucalcemia/euphosphatemia, and the use of aluminum-containing antacids, citrate-containing blood products, isotretinoin, and sucralfate. Although {GMC} has rarely been associated with epigastric pain and/or dyspepsia, most come to clinical attention owing to their accumulation of bone-seeking radiopharmaceuticals or represent a postmortem finding. The precise significance or mechanistic basis for {GMC} remains to be elucidated. However, their presence in gastric biopsies should be reported, as they may serve as an indicator for generalized metastatic calcification, especially in organs where they may be fatal, such as the heart. Furthermore, some examples of systemic calcification are reversible with normalization of biochemical parameters, which highlights the need for pathologists to report this finding when encountered in a premortem gastric biopsy.},
	pages = {224--228},
	number = {3},
	journaltitle = {Adv Anat Pathol},
	author = {Gorospe, M and Fadare, O},
	date = {2007},
	pmid = {17452819},
	keywords = {Humans, *Calcinosis, Gastric Mucosa/*pathology}
}

@article{wang_whole-genome_2014,
	title = {Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24816253},
	doi = {10.1038/ng.2983},
	abstract = {Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with {DNA} copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and epigenetic perturbations and unique mutational signatures. We identified previously known ({TP}53, {ARID}1A and {CDH}1) and new ({MUC}6, {CTNNA}2, {GLI}3, {RNF}43 and others) significantly mutated driver genes. Specifically, we found {RHOA} mutations in 14.3\% of diffuse-type tumors but not in intestinal-type tumors (P {\textbackslash}textless 0.001). The mutations clustered in recurrent hotspots affecting functional domains and caused defective {RHOA} signaling, promoting escape from anoikis in organoid cultures. The top perturbed pathways in gastric cancer included adherens junction and focal adhesion, in which {RHOA} and other mutated genes we identified participate as key players. These findings illustrate a multidimensional and comprehensive genomic landscape that highlights the molecular complexity of gastric cancer and provides a road map to facilitate genome-guided personalized therapy.},
	pages = {573--582},
	number = {6},
	journaltitle = {Nat Genet},
	author = {Wang, K and Yuen, S T and Xu, J and Lee, S P and Yan, H H and Shi, S T and Siu, H C and Deng, S and Chu, K M and Law, S and Chan, K H and Chan, A S and Tsui, W Y and Ho, S L and Chan, A K and Man, J L and Foglizzo, V and Ng, M K and Ching, Y P and Cheng, G H and Xie, T and Fernandez, J and Li, V S and Clevers, H and Rejto, P A and Mao, M and Leung, S Y},
	date = {2014},
	pmid = {24816253},
	keywords = {Human, Animals, Genetic, Genome, Humans, Mice, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Algorithms, *Gene Expression Regulation, *Mutation, Adherens Junctions, {DNA} Methylation, {DNA} Mutational Analysis, Epigenesis, Female, Gene Dosage, Genetic Variation, {HEK}293 Cells, Inbred C57BL, Male, Neoplastic, {rhoA} {GTP}-Binding Protein/genetics, Stomach Neoplasms/*genetics}
}

@article{vincenti_huvec_2011,
	title = {{HUVEC} respond to radiation by inducing the expression of pro-angiogenic {microRNAs}},
	volume = {175},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21361781},
	doi = {10.1667/RR2200.1},
	abstract = {{MicroRNAs} ({miRNAs}) represent a class of small non-coding {RNAs} that control gene expression by targeting {mRNAs} and triggering either repression of translation or {RNA} degradation. They have been shown to be involved in a variety of biological processes such as development, differentiation and cell cycle control, but little is known about their involvement in the response to irradiation. We showed here that in human umbilical vein endothelial cells ({HUVEC}) some {miRNAs} previously shown to have a crucial role in vascular biology are transiently modulated in response to a clinically relevant dose of ionizing radiation. In particular we identified an early transcriptional induction of several members of the {microRNA} cluster 17-92 and other {microRNAs} already known to be related to angiogenesis. At the same time we observed a peculiar behavior of the {miR}-221/222 cluster, suggesting an important role of these {microRNAs} in {HUVEC} homeostasis. We observed an increased efficiency in the formation of capillary-like structures in irradiated {HUVEC}. These results could lead to a new interpretation of the effect of ionizing radiation on endothelial cells and on the response of tumor endothelial bed cells to radiotherapy.},
	pages = {535--546},
	number = {5},
	journaltitle = {Radiat Res},
	author = {Vincenti, S and Brillante, N and Lanza, V and Bozzoni, I and Presutti, C and Chiani, F and Etna, M P and Negri, R},
	date = {2011},
	pmid = {21361781},
	keywords = {Humans, Binding Sites, 3' Untranslated Regions/genetics, Basic Helix-Loop-Helix Leucine Zipper Transcriptio, Capillaries/cytology, Cell Nucleus/metabolism/radiation effects, Dose-Response Relationship, Endothelial Cells/*metabolism/*radiation effects, Gene Expression Regulation/genetics/*radiation eff, {HeLa} Cells, Linear Energy Transfer, {MicroRNAs}/*genetics, Neovascularization, Oxidative Stress/genetics/radiation effects, Physiologic/*genetics/*radiati, Proto-Oncogene Proteins c-myc/metabolism, Radiation, Umbilical Cord/*cytology, X-Rays}
}

@article{bebarta_medium_2013,
	title = {Medium chain and behenic acid incorporated structured lipids from sal, mango and kokum fats by lipase acidolysis},
	volume = {136},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23122141},
	doi = {10.1016/j.foodchem.2012.08.051},
	abstract = {Medium chain ({MC}) and behenic fatty acids were incorporated into kokum, sal and mango fats using 1,3-specific lipase catalysed acidolysis. The incorporation of fatty acids increased with increase in concentration of fatty acids and duration of reaction. The order of incorporation of fatty acids was C22:0{\textbackslash}{textgreaterC}10:0{\textbackslash}{textgreaterC}8:0, to the extent of 53\%, 42.5\%, 35.8\%, respectively, after 16 h, using kokum as substrate. The same trend was observed with sal or mango fats as substrates though the percentages incorporated were different. The modified products with higher contents of {MC} were liquids with no solid fats, even at 0 degrees C, and which showed low cloud point due to an increase in triacylglycerols containing lower chain fatty acids. The modified products after incorporating both {MC} and C22:0 showed long melting ranges and were suitable for use in bakery, confectionery, etc. as vanaspati substitutes.},
	pages = {889--894},
	number = {2},
	journaltitle = {Food Chem},
	author = {Bebarta, B and M, J and Kotasthane, P and Sunkireddy, Y R},
	date = {2013},
	pmid = {23122141},
	keywords = {Fats/*chemical synthesis/chemistry, Fatty Acids/*chemistry, Lipase/*chemistry, Molecular Structure}
}

@article{zhao_polycomb_2008,
	title = {Polycomb proteins targeted by a short repeat {RNA} to the mouse X chromosome},
	volume = {322},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18974356},
	doi = {10.1126/science.1163045},
	abstract = {To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation ({XCI}) is initiated by expression of Xist, a 17-kb noncoding {RNA} ({ncRNA}) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase {ncRNA} ({RepA}) within Xist and identified the Polycomb complex, {PRC}2, as its direct target. {PRC}2 is initially recruited to the X by {RepA} {RNA}, with Ezh2 serving as the {RNA} binding subunit. The antisense Tsix {RNA} inhibits this interaction. {RepA} depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, {PRC}2 deficiency compromises Xist up-regulation. Therefore, {RepA}, together with {PRC}2, is required for the initiation and spread of {XCI}. We conclude that a {ncRNA} cofactor recruits Polycomb complexes to their target locus.},
	pages = {750--756},
	number = {5902},
	journaltitle = {Science},
	author = {Zhao, J and Sun, B K and Erwin, J A and Song, J J and Lee, J T},
	date = {2008},
	pmid = {18974356},
	keywords = {Animals, Mice, {RNA}, Nucleic Acid, Cell Differentiation, Cell Line, Chromatin Immunoprecipitation, Electrophoretic Mobility Shift Assay, Embryonic Stem Cells, Female, Fibroblasts, Long Untranslated, Male, Molecular Sequence Data, Polycomb-Group Proteins, Polymerase Chain Reaction, Repetitive Sequences, Repressor Proteins/*metabolism, Transgenic, Untranslated/genetics/*metabolism, Up-Regulation, X Chromosome Inactivation, X Chromosome/*metabolism}
}

@article{bard-chapeau_transposon_2014,
	title = {Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model},
	volume = {46},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24316982},
	doi = {10.1038/ng.2847},
	abstract = {The most common risk factor for developing hepatocellular carcinoma ({HCC}) is chronic infection with hepatitis B virus ({HBV}). To better understand the evolutionary forces driving {HCC}, we performed a near-saturating transposon mutagenesis screen in a mouse {HBV} model of {HCC}. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human {HCC}, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of {HCC}.},
	pages = {24--32},
	number = {1},
	journaltitle = {Nat Genet},
	author = {Bard-Chapeau, E A and Nguyen, A T and Rust, A G and Sayadi, A and Lee, P and Chua, B Q and New, L S and de Jong, J and Ward, J M and Chin, C K and Chew, V and Toh, H C and Abastado, J P and Benoukraf, T and Soong, R and Bard, F A and Dupuy, A J and Johnson, R L and Radda, G K and Chan, E C and Wessels, L F and Adams, D J and Jenkins, N A and Copeland, N G},
	date = {2014},
	pmid = {24316982},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, *Mutagenesis, Animal, Carcinoma, Chronic/*complications, Disease Models, {DNA} Transposable Elements, Hepatitis B, Hepatocellular/*genetics/metabolism/*vi, Insertional, Liver Neoplasms/*genetics/metabolism/*virology, Metabolic Networks and Pathways/genetics, Metabolomics/methods, Mutagenesis, Neoplastic, Pyruvic Acid/metabolism, Transgenic}
}

@article{marques_catalogues_2009,
	title = {Catalogues of mammalian long noncoding {RNAs}: modest conservation and incompleteness},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19895688},
	doi = {10.1186/gb-2009-10-11-r124},
	abstract = {{BACKGROUND}: Despite increasing interest in the noncoding fraction of transcriptomes, the number, species-conservation and functions, if any, of many non-protein-coding transcripts remain to be discovered. Two extensive long intergenic noncoding {RNA} ({ncRNA}) transcript catalogues are now available for mouse: over 3,000 {macroRNAs} identified by {cDNA} sequencing, and 1,600 long intergenic noncoding {RNA} ({lincRNA}) intervals that are predicted from chromatin-state maps. Previously we showed that {macroRNAs} tend to be more highly conserved than putatively neutral sequence, although only 5\% of bases are predicted as constrained. By contrast, over a thousand {lincRNAs} were reported as being highly conserved. This apparent difference may account for the surprisingly small fraction (11\%) of transcripts that are represented in both catalogues. Here we sought to resolve the reported discrepancy between the evolutionary rates for these two sets. {RESULTS}: Our analyses reveal {lincRNA} and {macroRNA} exon sequences to be subject to the same relatively low degree of sequence constraint. Nonetheless, our observations are consistent with the functionality of a fraction of {ncRNA} in these sets, with up to a quarter of {ncRNA} exons having evolved significantly slower than neighboring neutral sequence. The more tissue-specific {macroRNAs} are enriched in predicted {RNA} secondary structures and thus may often act in trans, whereas the more highly and broadly expressed {lincRNAs} appear more likely to act in the cis-regulation of adjacent transcription factor genes. {CONCLUSIONS}: Taken together, our results indicate that each of the two {ncRNA} catalogues unevenly and lightly samples the true, much larger, {ncRNA} repertoire of the mouse.},
	pages = {R124},
	number = {11},
	journaltitle = {Genome Biol},
	author = {Marques, A C and Ponting, C P},
	date = {2009},
	pmid = {19895688},
	keywords = {{DNA}, Sequence Analysis, Animals, Genetic, Humans, Mice, {RNA}, Exons, Untranslated/*genetics, Base Composition, Chromatin/metabolism, Complementary/metabolism, Computational Biology/methods, Evolution, Genomics/methods, Messenger/metabolism, Models, Molecular, {RNA}/metabolism}
}

@article{sunker_identification_2013,
	title = {Identification of {MRI}1, encoding translation initiation factor {eIF}-2B subunit alpha/beta/delta-like protein, as a candidate locus for infantile epilepsy with severe cystic degeneration of the brain},
	volume = {512},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23124037},
	doi = {10.1016/j.gene.2012.10.063},
	abstract = {Several neurodegenerative disorders are known to predominantly affect the white matter of the brain including vanishing white matter disease ({VWMD}), an autosomal recessive disorder characterized by leukodystrophy of varying severity in addition to variable systemic involvement. We report a consanguineous Arab family with three affected children, all of whom presented with severe neonatal epilepsy and profound neurodegenerative disease characterized by marked leukodystrophy with white matter cavitation mimicking {VWMD}. We combined autozygome and exome analysis to identify a novel variant in the gene encoding a member of the {eIF}2B-related family of proteins ({MRI}1). This is a poorly understood family of proteins of unclear function. Our results represent the first link between a variant in a member of this family and a human disease, and suggest that it converges with the highly homologous {eIF}2B, known to be mutated in {VWMD}, on the molecular pathogenesis of neurodegeneration.},
	pages = {450--452},
	number = {2},
	journaltitle = {Gene},
	author = {Sunker, A and Alkuraya, F S},
	date = {2013},
	pmid = {23124037},
	keywords = {Humans, *Genetic Loci, Adult, Aldose-Ketose Isomerases/*genetics/metabolism, Arabs, Epilepsies, Female, Heredodegenerative Disorders, Infant, Leukoencephalopathies/enzymology/*genetics/radiogr, Male, Myoclonic/enzymology/*genetics/radiogr, Nervous System/enzym, Newborn}
}

@article{goff_linking_2015,
	title = {Linking {RNA} biology to {lncRNAs}},
	volume = {25},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26430155},
	doi = {10.1101/gr.191122.115},
	abstract = {The regulatory potential of {RNA} has never ceased to amaze: from {RNA} catalysis, to {RNA}-mediated splicing, to {RNA}-based silencing of an entire chromosome during dosage compensation. More recently, thousands of long noncoding {RNA} ({lncRNA}) transcripts have been identified, the majority with unknown function. Thus, it is tempting to think that these {lncRNAs} represent a cadre of new factors that function through ribonucleic mechanisms. Some evidence points to several {lncRNAs} with tantalizing physiological contributions and thought-provoking molecular modalities. However, dissecting the {RNA} biology of {lncRNAs} has been difficult, and distinguishing the independent contributions of functional {RNAs} from underlying {DNA} elements, or the local act of transcription, is challenging. Here, we aim to survey the existing literature and highlight future approaches that will be needed to link the {RNA}-based biology and mechanisms of {lncRNAs} in vitro and in vivo.},
	pages = {1456--1465},
	number = {10},
	journaltitle = {Genome Res},
	author = {Goff, L A and Rinn, J L},
	date = {2015},
	pmid = {26430155},
	keywords = {Animals, Humans, Regulatory Sequences, Ribonucleic Acid, {RNA}, Catalytic, Long Noncoding/*physiology, {RNA}/*physiology}
}

@article{prislei_two_1993,
	title = {Two different {snoRNAs} are encoded in introns of amphibian and human L1 ribosomal protein genes},
	volume = {21},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7507233},
	abstract = {We previously reported that the third intron of the X.laevis L1 ribosomal protein gene encodes for a {snoRNA} called U16. Here we show that four different introns of the same gene contain another previously uncharacterized {snoRNA} (U18) which is associated with fibrillarin in the nucleolus and which originates by processing of the pre-{mRNA}. The pathway of U18 {RNA} release from the pre-{mRNA} is the same as the one described for U16: primary endonucleolytic cleavages upstream and downstream of the U18 coding region produce a pre-U18 {RNA} which is subsequently trimmed to the mature form. Both the gene organization and processing of U18 are conserved in the corresponding genes of X.tropicalis and H.sapiens. The L1 gene thus has a composite structure, highly conserved in evolution, in which sequences coding for a ribosomal protein are intermingled with sequences coding for two different {snoRNAs}. The nucleolar localization of these different components suggests some common function on ribosome biosynthesis.},
	pages = {5824--5830},
	number = {25},
	journaltitle = {Nucleic Acids Res},
	author = {Prislei, S and Michienzi, A and Presutti, C and Fragapane, P and Bozzoni, I},
	date = {1993},
	pmid = {7507233},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, {RNA}/*genetics, *Introns, Blotting, Cloning, Dna, Microinjections, Molecular, Molecular Sequence Data, Northern, Oocytes, Phylogeny, Ribonucleoproteins, Ribosomal Proteins/*genetics, Small Nuclear/*genetics, Xenopus, Xenopus laevis}
}

@article{young_identification_2012,
	title = {Identification and properties of 1,119 candidate {lincRNA} loci in the Drosophila melanogaster genome},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22403033},
	doi = {10.1093/gbe/evs020},
	abstract = {The functional repertoire of long intergenic noncoding {RNA} ({lincRNA}) molecules has begun to be elucidated in mammals. Determining the biological relevance and potential gene regulatory mechanisms of these enigmatic molecules would be expedited in a more tractable model organism, such as Drosophila melanogaster. To this end, we defined a set of 1,119 putative {lincRNA} genes in D. melanogaster using {modENCODE} whole transcriptome ({RNA}-seq) data. A large majority (1.1 of 1.3 Mb; 85\%) of these bases were not previously reported by {modENCODE} as being transcribed. Significant selective constraint on the sequences of these loci predicts that virtually all have sustained functionality across the Drosophila clade. We observe biases in {lincRNA} genomic locations and expression profiles that are consistent with some of these {lincRNAs} being involved in the regulation of neighboring protein-coding genes with developmental functions. We identify {lincRNAs} that may be important in the developing nervous system and in male-specific organs, such as the testes. {LincRNA} loci were also identified whose positions, relative to nearby protein-coding loci, are equivalent between D. melanogaster and mouse. This study predicts that the genomes of not only vertebrates, such as mammals, but also an invertebrate (fruit fly) harbor large numbers of {lincRNA} loci. Our findings now permit exploitation of Drosophila genetics for the investigation of {lincRNA} mechanisms, including {lincRNAs} with potential functional analogues in mammals.},
	pages = {427--442},
	number = {4},
	journaltitle = {Genome Biol Evol},
	author = {Young, R S and Marques, A C and Tibbit, C and Haerty, W and Bassett, A R and Liu, J L and Ponting, C P},
	date = {2012},
	pmid = {22403033},
	keywords = {Animals, Mice, {RNA}, *Genome, Drosophila melanogaster/*genetics, Evolution, Female, Insect, Male, Molecular, Molecular Sequence Annotation, Untranslated/*genetics/*isolation \& purificat}
}

@article{guttman_lincrnas_2011,
	title = {{lincRNAs} act in the circuitry controlling pluripotency and differentiation},
	volume = {477},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21874018},
	doi = {10.1038/nature10398},
	abstract = {Although thousands of large intergenic non-coding {RNAs} ({lincRNAs}) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most {lincRNAs} expressed in mouse embryonic stem ({ES}) cells and characterized the effects on gene expression. Here we show that knockdown of {lincRNAs} has major consequences on gene expression patterns, comparable to knockdown of well-known {ES} cell regulators. Notably, {lincRNAs} primarily affect gene expression in trans. Knockdown of dozens of {lincRNAs} causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate {lincRNAs} into the molecular circuitry of {ES} cells and show that {lincRNA} genes are regulated by key transcription factors and that {lincRNA} transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that {lincRNAs} have key roles in the circuitry controlling {ES} cell state.},
	pages = {295--300},
	number = {7364},
	journaltitle = {Nature},
	author = {Guttman, M and Donaghey, J and Carey, B W and Garber, M and Grenier, J K and Munson, G and Young, G and Lucas, A B and Ach, R and Bruhn, L and Yang, X and Amit, I and Meissner, A and Regev, A and Rinn, J L and Root, D E and Lander, E S},
	date = {2011},
	pmid = {21874018},
	keywords = {Animals, Mice, {RNA}, Protein Binding, Transcription Factors/metabolism, Cell Differentiation/*genetics, Cell Lineage/genetics, Chromatin/genetics/metabolism, Gene Expression Regulation/genetics, Gene Knockdown Techniques, Pluripotent Stem Cells/*cytology/*metabolism, Untranslated/*genetics/*metabolism}
}

@article{simon_genomic_2011,
	title = {The genomic binding sites of a noncoding {RNA}},
	volume = {108},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22143764},
	doi = {10.1073/pnas.1113536108},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) have important regulatory roles and can function at the level of chromatin. To determine where {lncRNAs} bind to chromatin, we developed capture hybridization analysis of {RNA} targets ({CHART}), a hybridization-based technique that specifically enriches endogenous {RNAs} along with their targets from reversibly cross-linked chromatin extracts. {CHART} was used to enrich the {DNA} and protein targets of endogenous {lncRNAs} from flies and humans. This analysis was extended to genome-wide mapping of {roX}2, a well-studied {ncRNA} involved in dosage compensation in Drosophila. {CHART} revealed that {roX}2 binds at specific genomic sites that coincide with the binding sites of proteins from the male-specific lethal complex that affects dosage compensation. These results reveal the genomic targets of {roX}2 and demonstrate how {CHART} can be used to study {RNAs} in a manner analogous to chromatin immunoprecipitation for proteins.},
	pages = {20497--20502},
	number = {51},
	journaltitle = {Proc Natl Acad Sci U S A},
	author = {Simon, M D and Wang, C I and Kharchenko, P V and West, J A and Chapman, B A and Alekseyenko, A A and Borowsky, M L and Kuroda, M I and Kingston, R E},
	date = {2011},
	pmid = {22143764},
	keywords = {Animals, Genetic, {RNA}, Binding Sites, Untranslated/*genetics, *Genomics, Amino Acid Motifs, Chromatin Immunoprecipitation, Chromatin/chemistry/genetics, Dosage Compensation, Drosophila Proteins/*genetics, Drosophila/*genetics, Male, Models, Nucleic Acid Hybridization, Ribonuclease H/chemistry, {RNA}-Binding Proteins/*genetics}
}

@article{jackson_mechanism_2010,
	title = {The mechanism of eukaryotic translation initiation and principles of its regulation},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20094052},
	doi = {10.1038/nrm2838},
	abstract = {Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific {RNA}-binding proteins and {microRNAs} (which affect individual {mRNAs}).},
	pages = {113--127},
	number = {2},
	journaltitle = {Nat Rev Mol Cell Biol},
	author = {Jackson, R J and Hellen, C U and Pestova, T V},
	date = {2010},
	pmid = {20094052},
	keywords = {Animals, Humans, *Gene Expression Regulation, *Protein Biosynthesis, Eukaryota/chemistry/*genetics/*metabolism, Eukaryotic Initiation Factors/chemistry/genetics/*, {MicroRNAs}/genetics, {RNA}-Binding Proteins/genetics/metabolism}
}

@article{kimura_simple_1980,
	title = {A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences},
	volume = {16},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/7463489},
	abstract = {Some simple formulae were obtained which enable us to estimate evolutionary distances in terms of the number of nucleotide substitutions (and, also, the evolutionary rates when the divergence times are known). In comparing a pair of nucleotide sequences, we distinguish two types of differences; if homologous sites are occupied by different nucleotide bases but both are purines or both pyrimidines, the difference is called type I (or "transition" type), while, if one of the two is a purine and the other is a pyrimidine, the difference is called type {II} (or "transversion" type). Letting P and Q be respectively the fractions of nucleotide sites showing type I and type {II} differences between two sequences compared, then the evolutionary distance per site is K = -(1/2) ln [(1-2P-Q) square root of 1-2Q]. The evolutionary rate per year is then given by k = K/(2T), where T is the time since the divergence of the two sequences. If only the third codon positions are compared, the synonymous component of the evolutionary base substitutions per site is estimated by K'S = -(1/2) ln (1-2P-Q). Also, formulae for standard errors were obtained. Some examples were worked out using reported globin sequences to show that synonymous substitutions occur at much higher rates than amino acid-altering substitutions in evolution.},
	pages = {111--120},
	number = {2},
	journaltitle = {J Mol Evol},
	author = {Kimura, M},
	date = {1980},
	pmid = {7463489},
	keywords = {Animals, Humans, Proteins/genetics, *Base Sequence, *Biological Evolution, Biological, {DNA}/*genetics, Mathematics, Models, Mutation, Probability, Species Specificity}
}

@article{croisille_precision_1998,
	title = {Precision of myocardial contour estimation from tagged {MR} images with a "black-blood" technique},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9484541},
	abstract = {{RATIONALE} {AND} {OBJECTIVES}: The authors determined whether blood presaturation of tagged magnetic resonance ({MR}) images affects identification of left ventricular endocardial borders. {MATERIALS} {AND} {METHODS}: Three healthy volunteers underwent {MR} imaging performed with a breath-hold segmented spoiled gradient-recalled-echo sequence with tissue tagging. Two saturation pulses (in the basal and apical regions) were used to generate black-blood images. Manual segmentation of endocardial contours on black-blood and white-blood images was performed independently by five observers. {RESULTS}: Endocardial borders were better identified on black-blood images compared with white-blood images, especially in the early systolic phases. Interobserver variability in contour estimation was significantly higher for white-blood images (P {\textbackslash}textless .001) and was twice that for corresponding black-blood images during early systole. Contour variability appeared to be affected mainly by tag-to-myocardium contrast (P = .009) and myocardium-to-chamber contrast (P = .05). {CONCLUSION}: Blood presaturation of tagged {MR} images improves reliability of contour segmentation.},
	pages = {93--100},
	number = {2},
	journaltitle = {Acad Radiol},
	author = {Croisille, P and Guttman, M A and Atalar, E and {McVeigh}, E R and Zerhouni, E A},
	date = {1998},
	pmid = {9484541},
	keywords = {Humans, Reproducibility of Results, Adult, Blood, Cine/*methods, Color, Computer-Assisted, Endocardium/anatomy \& histology, Female, Heart Ventricles/anatomy \& histology, Heart/*anatomy \& histology, Image Enhancement/*methods, Image Processing, Magnetic Resonance Imaging, Male, Observer Variation, Papillary Muscles/anatomy \& histology, Regression Analysis, Systole}
}

@article{morais-de-sa_adherens_2013,
	title = {Adherens junctions determine the apical position of the midbody during follicular epithelial cell division},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23774295},
	doi = {10.1038/embor.2013.85},
	abstract = {Cytokinesis is asymmetric along the apical-basal axis of epithelial cells, positioning the midbody near the apical domain. However, little is known about the mechanism and purpose of this asymmetry. We use live imaging of Drosophila follicle cell division to show that asymmetric cytokinesis does not result from intrinsic polarization of the main contractile ring components. We show that adherens junctions ({AJs}) maintain close contact with the apical side of the contractile ring during cytokinesis. Asymmetric distribution of {AJ} components within follicle cells and in the otherwise unpolarized S2 cells is sufficient to recruit the midbody, revealing that asymmetric cytokinesis is determined by apical {AJs} in the epithelia. We further show that ectopic midbody localization induces epithelial invaginations, shifting the position of the apical interface between daughter cells relative to the {AB} axis of the tissue. Thus, apical midbody localization is essential to maintain epithelial tissue architecture during proliferation.},
	pages = {696--703},
	number = {8},
	journaltitle = {{EMBO} Rep},
	author = {Morais-de-Sa, E and Sunkel, C},
	date = {2013},
	pmid = {23774295},
	keywords = {Animals, Adherens Junctions/*physiology/ultrastructure, Cell Polarity, Contractile Proteins/genetics/metabolism, Cytokinesis, Drosophila Proteins/*genetics/metabolism, Drosophila/cytology/*physiology/ultrastructure, Epithelial Cells/*physiology/ultrastructure, Gene Expression, Kinesin/genetics/metabolism, Myosin Light Chains/genetics/metabolism, Myosin Type {II}/genetics/metabolism, Time-Lapse Imaging}
}

@article{guo_mammalian_2010,
	title = {Mammalian {microRNAs} predominantly act to decrease target {mRNA} levels},
	volume = {466},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20703300},
	doi = {10.1038/nature09267},
	abstract = {{MicroRNAs} ({miRNAs}) are endogenous approximately 22-nucleotide {RNAs} that mediate important gene-regulatory events by pairing to the {mRNAs} of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased {mRNA} levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on {mRNA} levels. For both ectopic and endogenous {miRNA} regulatory interactions, lowered {mRNA} levels account for most ({\textbackslash}textgreater/=84\%) of the decreased protein production. These results show that changes in {mRNA} levels closely reflect the impact of {miRNAs} on gene expression and indicate that destabilization of target {mRNAs} is the predominant reason for reduced protein output.},
	pages = {835--840},
	number = {7308},
	journaltitle = {Nature},
	author = {Guo, H and Ingolia, N T and Weissman, J S and Bartel, D P},
	date = {2010},
	pmid = {20703300},
	keywords = {Animals, Genetic, Humans, Mice, {RNA}, 3' Untranslated Regions/genetics, Down-Regulation/*genetics, {HeLa} Cells, Mammals/genetics, Messenger/analysis/*genetics/*metabolism, {MicroRNAs}/*genetics/*metabolism, Models, Open Reading Frames/genetics, Post-Transcriptional/genetics, Protein Biosynthesis/genetics, Ribosomes/genetics/metabolism, {RNA} Processing, {RNA} Stability/*genetics}
}

@article{zhang_novel_2014,
	title = {A novel {RNA} motif mediates the strict nuclear localization of a long noncoding {RNA}},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24732794},
	doi = {10.1128/MCB.01673-13},
	abstract = {The ubiquitous presence of long noncoding {RNAs} ({lncRNAs}) in eukaryotes points to the importance of understanding how their sequences impact function. As many {lncRNAs} regulate nuclear events and thus must localize to nuclei, we analyzed the sequence requirements for nuclear localization in an intergenic {lncRNA} named {BORG} ({BMP}2-{OP}1-responsive gene), which is both spliced and polyadenylated but is strictly localized in nuclei. Subcellular localization of {BORG} was not dependent on the context or level of its expression or decay but rather depended on the sequence of the mature, spliced transcript. Mutational analyses indicated that nuclear localization of {BORG} was mediated through a novel {RNA} motif consisting of the pentamer sequence {AGCCC} with sequence restrictions at positions -8 (T or A) and -3 (G or C) relative to the first nucleotide of the pentamer. Mutation of the motif to a scrambled sequence resulted in complete loss of nuclear localization, while addition of even a single copy of the motif to a cytoplasmically localized {RNA} was sufficient to impart nuclear localization. Further, the presence of this motif in other cellular {RNAs} showed a direct correlation with nuclear localization, suggesting that the motif may act as a general nuclear localization signal for cellular {RNAs}.},
	pages = {2318--2329},
	number = {12},
	journaltitle = {Mol Cell Biol},
	author = {Zhang, B and Gunawardane, L and Niazi, F and Jahanbani, F and Chen, X and Valadkhan, S},
	date = {2014},
	pmid = {24732794}
}

@article{beniaminov_distinctive_2008,
	title = {Distinctive structures between chimpanzee and human in a brain noncoding {RNA}},
	volume = {14},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18511501},
	doi = {10.1261/rna.1054608},
	abstract = {Human accelerated region 1 ({HAR}1) is a short {DNA} region identified recently to have evolved the most rapidly among highly constrained regions since the divergence from our common ancestor with chimpanzee. It is transcribed as part of a noncoding {RNA} specifically expressed in the developing human neocortex. Employing a panoply of enzymatic and chemical probes, our analysis of {HAR}1 {RNA} proposed a secondary structure model differing from that published. Most surprisingly, we discovered that the substitutions between the chimpanzee and human sequences led the human {HAR}1 {RNA} to adopt a cloverleaf-like structure instead of an extended and unstable hairpin in the chimpanzee sequence. Thus, the rapid evolutionary changes resulted in a profound rearrangement of {HAR}1 {RNA} structure. Altogether, our results provide a structural context for elucidating {HAR}1 {RNA} function.},
	pages = {1270--1275},
	number = {7},
	journaltitle = {{RNA}},
	author = {Beniaminov, A and Westhof, E and Krol, A},
	date = {2008},
	pmid = {18511501},
	keywords = {Human, Animals, Base Sequence, Genome, Humans, {RNA}, Brain/*metabolism, Evolution, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Pan troglodytes/*genetics, Untranslated/*chemistry}
}

@article{janga_situ_2013,
	title = {In situ absorption and relative bioavailability studies of zaleplon loaded self-nanoemulsifying powders},
	volume = {30},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22894164},
	doi = {10.3109/02652048.2012.714408},
	abstract = {Self-nanoemulsifying drug delivery systems ({SNEDDSs}) offer potential as suitable carriers for improved oral delivery of poorly soluble and low bioavailable drugs. To derive self-nanoemulsifying powders ({SNEPs}), the optimized Z-{SNEDDS} formulation was adsorbed onto different carriers and based on micromeritics the formulation loaded onto neusilin {US}2 ({SNEP}-N) was selected for further characterization. The solid-state characterization (scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction) studies unravel the transformation of native crystalline state to amorphous and/or molecular state. The higher predictive effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of {SNEPs} for augment in absorption across gastrointestinal barrier. Overall a 3.5-fold enhancement in the extent of absorption of zaleplon from {SNEP}-N formulation proves the feasibility of {SNEPs} formulation for improved oral delivery of zaleplon.},
	pages = {161--172},
	number = {2},
	journaltitle = {J Microencapsul},
	author = {Janga, K Y and Jukanti, R and Sunkavalli, S and Velpula, A and Bandari, S and Kandadi, P and Veerareddy, P R},
	date = {2013},
	pmid = {22894164},
	keywords = {Animals, Humans, *Acetamides/chemistry/pharmacokinetics/pharmacolog, *Aluminum Silicates/chemistry/pharmacokinetics/pha, *Anticonvulsants/chemistry/pharmacokinetics/pharma, *Drug Delivery Systems, *Magnesium/chemistry/pharmacokinetics/pharmacology, *Pyrimidines/chemistry/pharmacokinetics/pharmacolo, Administration, Aluminum Compounds, Emulsions, Intestinal Absorption/*drug effects, Magnesium Compounds, Male, Oral, Particle Size, Rats, Silicates, Wistar}
}

@article{pierandrei-amaldi_expression_1988,
	title = {Expression of the gene for ribosomal protein L1 in Xenopus embryos: alteration of gene dosage by microinjection},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3356338},
	abstract = {Cloned gene for Xenopus ribosomal protein L1 was injected into fertilized eggs, and its expression was analyzed during the period of embryo development when the {mRNAs} produced by the endogenous ribosomal protein genes are still silent due to a translational control. The injected genes replicated extensively, and a 10-fold excess of L1 mature transcript accumulated in the embryo. This was accompanied by a small amount of incompletely processed L1 {RNA} that still contained one out of nine introns, a molecule never observed in normal conditions. The excess mature L1 {mRNA} was distributed between polysomes and messenger ribonucleoproteins ({mRNPs}) in the same relative proportion observed in control embryos of the same stage. Therefore, more L1 {mRNA} was loaded onto polysomes and caused the appearance of L1 protein when this was not yet detectable in control embryos. The results suggest a relationship between the excess amount of L1 protein and the alteration in processing of its transcripts.},
	pages = {23--31},
	number = {1},
	journaltitle = {Genes Dev},
	author = {Pierandrei-Amaldi, P and Bozzoni, I and Cardinali, B},
	date = {1988},
	pmid = {3356338},
	keywords = {Animals, Genetic, {RNA}, Transcription, Gene Expression Regulation, Messenger/genetics, Cloning, Genes, Microinjections, Molecular, Oocytes, Protein Biosynthesis, Ribosomal Proteins/*genetics, Xenopus laevis/*embryology/genetics}
}

@article{tominaga-yamanaka_nf90_2012,
	title = {{NF}90 coordinately represses the senescence-associated secretory phenotype},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23117626},
	abstract = {A hallmark trait of cellular senescence is the acquisition of a senescence-associated secretory phenotype ({SASP}). {SASP} factors include cytokines and their receptors ({IL}-6, {IL}-8, osteoprotegerin, {GM}-{CSF}), chemokines and their ligands ({MCP}-1, {HCC}4), and oncogenes (Gro1 and Gro2), many of them encoded by {mRNAs} whose stability and translation are tightly regulated. Using two models of human fibroblast senescence ({WI}-38 and {IDH}4 cells), we report the identification of {RNA}-binding protein {NF}90 as a post-transcriptional repressor of several {SASP} factors. In 'young', proliferating fibroblasts, {NF}90 was highly abundant, associated with numerous {SASP} {mRNAs}, and inhibited their expression. By contrast, senescent cells expressed low levels of {NF}90, thus allowing {SASP} factor expression to increase. {NF}90 elicited these effects mainly by repressing the translation of target {SASP} {mRNAs}, since silencing {NF}90 did not increase the steady-state levels of {SASP} {mRNAs} but elevated key {SASP} factors including {MCP}-1, {GROa}, {IL}-6, and {IL}-8. Our findings indicate that {NF}90 contributes to maintaining low levels of {SASP} factors in non-senescent cells, while {NF}90 reduction in senescent cells allows {SASP} factor expression to rise.},
	pages = {695--708},
	number = {10},
	journaltitle = {Aging (Albany {NY})},
	author = {Tominaga-Yamanaka, K and Abdelmohsen, K and Martindale, J L and Yang, X and Taub, D D and Gorospe, M},
	date = {2012},
	pmid = {23117626},
	keywords = {Animals, Humans, {RNA}, *Cell Aging, Aging/metabolism, Cell Line, Chemokine {CCL}2/metabolism, Chemokine {CXCL}1/metabolism, Fibroblasts/*physiology, Interleukin-6/metabolism, Interleukin-8/metabolism, Messenger/metabolism, Nuclear Factor 90 Proteins/*metabolism, Phenotype}
}

@article{mazan-mamczarz_translational_2006,
	title = {Translational repression by {RNA}-binding protein {TIAR}},
	volume = {26},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16537914},
	doi = {10.1128/MCB.26.7.2716-2727.2006},
	abstract = {The {RNA}-binding protein {TIAR} has been proposed to inhibit protein synthesis transiently by promoting the formation of translationally silent stress granules. Here, we report the selective binding of {TIAR} to several {mRNAs} encoding translation factors such as eukaryotic initiation factor 4A ({eIF}4A) and {eIF}4E (translation initiation factors), {eEF}1B (a translation elongation factor), and c-Myc (which transcriptionally controls the expression of numerous translation regulatory proteins). {TIAR} bound the 3'-untranslated regions of these {mRNAs} and potently suppressed their translation, particularly in response to low levels of short-wavelength {UV} ({UVC}) irradiation. The {UVC}-imposed global inhibition of the cellular translation machinery was significantly relieved after silencing of {TIAR} expression. We propose that the {TIAR}-mediated inhibition of translation factor expression elicits a sustained repression of protein biosynthesis in cells responding to stress.},
	pages = {2716--2727},
	number = {7},
	journaltitle = {Mol Cell Biol},
	author = {Mazan-Mamczarz, K and Lal, A and Martindale, J L and Kawai, T and Gorospe, M},
	date = {2006},
	pmid = {16537914},
	keywords = {Humans, {RNA}, Protein Binding, Cultured, *Protein Biosynthesis/radiation effects, Eukaryotic Initiation Factors/genetics, Gene Silencing, Messenger/metabolism, Repressor Proteins/*metabolism, {RNA}-Binding Proteins/*metabolism, Substrate Specificity, Tumor Cells, Ultraviolet Rays}
}

@article{pedersen_identification_2006,
	title = {Identification and classification of conserved {RNA} secondary structures in the human genome},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16628248},
	doi = {10.1371/journal.pcbi.0020033},
	abstract = {The discoveries of {microRNAs} and riboswitches, among others, have shown functional {RNAs} to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional {RNAs} encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional {RNAs}. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate {RNA} structures. This screen finds a large number of known functional {RNAs}, including 195 {miRNAs}, 62 histone 3'{UTR} stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new {miRNA} candidates, as well as new candidate selenocysteine insertion sites, {RNA} editing hairpins, {RNAs} involved in transcript auto regulation, and many folds that form singletons or small functional {RNA} families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional {RNAs} and present specific predictions to facilitate their further characterization.},
	pages = {e33},
	number = {4},
	journaltitle = {{PLoS} Comput Biol},
	author = {Pedersen, J S and Bejerano, G and Siepel, A and Rosenbloom, K and Lindblad-Toh, K and Lander, E S and Kent, J and Miller, W and Haussler, D},
	date = {2006},
	pmid = {16628248},
	keywords = {Comparative genomics, Human, Sequence Analysis, 3' Untranslated Regions, Animals, Conserved Sequence, Genome, Humans, Mice, *Genome, Computational Biology, *Nucleic Acid Conformation, Chickens, Computational Biology/methods, Dogs, {MicroRNAs}, {MicroRNAs}/*chemistry, Nucleic Acid Conformation, Rats, {RNA}/*methods, Tetraodontiformes, Zebrafish, Sequence Analysis, {RNA}, Genome, Human, Human genomics, Mammalian genomics, {RNA} stem-loop structure, {RNA} structure, Sequence alignment, Small nucleolar {RNAs}},
	file = {Full Text:/home/jlagarde/Zotero/storage/EJPZ9YEF/Pedersen et al. - 2006 - Identification and classification of conserved RNA.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/29CSPTC5/Pedersen et al. - 2006 - Identification and classification of conserved RNA.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/MNEYMAJ5/Pedersen et al. - 2006 - Identification and Classification of Conserved RNA.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/3APIL52E/article.html:text/html}
}

@article{galban_influence_2003,
	title = {Influence of the {RNA}-binding protein {HuR} in {pVHL}-regulated p53 expression in renal carcinoma cells},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/14517280},
	abstract = {A recent analysis of gene expression in renal cell carcinoma cells led to the identification of {mRNAs} whose translation was dependent on the presence of the von Hippel-Lindau ({VHL}) tumor suppressor gene product, {pVHL}. Here, we investigate the finding that {pVHL}-expressing {RCC} cells ({VHL}(+)) exhibited elevated levels of polysome-associated p53 {mRNA} and increased p53 protein levels compared with {VHL}-defective ({VHL}(-)) cells. Our findings indicate that p53 translation is specifically heightened in {VHL}(+) cells, given that (i) p53 {mRNA} abundance in {VHL}(+) and {VHL}(-) cells was comparable, (ii) p53 degradation did not significantly influence p53 expression, and (iii) p53 synthesis was markedly induced in {VHL}(+) cells. Electrophoretic mobility shift and immunoprecipitation assays to detect endogenous and radiolabeled p53 transcripts revealed that the {RNA}-binding protein {HuR}, previously shown to regulate {mRNA} turnover and translation, was capable of binding to the 3' untranslated region of the p53 {mRNA} in a {VHL}-dependent fashion. Interestingly, while whole-cell levels of {HuR} in {VHL}(+) and {VHL}(-) cells were comparable, {HuR} was markedly more abundant in the cytoplasmic and polysome-associated fractions of {VHL}(+) cells. In keeping with earlier reports, the elevated cytoplasmic {HuR} in {VHL}(+) cells was likely due to the reduced {AMP}-activated kinase activity in these cells. Demonstration that {HuR} indeed contributed to the increased expression of p53 in {VHL}(+) cells was obtained through use of {RNA} interference, which effectively reduced {HuR} expression and in turn caused marked decreases in p53 translation and p53 abundance. Taken together, our findings support a role for {pVHL} in elevating p53 expression, implicate {HuR} in enhancing {VHL}-mediated p53 translation, and suggest that {VHL}-mediated p53 upregulation may contribute to {pVHL}'s tumor suppressive functions in renal cell carcinoma.},
	pages = {7083--7095},
	number = {20},
	journaltitle = {Mol Cell Biol},
	author = {Galban, S and Martindale, J L and Mazan-Mamczarz, K and Lopez de Silanes, I and Fan, J and Wang, W and Decker, J and Gorospe, M},
	date = {2003},
	pmid = {14517280},
	keywords = {{DNA}, 3' Untranslated Regions, Base Sequence, Humans, {RNA}, Protein Binding, Oligonucleotide Array Sequence Analysis, *Antigens, *Gene Expression Regulation, Actins/metabolism, Adenylate Kinase/metabolism, Blotting, Carcinoma, Cell Line, Complementary/metabolism, Cytoplasm/metabolism, Fluorescence, Hu Paraneoplastic Encephalomyelitis Antigens, Kidney Neoplasms/*metabolism, Messenger/metabolism, Microscopy, Molecular Sequence Data, Neoplastic, Northern, Plasmids/metabolism, Polyribosomes/metabolism, Precipitin Tests, Protein Biosynthesis, Renal Cell/*metabolism, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Interference, {RNA}-Binding Proteins/metabolism/*physiology, {RNA}/metabolism, Small Interfering/metabolism, Surface, Time Factors, Transfection, Tumor, Tumor Suppressor Protein p53/*metabolism, Tumor Suppressor Proteins/*metabolism, Ubiquitin-Protein Ligases/*metabolism, Up-Regulation, Von Hippel-Lindau Tumor Suppressor Protein, Western}
}

@article{lanz_steroid_1999,
	title = {A steroid receptor coactivator, {SRA}, functions as an {RNA} and is present in an {SRC}-1 complex},
	volume = {97},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/10199399},
	abstract = {Nuclear receptors play critical roles in the regulation of eukaryotic gene expression. We report the isolation and functional characterization of a novel transcriptional coactivator, termed steroid receptor {RNA} activator ({SRA}). {SRA} is selective for steroid hormone receptors and mediates transactivation via their amino-terminal activation function. We provide functional and mechanistic evidence that {SRA} acts as an {RNA} transcript; transfected {SRA}, unlike other steroid receptor coregulators, functions in the presence of cycloheximide, and {SRA} mutants containing multiple translational stop signals retain their ability to activate steroid receptor-dependent gene expression. Biochemical fractionation shows that {SRA} exists in distinct ribonucleoprotein complexes, one of which contains the nuclear receptor coactivator steroid receptor coactivator 1. We suggest that {SRA} may act to confer functional specificity upon multiprotein complexes recruited by liganded receptors during transcriptional activation.},
	pages = {17--27},
	number = {1},
	journaltitle = {Cell},
	author = {Lanz, R B and {McKenna}, N J and Onate, S A and Albrecht, U and Wong, J and Tsai, S Y and Tsai, M J and O'Malley, B W},
	date = {1999},
	pmid = {10199399},
	keywords = {{DNA}, Animals, Base Sequence, Humans, Mice, Nucleic Acid, Complementary/isolation \& purification, Cytoplasmic and Nuclear/physiology, Histone Acetyltransferases, Macromolecular Substances, Molecular Sequence Data, Multiprotein Complexes, Nuclear Receptor Coactivator 1, Receptors, {RNA}/*physiology, Sequence Homology, Steroid/genetics/*physiology, Trans-Activators/genetics/*physiology, Transcription Factors/chemistry/*physiology}
}

@article{ferreira_transcriptome_2014,
	title = {Transcriptome characterization by {RNA} sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia},
	volume = {24},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24265505},
	doi = {10.1101/gr.152132.112},
	abstract = {Chronic lymphocytic leukemia ({CLL}) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep {RNA} sequencing in different subpopulations of normal B-lymphocytes and {CLL} cells from a cohort of 98 patients, and characterized the {CLL} transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the {CLL} and normal B cells, including protein-coding genes, noncoding {RNAs}, and pseudogenes. Transposable elements are globally derepressed in {CLL} cells. In addition, two thousand genes-most of which are not differentially expressed-exhibit {CLL}-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in {CLL}, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in {CLL}. Clustering of the {CLL} samples according to {RNA}-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable ({IGHV}) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through {DNA} microarrays. Further analysis shows that B-cell receptor ({BCR}) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences.},
	pages = {212--226},
	number = {2},
	journaltitle = {Genome Res},
	author = {Ferreira, P G and Jares, P and Rico, D and Gomez-Lopez, G and Martinez-Trillos, A and Villamor, N and Ecker, S and Gonzalez-Perez, A and Knowles, D G and Monlong, J and Johnson, R and Quesada, V and Djebali, S and Papasaikas, P and Lopez-Guerra, M and Colomer, D and Royo, C and Cazorla, M and Pinyol, M and Clot, G and Aymerich, M and Rozman, M and Kulis, M and Tamborero, D and Gouin, A and Blanc, J and Gut, M and Gut, I and Puente, X S and Pisano, D G and Martin-Subero, J I and Lopez-Bigas, N and Lopez-Guillermo, A and Valencia, A and Lopez-Otin, C and Campo, E and Guigo, R},
	date = {2014},
	pmid = {24265505}
}

@article{kralj_characterization_2013,
	title = {Characterization of in vitro transcription amplification linearity and variability in the low copy number regime using External {RNA} Control Consortium ({ERCC}) spike-ins},
	volume = {405},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23086083},
	doi = {10.1007/s00216-012-6445-1},
	abstract = {Using spike-in controls designed to mimic mammalian {mRNA} species, we used the quantitative reverse transcription polymerase chain reaction ({RT}-{qPCR}) to assess the performance of in vitro transcription ({IVT}) amplification process of small samples. We focused especially on the confidence of the transcript level measurement, which is essential for differential gene expression analyses. {IVT} reproduced gene expression profiles down to approximately 100 absolute input copies. However, a {RT}-{qPCR} analysis of the antisense {RNA} showed a systematic bias against low copy number transcripts, regardless of sequence. Experiments also showed that noise increases with decreasing copy number. First-round {IVT} preserved the gene expression information within a sample down to the 100 copy level, regardless of total input sample amount. However, the amplification was nonlinear under low total {RNA} input/long {IVT} conditions. Variability of the amplification increased predictably with decreasing input copy number. For the small enrichments of interest in typical differential gene expression studies (e.g., twofold changes), the bias from {IVT} reactions is unlikely to affect the results. In limited cases, some transcript-specific differential gene expression values will need adjustment to reflect this bias. Proper experimental design with reasonable detection limits will yield differential gene expression capability even between low copy number transcripts.},
	pages = {315--320},
	number = {1},
	journaltitle = {Anal Bioanal Chem},
	author = {Kralj, J G and Salit, M L},
	date = {2013},
	pmid = {23086083},
	keywords = {Genetic, Humans, {RNA}, Transcription, Gene Expression Regulation, Gene Expression Profiling, Reproducibility of Results, *Gene Dosage, Analytical, Antisense/metabolism, Chemistry Techniques, {DNA} Primers, Jurkat Cells, Messenger/metabolism, Nucleic Acid Amplification Techniques/methods, Regression Analysis, Reverse Transcriptase Polymerase Chain Reaction/me, {RNA}/*analysis}
}

@article{gennari_additive_2002,
	title = {Additive and antagonist effects of therapeutic gene combinations for suppression of {HIV}-1 infection},
	volume = {55},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12076753},
	abstract = {A previously described Moloney-based vector expressing a double copy anti-tat antisense {tRNA} ({DC}-{tRNA}-{AT}) (Biasolo et al., 1996. J. Virol. 70, 2154-2161) was modified to increase the copy number of the antisense molecule and to target the intra-cytoplasmic localization of the {HIV} genome. To this end, an anti-U5 hammerhead ribozyme, engineered as a hybrid small adenoviral {VAI} {RNA} ({VAIalpha}), was inserted into the vector as a single molecule or in combination with the double copy anti-tat sequence. The retroviral vector expressing only {VAIalpha} ({DC}-{VAIalpha}) inhibited {HIV}-1 replication to an extent comparable to that of {DC}-{tRNA}-{AT}. A more effective inhibition was produced by the vector expressing multiple copies of the anti-tat antisense ({DC}-6tRNA-{AT}). This higher effectiveness correlated with anti-tat stochiometry, i.e. with the absolute number of therapeutic molecules being produced on a per cell basis at the steady state. Surprisingly, when the {tRNA}-{AT} and {VAIalpha} genes were combined in the same vector ({DC}-{AT}-{VAIalpha}), an enhancement of viral replication was noticed. This study indicates that it is possible to potentiate the antiviral activity of a retroviral vector by increasing the steady-state level of the therapeutic molecule. Results also show that the combined expression of two singularly active therapeutic {RNAs} can have antagonistic rather than synergistic effects.},
	pages = {77--90},
	number = {1},
	journaltitle = {Antiviral Res},
	author = {Gennari, F and Biasolo, M A and Cancellotti, E and Radaelli, A and De Giuli Morghen, C and Bozzoni, I and Cereda, P M and Mengoli, C and Palu, G and Parolin, C},
	date = {2002},
	pmid = {12076753},
	keywords = {Humans, {RNA}, *Genetic Therapy, *Genetic Vectors, *{HIV}-1/physiology, Adenoviridae/genetics, Antisense/chemistry/genetics, Catalytic/genetics, Gene Products, Human Immunodeficiency Virus, Jurkat Cells, Retroviridae/genetics, Statistics as Topic, tat Gene Products, tat/genetics, Transfection, Virus Replication}
}

@article{lipovich_comparative_2002,
	title = {Comparative genomics comes of age},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12186641},
	abstract = {A report on the 2002 annual Cold Spring Harbor Laboratory meeting on Genome Sequencing and Biology, Cold Spring Harbor, {NY}, {USA}, 7-11 May 2002.},
	pages = {REPORTS4024},
	number = {8},
	journaltitle = {Genome Biol},
	author = {Lipovich, L},
	date = {2002},
	pmid = {12186641},
	keywords = {Human, {DNA}, Animals, Genome, Humans, Antisense/genetics, Base Sequence/genetics, Complementary/genetics, Conserved Sequence/genetics, Genomic Imprinting/genetics, Genomics/*methods/trends, Pan troglodytes, Phenotype, Species Specificity}
}

@article{zahn_agemap:_2007,
	title = {{AGEMAP}: a gene expression database for aging in mice},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18081424},
	doi = {10.1371/journal.pgen.0030201},
	abstract = {We present the {AGEMAP} (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The {AGEMAP} database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1) a pattern common to neural tissues, (2) a pattern for vascular tissues, and (3) a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different.},
	pages = {e201},
	number = {11},
	journaltitle = {{PLoS} Genet},
	author = {Zahn, J M and Poosala, S and Owen, A B and Ingram, D K and Lustig, A and Carter, A and Weeraratna, A T and Taub, D D and Gorospe, M and Mazan-Mamczarz, K and Lakatta, E G and Boheler, K R and Xu, X and Mattson, M P and Falco, G and Ko, M S and Schlessinger, D and Firman, J and Kummerfeld, S K and Wood 3rd, W H and Zonderman, A B and Kim, S K and Becker, K G},
	date = {2007},
	pmid = {18081424},
	keywords = {Animals, Genetic, Humans, Mice, Gene Expression Profiling, Organ Specificity, *Databases, *Gene Expression Regulation, Aging/*genetics, Diptera/genetics, Helminths/genetics, Species Specificity}
}

@article{gonzalez-perez_intogen-mutations_2013,
	title = {{IntOGen}-mutations identifies cancer drivers across tumor types},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24037244},
	doi = {10.1038/nmeth.2642},
	abstract = {The {IntOGen}-mutations platform (http://www.intogen.org/mutations/) summarizes somatic mutations, genes and pathways involved in tumorigenesis. It identifies and visualizes cancer drivers, analyzing 4,623 exomes from 13 cancer sites. It provides support to cancer researchers, aids the identification of drivers across tumor cohorts and helps rank mutations for better clinical decision-making.},
	pages = {1081--1082},
	number = {11},
	journaltitle = {Nat Methods},
	author = {Gonzalez-Perez, A and Perez-Llamas, C and Deu-Pons, J and Tamborero, D and Schroeder, M P and Jene-Sanz, A and Santos, A and Lopez-Bigas, N},
	date = {2013},
	pmid = {24037244},
	keywords = {Humans, *Mutation, Exome, Neoplasms/classification/*genetics/pathology}
}

@article{liu_noncode:_2005,
	title = {{NONCODE}: an integrated knowledge database of non-coding {RNAs}},
	volume = {33},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15608158},
	doi = {10.1093/nar/gki041},
	abstract = {{NONCODE} is an integrated knowledge database dedicated to non-coding {RNAs} ({ncRNAs}), that is to say, {RNAs} that function without being translated into proteins. All {ncRNAs} in {NONCODE} were filtered automatically from literature and {GenBank}, and were later manually curated. The distinctive features of {NONCODE} are as follows: (i) the {ncRNAs} in {NONCODE} include almost all the types of {ncRNAs}, except transfer {RNAs} and ribosomal {RNAs}. (ii) All {ncRNA} sequences and their related information (e.g. function, cellular role, cellular location, chromosomal information, etc.) in {NONCODE} have been confirmed manually by consulting relevant literature: more than 80\% of the entries are based on experimental data. (iii) Based on the cellular process and function, which a given {ncRNA} is involved in, we introduced a novel classification system, labeled process function class, to integrate existing classification systems. (iv) In addition, some 1100 {ncRNAs} have been grouped into nine other classes according to whether they are specific to gender or tissue or associated with tumors and diseases, etc. (v) {NONCODE} provides a user-friendly interface, a visualization platform and a convenient search option, allowing efficient recovery of sequence, regulatory elements in the flanking sequences, secondary structure, related publications and other information. The first release of {NONCODE} (v1.0) contains 5339 non-redundant sequences from 861 organisms, including eukaryotes, eubacteria, archaebacteria, virus and viroids. Access is free for all users through a web interface at http://noncode.bioinfo.org.cn.},
	pages = {D112--5},
	issue = {Database issue},
	journaltitle = {Nucleic Acids Res},
	author = {Liu, C and Bai, B and Skogerbo, G and Cai, L and Deng, W and Zhang, Y and Bu, D and Zhao, Y and Chen, R},
	date = {2005},
	pmid = {15608158},
	keywords = {Base Sequence, {RNA}, Nucleic Acid, *Databases, Systems Integration, Untranslated/*chemistry/classification}
}

@article{sun_utilizing_2013,
	title = {Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23892401},
	doi = {10.1093/nar/gkt646},
	abstract = {It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index ({CNCI}), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. {CNCI} is effective for classifying incomplete transcripts and sense-antisense pairs. The implementation of {CNCI} offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding {RNA} catalog of orangutan. {CNCI} software is available at http://www.bioinfo.org/software/cnci.},
	pages = {e166},
	number = {17},
	journaltitle = {Nucleic Acids Res},
	author = {Sun, L and Luo, H and Bu, D and Zhao, G and Yu, K and Zhang, C and Liu, Y and Chen, R and Zhao, Y},
	date = {2013},
	pmid = {23892401},
	keywords = {*Software, Sequence Analysis, Animals, Humans, Mice, {RNA}, Gene Expression Profiling, Long Noncoding/*chemistry/classification, Pongo/genetics, Proteins/*genetics, {RNA}/*methods}
}

@article{marasa_increased_2009,
	title = {Increased {MKK}4 abundance with replicative senescence is linked to the joint reduction of multiple {microRNAs}},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19861690},
	doi = {10.1126/scisignal.2000442},
	abstract = {{MKK}4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of {MKK}4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four {microRNAs} ({miR}-15b, {miR}-24, {miR}-25, and {miR}-141) that target the {MKK}4 messenger {RNA} ({mRNA}); the abundance of these {microRNAs} decreased during replicative senescence. Individually modulating the amount of each {microRNA} did not modify {MKK}4 abundance, but their concomitant overexpression decreased and their joint reduction increased {MKK}4 abundance. Reporter analyses indicated that these {microRNAs} acted through the {MKK}4 5' and 3' untranslated regions. Elevated {MKK}4 abundance inhibited cell proliferation and increased the phosphorylation and activity of p38 and {PRAK} (p38-regulated/activated protein kinase). Thus, multiple {microRNAs} acting on a single target, the {MKK}4 {mRNA}, collectively influence {MKK}4 abundance during replicative senescence.},
	pages = {ra69},
	number = {94},
	journaltitle = {Sci Signal},
	author = {Marasa, B S and Srikantan, S and Masuda, K and Abdelmohsen, K and Kuwano, Y and Yang, X and Martindale, J L and Rinker-Schaeffer, C W and Gorospe, M},
	date = {2009},
	pmid = {19861690},
	keywords = {3' Untranslated Regions, Base Sequence, Humans, {RNA}, Cells, Cultured, *Cell Aging, Cell Proliferation, {DNA} Primers, Immunohistochemistry, {MAP} Kinase Kinase 4/genetics/*metabolism, Messenger/genetics/metabolism, {MicroRNAs}/*metabolism, Protein Biosynthesis, Signal Transduction}
}

@article{galban_von_2003,
	title = {von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of {cDNA} arrays},
	volume = {23},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/12640117},
	abstract = {Based on evidence that the von Hippel-Lindau ({VHL}) tumor suppressor protein is associated with polysomes and interacts with translation regulatory factors, we set out to investigate the potential influence of {pVHL} on protein translation. To this end, renal cell carcinoma ({RCC}) cells that either lacked {pVHL} or expressed {pVHL} through stable transfection were used to prepare {RNA} from cytosolic (unbound) and polysome-bound fractions. Hybridization of {cDNA} arrays using {RNA} from each fraction revealed a subset of transcripts whose abundance in polysomes decreased when {pVHL} function was restored. The tumor necrosis factor alpha ({TNF}-alpha) {mRNA} was identified as one of the transcripts that preferentially associated with polysomes in {pVHL}-deficient cells. Additional evidence that the {TNF}-alpha {mRNA} was a target of translational repression by {pVHL} was obtained from reporter gene assays, which further revealed that {pVHL}'s inhibitory influence on protein synthesis occurred through the {TNF}-alpha 3'-untranslated region. Our findings uncover a novel function for the {pVHL} tumor suppressor protein as regulator of protein translation.},
	pages = {2316--2328},
	number = {7},
	journaltitle = {Mol Cell Biol},
	author = {Galban, S and Fan, J and Martindale, J L and Cheadle, C and Hoffman, B and Woods, M P and Temeles, G and Brieger, J and Decker, J and Gorospe, M},
	date = {2003},
	pmid = {12640117},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Cultured, *Tumor Suppressor Proteins, *Ubiquitin-Protein Ligases, 3' Untranslated Regions/physiology, Blotting, Carcinoma, Cytosol/chemistry/metabolism, Enzyme-Linked Immunosorbent Assay, Genes, Ligases/deficiency/genetics/*metabolism, Messenger/analysis/metabolism, Neoplastic/physiology, Northern, Polyribosomes/chemistry/metabolism, Protein Biosynthesis/*physiology, Renal Cell/genetics/*metabolism, Reporter, Transfection, Tumor Cells, Tumor Necrosis Factor-alpha/biosynthesis/*genetics, Tumor Suppressor/*physiology, Von Hippel-Lindau Tumor Suppressor Protein}
}

@article{jagadeeswaran_redox_2013,
	title = {Redox signaling mediates the expression of a sulfate-deprivation-inducible {microRNA}395 in Arabidopsis},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24164591},
	doi = {10.1111/tpj.12364},
	abstract = {{MicroRNA}395 ({miR}395) is a conserved {miRNA} that targets a low-affinity sulfate transporter ({AST}68) and three {ATP} sulfurylases ({APS}1, {APS}3 and {APS}4) in higher plants. In this study, At2g28780 was confirmed as another target of {miR}395 in Arabidopsis. Interestingly, several dicots contained genes homologous to At2g28780 and a cognate {miR}395 complementary site but possess a gradient of mismatches at the target site. It is well established that {miR}395 is induced during S deprivation in Arabidopsis; however, the signaling pathways that mediate this regulation are unknown. Several findings in the present study demonstrate that redox signaling plays an important role in induction of {miR}395 during S deprivation. These include the following results: (i) glutathione ({GSH}) supplementation suppressed {miR}395 induction in S-deprived plants (ii) {miR}395 is induced in Arabidopsis seedlings exposed to Arsenate or Cu2+ , which induces oxidative stress (iii), S deprivation-induced oxidative stress, and (iv) compromised induction of {miR}395 during S deprivation in cad2 mutant (deficient in {GSH} biosynthesis) that is defective in glutaredoxin-dependent redox signaling and ntra/ntrb (defective in thioredoxin reductases a and b) double mutants that are defective in thioredoxin-dependent redox signaling. Collectively, these findings strongly support the involvement of redox signaling in inducing the expression of {miR}395 during S deprivation in Arabidopsis.},
	journaltitle = {Plant J},
	author = {Jagadeeswaran, G and Li, Y F and Sunkar, R},
	date = {2013},
	pmid = {24164591}
}

@article{cacchiarelli_mir-31_2011,
	title = {{miR}-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy},
	volume = {12},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21212803},
	doi = {10.1038/embor.2010.208},
	abstract = {Duchenne muscular dystrophy ({DMD})–which is caused by mutations in the dystrophin gene-is one of the most severe myopathies. Among therapeutic strategies, exon skipping allows the rescue of dystrophin synthesis through the production of a shorter but functional messenger {RNA}. Here, we report the identification of a {microRNA}–{miR}-31–that represses dystrophin expression by targeting its 3' untranslated region. In human {DMD} myoblasts treated with exon skipping, we demonstrate that {miR}-31 inhibition increases dystrophin rescue. These results indicate that interfering with {miR}-31 activity can provide an ameliorating strategy for those {DMD} therapies that are aimed at efficiently recovering dystrophin synthesis.},
	pages = {136--141},
	number = {2},
	journaltitle = {{EMBO} Rep},
	author = {Cacchiarelli, D and Incitti, T and Martone, J and Cesana, M and Cazzella, V and Santini, T and Sthandier, O and Bozzoni, I},
	date = {2011},
	pmid = {21212803},
	keywords = {3' Untranslated Regions, Animals, Humans, Mice, {RNA}, Gene Expression Profiling, Cells, Cultured, Cell Differentiation, Duchenne/*metabolism/pathology, Dystrophin/*biosynthesis/genetics, Inbred mdx, Messenger/metabolism, {MicroRNAs}/*biosynthesis, Muscular Dystrophy, Myotonia Congenita/metabolism/pathology, {RNA} Interference, Satellite Cells, Skeletal Muscle/cytology/metaboli}
}

@article{rours_chlamydia_2008,
	title = {Chlamydia trachomatis as a cause of neonatal conjunctivitis in Dutch infants},
	volume = {121},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/18245405},
	doi = {10.1542/peds.2007-0153},
	abstract = {{BACKGROUND}: Chlamydia trachomatis is the most common sexually transmitted pathogen in adults, which at delivery may be transmitted from mother to child and cause conjunctivitis and pneumonia. In The Netherlands, prenatal chlamydial screening and treatment of pregnant women is not routine practice. The contribution of C. trachomatis to neonatal ophthalmic disease has not been studied in The Netherlands and remains unclear. {METHODS}: At the Sophia Children's Hospital and Rotterdam Eye Hospital, 2 cohorts of infants {\textbackslash}textless3 months of age presenting with conjunctivitis were studied, 1 retrospectively (July 1996 to July 2001) and 1 prospectively (September 2001 to September 2002). Laboratory diagnosis was based on bacterial culture and polymerase chain reaction for C. trachomatis. {RESULTS}: C. trachomatis was detected in 27 (64\%) of 42 retrospectively studied infants and 14 (61\%) of 23 prospectively studied infants. Mucopurulent discharge was present in 35 (95\%) of 37, swelling of the eyes in 27 (73\%) of 37, conjunctival erythema in 24 (65\%) of 37, respiratory symptoms in 14 (38\%) of 37, and feeding problems in 5 (14\%) of 37 infants respectively. Before microbiological diagnosis, general practitioners prescribed antichlamydial antibiotics locally to 5 (12\%) of 41 and systemically to 4 (10\%) of 41 infants who tested positive for chlamydia, and ophthalmologists prescribed to 21 (51\%) of 41 and 7 (17\%) of 41, respectively. {CONCLUSIONS}: C. trachomatis was the major cause of bacterial conjunctivitis in this population. Clinically, differentiation from other pathogens was not possible. Many infants who tested positive for chlamydia did not receive appropriate antibiotic treatment.},
	pages = {e321--6},
	number = {2},
	journaltitle = {Pediatrics},
	author = {Rours, I G and Hammerschlag, M R and Ott, A and De Faber, T J and Verbrugh, H A and de Groot, R and Verkooyen, R P},
	date = {2008},
	pmid = {18245405},
	keywords = {Humans, Administration, Anti-Bacterial Agents/therapeutic use, Chlamydia trachomatis/*isolation \& purification, Conjunctivitis, Female, Inclusion/diagnosis/drug therapy/*, Infant, Male, Netherlands/epidemiology, Newborn, Prospective Studies, Retrospective Studies, Topical}
}

@article{panchatcharam_lipid_2013,
	title = {Lipid phosphate phosphatase 3 negatively regulates smooth muscle cell phenotypic modulation to limit intimal hyperplasia},
	volume = {33},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23104851},
	doi = {10.1161/ATVBAHA.112.300527},
	abstract = {{OBJECTIVE}: The lipid phosphate phosphatase 3 ({LPP}3) degrades bioactive lysophospholipids, including lysophosphatidic acid and sphingosine-1-phosphate, and thereby terminates their signaling effects. Although emerging evidence links lysophosphatidic acid to atherosclerosis and vascular injury responses, little is known about the role of vascular {LPP}3. The goal of this study was to determine the role of {LPP}3 in the development of vascular neointima formation and smooth muscle cells ({SMC}) responses. {METHODS} {AND} {RESULTS}: We report that {LPP}3 is expressed in vascular {SMC} after experimental arterial injury. Using gain- and loss-of-function approaches, we establish that a major function of {LPP}3 in isolated {SMC} cells is to attenuate proliferation (extracellular signal-regulated kinases) activity, Rho activation, and migration in response to serum and lysophosphatidic acid. These effects are at least partially a consequence of {LPP}3-catalyzed lysophosphatidic acid hydrolysis. Mice with selective inactivation of {LPP}3 in {SMC} display an exaggerated neointimal response to injury. {CONCLUSIONS}: Our observations suggest that {LPP}3 serves as an intrinsic negative regulator of {SMC} phenotypic modulation and inflammation after vascular injury, in part, by regulating lysophospholipid signaling. These findings may provide a mechanistic link to explain the association between a {PPAP}2B polymorphism and coronary artery disease risk.},
	pages = {52--59},
	number = {1},
	journaltitle = {Arterioscler Thromb Vasc Biol},
	author = {Panchatcharam, M and Miriyala, S and Salous, A and Wheeler, J and Dong, A and Mueller, P and Sunkara, M and Escalante-Alcalde, D and Morris, A J and Smyth, S S},
	date = {2013},
	pmid = {23104851},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, *Cell Proliferation, Animal, Carotid Artery, Carotid Artery Injuries/enzymology/genetics/pathol, Cell Movement, Common/enzymology/pathology, Disease Models, Enzyme Activation, Extracellular Signal-Regulated {MAP} Kinases/metabol, Genotype, {HEK}293 Cells, Hydrolysis, Hyperplasia, Inbred C57BL, Knockout, Lysophospholipids/metabolism, Muscle, Myocytes, Neointima, Phenotype, Phosphatidate Phosphatase/deficiency/genetics/*met, rho-Associated Kinases/metabolism, Signal Transduction, Smooth, Smooth Muscle/*enzymology/pathology, Time Factors, Transfection, Vascular/*enzymology/pathology}
}

@article{rapino_c/ebpalpha_2013,
	title = {C/{EBPalpha} induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23545498},
	doi = {10.1016/j.celrep.2013.03.003},
	abstract = {Earlier work demonstrated that the transcription factor C/{EBPalpha} can convert immature and mature murine B lineage cells into functional macrophages. Testing {\textbackslash}textgreater20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/{EBPalpha} is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/{EBPalphaER}, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/{EBPalpha} was inactivated, a hallmark of cell reprogramming. Interestingly, C/{EBPalpha} induction also impaired the cells' tumorigenicity. Likewise, C/{EBPalpha} efficiently converted a lymphoblastic leukemia B cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced by C/{EBPalpha} to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies.},
	pages = {1153--1163},
	number = {4},
	journaltitle = {Cell Rep},
	author = {Rapino, F and Robles, E F and Richter-Larrea, J A and Kallin, E M and Martinez-Climent, J A and Graf, T},
	date = {2013},
	pmid = {23545498},
	keywords = {Transcriptome, Animals, Humans, Mice, Antineoplastic Agents, B-Cell/drug therapy/metabolism/mortality, {CCAAT}-Enhancer-Binding Protein-alpha/*metabolism, Cell Line, Cell Lineage, Cell Transdifferentiation/drug effects, Heterologous, Hormonal/therapeutic use/to, Leukemia/metabolism/pathology, Lymphoma, Macrophages/*cytology/metabolism, Phagocytosis, Tamoxifen/therapeutic use/toxicity, Transplantation, Tumor}
}

@article{cheadle_stability_2005,
	title = {Stability regulation of {mRNA} and the control of gene expression},
	volume = {1058},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16394137},
	doi = {10.1196/annals.1359.026},
	abstract = {Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. Standard techniques measure changes in total cellular poly(A) {mRNA} levels. The assumption that changes in gene expression as measured by these techniques are directly and well correlated with changes in rates of new gene synthesis form the basis of attempts to connect coordinated changes in gene expression with shared transcription regulatory elements. Yet systematic attempts at this approach remain difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and {mRNA} turnover events which, together, directly influence steady-state {mRNA} levels. Recent technical advances have led to the successful scale-up and application of nuclear run-on procedures directly to microarrays. This development has allowed a gene-by-gene comparison between new gene synthesis in the nucleus and measured changes in total cellular {polyA} {mRNA}. Results from these studies have begun to challenge the strict interpretation of changes in gene expression measured by conventional microarrays as being closely correlated with changes in {mRNA} transcription rate, but rather they tend to support the significant expansion of the role played by changes in {mRNA} stability regulation to standard analyses of gene expression. Gene expression profiles obtained from both {polyA} {mRNA} (whole-cell) and nuclear run-on (newly transcribed) {RNA} across a time course of one hour following the activation of human Jurkat T cells with {PMA} plus ionomycin revealed that regulation of {mRNA} stability may account for as much as 50\% of all measurements of changes in total cellular {polyA} {mRNA} in this system. Stability regulation was inferred by the absence of corresponding regulation of nuclear gene transcription activity for groups of genes strongly regulated at the whole cell level and which were also resistant to inhibition by Actinomycin D pre-treatment. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. It is proposed that the regulation of {mRNA} stability in response to external stimuli contributes significantly to observed changes in gene expression as measured by high throughput systems.},
	pages = {196--204},
	journaltitle = {Ann N Y Acad Sci},
	author = {Cheadle, C and Fan, J and Cho-Chung, Y S and Werner, T and Ray, J and Do, L and Gorospe, M and Becker, K G},
	date = {2005},
	pmid = {16394137},
	keywords = {Genetic, Humans, {RNA}, Transcription, Oligonucleotide Array Sequence Analysis, *Gene Expression Regulation, Cell Line, Cell Nucleus/metabolism, Dactinomycin/pharmacology, Gene Expression, Ionomycin/pharmacology, Jurkat Cells, Messenger/*metabolism, Phorbol Esters/chemistry, {RNA}/metabolism, Time Factors, Tumor}
}

@article{bassett_highly_2013,
	title = {Highly efficient targeted mutagenesis of Drosophila with the {CRISPR}/Cas9 system},
	volume = {4},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23827738},
	doi = {10.1016/j.celrep.2013.06.020},
	abstract = {Here, we present a simple and highly efficient method for generating and detecting mutations of any gene in Drosophila melanogaster through the use of the {CRISPR}/Cas9 system (clustered regularly interspaced palindromic repeats/{CRISPR}-associated). We show that injection of {RNA} into the Drosophila embryo can induce highly efficient mutagenesis of desired target genes in up to 88\% of injected flies. These mutations can be transmitted through the germline to make stable lines. Our system provides at least a 10-fold improvement in efficiency over previously published reports, enabling wider application of this technique. We also describe a simple and highly sensitive method of detecting mutations in the target gene by high-resolution melt analysis and discuss how the new technology enables the study of gene function.},
	pages = {220--228},
	number = {1},
	journaltitle = {Cell Rep},
	author = {Bassett, A R and Tibbit, C and Ponting, C P and Liu, J L},
	date = {2013},
	pmid = {23827738},
	keywords = {Animals, Base Sequence, *Germ-Line Mutation, Clustered Regularly Interspaced Short Palindromic, Drosophila/*genetics, Endodeoxyribonucleases/*genetics/metabolism, Molecular Sequence Data, Mutagenesis, Site-Directed/*methods}
}

@article{schad_exon-phase_2013,
	title = {Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome},
	volume = {41},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23460204},
	doi = {10.1093/nar/gkt110},
	abstract = {A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions ({\textbackslash}textgreater70\% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins ({\textbackslash}textgreater70\% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. {SH}3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome.},
	pages = {4409--4422},
	number = {8},
	journaltitle = {Nucleic Acids Res},
	author = {Schad, E and Kalmar, L and Tompa, P},
	date = {2013},
	pmid = {23460204},
	keywords = {Human, Humans, *Genome, *Evolution, *Exons, Molecular, Protein Conformation, Proteins/chemistry/*genetics}
}

@article{calaluce_rna_2010,
	title = {The {RNA} binding protein {HuR} differentially regulates unique subsets of {mRNAs} in estrogen receptor negative and estrogen receptor positive breast cancer},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20370918},
	doi = {10.1186/1471-2407-10-126},
	abstract = {{BACKGROUND}: The discordance between steady-state levels of {mRNAs} and protein has been attributed to posttranscriptional control mechanisms affecting {mRNA} stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of {mRNA}, may miss important {mRNA} targets owing to significant posttranscriptional gene regulation by {RNA} binding proteins ({RBPs}). {METHODS}: The ribonomic approach, utilizing {RNA} immunoprecipitation hybridized to microarray ({RIP}-Chip), provides global identification of putative endogenous {mRNA} targets of different {RBPs}. {HuR} is an {RBP} that binds to the {AU}-rich elements ({ARE}) of labile {mRNAs}, such as proto-oncogenes, facilitating their translation into protein. {HuR} has been shown to play a role in cancer progression and elevated levels of cytoplasmic {HuR} directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. {HuR} has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. {RESULTS}: We used {HuR} {RIP}-Chip as a comprehensive and systematic method to survey breast cancer target genes in both {MCF}-7 (estrogen receptor positive, {ER}+) and {MDA}-{MB}-231 (estrogen receptor negative, {ER}-) breast cancer cell lines. We identified unique subsets of {HuR}-associated {mRNAs} found individually or in both cell types. Two novel {HuR} targets, {CD}9 and {CALM}2 {mRNAs}, were identified and validated by quantitative {RT}-{PCR} and biotin pull-down analysis. {CONCLUSION}: This is the first report of a side-by-side genome-wide comparison of {HuR}-associated targets in wild type {ER}+ and {ER}- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in {ER}+ and {ER}- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by {HuR} was contingent upon the cellular environment.},
	pages = {126},
	journaltitle = {{BMC} Cancer},
	author = {Calaluce, R and Gubin, M M and Davis, J W and Magee, J D and Chen, J and Kuwano, Y and Gorospe, M and Atasoy, U},
	date = {2010},
	pmid = {20370918},
	keywords = {Humans, {RNA}, Oligonucleotide Array Sequence Analysis, *Gene Expression Regulation, Antigens, Biotin/chemistry, Breast Neoplasms/*genetics/metabolism, Calmodulin/genetics/metabolism, {CD}/genetics/metabolism, {CD}9, Cell Line, Estrogen/*biosynthesis/genetics, Hu Paraneoplastic Encephalomyelitis Antigens, Immunoprecipitation, Membrane Glycoproteins/genetics/metabolism, Messenger/biosynthesis/*genetics, Neoplastic, Receptors, {RNA}-Binding Proteins/*genetics/metabolism, Surface/*genetics/metabolism, Tumor}
}

@article{horvath_beating_2007,
	title = {Beating heart aortic valve replacement using real-time {MRI} guidance},
	volume = {2},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22436922},
	doi = {10.1097/IMI.0b013e31805b8280},
	abstract = {{OBJECTIVE}: : The principal limitations of percutaneous techniques to replace the aortic valve are detailed visualization and durable prostheses. We report the feasibility of using real-time magnetic resonance imaging ({MRI}) to provide precise anatomic detail and visual feedback to implant a proven bioprosthesis. {METHODS}: : Twelve domestic pigs were anesthetized, and, through a minimally invasive approach using real-time {MRI} guidance, underwent aortic valve replacement. This was accomplished on the beating heart by using a commercially available bioprosthesis. {MRI} was used to precisely identify the anatomic landmarks of the aortic annulus, coronary artery ostia, and the mitral valve leaflets. Additional intraoperative perfusion, flow velocity, and functional imaging were used to confirm adequacy of placement and function of the valve. {RESULTS}: : Under real-time {MRI}, multiple oblique planes were prescribed to delineate the anatomy of the native aortic valve and left ventricular outflow track. Enhanced by the use of an active marker wire, this imaging allowed correct placement and orientation of the valve. Through a transapical approach, a series of bioprosthetic aortic valves (21 to 25 mm) were inserted. The time to implantation after the placement of the trocar to deployment of the valve was less than 90 seconds. The average procedure duration was less than 40 minutes {CONCLUSIONS}: : Real-time {MRI} provides excellent anatomic detail and intraoperative assessment that permits placement of durable valve prostheses on the beating heart without the limitations of percutaneous approaches.},
	pages = {51--55},
	number = {2},
	journaltitle = {Innovations (Phila)},
	author = {Horvath, K A and Guttman, M and Li, M and Lederman, R J and Mazilu, D and Kocaturk, O and Karmarkar, P V and Hunt, T and Kozlov, S and {McVeigh}, E R},
	date = {2007},
	pmid = {22436922}
}

@article{reith_blood-brain_1990,
	title = {Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat},
	volume = {10},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2117017},
	doi = {10.1038/jcbfm.1990.124},
	abstract = {In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine ({FDOPA}), we discovered a major discrepancy between the {DOPA} decarboxylase activity reported in the literature and the rate of {FDOPA} decarboxylation measured in the study. "Donor" rats received intravenous injections of 6 {mCi} fluorine-18-labeled {FDOPA}. The donor rats synthesized methyl-{FDOPA}. Arterial plasma, containing both {FDOPA} and methyl-{FDOPA}, was sampled from the donor rats at different times and reinjected into "recipient" rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-{FDOPA} permeability in the blood-brain barrier was twice that of {FDOPA}, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of {FDOPA} (and hence of methyl-{FDOPA}), which averaged 0.081 min-1. In the striatum, the measured average {FDOPA} decarboxylation rate constant ({kD}3) was 0.010 min-1, or no more than 1\% of the rate of striatal decarboxylation of {DOPA} measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine ({DA}) pools, of which only {DA} in the large pool is protected from metabolism. Hence, no more than 1\% of the quantity of fluoro-{DA} theoretically synthesized was actually retained in striatum.},
	pages = {707--719},
	number = {5},
	journaltitle = {J Cereb Blood Flow Metab},
	author = {Reith, J and Dyve, S and Kuwabara, H and Guttman, M and Diksic, M and Gjedde, A},
	date = {1990},
	pmid = {2117017},
	keywords = {Animals, *Blood-Brain Barrier, Brain/metabolism, Decarboxylation, Dihydroxyphenylalanine/*analogs \& derivatives/meta, Dopa Decarboxylase/metabolism, Fluorine Radioisotopes/diagnostic use, Inbred Strains, Linear Models, Models, Neurological, Rats}
}

@article{dasari_clinical_2014,
	title = {Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses},
	volume = {13},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24650283},
	doi = {10.1021/pr4011475},
	abstract = {Shotgun proteomics of hereditary amyloid deposits generates all the information necessary to identify pathogenic mutant peptides and proteins. However, these mutant peptides are invisible to traditional database search strategies. We developed a two-pronged informatics workflow for detecting both known and novel amyloidogenic mutations from clinical proteomics data sets. We implemented the workflow in a {CAP}/{CLIA} certified clinical laboratory dedicated for proteomic subtyping of amyloid deposits extracted from formalin-fixed paraffin-embedded specimens. Performance of the workflow was characterized on a validation cohort of 49 hereditary amyloid samples, with confirmed mutations, and 85 controls. The sensitivity, specificity, positive predictive value, and negative predictive value of the known mutation detection workflow were determined to be 92\%, 100\%, 100\%, and 96\%, respectively. For novel mutation detection workflow, these performance parameters were 82\%, 99\%, 99\%, and 90\%, respectively. Validated workflow was applied to detect amyloidogenic mutations from a clinical cohort of 150 amyloid samples. The known mutation detection workflow detected rare frame shift mutations in apolipoprotein A1 and fibrinogen alpha amyloid deposits. The novel mutation detection workflow uncovered unanticipated mutations (W22G and C71Y) of the serum amyloid A4 protein present in patient amyloid deposits. In summary, clinical amyloid proteomics data sets contain mutant peptides of clinical significance that are recoverable with improved bioinformatics.},
	pages = {2352--2358},
	number = {5},
	journaltitle = {J Proteome Res},
	author = {Dasari, S and Theis, J D and Vrana, J A and Zenka, R M and Zimmermann, M T and Kocher, J P and Highsmith Jr., W E and Kurtin, P J and Dogan, A},
	date = {2014},
	pmid = {24650283}
}

@article{cheng_understanding_2012,
	title = {Understanding transcriptional regulation by integrative analysis of transcription factor binding data},
	volume = {22},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22955978},
	doi = {10.1101/gr.136838.111},
	abstract = {Statistical models have been used to quantify the relationship between gene expression and transcription factor ({TF}) binding signals. Here we apply the models to the large-scale data generated by the {ENCODE} project to study transcriptional regulation by {TFs}. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites ({TSSs}) captured by different technologies and {RNA} extraction protocols. In general, the expression levels of {TSSs} with high {CpG} content are more predictable than those with low {CpG} content. For genes with alternative {TSSs}, the expression levels of downstream {TSSs} are more predictable than those of the upstream ones. Different {TF} categories and specific {TFs} vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of {TSS} can be precisely reflected by the difference of {TF}-binding signals in a quantitative manner, arguing against the conventional on-and-off model of {TF} binding. Finally, we explore the relationships between {TF}-binding signals and other chromatin features such as histone modifications and {DNase} hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.},
	pages = {1658--1667},
	number = {9},
	journaltitle = {Genome Res},
	author = {Cheng, C and Alexander, R and Min, R and Leng, J and Yip, K Y and Rozowsky, J and Yan, K K and Dong, X and Djebali, S and Ruan, Y and Davis, C A and Carninci, P and Lassman, T and Gingeras, T R and Guigo, R and Birney, E and Weng, Z and Snyder, M and Gerstein, M},
	date = {2012},
	pmid = {22955978},
	keywords = {Genetic, Humans, Promoter Regions, Transcription Initiation Site, *Transcription, *Gene Expression Regulation, *Genomics, Base Composition, Binding Sites/genetics, Biological, Cell Line, Chromatin/genetics/metabolism, Computational Biology/methods, Histones/genetics, Models, Protein Binding/genetics, Transcription Factors/*metabolism}
}

@article{yildirim_xist_2013,
	title = {Xist {RNA} is a potent suppressor of hematologic cancer in mice},
	volume = {152},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23415223},
	doi = {10.1016/j.cell.2013.01.034},
	abstract = {X chromosome aneuploidies have long been associated with human cancers, but causality has not been established. In mammals, X chromosome inactivation ({XCI}) is triggered by Xist {RNA} to equalize gene expression between the sexes. Here we delete Xist in the blood compartment of mice and demonstrate that mutant females develop a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed {MPN}/{MDS}) with 100\% penetrance. Significant disease components include primary myelofibrosis, leukemia, histiocytic sarcoma, and vasculitis. Xist-deficient hematopoietic stem cells ({HSCs}) show aberrant maturation and age-dependent loss. Reconstitution experiments indicate that {MPN}/{MDS} and myelofibrosis are of hematopoietic rather than stromal origin. We propose that Xist loss results in X reactivation and consequent genome-wide changes that lead to cancer, thereby causally linking the X chromosome to cancer in mice. Thus, Xist {RNA} not only is required to maintain {XCI} but also suppresses cancer in vivo.},
	pages = {727--742},
	number = {4},
	journaltitle = {Cell},
	author = {Yildirim, E and Kirby, J E and Brown, D E and Mercier, F E and Sadreyev, R I and Scadden, D T and Lee, J T},
	date = {2013},
	pmid = {23415223},
	keywords = {Animals, Mice, {RNA}, Long Noncoding/*genetics, *Genes, Bone Marrow/physiopathology, Female, Genes, Hematopoietic Stem Cells/metabolism, Lethal, Male, Myelodysplastic Syndromes/*genetics, Myeloproliferative Disorders/*genetics, Primary Myelofibrosis/genetics, Splenomegaly/metabolism, Tumor Suppressor, X Chromosome Inactivation}
}

@article{lucioli_gene_1988,
	title = {Gene dosage alteration of L2 ribosomal protein genes in Saccharomyces cerevisiae: effects on ribosome synthesis},
	volume = {8},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/3062369},
	abstract = {In Saccharomyces cerevisiae, the genes coding for the ribosomal protein L2 are present in two copies per haploid genome. The two copies, which encode proteins differing in only a few amino acids, contribute unequally to the L2 {mRNA} pool: the L2A copy makes 72\% of the {mRNA}, while the L2B copy makes only 28\%. Disruption of the L2B gene (delta B strain) did not lead to any phenotypic alteration, whereas the inactivation of the L2A copy (delta A strain) produced a slow-growth phenotype associated with decreased accumulation of 60S subunits and ribosomes. No intergenic compensation occurred at the transcriptional level in the disrupted strains; in fact, delta A strains contained reduced levels of L2 {mRNA}, whereas delta B strains had almost normal levels. The wild-type phenotype was restored in the delta A strains by transformation with extra copies of the intact L2A or L2B gene. As already shown for other duplicated genes (Kim and Warner, J. Mol. Biol. 165:79-89, 1983; Leeret al., Curr. Genet. 9:273-277, 1985), the difference in expression of the two gene copies could be accounted for via differential transcription activity. Sequence comparison of the {rpL}2 promoter regions has shown the presence of canonical {HOMOL}1 boxes which are slightly different in the two genes.},
	pages = {4792--4798},
	number = {11},
	journaltitle = {Mol Cell Biol},
	author = {Lucioli, A and Presutti, C and Ciafre, S and Caffarelli, E and Fragapane, P and Bozzoni, I},
	date = {1988},
	pmid = {3062369},
	keywords = {Base Sequence, Genetic, Promoter Regions, {RNA}, Gene Expression Regulation, Messenger/genetics, *Genes, Fungal, Fungal/genetics, Molecular Sequence Data, Multigene Family, Mutation, Phenotype, Ribosomal Proteins/*genetics, Ribosomes/*metabolism, Saccharomyces cerevisiae/*genetics/metabolism}
}

@article{ingolia_ribosome_2014,
	title = {Ribosome profiling: new views of translation, from single codons to genome scale},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24468696},
	doi = {10.1038/nrg3645},
	abstract = {Genome-wide analyses of gene expression have so far focused on the abundance of {mRNA} species as measured either by microarray or, more recently, by {RNA} sequencing. However, neither approach provides information on protein synthesis, which is the true end point of gene expression. Ribosome profiling is an emerging technique that uses deep sequencing to monitor in vivo translation. Studies using ribosome profiling have already provided new insights into the identity and the amount of proteins that are produced by cells, as well as detailed views into the mechanism of protein synthesis itself.},
	pages = {205--213},
	number = {3},
	journaltitle = {Nat Rev Genet},
	author = {Ingolia, N T},
	date = {2014},
	pmid = {24468696}
}

@article{johnson_regulation_2009,
	title = {Regulation of neural {macroRNAs} by the transcriptional repressor {REST}},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19050060},
	doi = {10.1261/rna.1127009},
	abstract = {The essential transcriptional repressor {REST} (repressor element 1-silencing transcription factor) plays central roles in development and human disease by regulating a large cohort of neural genes. These have conventionally fallen into the class of known, protein-coding genes; recently, however, several noncoding {microRNA} genes were identified as {REST} targets. Given the widespread transcription of messenger {RNA}-like, noncoding {RNAs} ("{macroRNAs}"), some of which are functional and implicated in disease in mammalian genomes, we sought to determine whether this class of noncoding {RNAs} can also be regulated by {REST}. By applying a new, unbiased target gene annotation pipeline to computationally discovered {REST} binding sites, we find that 23\% of mammalian {REST} genomic binding sites are within 10 kb of a {macroRNA} gene. These putative target genes were overlooked by previous studies. Focusing on a set of 18 candidate {macroRNA} targets from mouse, we experimentally demonstrate that two are regulated by {REST} in neural stem cells. Flanking protein-coding genes are, at most, weakly repressed, suggesting specific targeting of the {macroRNAs} by {REST}. Similar to the majority of known {REST} target genes, both of these {macroRNAs} are induced during nervous system development and have neurally restricted expression profiles in adult mouse. We observe a similar phenomenon in human: the {DiGeorge} syndrome-associated noncoding {RNA}, {DGCR}5, is repressed by {REST} through a proximal upstream binding site. Therefore neural {macroRNAs} represent an additional component of the {REST} regulatory network. These {macroRNAs} are new candidates for understanding the role of {REST} in neuronal development, neurodegeneration, and cancer.},
	pages = {85--96},
	number = {1},
	journaltitle = {{RNA}},
	author = {Johnson, R and Teh, C H and Jia, H and Vanisri, R R and Pandey, T and Lu, Z H and Buckley, N J and Stanton, L W and Lipovich, L},
	date = {2009},
	pmid = {19050060},
	keywords = {Animals, Genetic, Humans, Mice, {RNA}, Binding Sites, *Transcription, Cells, Cultured, {DiGeorge} Syndrome/genetics/metabolism, {HeLa} Cells, Neurons/*metabolism, Repressor Proteins/genetics/*metabolism, Stem Cells/metabolism, Untranslated/*metabolism}
}

@article{graur_immortality_2013,
	title = {On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of {ENCODE}},
	volume = {5},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23431001},
	doi = {10.1093/gbe/evt028},
	abstract = {A recent slew of {ENCyclopedia} Of {DNA} Elements ({ENCODE}) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80\% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10\%. Thus, according to the {ENCODE} Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 - 10 = 70\% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these "functional" regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used "causal role" definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as "affirming the consequent," by failing to appreciate the crucial difference between "junk {DNA}" and "garbage {DNA}," by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The {ENCODE} results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.},
	pages = {578--590},
	number = {3},
	journaltitle = {Genome Biol Evol},
	author = {Graur, D and Zheng, Y and Price, N and Azevedo, R B and Zufall, R A and Elhaik, E},
	date = {2013},
	pmid = {23431001},
	keywords = {Human, Animals, Genetic, Humans, *Genome, Nucleic Acid, *Databases, *Evolution, {DNA} Methylation, Human Genome Project, Molecular, Primates/genetics, Selection, Transcription Factors/genetics/metabolism}
}

@article{yang_prostaglandin_2004,
	title = {Prostaglandin A2-mediated stabilization of p21 {mRNA} through an {ERK}-dependent pathway requiring the {RNA}-binding protein {HuR}},
	volume = {279},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15371446},
	doi = {10.1074/jbc.M407535200},
	abstract = {Treatment with the stress agent prostaglandin A2 ({PGA}2) induces expression of the cyclin-dependent kinase inhibitor p21. Here, we present evidence that p21 expression increases through {PGA}2-triggered stabilization of the p21 {mRNA} and further show that these events require the mitogen-activated protein ({MAP}) kinase {ERK}. Binding experiments using either endogenous p21 {mRNA} or in vitro-labeled p21 transcripts revealed a specific {PGA}2-dependent association of the p21 {mRNA} with the {RNA}-binding protein {HuR}. Interestingly, although inhibition of the {ERK} pathway did not prevent the {PGA}2-triggered increase in cytoplasmic {HuR}, it did impair the formation of endogenous and in vitro [{HuR}-p21 {mRNA}] complexes and further prevented the {PGA}2-mediated stabilization of the p21 {mRNA}, suggesting that {ERK}-mediated events were required for binding {HuR} to the p21 {mRNA} and preventing its decay. {RNA} interference-based knockdown of {HuR} abundance further served to demonstrate the contribution of {HuR}-mediated p21 {mRNA} stabilization toward enhancing p21 expression after {PGA}2 treatment. Collectively, our results indicate that {PGA}2 stabilizes the p21 {mRNA} through an {ERK}-independent increase in cytoplasmic {HuR} levels and an {ERK}-dependent association of {HuR} with the p21 {mRNA}.},
	pages = {49298--49306},
	number = {47},
	journaltitle = {J Biol Chem},
	author = {Yang, X and Wang, W and Fan, J and Lal, A and Yang, D and Cheng, H and Gorospe, M},
	date = {2004},
	pmid = {15371446},
	keywords = {{DNA}, 3' Untranslated Regions, Humans, {RNA}, Protein Binding, Antigens, Biotin/chemistry, Blotting, Calcium/metabolism, Cell Cycle Proteins/chemistry/*metabolism, Cell Line, Cell Nucleus/metabolism, Cell Proliferation, Complementary/metabolism, Cross-Linking Reagents/pharmacology, Cyclin-Dependent Kinase Inhibitor p21, Cytoplasm/metabolism, Dactinomycin/pharmacology, Dose-Response Relationship, Drug, Enzyme Inhibitors/pharmacology, Hu Paraneoplastic Encephalomyelitis Antigens, Immunoprecipitation, Kinetics, Messenger/metabolism, Mitogen-Activated Protein Kinase 3/*metabolism, Northern, Prostaglandins A/*metabolism, Reverse Transcriptase Polymerase Chain Reaction, {RNA}-Binding Proteins/*chemistry, Signal Transduction, Surface/*chemistry, Time Factors, Transfection, Tumor, Ultraviolet Rays, Western}
}

@article{sunkesula_potential_2013,
	title = {Potential for transmission of spores by patients awaiting laboratory testing to confirm suspected Clostridium difficile infection},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23388367},
	doi = {10.1086/669510},
	abstract = {In a prospective study of inpatients tested for Clostridium difficile infection ({CDI}), skin and environmental contamination were common at the time of the order for {CDI} testing, and there were often delays in completion of testing. Preemptive isolation of patients with suspected {CDI} may reduce the risk of transmission.},
	pages = {306--308},
	number = {3},
	journaltitle = {Infect Control Hosp Epidemiol},
	author = {Sunkesula, V C and Kundrapu, S and Jury, L A and Deshpande, A and Sethi, A K and Donskey, C J},
	date = {2013},
	pmid = {23388367},
	keywords = {Humans, *Clostridium difficile, *Delayed Diagnosis, 80 and over, Aged, Bacterial, Clostridium Infections/complications/*diagnosis/*t, Diarrhea/etiology, Female, Hand/microbiology, Hospitalization, Male, Middle Aged, Patient Isolation, Practice Guidelines as Topic, Prospective Studies, Spores, Time Factors}
}

@article{dang_eukaryotic_2006,
	title = {Eukaryotic initiation factor 2alpha-independent pathway of stress granule induction by the natural product pateamine A},
	volume = {281},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16951406},
	doi = {10.1074/jbc.M606149200},
	abstract = {Stress granules are aggregates of small ribosomal subunits, {mRNA}, and numerous associated {RNA}-binding proteins that include several translation initiation factors. Stress granule assembly occurs in the cytoplasm of higher eukaryotic cells under a wide variety of stress conditions, including heat shock, {UV} irradiation, hypoxia, and exposure to arsenite. Thus far, a unifying principle of eukaryotic initiation factor 2alpha phosphorylation prior to stress granule formation has been observed from the majority of experimental evidence. Pateamine A, a natural product isolated from marine sponge, was recently reported to inhibit eukaryotic translation initiation and induce the formation of stress granules. In this report, the protein composition and fundamental progression of stress granule formation and disassembly induced by pateamine A was found to be similar to that for arsenite. However, pateamine A-induced stress granules were more stable and less prone to disassembly than those formed in the presence of arsenite. Most significantly, pateamine A induced stress granules independent of eukaryotic initiation factor 2alpha phosphorylation, suggesting an alternative mechanism of formation from that previously described for other cellular stresses. Taking into account the known inhibitory effect of pateamine A on eukaryotic translation initiation, a model is proposed to account for the induction of stress granules by pateamine A as well as other stress conditions through perturbation of any steps prior to the rejoining of the 60S ribosomal subunit during the entire translation initiation process.},
	pages = {32870--32878},
	number = {43},
	journaltitle = {J Biol Chem},
	author = {Dang, Y and Kedersha, N and Low, W K and Romo, D and Gorospe, M and Kaufman, R and Anderson, P and Liu, J O},
	date = {2006},
	pmid = {16951406},
	keywords = {Animals, Humans, Mice, {RNA}, Arsenites/pharmacology, Biological Markers/metabolism, Biological Products/*chemistry, Cell Line, Cytoplasmic Granules/*metabolism, Direct, Dose-Response Relationship, Drug, Epoxy Compounds/*pharmacology, Eukaryotic Initiation Factor-2/*antagonists \& inhi, Fibroblasts/drug effects, Fluorescent Antibody Technique, {HeLa} Cells, Macrolides/*pharmacology, Messenger/metabolism, Osteosarcoma/pathology, Oxidative Stress/*drug effects/physiology, Thiazoles/*pharmacology, Time Factors, Tumor}
}

@article{kallin_tet2_2012,
	title = {Tet2 facilitates the derepression of myeloid target genes during {CEBPalpha}-induced transdifferentiation of pre-B cells},
	volume = {48},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22981865},
	doi = {10.1016/j.molcel.2012.08.007},
	abstract = {The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated. An ideal system to study the role of Tet2 in myelopoeisis is {CEBPalpha}-induced transdifferentiation of pre-B cells into macrophages. Here we found that {CEBPalpha} binds to upstream regions of Tet2 and that the gene becomes activated. Tet2 knockdowns impaired the upregulation of macrophage markers as well as phagocytic capacity, suggesting that the enzyme is required for both early and late stage myeloid differentiation. A slightly weaker effect was seen in primary cells with a Tet2 ablation. Expression arrays of transdifferentiating cells with Tet2 knockdowns permitted the identification of a small subset of myeloid genes whose upregulation was blunted. Activation of these target genes was accompanied by rapid increases of promoter hydroxy-methylation. Our observations indicate that Tet2 helps {CEBPalpha} rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages.},
	pages = {266--276},
	number = {2},
	journaltitle = {Mol Cell},
	author = {Kallin, E M and Rodriguez-Ubreva, J and Christensen, J and Cimmino, L and Aifantis, I and Helin, K and Ballestar, E and Graf, T},
	date = {2012},
	pmid = {22981865},
	keywords = {Humans, Gene Expression Regulation, *{DNA}-Binding Proteins/genetics/metabolism, *Macrophages/cytology/metabolism, *Myeloid Cells/cytology/metabolism, *Precursor Cells, *Proto-Oncogene Proteins/genetics/metabolism, Azacitidine/pharmacology, B-Lymphoid/cytology/metabolism, {CCAAT}-Enhancer-Binding Proteins/genetics/metabolis, Cell Differentiation, Cell Line, Cell Transdifferentiation/drug effects, Developmental, Gene Knockdown Techniques, Hematopoietic Stem Cells/cytology/metabolism, Myelopoiesis}
}

@article{benjamini_controlling_1995,
	title = {Controlling the false discovery rate: a practical and powerful approach to multiple testing},
	volume = {57},
	pages = {289--300},
	number = {1},
	journaltitle = {Journal of the Royal Statistical Society, Series B},
	author = {Benjamini, Yoav and Hochberg, Yosef},
	date = {1995}
}

@article{sabarinathan_rnasnp:_2013,
	title = {{RNAsnp}: efficient detection of local {RNA} secondary structure changes induced by {SNPs}},
	volume = {34},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23315997},
	doi = {10.1002/humu.22273},
	abstract = {Structural characteristics are essential for the functioning of many noncoding {RNAs} and cis-regulatory elements of {mRNAs}. {SNPs} may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. {RNA} folding algorithms can provide detailed insights into structural effects of {SNPs}. The global measures employed so far suffer from limited accuracy of folding programs on large {RNAs} and are computationally too demanding for genome-wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild-type. These local regions are approximated in a "screening mode" that is intended for genome-wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the {RNAsnp} software uses extensive precomputed tables of the distribution of {SNP} effects as function of length and {GC} content. {RNAsnp} thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 {SNPs} associated with human-inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of {mRNAs}.},
	pages = {546--556},
	number = {4},
	journaltitle = {Hum Mutat},
	author = {Sabarinathan, R and Tafer, H and Seemann, S E and Hofacker, I L and Stadler, P F and Gorodkin, J},
	date = {2013},
	pmid = {23315997},
	keywords = {*Software, Humans, Algorithms, *Polymorphism, Genetic Association Studies, Nucleic Acid Conformation, {RNA} Folding, {RNA}/*chemistry/*genetics, Single Nucleotide}
}

@article{van_heesch_extensive_2014,
	title = {Extensive localization of long noncoding {RNAs} to the cytosol and mono- and polyribosomal complexes},
	volume = {15},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24393600},
	doi = {10.1186/gb-2014-15-1-r6},
	abstract = {{BACKGROUND}: Long noncoding {RNAs} ({lncRNAs}) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some {lncRNAs} are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To obtain a comprehensive understanding of the extent to which {lncRNAs} bind ribosomes, we performed systematic {RNA} sequencing on ribosome-associated {RNA} pools obtained through ribosomal fractionation and compared the {RNA} content with nuclear and (non-ribosome bound) cytosolic {RNA} pools. {RESULTS}: The {RNA} composition of the subcellular fractions differs significantly from each other, but {lncRNAs} are found in all locations. A subset of specific {lncRNAs} is enriched in the nucleus but surprisingly the majority is enriched in the cytosol and in ribosomal fractions. The ribosomal enriched {lncRNAs} include H19 and {TUG}1. {CONCLUSIONS}: Most studies on {lncRNAs} have focused on the regulatory function of these transcripts in the nucleus. We demonstrate that only a minority of all {lncRNAs} are nuclear enriched. Our findings suggest that many {lncRNAs} may have a function in cytoplasmic processes, and in particular in ribosome complexes.},
	pages = {R6},
	number = {1},
	journaltitle = {Genome Biol},
	author = {van Heesch, S and van Iterson, M and Jacobi, J and Boymans, S and Essers, P B and de Bruijn, E and Hao, W and Macinnes, A W and Cuppen, E and Simonis, M},
	date = {2014},
	pmid = {24393600}
}

@article{tamborero_comprehensive_2013,
	title = {Comprehensive identification of mutational cancer driver genes across 12 tumor types},
	volume = {3},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24084849},
	doi = {10.1038/srep02650},
	abstract = {With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner. However, obtaining a complete catalog of cancer genes is difficult due to the heterogeneous molecular nature of the disease and the limitations of available computational methods. Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. We provide a list of 291 high-confidence cancer driver genes acting on 3,205 tumors from 12 different cancer types. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumor type. The novel driver candidates complement our current picture of the emergence of these diseases. In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.},
	pages = {2650},
	journaltitle = {Sci Rep},
	author = {Tamborero, D and Gonzalez-Perez, A and Perez-Llamas, C and Deu-Pons, J and Kandoth, C and Reimand, J and Lawrence, M S and Getz, G and Bader, G D and Ding, L and Lopez-Bigas, N},
	date = {2013},
	pmid = {24084849},
	keywords = {Genomics/*methods, Humans, Reproducibility of Results, *Carcinogens, *Mutation, Cell Transformation, {DNA} Mutational Analysis/*methods, Gene Regulatory Networks, Genetic Association Studies, Neoplasms/*genetics/metabolism, Neoplastic/*genetics/metaboli, Signal Transduction}
}

@article{li_pharmacological_2001,
	title = {Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53},
	volume = {61},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11245456},
	abstract = {Fatty acid synthetic metabolism is abnormally elevated in tumor cells, and pharmacological inhibitors of the anabolic enzyme fatty acid synthase ({FAS}), including the natural product cerulenin and the novel synthetic compound c75, are selective inhibitors of tumor cell growth. We have recently reported that these two {FAS} inhibitors both produce rapid, potent inhibition of {DNA} replication and S-phase progression in human cancer cells, as well as apoptotic death. Here we report an additional characterization of the cellular response to {FAS} inhibition. {RKO} colon carcinoma cells were selected for study because they undergo little apoptosis within the first 24 h after {FAS} inhibition. Instead, {RKO} cells exhibited a biphasic stress response with a transient accumulation in S and G2 at 4 and 8 h that corresponds to a marked reduction in cyclin A- and B1-associated kinase activities, and then by accumulation of p53 and p21 proteins at 16 and 24 h and growth arrest in G1 and G2. The response of {RKO} cells to {FAS} inhibition resembled a genotoxic stress response, but {DNA} damage did not appear to be an important downstream effect of {FAS} inhibition, because none was detected using the single cell gel electrophoresis assay (comet assay) to assess {DNA} damage. p53 function is probably important in protecting {RKO} cells from {FAS} inhibition because, similar to many other tumor lines, {RKO} cells expressing a dominant negative mutant p53 gene underwent extensive apoptosis within 24 h after {FAS} inhibition. Sensitization of cells to {FAS} inhibitors by the loss of p53 raises the possibility that these agents may be clinically useful against malignancies carrying p53 mutations. Whereas induction of apoptosis appeared related to accumulation of the substrate, malonyl-{CoA}, after {FAS} inhibition, the cytostatic effects were independent of malonyl-{CoA} accumulation and may have resulted from product depletion.},
	pages = {1493--1499},
	number = {4},
	journaltitle = {Cancer Res},
	author = {Li, J N and Gorospe, M and Chrest, F J and Kumaravel, T S and Evans, M K and Han, W F and Pizer, E S},
	date = {2001},
	pmid = {11245456},
	keywords = {Humans, Cultured, Colonic Neoplasms/enzymology/pathology, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases/antagonists \& inhibitors/, Cyclins/biosynthesis, Enzyme Activation, Fatty Acid Synthases/*antagonists \& inhibitors, G2 Phase/drug effects, Malonyl Coenzyme A/metabolism, S Phase/drug effects, Tumor Cells, Tumor Suppressor Protein p53/biosynthesis/*physiol}
}

@article{spallotta_detrimental_2013,
	title = {Detrimental effect of class-selective histone deacetylase inhibitors during tissue regeneration following hindlimb ischemia},
	volume = {288},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23836913},
	doi = {10.1074/jbc.M113.484337},
	abstract = {Histone deacetylase inhibitors ({DIs}) are promising drugs for the treatment of several pathologies including ischemic and failing heart where they demonstrated efficacy. However, adverse side effects and cardiotoxicity have also been reported. Remarkably, no information is available about the effect of {DIs} during tissue regeneration following acute peripheral ischemia. In this study, mice made ischemic by femoral artery excision were injected with the {DIs} {MS}275 and {MC}1568, selective for class I and {IIa} histone deacetylases ({HDACs}), respectively. In untreated mice, soon after damage, class {IIa} {HDAC} phosphorylation and nuclear export occurred, paralleled by dystrophin and neuronal nitric-oxide synthase ({nNOS}) down-regulation and decreased protein phosphatase 2A activity. Between 14 and 21 days after ischemia, dystrophin and {nNOS} levels recovered, and class {IIa} {HDACs} relocalized to the nucleus. In this condition, the {MC}1568 compound increased the number of newly formed muscle fibers but delayed their terminal differentiation, whereas {MS}275 abolished the early onset of the regeneration process determining atrophy and fibrosis. The selective {DIs} had differential effects on the vascular compartment: {MC}1568 increased arteriogenesis whereas {MS}275 inhibited it. Capillarogenesis did not change. Chromatin immunoprecipitations revealed that class {IIa} {HDAC} complexes bind promoters of proliferation-associated genes and of class I {HDAC}1 and 2, highlighting a hierarchical control between class {II} and I {HDACs} during tissue regeneration. Our findings indicate that class-selective {DIs} interfere with normal mouse ischemic hindlimb regeneration and suggest that their use could be limited by alteration of the regeneration process in peripheral ischemic tissues.},
	pages = {22915--22929},
	number = {32},
	journaltitle = {J Biol Chem},
	author = {Spallotta, F and Tardivo, S and Nanni, S and Rosati, J D and Straino, S and Mai, A and Vecellio, M and Valente, S and Capogrossi, M C and Farsetti, A and Martone, J and Bozzoni, I and Pontecorvi, A and Gaetano, C and Colussi, C},
	date = {2013},
	pmid = {23836913},
	keywords = {Animals, Mice, *Ischemia/drug therapy/metabolism/pathology, *Muscle, Benzamides/*adverse effects/pharmacology, Dystrophin/metabolism, Hindlimb/*blood supply/metabolism/pathology, Histone Deacetylase Inhibitors/*adverse effects/ph, Histone Deacetylases/metabolism, Hydroxamic Acids/*adverse effects/pharmacology, Male, Nitric Oxide Synthase Type I/metabolism, Protein Phosphatase 2/metabolism, Pyridines/*adverse effects/pharmacology, Pyrroles/*adverse effects/pharmacology, Regeneration/*drug effects, Skeletal/blood supply/metabolism/patholog, Time Factors}
}

@article{nervi_emerging_2007,
	title = {Emerging role for {microRNAs} in acute promyelocytic leukemia},
	volume = {313},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17217039},
	abstract = {Hematopoiesis is highly controlled by lineage-specific transcription factors that, by interacting with specific {DNA} sequences, directly activate or repress specific gene expression. These transcription factors have been found mutated or altered by chromosomal translocations associated with leukemias, indicating their role in the pathogenesis of these malignancies. The post-genomic era, however, has shown that transcription factors are not the only key regulators of gene expression. Epigenetic mechanisms such as {DNA} methylation, posttranslational modifications of histones, remodeling of nucleosomes, and expression of small regulatory {RNAs} all contribute to the regulation of gene expression and determination of cell and tissue specificity. Deregulation ofthese epigenetic mechanisms cooperates with genetic alterations to the establishment and progression of tumors. {MicroRNAs} ({miRNAs}) are negative regulators of the expression of genes involved in development, differentiation, proliferation, and apoptosis. Their expression appears to be tissue-specific and highly regulated according to the cell's developmental lineage and stage. Interestingly, {miRNAs} expressed in hematopoietic cells have been found mutated or altered by chromosomal translocations associated with leukemias. The expression levels of a specific {miR}-223 correlate with the differentiation fate of myeloid precursors. The activation of both pathways of transcriptional regulation by the myeloid lineage-specific transcription factor C/{EBPalpha} ({CCAAT}/enhancer-binding protein-alpha), and posttranscriptional regulation by {miR}-223 appears essential for granulocytic differentiation and clinical response of acute promyelocytic leukemia ({APL}) blasts to all-trans retinoic acid ({ATRA}). Together, this evidence underlies transcription factors, chromatin remodeling, and {miRNAs} as ultimate determinants for the correct organization of cell type-specific gene arrays and hematopoietic differentiation, therefore providing new targets for the diagnosis and treatment of leukemias.},
	pages = {73--84},
	journaltitle = {Curr Top Microbiol Immunol},
	author = {Nervi, C and Fazi, F and Rosa, A and Fatica, A and Bozzoni, I},
	date = {2007},
	pmid = {17217039},
	keywords = {Humans, Gene Expression Regulation, Acute/genetics/*physiopat, {CCAAT}-Enhancer-Binding Protein-alpha/genetics/meta, Hematopoiesis/genetics/physiology, Leukemia, {MicroRNAs}/genetics/*metabolism, {NFI} Transcription Factors/genetics/metabolism, Promyelocytic}
}

@article{anders_differential_2010,
	title = {Differential expression analysis for sequence count data},
	volume = {11},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20979621},
	doi = {10.1186/gb-2010-11-10-r106},
	abstract = {High-throughput sequencing assays such as {RNA}-Seq, {ChIP}-Seq or barcode counting provide quantitative readouts in the form of count data. To infer differential signal in such data correctly and with good statistical power, estimation of data variability throughout the dynamic range and a suitable error model are required. We propose a method based on the negative binomial distribution, with variance and mean linked by local regression and present an implementation, {DESeq}, as an R/Bioconductor package.},
	pages = {R106},
	number = {10},
	journaltitle = {Genome Biol},
	author = {Anders, S and Huber, W},
	date = {2010},
	pmid = {20979621},
	keywords = {Gene Expression Profiling/*methods, Sequence Analysis, Animals, Genetic, Binomial Distribution, Chromatin Immunoprecipitation/methods, Computational Biology/*methods, Drosophila/genetics, High-Throughput Nucleotide Sequencing/methods, Linear Models, Models, {RNA}/*methods, Saccharomyces cerevisiae/genetics, Stem Cells, Tissue Culture Techniques}
}

@article{grzechnik_terminate_2014,
	title = {Terminate and make a loop: regulation of transcriptional directionality},
	volume = {39},
	issn = {09680004},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24928762 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4085477 http://linkinghub.elsevier.com/retrieve/pii/S0968000414000851},
	doi = {10.1016/j.tibs.2014.05.001},
	abstract = {Bidirectional promoters are a common feature of many eukaryotic organisms from yeast to humans. {RNA} Polymerase {II} that is recruited to this type of promoter can start transcribing in either direction using alternative {DNA} strands as the template. Such promiscuous transcription can lead to the synthesis of unwanted transcripts that may have negative effects on gene expression. Recent studies have identified transcription termination and gene looping as critical players in the enforcement of promoter directionality. Interestingly, both mechanisms share key components. Here, we focus on recent findings relating to the transcriptional output of bidirectional promoters.},
	pages = {319--327},
	number = {7},
	journaltitle = {Trends in Biochemical Sciences},
	author = {Grzechnik, Pawel and Tan-Wong, Sue Mei and Proudfoot, Nick J.},
	date = {2014-07},
	pmid = {24928762},
	keywords = {bidirectional promoters, gene loops, transcriptional termination}
}

@article{quinn_unique_2015,
	title = {Unique features of long non-coding {RNA} biogenesis and function},
	volume = {17},
	issn = {1471-0056},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26666209 http://www.nature.com/doifinder/10.1038/nrg.2015.10},
	doi = {10.1038/nrg.2015.10},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are a diverse class of {RNAs} that engage in numerous biological processes across every branch of life. Although initially discovered as {mRNA}-like transcripts that do not encode proteins, recent studies have revealed features of {lncRNAs} that further distinguish them from {mRNAs}. In this Review, we describe special events in the lifetimes of {lncRNAs} - before, during and after transcription - and discuss how these events ultimately shape the unique characteristics and functional roles of {lncRNAs}.},
	pages = {47--62},
	number = {1},
	journaltitle = {Nature Reviews Genetics},
	author = {Quinn, Jeffrey J. and Chang, Howard Y.},
	date = {2015-12},
	pmid = {26666209}
}

@article{jin_ground_2017,
	title = {The Ground State and Evolution of Promoter Region Directionality},
	issn = {00928674},
	url = {http://linkinghub.elsevier.com/retrieve/pii/S0092867417308139},
	doi = {10.1016/j.cell.2017.07.006},
	journaltitle = {Cell},
	author = {Jin, Yi and Eser, Umut and Struhl, Kevin and Churchman, L. Stirling},
	date = {2017-08}
}

@article{travers_flexible_2010,
	title = {A flexible and efficient template format for circular consensus sequencing and {SNP} detection.},
	volume = {38},
	issn = {1362-4962},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20571086 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2926623},
	doi = {10.1093/nar/gkq543},
	abstract = {A novel template design for single-molecule sequencing is introduced, a structure we refer to as a {SMRTbell} template. This structure consists of a double-stranded portion, containing the insert of interest, and a single-stranded hairpin loop on either end, which provides a site for primer binding. Structurally, this format resembles a linear double-stranded molecule, and yet it is topologically circular. When placed into a single-molecule sequencing reaction, the {SMRTbell} template format enables a consensus sequence to be obtained from multiple passes on a single molecule. Furthermore, this consensus sequence is obtained from both the sense and antisense strands of the insert region. In this article, we present a universal method for constructing these templates, as well as an application of their use. We demonstrate the generation of high-quality consensus accuracy from single molecules, as well as the use of {SMRTbell} templates in the identification of rare sequence variants.},
	pages = {e159},
	number = {15},
	journaltitle = {Nucleic acids research},
	author = {Travers, Kevin J and Chin, Chen-Shan and Rank, David R and Eid, John S and Turner, Stephen W},
	date = {2010-08},
	pmid = {20571086},
	file = {Attachment:/home/jlagarde/Zotero/storage/ABSGTTUF/Travers et al. - 2010 - A flexible and efficient template format for circular consensus sequencing and SNP detection.pdf:application/pdf}
}

@article{iaccarino_lncrnas_2017,
	title = {{lncRNAs} and {MYC}: An Intricate Relationship},
	volume = {18},
	issn = {1422-0067},
	url = {http://www.mdpi.com/1422-0067/18/7/1497},
	doi = {10.3390/ijms18071497},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are emerging as important regulators of gene expression networks, acting either at the transcriptional level, by influencing histone modifications, or at the post-transcriptional level, by controlling {mRNA} stability and translation. Among the gene expression networks known to influence the process of oncogenic transformation, the one controlled by the proto-oncogene {MYC} is one of the most frequently deregulated in cancer. In B-cell lymphomas, the {MYC} gene is subject to chromosomal rearrangements that result in {MYC} overexpression. In many other cancers, the region surrounding {MYC} is subject to gene amplification. {MYC} expression is also controlled at the level of protein and {mRNA} stability. Neoplastic lesions affecting {MYC} expression are responsible for a drastic change in the number and the type of genes that are transcriptionally controlled by {MYC}, depending on differential promoter affinities. Transcriptome profiling of tumor samples has shown that several {lncRNAs} can be found differentially regulated by {MYC} in different cancer types and many of them can influence cancer cell viability and proliferation. At the same time, {lncRNAs} have been shown to be able to control the expression of {MYC} itself, both at transcriptional and post-transcriptional levels. Given that targeting the {MYC}-dependent transcriptional program has the potential to reach broad anticancer activity, molecular dissection of the complex regulatory mechanisms governing {MYC} expression will be crucial in the future for the identification of novel therapeutic strategies.},
	pages = {1497},
	number = {7},
	journaltitle = {International Journal of Molecular Sciences},
	author = {Iaccarino, Ingram and {Ingram}},
	date = {2017-07},
	keywords = {cancer, {lncRNAs}, {MYC}, transcription regulation, transcriptome profiling},
	file = {Attachment:/home/jlagarde/Zotero/storage/VEELL3TL/Iaccarino, Ingram - 2017 - lncRNAs and MYC An Intricate Relationship.pdf:application/pdf}
}

@article{sahraeian_gaining_2017,
	title = {Gaining comprehensive biological insight into the transcriptome by performing a broad-spectrum {RNA}-seq analysis.},
	volume = {8},
	issn = {2041-1723},
	url = {http://www.nature.com/articles/s41467-017-00050-4 http://www.ncbi.nlm.nih.gov/pubmed/28680106},
	doi = {10.1038/s41467-017-00050-4},
	abstract = {{RNA}-sequencing ({RNA}-seq) is an essential technique for transcriptome studies, hundreds of analysis tools have been developed since it was debuted. Although recent efforts have attempted to assess the latest available tools, they have not evaluated the analysis workflows comprehensively to unleash the power within {RNA}-seq. Here we conduct an extensive study analysing a broad spectrum of {RNA}-seq workflows. Surpassing the expression analysis scope, our work also includes assessment of {RNA} variant-calling, {RNA} editing and {RNA} fusion detection techniques. Specifically, we examine both short- and long-read {RNA}-seq technologies, 39 analysis tools resulting in ∼120 combinations, and ∼490 analyses involving 15 samples with a variety of germline, cancer and stem cell data sets. We report the performance and propose a comprehensive {RNA}-seq analysis protocol, named {RNACocktail}, along with a computational pipeline achieving high accuracy. Validation on different samples reveals that our proposed protocol could help researchers extract more biologically relevant predictions by broad analysis of the transcriptome.{RNA}-seq is widely used for transcriptome analysis. Here, the authors analyse a wide spectrum of {RNA}-seq workflows and present a comprehensive analysis protocol named {RNACocktail} as well as a computational pipeline leveraging the widely used tools for accurate {RNA}-seq analysis.},
	pages = {59},
	number = {1},
	journaltitle = {Nature communications},
	author = {Sahraeian, Sayed Mohammad Ebrahim and Mohiyuddin, Marghoob and Sebra, Robert and Tilgner, Hagen and Afshar, Pegah T and Au, Kin Fai and Bani Asadi, Narges and Gerstein, Mark B and Wong, Wing Hung and Snyder, Michael P and Schadt, Eric and Lam, Hugo Y K},
	date = {2017-07},
	pmid = {28680106}
}

@article{au_characterization_2013,
	title = {Characterization of the human {ESC} transcriptome by hybrid sequencing},
	volume = {110},
	issn = {0027-8424},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24282307 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3864310 http://www.pnas.org/cgi/doi/10.1073/pnas.1320101110},
	doi = {10.1073/pnas.1320101110},
	abstract = {Although transcriptional and posttranscriptional events are detected in {RNA}-Seq data from second-generation sequencing, full-length {mRNA} isoforms are not captured. On the other hand, third-generation sequencing, which yields much longer reads, has current limitations of lower raw accuracy and throughput. Here, we combine second-generation sequencing and third-generation sequencing with a custom-designed method for isoform identification and quantification to generate a high-confidence isoform dataset for human embryonic stem cells ({hESCs}). We report 8,084 {RefSeq}-annotated isoforms detected as full-length and an additional 5,459 isoforms predicted through statistical inference. Over one-third of these are novel isoforms, including 273 {RNAs} from gene loci that have not previously been identified. Further characterization of the novel loci indicates that a subset is expressed in pluripotent cells but not in diverse fetal and adult tissues; moreover, their reduced expression perturbs the network of pluripotency-associated genes. Results suggest that gene identification, even in well-characterized human cell lines and tissues, is likely far from complete.},
	pages = {E4821--E4830},
	number = {50},
	journaltitle = {Proceedings of the National Academy of Sciences},
	author = {Au, K. F. and Sebastiano, V. and Afshar, P. T. and Durruthy, J. D. and Lee, L. and Williams, B. A. and van Bakel, H. and Schadt, E. E. and Reijo-Pera, R. A. and Underwood, J. G. and Wong, W. H.},
	date = {2013-12},
	pmid = {24282307},
	keywords = {{PacBio}, alternative splicing, {hESC} transcriptome, isoform discovery, {lncNRA}},
	file = {Characterization of the human ESC transcriptome by hybrid sequencing:/home/jlagarde/Zotero/storage/5Q6Z7ZLB/au2013.pdf:application/pdf;Characterization of the human ESC transcriptome by hybrid sequencing:/home/jlagarde/Zotero/storage/TLB8Q7S3/au2013.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/C7VWCIRC/Au et al. - 2013 - Characterization of the human ESC transcriptome by.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/DGU6I8XK/Au et al. - 2013 - Characterization of the human ESC transcriptome by.html:text/html}
}

@article{werner_nuclear_2015,
	title = {Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding {RNAs} Adjacent to Active Genes},
	volume = {12},
	issn = {22111247},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26257179 http://linkinghub.elsevier.com/retrieve/pii/S2211124715007937},
	doi = {10.1016/j.celrep.2015.07.033},
	abstract = {A number of long noncoding {RNAs} ({lncRNAs}) have been reported to regulate transcription via recruitment of chromatin modifiers or bridging distal enhancer elements to gene promoters. However, the generality of these modes of regulation and the mechanisms of chromatin attachment for thousands of unstudied human {lncRNAs} remain unclear. To address these questions, we performed stringent nuclear fractionation coupled to {RNA} sequencing. We provide genome-wide identification of human chromatin-associated {lncRNAs} and demonstrate tethering of {RNA} to chromatin by {RNAPII} is a pervasive mechanism of attachment. We also uncovered thousands of chromatin-enriched {RNAs} ({cheRNAs}) that share molecular properties with known {lncRNAs}. Although distinct from {eRNAs} derived from active prototypical enhancers, the production of {cheRNAs} is strongly correlated with the expression of neighboring protein-coding genes. This work provides an updated framework for nuclear {RNA} organization that includes a large chromatin-associated transcript population correlated with active genes and may prove useful in de novo enhancer annotation.},
	pages = {1089--1098},
	number = {7},
	journaltitle = {Cell Reports},
	author = {Werner, Michael S. and Ruthenburg, Alexander J.},
	date = {2015-08},
	pmid = {26257179}
}

@article{misra_polyadenylation_2016,
	title = {From polyadenylation to splicing: Dual role for {mRNA} 3' end formation factors.},
	volume = {13},
	issn = {1555-8584},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26891005 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4829302},
	doi = {10.1080/15476286.2015.1112490},
	abstract = {Recent genome-wide protein-{RNA} interaction studies have significantly reshaped our understanding of the role of {mRNA} 3' end formation factors in {RNA} biology. Originally thought to function solely in mediating cleavage and polyadenylation of {mRNAs} during their maturation, 3' end formation factors have now been shown to play a role in alternative splicing, even at internal introns–an unanticipated role for factors thought only to act at the 3' end of the {mRNA}. Here, we discuss the recent advances in our understanding of the role of 3' end formation factors in promoting global changes in alternative splicing at internal exon-intron junctions and how they act as cofactors for well known splicing regulators. Additionally, we review the mechanism by which these factors affect the recruitment of early intron recognition components to the 5' and 3' splice site. Our understanding of the roles of 3' end formation factors is still evolving, and the final picture might be more complex than originally envisioned.},
	pages = {259--64},
	number = {3},
	journaltitle = {{RNA} biology},
	author = {Misra, Ashish and Green, Michael R},
	date = {2016},
	pmid = {26891005},
	keywords = {Alternative splicing, {CPSF}, {mRNA} 3' end processing, polyadenylation, {SYMPK}},
	file = {Attachment:/home/jlagarde/Zotero/storage/3VIZMTC3/Misra, Green - 2016 - From polyadenylation to splicing Dual role for mRNA 3' end formation factors.pdf:application/pdf}
}

@article{mcmurry_identifiers_2017,
	title = {Identifiers for the 21st century: How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data},
	volume = {15},
	issn = {1545-7885},
	url = {http://dx.plos.org/10.1371/journal.pbio.2001414},
	doi = {10.1371/journal.pbio.2001414},
	pages = {e2001414},
	number = {6},
	journaltitle = {{PLOS} Biology},
	author = {{McMurry}, Julie A. and Juty, Nick and Blomberg, Niklas and Burdett, Tony and Conlin, Tom and Conte, Nathalie and Courtot, M?lanie and Deck, John and Dumontier, Michel and Fellows, Donal K. and Gonzalez-Beltran, Alejandra and Gormanns, Philipp and Grethe, Jeffrey and Hastings, Janna and H?rich?, Jean-Karim and Hermjakob, Henning and Ison, Jon C. and Jimenez, Rafael C. and Jupp, Simon and Kunze, John and Laibe, Camille and Le Nov?re, Nicolas and Malone, James and Martin, Maria Jesus and {McEntyre}, Johanna R. and Morris, Chris and Muilu, Juha and M?ller, Wolfgang and Rocca-Serra, Philippe and Sansone, Susanna-Assunta and Sariyar, Murat and Snoep, Jacky L. and Soiland-Reyes, Stian and Stanford, Natalie J. and Swainston, Neil and Washington, Nicole and Williams, Alan R. and Wimalaratne, Sarala M. and Winfree, Lilly M. and Wolstencroft, Katherine and Goble, Carole and Mungall, Christopher J. and Haendel, Melissa A. and Parkinson, Helen},
	date = {2017-06},
	file = {Attachment:/home/jlagarde/Zotero/storage/2JAG8AM8/McMurry et al. - 2017 - Identifiers for the 21st century How to design, provision, and reuse persistent identifiers to maximize utility.pdf:application/pdf}
}

@article{hitz_snovault_2017,
	title = {{SnoVault} and {encodeD}: A novel object-based storage system and applications to {ENCODE} metadata},
	volume = {12},
	issn = {1932-6203},
	url = {http://dx.plos.org/10.1371/journal.pone.0175310},
	doi = {10.1371/journal.pone.0175310},
	pages = {e0175310},
	number = {4},
	journaltitle = {{PLOS} {ONE}},
	author = {Hitz, Benjamin C. and Rowe, Laurence D. and Podduturi, Nikhil R. and Glick, David I. and Baymuradov, Ulugbek K. and Malladi, Venkat S. and Chan, Esther T. and Davidson, Jean M. and Gabdank, Idan and Narayana, Aditi K. and Onate, Kathrina C. and Hilton, Jason and Ho, Marcus C. and Lee, Brian T. and Miyasato, Stuart R. and Dreszer, Timothy R. and Sloan, Cricket A. and Strattan, J. Seth and Tanaka, Forrest Y. and Hong, Eurie L. and Cherry, J. Michael},
	editor = {Zhang, Zhang},
	date = {2017-04},
	file = {Attachment:/home/jlagarde/Zotero/storage/WRPMTCQS/Hitz et al. - 2017 - SnoVault and encodeD A novel object-based storage system and applications to ENCODE metadata.pdf:application/pdf}
}

@article{burset_evaluation_1996,
	title = {Evaluation of Gene Structure Prediction Programs},
	volume = {34},
	issn = {08887543},
	doi = {10.1006/geno.1996.0298},
	abstract = {We evaluate a number of computer programs designed to predict the structure of protein coding genes in genomic {DNA} sequences. Computational gene identification is set to play an increasingly important role in the development of the genome projects, as emphasis turns from mapping to large-scale sequencing. The evaluation presented here serves both to assess the current status of the problem and to identify the most promising approaches to ensure further progress. The programs analyzed were uniformly tested on a large set of vertebrate sequences with simple gene structure, and several measures of predictive accuracy were computed at the nucleotide, exon, and protein product levels. The results indicated that the predictive accuracy of the programs analyzed was lower than originally found. The accuracy was even lower when considering only those sequences that had recently been entered and that did not show any similarity to previously entered sequences. This indicates that the programs are overly dependent on the particularities of the examples they learn from. For most of the programs, accuracy in this test set ranged from 0.60 to 0.70 as measured by the Correlation Coefficient (where 1.0 corresponds to a perfect prediction and 0.0 is the value expected for a random prediction), and the average percentage of exons exactly identified was less than 50\%. Only those programs including protein sequence database searches showed substantially greater accuracy. The accuracy of the programs was severely affected by relatively high rates of sequence errors. Since the set on which the programs were tested included only relatively short sequences with simple gene structure, the accuracy of the programs is likely to be even lower when used for large uncharacterized genomic sequences with complex structure. While in such cases, programs currently available may still be of great use in pinpointing the regions likely to contain exons, they are far from being powerful enough to elucidate its genomic structure completely.},
	pages = {353--367},
	number = {3},
	journaltitle = {Genomics},
	author = {Burset, Moises and Guigo, Roderic},
	date = {1996-06},
	pmid = {8786136}
}

@article{chen_lncrnadisease:_2013,
	title = {{LncRNADisease}: a database for long-non-coding {RNA}-associated diseases},
	volume = {41},
	issn = {0305-1048},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23175614 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3531173 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gks1099},
	doi = {10.1093/nar/gks1099},
	abstract = {In this article, we describe a long-non-coding {RNA} ({lncRNA}) and disease association database ({LncRNADisease}), which is publicly accessible at http://cmbi.bjmu.edu.cn/lncrnadisease. In recent years, a large number of {lncRNAs} have been identified and increasing evidence shows that {lncRNAs} play critical roles in various biological processes. Therefore, the dysfunctions of {lncRNAs} are associated with a wide range of diseases. It thus becomes important to understand {lncRNAs}' roles in diseases and to identify candidate {lncRNAs} for disease diagnosis, treatment and prognosis. For this purpose, a high-quality {lncRNA}-disease association database would be extremely beneficial. Here, we describe the {LncRNADisease} database that collected and curated approximately 480 entries of experimentally supported {lncRNA}-disease associations, including 166 diseases. {LncRNADisease} also curated 478 entries of {lncRNA} interacting partners at various molecular levels, including protein, {RNA}, {miRNA} and {DNA}. Moreover, we annotated {lncRNA}-disease associations with genomic information, sequences, references and species. We normalized the disease name and the type of {lncRNA} dysfunction and provided a detailed description for each entry. Finally, we developed a bioinformatic method to predict novel {lncRNA}-disease associations and integrated the method and the predicted associated diseases of 1564 human {lncRNAs} into the database.},
	pages = {D983--D986},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Chen, G. and Wang, Z. and Wang, D. and Qiu, C. and Liu, M. and Chen, X. and Zhang, Q. and Yan, G. and Cui, Q.},
	date = {2013-01},
	pmid = {23175614}
}

@article{wapinski_long_2011,
	title = {Long noncoding {RNAs} and human disease},
	volume = {21},
	issn = {09628924},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21550244 http://linkinghub.elsevier.com/retrieve/pii/S0962892411000614},
	doi = {10.1016/j.tcb.2011.04.001},
	abstract = {A new class of transcripts, long noncoding {RNAs} ({lncRNAs}), has been recently found to be pervasively transcribed in the genome. Multiple lines of evidence increasingly link mutations and dysregulations of {lncRNAs} to diverse human diseases. Alterations in the primary structure, secondary structure, and expression levels of {lncRNAs} as well as their cognate {RNA}-binding proteins underlie diseases ranging from neurodegeneration to cancer. Recent progress suggests that the involvement of {lncRNAs} in human diseases could be far more prevalent than previously appreciated. We review the evidence linking {lncRNAs} to diverse human diseases and highlight fundamental concepts in {lncRNA} biology that still need to be clarified to provide a robust framework for {lncRNA} genetics.},
	pages = {354--361},
	number = {6},
	journaltitle = {Trends in Cell Biology},
	author = {Wapinski, Orly and Chang, Howard Y.},
	date = {2011-06},
	pmid = {21550244}
}

@article{sanfilippo_genome-wide_2017,
	title = {Genome-wide profiling of the 3' ends of polyadenylated {RNAs}},
	issn = {10462023},
	url = {http://www.sciencedirect.com/science/article/pii/S1046202317301378},
	doi = {10.1016/j.ymeth.2017.06.003},
	abstract = {Alternative polyadenylation ({APA}) diversifies the 3' termini of a majority of {mRNAs} in most eukaryotes, and is consequently inferred to have substantial consequences for the utilization of post-transcriptional regulatory mechanisms. Since conventional {RNA}-sequencing methods do not accurately define {mRNA} termini, a number of protocols have been developed that permit sequencing of the 3' ends of polyadenylated transcripts (3'-seq). We present here our experimental protocol to generate 3'-seq libraries using a {dT}-priming approach, including extensive details on considerations that will enable successful library cloning. We pair this with a set of computational tools that allow the user to process the raw sequence data into a filtered set of clusters that represent high-confidence functional polyadenylation sites. The data are single-nucleotide resolution and quantitative, and can be used for downstream analyses of {APA}.},
	journaltitle = {Methods},
	author = {Sanfilippo, Piero and Miura, Pedro and Lai, Eric C.},
	date = {2017}
}

@article{wu_full-length_2015,
	title = {Full-length single-cell {RNA}-seq applied to a viral human cancer: applications to {HPV} expression and splicing analysis in {HeLa} S3 cells},
	volume = {4},
	issn = {2047-217X},
	url = {https://academic.oup.com/gigascience/article-lookup/doi/10.1186/s13742-015-0091-4},
	doi = {10.1186/s13742-015-0091-4},
	pages = {51},
	number = {1},
	journaltitle = {{GigaScience}},
	author = {Wu, Liang and Zhang, Xiaolong and Zhao, Zhikun and Wang, Ling and Li, Bo and Li, Guibo and Dean, Michael and Yu, Qichao and Wang, Yanhui and Lin, Xinxin and Rao, Weijian and Mei, Zhanlong and Li, Yang and Jiang, Runze and Yang, Huan and Li, Fuqiang and Xie, Guoyun and Xu, Liqin and Wu, Kui and Zhang, Jie and Chen, Jianghao and Wang, Ting and Kristiansen, Karsten and Zhang, Xiuqing and Li, Yingrui and Yang, Huanming and Wang, Jian and Hou, Yong and Xu, Xun},
	date = {2015-12}
}

@article{deng_long_2015,
	title = {Long noncoding {RNA} {CCAT}1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge},
	volume = {34},
	issn = {1756-9966},
	url = {http://jeccr.biomedcentral.com/articles/10.1186/s13046-015-0136-7},
	doi = {10.1186/s13046-015-0136-7},
	pages = {18},
	number = {1},
	journaltitle = {Journal of Experimental \& Clinical Cancer Research},
	author = {Deng, Liang and Yang, Shi-Bin and Xu, Feng-Feng and Zhang, Ji-Hong},
	date = {2015}
}

@article{he_c-myc-activated_2014,
	title = {C-Myc-activated long noncoding {RNA} {CCAT}1 promotes colon cancer cell proliferation and invasion},
	volume = {35},
	issn = {1010-4283},
	url = {http://link.springer.com/10.1007/s13277-014-2526-4},
	doi = {10.1007/s13277-014-2526-4},
	pages = {12181--12188},
	number = {12},
	journaltitle = {Tumor Biology},
	author = {He, Xiaolu and Tan, Xueming and Wang, Xiang and Jin, Heiying and Liu, Li and Ma, Limei and Yu, Hong and Fan, Zhining},
	date = {2014-12},
	file = {Attachment:/home/jlagarde/Zotero/storage/PTG5NUSB/He et al. - 2014 - C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion.pdf:application/pdf}
}

@article{huppi_8q24_2012,
	title = {The 8q24 Gene Desert: An Oasis of Non-Coding Transcriptional Activity},
	volume = {3},
	issn = {1664-8021},
	url = {http://journal.frontiersin.org/article/10.3389/fgene.2012.00069/abstract},
	doi = {10.3389/fgene.2012.00069},
	abstract = {Understanding the functional effects of the wide-range of aberrant genetic characteristics associated with the human chromosome 8q24 region in cancer remains daunting due to the complexity of the locus. The most logical target for study remains the {MYC} protooncogene, a prominent resident of 8q24 that was first identified more than a quarter of a century ago. However, many of the amplifications, translocation breakpoints and viral integration sites associated with 8q24 are often found throughout large regions surrounding the {MYC} locus and often include other loci. In addition, Chr. 8q24 is host to a number of {SNPs} associated with cancer risk. Yet, the lack of a direct correlation between cancer risk alleles and {MYC} expression has also raised the specter of doubt that {MYC} is the sole target of these genetic associations. The 8q24 region has been described as a “gene desert” because of the paucity of functionally annotated genes located within this region. In this review, we examine the current evidence for the involvement of other loci within the 8q24 region, most of which are non-coding transcripts, either in concert with {MYC} or independent of {MYC}, as possible candidate gene targets in malignancy.},
	pages = {69},
	journaltitle = {Frontiers in Genetics},
	author = {Huppi, Konrad and Pitt, Jason J. and Wahlberg, Brady M. and Caplen, Natasha J.},
	date = {2012},
	keywords = {{MYC}, 8q24, {miR}-1204, {PVT}1}
}

@article{grisanzio_chromosome_2010,
	title = {Chromosome 8q24-Associated Cancers and {MYC}},
	volume = {1},
	issn = {1947-6019},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21779458 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3092220 http://gan.sagepub.com/lookup/doi/10.1177/1947601910381380},
	doi = {10.1177/1947601910381380},
	abstract = {Genome-wide association studies ({GWAS}) have successfully identified common polymorphisms that are strongly associated with many traits, including cancer. A gene desert located on chromosome 8q24 is associated with multiple cancer types. One of the closest genes is the {MYC} proto-oncogene. Investigations are now turning toward a mechanistic understanding of these (and other) risk loci. Recent studies demonstrate that the 8q24 loci are enhancers and that they physically interact with {MYC}. A still unresolved issue is the absence of a consistent association between genotype status at the risk loci and steady-state {MYC} expression levels in adult human tissues. Clarifying the function of the 8q24 variants and their link to {MYC} regulation by further in vivo and in vitro functional studies will allow a deeper understanding of the mechanisms underlying human cancer development.},
	pages = {555--559},
	number = {6},
	journaltitle = {Genes \& Cancer},
	author = {Grisanzio, C. and Freedman, M. L.},
	date = {2010-06},
	pmid = {21779458},
	keywords = {cancer, 8q24, association studies, genomics}
}

@article{xiang_human_2014,
	title = {Human colorectal cancer-specific {CCAT}1-L {lncRNA} regulates long-range chromatin interactions at the {MYC} locus},
	volume = {24},
	issn = {1001-0602},
	url = {http://www.nature.com/doifinder/10.1038/cr.2014.35},
	doi = {10.1038/cr.2014.35},
	pages = {513--531},
	number = {5},
	journaltitle = {Cell Research},
	author = {Xiang, Jian-Feng and Yin, Qing-Fei and Chen, Tian and Zhang, Yang and Zhang, Xiao-Ou and Wu, Zheng and Zhang, Shaofeng and Wang, Hai-Bin and Ge, Junhui and Lu, Xuhua and Yang, Li and Chen, Ling-Ling},
	date = {2014-05}
}

@article{younger_lnc-ing_2014,
	title = {'Lnc'-ing enhancers to {MYC} regulation},
	volume = {24},
	issn = {1001-0602},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24777251 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4042177 http://www.nature.com/doifinder/10.1038/cr.2014.54},
	doi = {10.1038/cr.2014.54},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are emerging as important functional components in the establishment of long-range chromosomal interactions. In a recent paper published in Cell Research, Xiang et al. provide mechanistic insight into this phenomenon by characterizing the role of {CCAT}1-L, a colorectal cancer-specific {lncRNA}, in intra-chromosome looping between the {MYC} gene promoter and distal upstream enhancer elements that regulate {MYC} transcription.},
	pages = {643--644},
	number = {6},
	journaltitle = {Cell Research},
	author = {Younger, Scott T and Rinn, John L},
	date = {2014-06},
	pmid = {24777251}
}

@article{teerlink_genome-wide_2016,
	title = {Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21},
	volume = {135},
	issn = {0340-6717},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27262462 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5020907 http://link.springer.com/10.1007/s00439-016-1690-6},
	doi = {10.1007/s00439-016-1690-6},
	abstract = {Previous genome-wide association studies ({GWAS}) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics ({ICPCG}) has now performed a {GWAS} of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism ({SNP}) platform. The {GWAS} identified a significant evidence for association for {SNPs} in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, {SNP} rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the {GWAS} cohort were genotyped for this {SNP}, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 \%) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare {SNPs} (dosage minor allele frequencies {\textbackslash}textless1.7 \%), rs183373024 ({PRNCR}1), previously associated {SNP} rs188140481, and rs138042437 ({CASC}19). Strong evidence for co-segregation of a {SNP} on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus.},
	pages = {923--938},
	number = {8},
	journaltitle = {Human Genetics},
	author = {Teerlink, Craig C. and Leongamornlert, Daniel and Dadaev, Tokhir and Thomas, Alun and Farnham, James and Stephenson, Robert A. and Riska, Shaun and {McDonnell}, Shannon K. and Schaid, Daniel J. and Catalona, William J. and Zheng, S. Lilly and Cooney, Kathleen A. and Ray, Anna M. and Zuhlke, Kimberly A. and Lange, Ethan M. and Giles, Graham G. and Southey, Melissa C. and Fitzgerald, Liesel M. and Rinckleb, Antje and Luedeke, Manuel and Maier, Christiane and Stanford, Janet L. and Ostrander, Elaine A. and Kaikkonen, Elina M. and Sipeky, Csilla and Tammela, Teuvo and Schleutker, Johanna and Wiley, Kathleen E. and Isaacs, Sarah D. and Walsh, Patrick C. and Isaacs, William B. and Xu, Jianfeng and Cancel-Tassin, Geraldine and Cussenot, Olivier and Mandal, Diptasri and Laurie, Cecelia and Laurie, Cathy and Thibodeau, Stephen N. and Eeles, Rosalind A. and Kote-Jarai, Zsofia and Cannon-Albright, Lisa and Kote-Jarai, Zsofia and Cannon-Albright, Lisa},
	date = {2016-08},
	pmid = {27262462}
}

@article{adey_haplotype-resolved_2013,
	title = {The haplotype-resolved genome and epigenome of the aneuploid {HeLa} cancer cell line.},
	volume = {500},
	issn = {1476-4687},
	url = {http://www.nature.com/doifinder/10.1038/nature12064 http://www.ncbi.nlm.nih.gov/pubmed/23925245 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3740412},
	doi = {10.1038/nature12064},
	abstract = {The {HeLa} cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro. The robust growth and unrestricted distribution of {HeLa} cells resulted in its broad adoption–both intentionally and through widespread cross-contamination–and for the past 60 years it has served a role analogous to that of a model organism. The cumulative impact of the {HeLa} cell line on research is demonstrated by its occurrence in more than 74,000 {PubMed} abstracts (approximately 0.3\%). The genomic architecture of {HeLa} remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the {HeLa} {CCL}-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for {HeLa} S3 and eight additional strains. We find that {HeLa} is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 ({HPV}-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with {RNA}-seq and {ENCODE} Project data sets to phase the {HeLa} epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene {MYC} by the integrated {HPV}-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on {HeLa}, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.},
	pages = {207--11},
	number = {7461},
	journaltitle = {Nature},
	author = {Adey, Andrew and Burton, Joshua N and Kitzman, Jacob O and Hiatt, Joseph B and Lewis, Alexandra P and Martin, Beth K and Qiu, Ruolan and Lee, Choli and Shendure, Jay},
	date = {2013-08},
	pmid = {23925245}
}

@article{landry_genomic_2013,
	title = {The genomic and transcriptomic landscape of a {HeLa} cell line.},
	volume = {3},
	issn = {2160-1836},
	url = {http://g3journal.org/lookup/doi/10.1534/g3.113.005777 http://www.ncbi.nlm.nih.gov/pubmed/23550136 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3737162},
	doi = {10.1534/g3.113.005777},
	abstract = {{HeLa} is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using {HeLa} cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a {HeLa} cell line. We performed {DNA} and {RNA} sequencing of a {HeLa} Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the {HeLa} gene expression profile revealed that several pathways, including cell cycle and {DNA} repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the {HeLa} genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of {HeLa} cells when designing and interpreting experiments, and has implications for the use of {HeLa} as a model of human biology.},
	pages = {1213--24},
	number = {8},
	journaltitle = {G3 (Bethesda, Md.)},
	author = {Landry, Jonathan J M and Pyl, Paul Theodor and Rausch, Tobias and Zichner, Thomas and Tekkedil, Manu M and Stütz, Adrian M and Jauch, Anna and Aiyar, Raeka S and Pau, Gregoire and Delhomme, Nicolas and Gagneur, Julien and Korbel, Jan O and Huber, Wolfgang and Steinmetz, Lars M},
	date = {2013-08},
	pmid = {23550136},
	keywords = {genomics, {HeLa} cell line, resource, transcriptomics, variation}
}

@article{martin_next-generation_2011,
	title = {Next-generation transcriptome assembly},
	volume = {12},
	issn = {1471-0056},
	url = {http://www.nature.com/doifinder/10.1038/nrg3068},
	doi = {10.1038/nrg3068},
	pages = {671--682},
	number = {10},
	journaltitle = {Nature Reviews Genetics},
	author = {Martin, Jeffrey A. and Wang, Zhong},
	date = {2011-09}
}

@article{deveson_dimensions_2017,
	title = {The Dimensions, Dynamics, and Relevance of the Mammalian Noncoding Transcriptome},
	issn = {01689525},
	url = {http://www.sciencedirect.com/science/article/pii/S0168952517300690},
	doi = {10.1016/j.tig.2017.04.004},
	abstract = {The combination of pervasive transcription and prolific alternative splicing produces a mammalian transcriptome of great breadth and diversity. The majority of transcribed genomic bases are intronic, antisense, or intergenic to protein-coding genes, yielding a plethora of short and long non-protein-coding regulatory {RNAs}. Long noncoding {RNAs} ({lncRNAs}) share most aspects of their biogenesis, processing, and regulation with {mRNAs}. However, {lncRNAs} are typically expressed in more restricted patterns, frequently from enhancers, and exhibit almost universal alternative splicing. These features are consistent with their role as modular epigenetic regulators. We describe here the key studies and technological advances that have shaped our understanding of the dimensions, dynamics, and biological relevance of the mammalian noncoding transcriptome.},
	journaltitle = {Trends in Genetics},
	author = {Deveson, Ira W. and Hardwick, Simon A. and Mercer, Tim R. and Mattick, John S.},
	date = {2017}
}

@article{li_sequence_2009,
	title = {The Sequence Alignment/Map format and {SAMtools}},
	volume = {25},
	issn = {1367-4803},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19505943 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2723002 https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btp352},
	doi = {10.1093/bioinformatics/btp352},
	abstract = {{SUMMARY} The Sequence Alignment/Map ({SAM}) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. {SAMtools} implements various utilities for post-processing alignments in the {SAM} format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. {AVAILABILITY} http://samtools.sourceforge.net.},
	pages = {2078--2079},
	number = {16},
	journaltitle = {Bioinformatics},
	author = {Li, H. and Handsaker, B. and Wysoker, A. and Fennell, T. and Ruan, J. and Homer, N. and Marth, G. and Abecasis, G. and Durbin, R. and {1000 Genome Project Data Processing Subgroup}},
	date = {2009-08},
	pmid = {19505943}
}

@article{pertea_stringtie_2015,
	title = {{StringTie} enables improved reconstruction of a transcriptome from {RNA}-seq reads},
	volume = {33},
	issn = {1087-0156},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25690850 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4643835 http://www.nature.com/doifinder/10.1038/nbt.3122},
	doi = {10.1038/nbt.3122},
	abstract = {Methods used to sequence the transcriptome often produce more than 200 million short sequences. We introduce {StringTie}, a computational method that applies a network flow algorithm originally developed in optimization theory, together with optional de novo assembly, to assemble these complex data sets into transcripts. When used to analyze both simulated and real data sets, {StringTie} produces more complete and accurate reconstructions of genes and better estimates of expression levels, compared with other leading transcript assembly programs including Cufflinks, {IsoLasso}, Scripture and Traph. For example, on 90 million reads from human blood, {StringTie} correctly assembled 10,990 transcripts, whereas the next best assembly was of 7,187 transcripts by Cufflinks, which is a 53\% increase in transcripts assembled. On a simulated data set, {StringTie} correctly assembled 7,559 transcripts, which is 20\% more than the 6,310 assembled by Cufflinks. As well as producing a more complete transcriptome assembly, {StringTie} runs faster on all data sets tested to date compared with other assembly software, including Cufflinks.},
	pages = {290--295},
	number = {3},
	journaltitle = {Nature Biotechnology},
	author = {Pertea, Mihaela and Pertea, Geo M and Antonescu, Corina M and Chang, Tsung-Cheng and Mendell, Joshua T and Salzberg, Steven L},
	date = {2015-02},
	pmid = {25690850},
	keywords = {Transcriptome, Humans, Algorithms, Software, {HEK}293 Cells, {RNA}, Messenger, Sequence Analysis, {RNA}},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/7CYBK5YX/Pertea et al. - 2015 - StringTie enables improved reconstruction of a tra.pdf:application/pdf}
}

@article{zhang_tissue-based_2015,
	title = {Tissue-Based Proteogenomics Reveals that Human Testis Endows Plentiful Missing Proteins.},
	volume = {14},
	issn = {1535-3907},
	url = {http://pubs.acs.org/doi/10.1021/acs.jproteome.5b00435 http://www.ncbi.nlm.nih.gov/pubmed/26282447},
	doi = {10.1021/acs.jproteome.5b00435},
	abstract = {Investigations of missing proteins ({MPs}) are being endorsed by many bioanalytical strategies. We proposed that proteogenomics of testis tissue was a feasible approach to identify more {MPs} because testis tissues have higher gene expression levels. Here we combined proteomics and transcriptomics to survey gene expression in human testis tissues from three post-mortem individuals. Proteins were extracted and separated with glycine- and tricine-{SDS}-{PAGE}. A total of 9597 protein groups were identified; of these, 166 protein groups were listed as {MPs}, including 138 groups (83.1\%) with transcriptional evidence. A total of 2948 proteins are designated as {MPs}, and 5.6\% of these were identified in this study. The high incidence of {MPs} in testis tissue indicates that this is a rich resource for {MPs}. Functional category analysis revealed that the biological processes that testis {MPs} are mainly involved in are sexual reproduction and spermatogenesis. Some of the {MPs} are potentially involved in tumorgenesis in other tissues. Therefore, this proteogenomics analysis of individual testis tissues provides convincing evidence of the discovery of {MPs}. All mass spectrometry data from this study have been deposited in the {ProteomeXchange} (data set identifier {PXD}002179).},
	pages = {3583--94},
	number = {9},
	journaltitle = {Journal of proteome research},
	author = {Zhang, Yao and Li, Qidan and Wu, Feilin and Zhou, Ruo and Qi, Yingzi and Su, Na and Chen, Lingsheng and Xu, Shaohang and Jiang, Tao and Zhang, Chengpu and Cheng, Gang and Chen, Xinguo and Kong, Degang and Wang, Yujia and Zhang, Tao and Zi, Jin and Wei, Wei and Gao, Yuan and Zhen, Bei and Xiong, Zhi and Wu, Songfeng and Yang, Pengyuan and Wang, Quanhui and Wen, Bo and He, Fuchu and Xu, Ping and Liu, Siqi},
	date = {2015-09},
	pmid = {26282447},
	keywords = {Chromosome-Centric Human Proteome Project, individual, missing proteins, proteome, testis, transcriptome}
}

@article{wright_improving_2016,
	title = {Improving {GENCODE} reference gene annotation using a high-stringency proteogenomics workflow.},
	volume = {7},
	issn = {2041-1723},
	url = {http://www.nature.com/doifinder/10.1038/ncomms11778 http://www.ncbi.nlm.nih.gov/pubmed/27250503 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4895710},
	doi = {10.1038/ncomms11778},
	abstract = {Complete annotation of the human genome is indispensable for medical research. The {GENCODE} consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to {GENCODE}. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence.},
	pages = {11778},
	journaltitle = {Nature communications},
	author = {Wright, James C and Mudge, Jonathan and Weisser, Hendrik and Barzine, Mitra P and Gonzalez, Jose M and Brazma, Alvis and Choudhary, Jyoti S and Harrow, Jennifer},
	date = {2016-06},
	pmid = {27250503}
}

@article{di_tommaso_nextflow_2017,
	title = {Nextflow enables reproducible computational workflows.},
	volume = {35},
	issn = {1546-1696},
	url = {http://www.nature.com/doifinder/10.1038/nbt.3820 http://www.ncbi.nlm.nih.gov/pubmed/28398311},
	doi = {10.1038/nbt.3820},
	pages = {316--319},
	number = {4},
	journaltitle = {Nature biotechnology},
	author = {Di Tommaso, Paolo and Chatzou, Maria and Floden, Evan W and Barja, Pablo Prieto and Palumbo, Emilio and Notredame, Cedric},
	date = {2017-04},
	pmid = {28398311}
}

@article{siepel_evolutionarily_2005,
	title = {Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes},
	volume = {15},
	issn = {1088-9051},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16024819 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1182216 http://www.genome.org/cgi/doi/10.1101/gr.3715005},
	doi = {10.1101/gr.3715005},
	abstract = {We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called {phastCons}, which is based on a two-state phylogenetic hidden Markov model (phylo-{HMM}). {PhastCons} works by fitting a phylo-{HMM} to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3\%-8\% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37\%-53\%), Caenorhabditis elegans (18\%-37\%), and Saccharaomyces cerevisiae (47\%-68\%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements ({HCEs}), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, {HCEs} are associated with the 3' {UTRs} of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding {HCEs} also show strong statistical evidence of an enrichment for {RNA} secondary structure.},
	pages = {1034--1050},
	number = {8},
	journaltitle = {Genome Research},
	author = {Siepel, A. and Bejerano, Gill and Pedersen, Jakob S and Hinrichs, Angie S and Hou, Minmei and Rosenbloom, Kate and Clawson, Hiram and Spieth, John and Hillier, Ladeana W and Richards, Stephen and Weinstock, George M and Wilson, Richard K and Gibbs, Richard A and Kent, W James and Miller, Webb and Haussler, David},
	date = {2005-08},
	pmid = {16024819},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/L4LNQI6H/Siepel et al. - 2005 - Evolutionarily conserved elements in vertebrate, i.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/C3T6NVQ3/1034.html:text/html}
}

@article{islam_characterization_2011,
	title = {Characterization of the single-cell transcriptional landscape by highly multiplex {RNA}-seq},
	volume = {21},
	issn = {1088-9051},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21543516 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3129258 http://genome.cshlp.org/cgi/doi/10.1101/gr.110882.110},
	doi = {10.1101/gr.110882.110},
	abstract = {Our understanding of the development and maintenance of tissues has been greatly aided by large-scale gene expression analysis. However, tissues are invariably complex, and expression analysis of a tissue confounds the true expression patterns of its constituent cell types. Here we describe a novel strategy to access such complex samples. Single-cell {RNA}-seq expression profiles were generated, and clustered to form a two-dimensional cell map onto which expression data were projected. The resulting cell map integrates three levels of organization: the whole population of cells, the functionally distinct subpopulations it contains, and the single cells themselves-all without need for known markers to classify cell types. The feasibility of the strategy was demonstrated by analyzing the transcriptomes of 85 single cells of two distinct types. We believe this strategy will enable the unbiased discovery and analysis of naturally occurring cell types during development, adult physiology, and disease.},
	pages = {1160--1167},
	number = {7},
	journaltitle = {Genome Research},
	author = {Islam, S. and Kjallquist, U. and Moliner, A. and Zajac, P. and Fan, J.-B. and Lonnerberg, P. and Linnarsson, S.},
	date = {2011-07},
	pmid = {21543516}
}

@article{macarthur_new_2017,
	title = {The new {NHGRI}-{EBI} Catalog of published genome-wide association studies ({GWAS} Catalog)},
	volume = {45},
	issn = {0305-1048},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27899670 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5210590 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1133},
	doi = {10.1093/nar/gkw1133},
	abstract = {The {NHGRI}-{EBI} {GWAS} Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to {EMBL}-{EBI}. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation interface. These developments have improved the data release frequency by increasing automation of curation and providing scaling improvements. The range of available Catalog data has also been extended with structured ancestry and recruitment information added for all studies. The infrastructure improvements also support scaling for larger arrays, exome and sequencing studies, allowing the Catalog to adapt to the needs of evolving study design, genotyping technologies and user needs in the future.},
	pages = {D896--D901},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {{MacArthur}, Jacqueline and Bowler, Emily and Cerezo, Maria and Gil, Laurent and Hall, Peggy and Hastings, Emma and Junkins, Heather and {McMahon}, Aoife and Milano, Annalisa and Morales, Joannella and Pendlington, Zoe May and Welter, Danielle and Burdett, Tony and Hindorff, Lucia and Flicek, Paul and Cunningham, Fiona and Parkinson, Helen},
	date = {2017-01},
	pmid = {27899670},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/H56EFJGE/MacArthur et al. - 2017 - The new NHGRI-EBI Catalog of published genome-wide.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/M89NE2I5/2605751.html:text/html}
}

@article{kundaje_integrative_2015,
	title = {Integrative analysis of 111 reference human epigenomes},
	volume = {518},
	issn = {0028-0836},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25693563 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4530010 http://www.nature.com/doifinder/10.1038/nature14248},
	doi = {10.1038/nature14248},
	abstract = {The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the {NIH} Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, {DNA} accessibility, {DNA} methylation and {RNA} expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.},
	pages = {317--330},
	number = {7539},
	journaltitle = {Nature},
	author = {Kundaje, Anshul and Meuleman, Wouter and Ernst, Jason and Bilenky, Misha and Yen, Angela and Heravi-Moussavi, Alireza and Kheradpour, Pouya and Zhang, Zhizhuo and Wang, Jianrong and Ziller, Michael J. and Amin, Viren and Whitaker, John W. and Schultz, Matthew D. and Ward, Lucas D. and Sarkar, Abhishek and Quon, Gerald and Sandstrom, Richard S. and Eaton, Matthew L. and Wu, Yi-Chieh and Pfenning, Andreas and Wang, Xinchen and {ClaussnitzerYaping} Liu, Melina and Coarfa, Cristian and Alan Harris, R. and Shoresh, Noam and Epstein, Charles B. and Gjoneska, Elizabeta and Leung, Danny and Xie, Wei and David Hawkins, R. and Lister, Ryan and Hong, Chibo and Gascard, Philippe and Mungall, Andrew J. and Moore, Richard and Chuah, Eric and Tam, Angela and Canfield, Theresa K. and Scott Hansen, R. and Kaul, Rajinder and Sabo, Peter J. and Bansal, Mukul S. and Carles, Annaick and Dixon, Jesse R. and Farh, Kai-How and Feizi, Soheil and Karlic, Rosa and Kim, Ah-Ram and Kulkarni, Ashwinikumar and Li, Daofeng and Lowdon, Rebecca and Elliott, {GiNell} and Mercer, Tim R. and Neph, Shane J. and Onuchic, Vitor and Polak, Paz and Rajagopal, Nisha and Ray, Pradipta and Sallari, Richard C. and Siebenthall, Kyle T. and Sinnott-Armstrong, Nicholas A. and Stevens, Michael and Thurman, Robert E. and Wu, Jie and Zhang, Bo and Zhou, Xin and Abdennur, Nezar and Adli, Mazhar and Akerman, Martin and Barrera, Luis and Antosiewicz-Bourget, Jessica and Ballinger, Tracy and Barnes, Michael J. and Bates, Daniel and Bell, Robert J. A. and Bennett, David A. and Bianco, Katherine and Bock, Christoph and Boyle, Patrick and Brinchmann, Jan and Caballero-Campo, Pedro and Camahort, Raymond and Carrasco-Alfonso, Marlene J. and Charnecki, Timothy and Chen, Huaming and Chen, Zhao and Cheng, Jeffrey B. and Cho, Stephanie and Chu, Andy and Chung, Wen-Yu and Cowan, Chad and Athena Deng, Qixia and Deshpande, Vikram and Diegel, Morgan and Ding, Bo and Durham, Timothy and Echipare, Lorigail and Edsall, Lee and Flowers, David and Genbacev-Krtolica, Olga and Gifford, Casey and Gillespie, Shawn and Giste, Erika and Glass, Ian A. and Gnirke, Andreas and Gormley, Matthew and Gu, Hongcang and Gu, Junchen and Hafler, David A. and Hangauer, Matthew J. and Hariharan, Manoj and Hatan, Meital and Haugen, Eric and He, Yupeng and Heimfeld, Shelly and Herlofsen, Sarah and Hou, Zhonggang and Humbert, Richard and Issner, Robbyn and Jackson, Andrew R. and Jia, Haiyang and Jiang, Peng and Johnson, Audra K. and Kadlecek, Theresa and Kamoh, Baljit and Kapidzic, Mirhan and Kent, Jim and Kim, Audrey and Kleinewietfeld, Markus and Klugman, Sarit and Krishnan, Jayanth and Kuan, Samantha and Kutyavin, Tanya and Lee, Ah-Young and Lee, Kristen and Li, Jian and Li, Nan and Li, Yan and Ligon, Keith L. and Lin, Shin and Lin, Yiing and Liu, Jie and Liu, Yuxuan and Luckey, C. John and Ma, Yussanne P. and Maire, Cecile and Marson, Alexander and Mattick, John S. and Mayo, Michael and {McMaster}, Michael and Metsky, Hayden and Mikkelsen, Tarjei and Miller, Diane and Miri, Mohammad and Mukame, Eran and Nagarajan, Raman P. and Neri, Fidencio and Nery, Joseph and Nguyen, Tung and O'Geen, Henriette and Paithankar, Sameer and Papayannopoulou, Thalia and Pelizzola, Mattia and Plettner, Patrick and Propson, Nicholas E. and Raghuraman, Sriram and Raney, Brian J. and Raubitschek, Anthony and Reynolds, Alex P. and Richards, Hunter and Riehle, Kevin and Rinaudo, Paolo and Robinson, Joshua F. and Rockweiler, Nicole B. and Rosen, Evan and Rynes, Eric and Schein, Jacqueline and Sears, Renee and Sejnowski, Terrence and Shafer, Anthony and Shen, Li and Shoemaker, Robert and Sigaroudinia, Mahvash and Slukvin, Igor and Stehling-Sun, Sandra and Stewart, Ron and Subramanian, Sai Lakshmi and Suknuntha, Kran and Swanson, Scott and Tian, Shulan and Tilden, Hannah and Tsai, Linus and Urich, Mark and Vaughn, Ian and Vierstra, Jeff and Vong, Shinny and Wagner, Ulrich and Wang, Hao and Wang, Tao and Wang, Yunfei and Weiss, Arthur and Whitton, Holly and Wildberg, Andre and Witt, Heather and Won, Kyoung-Jae and Xie, Mingchao and Xing, Xiaoyun and Xu, Iris and Xuan, Zhenyu and Ye, Zhen and Yen, Chia-an and Yu, Pengzhi and Zhang, Xian and Zhang, Xiaolan and Zhao, Jianxin and Zhou, Yan and Zhu, Jiang and Zhu, Yun and Ziegler, Steven and Beaudet, Arthur E. and Boyer, Laurie A. and De Jager, Philip L. and Farnham, Peggy J. and Fisher, Susan J. and Haussler, David and Jones, Steven J. M. and Li, Wei and Marra, Marco A. and {McManus}, Michael T. and Sunyaev, Shamil and Thomson, James A. and Tlsty, Thea D. and Tsai, Li-Huei and Wang, Wei and Waterland, Robert A. and Zhang, Michael Q. and Chadwick, Lisa H. and Bernstein, Bradley E. and Costello, Joseph F. and Ecker, Joseph R. and Hirst, Martin and Meissner, Alexander and Milosavljevic, Aleksandar and Ren, Bing and Stamatoyannopoulos, John A. and Wang, Ting and Kellis, Manolis and Kundaje, Anshul and Meuleman, Wouter and Ernst, Jason and Bilenky, Misha and Yen, Angela and Heravi-Moussavi, Alireza and Kheradpour, Pouya and Zhang, Zhizhuo and Wang, Jianrong and Ziller, Michael J. and Amin, Viren and Whitaker, John W. and Schultz, Matthew D. and Ward, Lucas D. and Sarkar, Abhishek and Quon, Gerald and Sandstrom, Richard S. and Eaton, Matthew L. and Wu, Yi-Chieh and Pfenning, Andreas R. and Wang, Xinchen and Claussnitzer, Melina and Liu, Yaping and Coarfa, Cristian and Harris, R. Alan and Shoresh, Noam and Epstein, Charles B. and Gjoneska, Elizabeta and Leung, Danny and Xie, Wei and Hawkins, R. David and Lister, Ryan and Hong, Chibo and Gascard, Philippe and Mungall, Andrew J. and Moore, Richard and Chuah, Eric and Tam, Angela and Canfield, Theresa K. and Hansen, R. Scott and Kaul, Rajinder and Sabo, Peter J. and Bansal, Mukul S. and Carles, Annaick and Dixon, Jesse R. and Farh, Kai-How and Feizi, Soheil and Karlic, Rosa and Kim, Ah-Ram and Kulkarni, Ashwinikumar and Li, Daofeng and Lowdon, Rebecca and Elliott, {GiNell} and Mercer, Tim R. and Neph, Shane J. and Onuchic, Vitor and Polak, Paz and Rajagopal, Nisha and Ray, Pradipta and Sallari, Richard C. and Siebenthall, Kyle T. and Sinnott-Armstrong, Nicholas A. and Stevens, Michael and Thurman, Robert E. and Wu, Jie and Zhang, Bo and Zhou, Xin and Beaudet, Arthur E. and Boyer, Laurie A. and De Jager, Philip L. and Farnham, Peggy J. and Fisher, Susan J. and Haussler, David and Jones, Steven J. M. and Li, Wei and Marra, Marco A. and {McManus}, Michael T. and Sunyaev, Shamil and Thomson, James A. and Tlsty, Thea D. and Tsai, Li-Huei and Wang, Wei and Waterland, Robert A. and Zhang, Michael Q. and Chadwick, Lisa H. and Bernstein, Bradley E. and Costello, Joseph F. and Ecker, Joseph R. and Hirst, Martin and Meissner, Alexander and Milosavljevic, Aleksandar and Ren, Bing and Stamatoyannopoulos, John A. and Wang, Ting and Kellis, Manolis},
	date = {2015-02},
	pmid = {25693563},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/UFUSZDNQ/Kundaje et al. - 2015 - Integrative analysis of 111 reference human epigen.pdf:application/pdf}
}

@article{li_rsem:_2011,
	title = {{RSEM}: accurate transcript quantification from {RNA}-Seq data with or without a reference genome},
	volume = {12},
	issn = {1471-2105},
	url = {http://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-12-323},
	doi = {10.1186/1471-2105-12-323},
	pages = {323},
	number = {1},
	journaltitle = {{BMC} Bioinformatics},
	author = {Li, Bo and Dewey, Colin N},
	date = {2011}
}

@article{knowles_grape_2013,
	title = {Grape {RNA}-Seq analysis pipeline environment},
	volume = {29},
	issn = {1367-4803},
	url = {https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btt016},
	doi = {10.1093/bioinformatics/btt016},
	pages = {614--621},
	number = {5},
	journaltitle = {Bioinformatics},
	author = {Knowles, D. G. and Roder, M. and Merkel, A. and Guigo, R.},
	date = {2013-03}
}

@article{lin_phylocsf:_2011,
	title = {{PhyloCSF}: a comparative genomics method to distinguish protein coding and non-coding regions},
	volume = {27},
	issn = {1367-4803},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21685081 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3117341 https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btr209},
	doi = {10.1093/bioinformatics/btr209},
	abstract = {{MOTIVATION} As high-throughput transcriptome sequencing provides evidence for novel transcripts in many species, there is a renewed need for accurate methods to classify small genomic regions as protein coding or non-coding. We present {PhyloCSF}, a novel comparative genomics method that analyzes a multispecies nucleotide sequence alignment to determine whether it is likely to represent a conserved protein-coding region, based on a formal statistical comparison of phylogenetic codon models. {RESULTS} We show that {PhyloCSF}'s classification performance in 12-species Drosophila genome alignments exceeds all other methods we compared in a previous study. We anticipate that this method will be widely applicable as the transcriptomes of many additional species, tissues and subcellular compartments are sequenced, particularly in the context of {ENCODE} and {modENCODE}, and as interest grows in long non-coding {RNAs}, often initially recognized by their lack of protein coding potential rather than conserved {RNA} secondary structures. {AVAILABILITY} {AND} {IMPLEMENTATION} The Objective Caml source code and executables for {GNU}/Linux and Mac {OS} X are freely available at http://compbio.mit.edu/{PhyloCSF} {CONTACT}: mlin@mit.edu; manoli@mit.edu.},
	pages = {i275--i282},
	number = {13},
	journaltitle = {Bioinformatics},
	author = {Lin, M. F. and Jungreis, I. and Kellis, M.},
	date = {2011-07},
	pmid = {21685081}
}

@article{wang_cpat:_2013,
	title = {{CPAT}: Coding-Potential Assessment Tool using an alignment-free logistic regression model},
	volume = {41},
	issn = {1362-4962},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23335781 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3616698 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkt006},
	doi = {10.1093/nar/gkt006},
	abstract = {Thousands of novel transcripts have been identified using deep transcriptome sequencing. This discovery of large and 'hidden' transcriptome rejuvenates the demand for methods that can rapidly distinguish between coding and noncoding {RNA}. Here, we present a novel alignment-free method, Coding Potential Assessment Tool ({CPAT}), which rapidly recognizes coding and noncoding transcripts from a large pool of candidates. To this end, {CPAT} uses a logistic regression model built with four sequence features: open reading frame size, open reading frame coverage, Fickett {TESTCODE} statistic and hexamer usage bias. {CPAT} software outperformed (sensitivity: 0.96, specificity: 0.97) other state-of-the-art alignment-based software such as Coding-Potential Calculator (sensitivity: 0.99, specificity: 0.74) and Phylo Codon Substitution Frequencies (sensitivity: 0.90, specificity: 0.63). In addition to high accuracy, {CPAT} is approximately four orders of magnitude faster than Coding-Potential Calculator and Phylo Codon Substitution Frequencies, enabling its users to process thousands of transcripts within seconds. The software accepts input sequences in either {FASTA}- or {BED}-formatted data files. We also developed a web interface for {CPAT} that allows users to submit sequences and receive the prediction results almost instantly.},
	pages = {e74--e74},
	number = {6},
	journaltitle = {Nucleic Acids Research},
	author = {Wang, Liguo and Park, Hyun Jung and Dasari, Surendra and Wang, Shengqin and Kocher, Jean-Pierre and Li, Wei},
	date = {2013-04},
	pmid = {23335781}
}

@article{pervouchine_intron-centric_2013,
	title = {Intron-centric estimation of alternative splicing from {RNA}-seq data},
	volume = {29},
	issn = {13674803},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23172860 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3546801},
	doi = {10.1093/bioinformatics/bts678},
	abstract = {{MOTIVATION}: Novel technologies brought in unprecedented amounts of high-throughput sequencing data along with great challenges in their analysis and interpretation. The percent-spliced-in ({PSI}, ) metric estimates the incidence of single-exon-skipping events and can be computed directly by counting reads that align to known or predicted splice junctions. However, the majority of human splicing events are more complex than single-exon skipping.\${\textbackslash}backslash\$n\${\textbackslash}backslash\${nRESULTS}: In this short report, we present a framework that generalizes the metric to arbitrary classes of splicing events. We change the view from exon centric to intron centric and split the value of into two indices, and , measuring the rate of splicing at the 5' and 3' end of the intron, respectively. The advantage of having two separate indices is that they deconvolute two distinct elementary acts of the splicing reaction. The completeness of splicing index is decomposed in a similar way. This framework is implemented as bam2ssj, a {BAM}-file-processing pipeline for strand-specific counting of reads that align to splice junctions or overlap with splice sites. It can be used as a consistent protocol for quantifying splice junctions from {RNA}-seq data because no such standard procedure currently exists.\${\textbackslash}backslash\$n\${\textbackslash}backslash\${nAVAILABILITY}: The C code of bam2ssj is open source and is available at https://github.com/pervouchine/bam2ssj\${\textbackslash}backslash\$n\${\textbackslash}backslash\${nCONTACT}: dp@crg.eu},
	pages = {273--274},
	number = {2},
	journaltitle = {Bioinformatics},
	author = {Pervouchine, Dmitri D and Knowles, David G and Guigó, Roderic},
	date = {2013-01},
	pmid = {23172860}
}

@article{soumillon_cellular_2013,
	title = {Cellular source and mechanisms of high transcriptome complexity in the mammalian testis.},
	volume = {3},
	issn = {2211-1247},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23791531 http://www.cell.com/article/S2211124713002489/fulltext},
	doi = {10.1016/j.celrep.2013.05.031},
	abstract = {Understanding the extent of genomic transcription and its functional relevance is a central goal in genomics research. However, detailed genome-wide investigations of transcriptome complexity in major mammalian organs have been scarce. Here, using extensive {RNA}-seq data, we show that transcription of the genome is substantially more widespread in the testis than in other organs across representative mammals. Furthermore, we reveal that meiotic spermatocytes and especially postmeiotic round spermatids have remarkably diverse transcriptomes, which explains the high transcriptome complexity of the testis as a whole. The widespread transcriptional activity in spermatocytes and spermatids encompasses protein-coding and long noncoding {RNA} genes but also poorly conserves intergenic sequences, suggesting that it may not be of immediate functional relevance. Rather, our analyses of genome-wide epigenetic data suggest that this prevalent transcription, which most likely promoted the birth of new genes during evolution, is facilitated by an overall permissive chromatin in these germ cells that results from extensive chromatin remodeling.},
	pages = {2179--90},
	number = {6},
	journaltitle = {Cell reports},
	author = {Soumillon, Magali and Necsulea, Anamaria and Weier, Manuela and Brawand, David and Zhang, Xiaolan and Gu, Hongcang and Barthès, Pauline and Kokkinaki, Maria and Nef, Serge and Gnirke, Andreas and Dym, Martin and de Massy, Bernard and Mikkelsen, Tarjei S and Kaessmann, Henrik},
	date = {2013-06},
	pmid = {23791531},
	keywords = {Transcriptome, Animals, Genetic, Humans, {RNA}, Transcription, Biological Evolution, Male, Mammals, {RNA}: genetics, Spermatocytes, Spermatocytes: cytology, Spermatocytes: physiology, Testis, Testis: cytology, Testis: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/D4B68VWJ/Soumillon et al. - 2013 - Cellular source and mechanisms of high transcriptome complexity in the mammalian testis.pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/AYIXQC7Z/Soumillon et al. - 2013 - Cellular source and mechanisms of high transcriptome complexity in the mammalian testis(2).pdf:application/pdf}
}

@article{wang_rna-seq:_2009,
	title = {{RNA}-Seq: a revolutionary tool for transcriptomics.},
	volume = {10},
	issn = {1471-0064},
	url = {http://www.nature.com/nrg/journal/v10/n1/full/nrg2484.html#B18},
	doi = {10.1038/nrg2484},
	abstract = {{RNA}-Seq is a recently developed approach to transcriptome profiling that uses deep-sequencing technologies. Studies using this method have already altered our view of the extent and complexity of eukaryotic transcriptomes. {RNA}-Seq also provides a far more precise measurement of levels of transcripts and their isoforms than other methods. This article describes the {RNA}-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes.},
	pages = {57--63},
	number = {1},
	journaltitle = {Nature reviews. Genetics},
	author = {Wang, Zhong and Gerstein, Mark and Snyder, Michael},
	date = {2009-01},
	langid = {english},
	pmid = {19015660},
	keywords = {Sequence Analysis, Animals, Base Sequence, Genetic, Humans, {RNA}, Transcription, Exons, Gene Expression Profiling, {RNA}: methods, Chromosome Mapping, Gene Expression Profiling: methods, Models, Molecular Sequence Data, {RNA}: analysis, Transcription, Genetic, Models, Genetic, Sequence Analysis, {RNA}},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/R2MJP82H/Wang et al. - 2009 - RNA-Seq a revolutionary tool for transcriptomics.pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/G5CGFZHW/Wang, Gerstein, Snyder - 2009 - RNA-Seq a revolutionary tool for transcriptomics.pdf:application/pdf}
}

@article{mattick_discovery_2015,
	title = {Discovery and annotation of long noncoding {RNAs}.},
	volume = {22},
	issn = {1545-9985},
	url = {http://dx.doi.org/10.1038/nsmb.2942 http://www.nature.com/doifinder/10.1038/nsmb.2942},
	doi = {10.1038/nsmb.2942},
	shorttitle = {Nat Struct Mol Biol},
	abstract = {Recent advances in {RNA}-sequencing technologies have led to the discovery of thousands of previously unannotated noncoding transcripts, including many long noncoding {RNAs} ({lncRNAs}) whose functions remain largely unknown. Here we discuss considerations and best practices in {lncRNA} identification and annotation, which we hope will foster functional and mechanistic exploration.},
	pages = {5--7},
	number = {1},
	journaltitle = {Nature structural \& molecular biology},
	author = {Mattick, John S and Rinn, John L},
	date = {2015-01},
	pmid = {25565026},
	keywords = {{RNA}, Untranslated, Gene Expression Regulation, Untranslated: genetics, Molecular Sequence Annotation, Molecular Biology, Molecular Biology: trends, Molecular Sequence Annotation: trends, Untranslated: physiology}
}

@article{chang_tail-seq:_2014,
	title = {{TAIL}-seq: genome-wide determination of poly(A) tail length and 3' end modifications.},
	volume = {53},
	issn = {1097-4164},
	url = {http://www.cell.com/article/S109727651400121X/fulltext http://www.sciencedirect.com/science/article/pii/S109727651400121X},
	doi = {10.1016/j.molcel.2014.02.007},
	abstract = {Global investigation of the 3' extremity of {mRNA} (3'-terminome), despite its importance in gene regulation, has not been feasible due to technical challenges associated with homopolymeric sequences and relative paucity of {mRNA}. We here develop a method, {TAIL}-seq, to sequence the very end of {mRNA} molecules. {TAIL}-seq allows us to measure poly(A) tail length at the genomic scale. Median poly(A) length is 50-100 nt in {HeLa} and {NIH} 3T3 cells. Poly(A) length correlates with {mRNA} half-life, but not with translational efficiency. Surprisingly, we discover widespread uridylation and guanylation at the downstream of poly(A) tail. The U tails are generally attached to short poly(A) tails ({\textbackslash}textless25 nt), while the G tails are found mainly on longer poly(A) tails ({\textbackslash}textgreater40 nt), implicating their generic roles in {mRNA} stability control. {TAIL}-seq is a potent tool to dissect dynamic control of {mRNA} turnover and translational control, and to discover unforeseen features of {RNA} cleavage and tailing.},
	pages = {1044--52},
	number = {6},
	journaltitle = {Molecular cell},
	author = {Chang, Hyeshik and Lim, Jaechul and Ha, Minju and Kim, V. Narry Narry},
	date = {2014-03},
	pmid = {24582499},
	keywords = {Sequence Analysis, 3' Untranslated Regions, Animals, Base Sequence, Genome, Humans, Mice, {RNA}, Gene Expression Regulation, {RNA}: methods, Half-Life, {HeLa} Cells, {MicroRNAs}, {MicroRNAs}: genetics, Molecular Sequence Data, {NIH} 3T3 Cells, Polyadenylation, {RNA} Stability, Signal Transduction, Guanine, Guanine: metabolism, {MicroRNAs}: metabolism, Uridine, Uridine: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/VCQYMPXC/Chang et al. - 2014 - TAIL-seq genome-wide determination of poly(A) tail length and 3' end modifications.pdf:application/pdf}
}

@article{beaudoing_patterns_2000,
	title = {Patterns of variant polyadenylation signal usage in human genes},
	volume = {10},
	issn = {10889051},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=310884&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.10.7.1001},
	abstract = {The formation of mature {mRNAs} in vertebrates involves the cleavage and polyadenylation of the pre-{mRNA}, 10-30 nt downstream of an {AAUAAA} or {AUUAAA} signal sequence. The extensive {cDNA} data now available shows that these hexamers are not strictly conserved. In order to identify variant polyadenylation signals on a large scale, we compared over 8700 human 3' untranslated sequences to 157,775 polyadenylated expressed sequence tags ({ESTs}), used as markers of actual {mRNA} 3' ends. About 5600 {EST}-supported putative {mRNA} 3' ends were collected and analyzed for significant hexameric sequences. Known polyadenylation signals were found in only 73\% of the 3' fragments. Ten single-base variants of the {AAUAAA} sequence were identified with a highly significant occurrence rate, potentially representing 14.9\% of the actual polyadenylation signals. Of the {mRNAs}, 28.6\% displayed two or more polyadenylation sites. In these {mRNAs}, the poly(A) sites proximal to the coding sequence tend to use variant signals more often, while the 3'-most site tends to use a canonical signal. The average number of {ESTs} associated with each signal type suggests that variant signals (including the common {AUUAAA}) are processed less efficiently than the canonical signal and could therefore be selected for regulatory purposes. However, the position of the site in the untranslated region may also play a role in polyadenylation rate.},
	pages = {1001--1010},
	number = {7},
	journaltitle = {Genome Research},
	author = {Beaudoing, Emmanuel and Freier, Susan and Wyatt, Jacqueline R. and Claverie, Jean Michel and Gautheret, Daniel},
	date = {2000-07},
	pmid = {10899149},
	keywords = {3' Untranslated Regions, Humans, {RNA}, Messenger, Messenger: metabolism, 3' Untranslated Regions: chemistry, 3' Untranslated Regions: metabolism, Amino Acid Motifs, Expressed Sequence Tags, Genes, Genetic Variation, Genetic Variation: genetics, Messenger: chemistry, Poly A, Post-Transcriptional, {RNA} Processing, Signal Transduction, Amino Acid Motifs: genetics, Poly A: chemistry, Poly A: genetics, Poly A: metabolism, Signal Transduction: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/6NNHP5X6/Beaudoing et al. - 2000 - Patterns of variant polyadenylation signal usage in human genes.pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/6KQ8VUAH/Beaudoing et al. - 2000 - Patterns of variant polyadenylation signal usage in human genes(2).pdf:application/pdf}
}

@article{bussotti_blastr_2011,
	title = {{BlastR} - fast and accurate database searches for non-coding {RNAs}.},
	volume = {39},
	issn = {1362-4962},
	url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkr335 http://www.ncbi.nlm.nih.gov/pubmed/21624887 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3167602},
	doi = {10.1093/nar/gkr335},
	abstract = {We present and validate {BlastR}, a method for efficiently and accurately searching non-coding {RNAs}. Our approach relies on the comparison of di-nucleotides using {BlosumR}, a new log-odd substitution matrix. In order to use {BlosumR} for comparison, we recoded {RNA} sequences into protein-like sequences. We then showed that {BlosumR} can be used along with the {BlastP} algorithm in order to search non-coding {RNA} sequences. Using Rfam as a gold standard, we benchmarked this approach and show {BlastR} to be more sensitive than {BlastN}. We also show that {BlastR} is both faster and more sensitive than {BlastP} used with a single nucleotide log-odd substitution matrix. {BlastR}, when used in combination with {WU}-{BlastP}, is about 5\% more accurate than {WU}-{BlastN} and about 50 times slower. The approach shown here is equally effective when combined with the {NCBI}-Blast package. The software is an open source freeware available from www.tcoffee.org/blastr.html.},
	pages = {6886--95},
	number = {16},
	journaltitle = {Nucleic acids research},
	author = {Bussotti, Giovanni and Raineri, Emanuele and Erb, Ionas and Zytnicki, Matthias and Wilm, Andreas and Beaudoing, Emmanuel and Bucher, Philipp and Notredame, Cedric},
	date = {2011-09},
	pmid = {21624887},
	file = {BlastR–fast and accurate database searches for non-coding RNAs.:/home/jlagarde/Zotero/storage/QE3YX46F/bussotti2011.pdf:application/pdf}
}

@article{marco-sola_gem_2012,
	title = {The {GEM} mapper: fast, accurate and versatile alignment by filtration.},
	volume = {9},
	issn = {1548-7105},
	doi = {10.1038/nmeth.2221},
	abstract = {Because of ever-increasing throughput requirements of sequencing data, most existing short-read aligners have been designed to focus on speed at the expense of accuracy. The Genome Multitool ({GEM}) mapper can leverage string matching by filtration to search the alignment space more efficiently, simultaneously delivering precision (performing fully tunable exhaustive searches that return all existing matches, including gapped ones) and speed (being several times faster than comparable state-of-the-art tools).},
	pages = {1185--8},
	number = {12},
	journaltitle = {Nature methods},
	author = {Marco-Sola, Santiago and Sammeth, Michael and Guigó, Roderic and Ribeca, Paolo},
	date = {2012-12},
	pmid = {23103880}
}

@article{quinlan_bedtools:_2010,
	title = {{BEDTools}: a flexible suite of utilities for comparing genomic features.},
	volume = {26},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/btq033},
	abstract = {{MOTIVATION}: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner. {RESULTS}: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data ({BED}) and General Feature Format ({GFF}) format. {BEDTools} also supports the comparison of sequence alignments in {BAM} format to both {BED} and {GFF} features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. {BEDTools} can be combined with one another as well as with standard {UNIX} commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets. {AVAILABILITY} {AND} {IMPLEMENTATION}: {BEDTools} was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools {CONTACT}: aaronquinlan@gmail.com; imh4y@virginia.edu {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at Bioinformatics online.},
	pages = {841--2},
	number = {6},
	journaltitle = {Bioinformatics (Oxford, England)},
	author = {Quinlan, Aaron R and Hall, Ira M},
	date = {2010-03},
	pmid = {20110278}
}

@article{ernst_chromhmm:_2012,
	title = {{ChromHMM}: automating chromatin-state discovery and characterization},
	volume = {9},
	issn = {1548-7091},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22373907 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3577932 http://www.nature.com/doifinder/10.1038/nmeth.1906},
	doi = {10.1038/nmeth.1906},
	pages = {215--216},
	number = {3},
	journaltitle = {Nature Methods},
	author = {Ernst, Jason and Kellis, Manolis},
	date = {2012-02},
	pmid = {22373907}
}

@article{su_comprehensive_2014,
	title = {A comprehensive assessment of {RNA}-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium},
	volume = {32},
	issn = {1087-0156},
	url = {http://www.nature.com/doifinder/10.1038/nbt.2957},
	doi = {10.1038/nbt.2957},
	pages = {903--914},
	number = {9},
	journaltitle = {Nature Biotechnology},
	author = {Su, Zhenqiang and \{{\textbackslash}textbackslash\}Labaj, Pawe\{{\textbackslash}textbackslash\}l P and Li, Sheng and Thierry-Mieg, Jean and Thierry-Mieg, Danielle and Shi, Wei and Wang, Charles and Schroth, Gary P and Setterquist, Robert A and Thompson, John F and Jones, Wendell D and Xiao, Wenzhong and Xu, Weihong and Jensen, Roderick V and Kelly, Reagan and Xu, Joshua and Conesa, Ana and Furlanello, Cesare and Gao, Hanlin and Hong, Huixiao and Jafari, Nadereh and Letovsky, Stan and Liao, Yang and Lu, Fei and Oakeley, Edward J and Peng, Zhiyu and Praul, Craig A and Santoyo-Lopez, Javier and Scherer, Andreas and Shi, Tieliu and Smyth, Gordon K and Staedtler, Frank and Sykacek, Peter and Tan, Xin-Xing and Thompson, E Aubrey and Vandesompele, Jo and Wang, May D and Wang, Jian and Wolfinger, Russell D and Zavadil, Jiri and Auerbach, Scott S and Bao, Wenjun and Binder, Hans and Blomquist, Thomas and Brilliant, Murray H and Bushel, Pierre R and Cai, Weimin and Catalano, Jennifer G and Chang, Ching-Wei and Chen, Tao and Chen, Geng and Chen, Rong and Chierici, Marco and Chu, Tzu-Ming and Clevert, Djork-Arné and Deng, Youping and Derti, Adnan and Devanarayan, Viswanath and Dong, Zirui and Dopazo, Joaquin and Du, Tingting and Fang, Hong and Fang, Yongxiang and Fasold, Mario and Fernandez, Anita and Fischer, Matthias and Furió-Tari, Pedro and Fuscoe, James C and Caimet, Florian and Gaj, Stan and Gandara, Jorge and Gao, Huan and Ge, Weigong and Gondo, Yoichi and Gong, Binsheng and Gong, Meihua and Gong, Zhuolin and Green, Bridgett and Guo, Chao and Guo, Lei and Guo, Li-Wu and Hadfield, James and Hellemans, Jan and Hochreiter, Sepp and Jia, Meiwen and Jian, Min and Johnson, Charles D and Kay, Suzanne and Kleinjans, Jos and Lababidi, Samir and Levy, Shawn and Li, Quan-Zhen and Li, Li and Li, Li and Li, Peng and Li, Yan and Li, Haiqing and Li, Jianying and Li, Shiyong and Lin, Simon M and López, Francisco J and Lu, Xin and Luo, Heng and Ma, Xiwen and Meehan, Joseph and Megherbi, Dalila B and Mei, Nan and Mu, Bing and Ning, Baitang and Pandey, Akhilesh and Pérez-Florido, Javier and Perkins, Roger G and Peters, Ryan and Phan, John H and Pirooznia, Mehdi and Qian, Feng and Qing, Tao and Rainbow, Lucille and Rocca-Serra, Philippe and Sambourg, Laure and Sansone, Susanna-Assunta and Schwartz, Scott and Shah, Ruchir and Shen, Jie and Smith, Todd M and Stegle, Oliver and Stralis-Pavese, Nancy and Stupka, Elia and Suzuki, Yutaka and Szkotnicki, Lee T and Tinning, Matthew and Tu, Bimeng and van Delft, Joost and Vela-Boza, Alicia and Venturini, Elisa and Walker, Stephen J and Wan, Liqing and Wang, Wei and Wang, Jinhui and Wang, Jun and Wieben, Eric D and Willey, James C and Wu, Po-Yen and Xuan, Jiekun and Yang, Yong and Ye, Zhan and Yin, Ye and Yu, Ying and Yuan, Yate-Ching and Zhang, John and Zhang, Ke K and Zhang, Wenqian and Zhang, Wenwei and Zhang, Yanyan and Zhao, Chen and Zheng, Yuanting and Zhou, Yiming and Zumbo, Paul and Tong, Weida and Kreil, David P and Mason, Christopher E and Shi, Leming},
	date = {2014-08}
}

@article{li_detecting_2014,
	title = {Detecting and correcting systematic variation in large-scale {RNA} sequencing data},
	volume = {32},
	issn = {1087-0156},
	url = {http://www.nature.com/doifinder/10.1038/nbt.3000},
	doi = {10.1038/nbt.3000},
	pages = {888--895},
	number = {9},
	journaltitle = {Nature Biotechnology},
	author = {Li, Sheng and \{{\textbackslash}textbackslash\}Labaj, Pawe\{{\textbackslash}textbackslash\}l P and Zumbo, Paul and Sykacek, Peter and Shi, Wei and Shi, Leming and Phan, John and Wu, Po-Yen and Wang, May and Wang, Charles and Thierry-Mieg, Danielle and Thierry-Mieg, Jean and Kreil, David P and Mason, Christopher E},
	date = {2014-08}
}

@article{li_multi-platform_2014,
	title = {Multi-platform assessment of transcriptome profiling using {RNA}-seq in the {ABRF} next-generation sequencing study},
	volume = {32},
	issn = {1087-0156},
	url = {http://www.nature.com/doifinder/10.1038/nbt.2972},
	doi = {10.1038/nbt.2972},
	pages = {915--925},
	number = {9},
	journaltitle = {Nature Biotechnology},
	author = {Li, Sheng and Tighe, Scott W and Nicolet, Charles M and Grove, Deborah and Levy, Shawn and Farmerie, William and Viale, Agnes and Wright, Chris and Schweitzer, Peter A and Gao, Yuan and Kim, Dewey and Boland, Joe and Hicks, Belynda and Kim, Ryan and Chhangawala, Sagar and Jafari, Nadereh and Raghavachari, Nalini and Gandara, Jorge and Garcia-Reyero, Natàlia and Hendrickson, Cynthia and Roberson, David and Rosenfeld, Jeffrey and Smith, Todd and Underwood, Jason G and Wang, May and Zumbo, Paul and Baldwin, Don A and Grills, George S and Mason, Christopher E},
	date = {2014-08},
	keywords = {Transcriptome, Gene Expression Profiling, High-Throughput Nucleotide Sequencing},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/V3EDE47F/Li et al. - 2014 - Multi-platform assessment of transcriptome profili.pdf:application/pdf}
}

@article{andersson_nuclear_2014,
	title = {Nuclear stability and transcriptional directionality separate functionally distinct {RNA} species},
	volume = {5},
	issn = {2041-1723},
	url = {http://www.nature.com/doifinder/10.1038/ncomms6336},
	doi = {10.1038/ncomms6336},
	pages = {5336},
	journaltitle = {Nature Communications},
	author = {Andersson, Robin and Refsing Andersen, Peter and Valen, Eivind and Core, Leighton J. and Bornholdt, Jette and Boyd, Mette and Heick Jensen, Torben and Sandelin, Albin},
	date = {2014-11},
	file = {Attachment:/home/jlagarde/Zotero/storage/9BFASLZX/Andersson et al. - 2014 - Nuclear stability and transcriptional directionality separate functionally distinct RNA species.pdf:application/pdf}
}

@article{jiang_synthetic_2011,
	title = {Synthetic spike-in standards for {RNA}-seq experiments.},
	volume = {21},
	issn = {1549-5469},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21816910 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3166838},
	doi = {10.1101/gr.121095.111},
	abstract = {High-throughput sequencing of {cDNA} ({RNA}-seq) is a widely deployed transcriptome profiling and annotation technique, but questions about the performance of different protocols and platforms remain. We used a newly developed pool of 96 synthetic {RNAs} with various lengths, and {GC} content covering a 2(20) concentration range as spike-in controls to measure sensitivity, accuracy, and biases in {RNA}-seq experiments as well as to derive standard curves for quantifying the abundance of transcripts. We observed linearity between read density and {RNA} input over the entire detection range and excellent agreement between replicates, but we observed significantly larger imprecision than expected under pure Poisson sampling errors. We use the control {RNAs} to directly measure reproducible protocol-dependent biases due to {GC} content and transcript length as well as stereotypic heterogeneity in coverage across transcripts correlated with position relative to {RNA} termini and priming sequence bias. These effects lead to biased quantification for short transcripts and individual exons, which is a serious problem for measurements of isoform abundances, but that can partially be corrected using appropriate models of bias. By using the control {RNAs}, we derive limits for the discovery and detection of rare transcripts in {RNA}-seq experiments. By using data collected as part of the model organism and human Encyclopedia of {DNA} Elements projects ({ENCODE} and {modENCODE}), we demonstrate that external {RNA} controls are a useful resource for evaluating sensitivity and accuracy of {RNA}-seq experiments for transcriptome discovery and quantification. These quality metrics facilitate comparable analysis across different samples, protocols, and platforms.},
	pages = {1543--51},
	number = {9},
	journaltitle = {Genome research},
	author = {Jiang, Lichun and Schlesinger, Felix and Davis, Carrie A and Zhang, Yu and Li, Renhua and Salit, Marc and Gingeras, Thomas R and Oliver, Brian},
	date = {2011-09},
	pmid = {21816910},
	keywords = {Animals, Humans, {RNA}, Gene Expression Profiling, Reproducibility of Results, Gene Library, High-Throughput Nucleotide Sequencing, Quality Control, Sensitivity and Specificity, Sequence Analysis, {RNA}, Bias},
	file = {Attachment:/home/jlagarde/Zotero/storage/BSBG2WLE/Jiang et al. - 2011 - Synthetic spike-in standards for RNA-seq experiments.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/MM8L6TIK/Jiang et al. - 2011 - Synthetic spike-in standards for RNA-seq experimen.pdf:application/pdf}
}

@article{li_modeling_2010,
	title = {Modeling non-uniformity in short-read rates in {RNA}-Seq data},
	volume = {11},
	issn = {1465-6906},
	url = {http://genomebiology.biomedcentral.com/articles/10.1186/gb-2010-11-5-r50},
	doi = {10.1186/gb-2010-11-5-r50},
	pages = {R50},
	number = {5},
	journaltitle = {Genome Biology},
	author = {Li, Jun and Jiang, Hui and Wong, Wing},
	date = {2010}
}

@article{tardaguila_sqanti:_2017,
	title = {{SQANTI}: extensive characterization of long read transcript sequences for quality control in full-length transcriptome identification and quantification},
	url = {http://biorxiv.org/content/early/2017/03/18/118083},
	journaltitle = {{bioRxiv}},
	author = {Tardaguila, Manuel and de la Fuente, Lorena and Marti, Cristina and Pereira, Cecile and del Risco, Hector and Ferrell, Marc and Mellado, Maravillas and Macchietto, Marissa and Verheggen, Kenneth and Edelmann, Mariola and Ezkurdia, Iakes and Vazquez, Jesus and Tress, Michael and Mortazavi, Ali and Martens, Lennart and Rodriguez-Navarro, Susana and Moreno, Victoria and Conesa, Ana},
	date = {2017}
}

@article{lejeune_mechanistic_2005,
	title = {Mechanistic links between nonsense-mediated {mRNA} decay and pre-{mRNA} splicing in mammalian cells},
	volume = {17},
	issn = {09550674},
	url = {http://linkinghub.elsevier.com/retrieve/pii/S0955067405000426},
	doi = {10.1016/j.ceb.2005.03.002},
	pages = {309--315},
	number = {3},
	journaltitle = {Current Opinion in Cell Biology},
	author = {Lejeune, Fabrice and Maquat, Lynne E},
	date = {2005-06}
}

@article{hon_atlas_2017,
	title = {An atlas of human long non-coding {RNAs} with accurate 5' ends},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature21374},
	doi = {10.1038/nature21374},
	journaltitle = {Nature},
	author = {Hon, Chung-Chau and Ramilowski, Jordan A. and Harshbarger, Jayson and Bertin, Nicolas and Rackham, Owen J. L. and Gough, Julian and Denisenko, Elena and Schmeier, Sebastian and Poulsen, Thomas M. and Severin, Jessica and Lizio, Marina and Kawaji, Hideya and Kasukawa, Takeya and Itoh, Masayoshi and Burroughs, A. Maxwell and Noma, Shohei and Djebali, Sarah and Alam, Tanvir and Medvedeva, Yulia A. and Testa, Alison C. and Lipovich, Leonard and Yip, Chi-Wai and Abugessaisa, Imad and Mendez, Mickaël and Hasegawa, Akira and Tang, Dave and Lassmann, Timo and Heutink, Peter and Babina, Magda and Wells, Christine A. and Kojima, Soichi and Nakamura, Yukio and Suzuki, Harukazu and Daub, Carsten O. and de Hoon, Michiel J. L. and Arner, Erik and Hayashizaki, Yoshihide and Carninci, Piero and Forrest, Alistair R. R.},
	date = {2017-03}
}

@article{koonin_splendor_2016,
	title = {Splendor and misery of adaptation, or the importance of neutral null for understanding evolution},
	volume = {14},
	issn = {1741-7007},
	url = {http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0338-2},
	doi = {10.1186/s12915-016-0338-2},
	abstract = {The study of any biological features, including genomic sequences, typically revolves around the question: what is this for? However, population genetic theory, combined with the data of comparative genomics, clearly indicates that such a “pan-adaptationist” approach is a fallacy. The proper question is: how has this sequence evolved? And the proper null hypothesis posits that it is a result of neutral evolution: that is, it survives by sheer chance provided that it is not deleterious enough to be efficiently purged by purifying selection. To claim adaptation, the neutral null has to be falsified. The adaptationist fallacy can be costly, inducing biologists to relentlessly seek function where there is none.},
	pages = {114},
	number = {1},
	journaltitle = {{BMC} Biology},
	author = {Koonin, Eugene V.},
	date = {2016-12},
	keywords = {general, Life Sciences},
	file = {Attachment:/home/jlagarde/Zotero/storage/JKJFDCCZ/Koonin - 2016 - Splendor and misery of adaptation, or the importance of neutral null for understanding evolution.pdf:application/pdf}
}

@article{akerman_human_2017,
	title = {Human Pancreatic β Cell {lncRNAs} Control Cell-Specific Regulatory Networks},
	volume = {25},
	issn = {15504131},
	url = {http://linkinghub.elsevier.com/retrieve/pii/S1550413116305952},
	doi = {10.1016/j.cmet.2016.11.016},
	pages = {400--411},
	number = {2},
	journaltitle = {Cell Metabolism},
	author = {Akerman, Ildem and Tu, Zhidong and Beucher, Anthony and Rolando, Delphine M.Y. and Sauty-Colace, Claire and Benazra, Marion and Nakic, Nikolina and Yang, Jialiang and Wang, Huan and Pasquali, Lorenzo and Moran, Ignasi and Garcia-Hurtado, Javier and Castro, Natalia and Gonzalez-Franco, Roser and Stewart, Andrew F. and Bonner, Caroline and Piemonti, Lorenzo and Berney, Thierry and Groop, Leif and Kerr-Conte, Julie and Pattou, Francois and Argmann, Carmen and Schadt, Eric and Ravassard, Philippe and Ferrer, Jorge},
	date = {2017-02}
}

@article{pertea_transcript-level_2016,
	title = {Transcript-level expression analysis of {RNA}-seq experiments with {HISAT}, {StringTie} and Ballgown},
	volume = {11},
	issn = {1754-2189},
	url = {http://www.nature.com/doifinder/10.1038/nprot.2016.095},
	doi = {10.1038/nprot.2016.095},
	pages = {1650--1667},
	number = {9},
	journaltitle = {Nature Protocols},
	author = {Pertea, Mihaela and Kim, Daehwan and Pertea, Geo M and Leek, Jeffrey T and Salzberg, Steven L},
	date = {2016-08}
}

@article{bonfert_prediction_2017,
	title = {Prediction of Poly(A) Sites by Poly(A) Read Mapping},
	volume = {12},
	issn = {1932-6203},
	url = {http://dx.plos.org/10.1371/journal.pone.0170914},
	doi = {10.1371/journal.pone.0170914},
	pages = {e0170914},
	number = {1},
	journaltitle = {{PLOS} {ONE}},
	author = {Bonfert, Thomas and Friedel, Caroline C. and Giammartino, {DC} Di and Nishida, K and Manley, {JL} and Sandberg, R and Neilson, {JR} and Sarma, A and Sharp, {PA} and Burge, {CB} and Mayr, C and Bartel, {DP} and Zhang, H and Lee, {JY} and Tian, B and Smibert, P and Miura, P and Westholm, {JO} and Shenker, S and May, G and Duff, {MO} and Ji, Z and Lee, {JY} and Pan, Z and Jiang, B and Tian, B and Ulitsky, I and Shkumatava, A and Jan, {CH} and Subtelny, {AO} and Koppstein, D and Bell, {GW} and Hilgers, V and Perry, {MW} and Hendrix, D and Stark, A and Levine, M and Haley, B and Nagalakshmi, U and Wang, Z and Waern, K and Shou, C and Raha, D and Gerstein, M and Pickrell, {JK} and Marioni, {JC} and Pai, {AA} and Degner, {JF} and Engelhardt, {BE} and Nkadori, E and Djebali, S and Davis, {CA} and Merkel, A and Dobin, A and Lassmann, T and Mortazavi, A and Marioni, {JC} and Mason, {CE} and Mane, {SM} and Stephens, M and Gilad, Y and Anders, S and Huber, W and Mortazavi, A and Williams, {BA} and {McCue}, K and Schaeffer, L and Wold, B and Trapnell, C and Williams, {BA} and Pertea, G and Mortazavi, A and Kwan, G and van Baren, {MJ} and Shepard, {PJ} and Choi, {EA} and Lu, J and Flanagan, {LA} and Hertel, {KJ} and Shi, Y and Derti, A and Garrett-Engele, P and Macisaac, {KD} and Stevens, {RC} and Sriram, S and Chen, R and Wilkening, S and Pelechano, V and Jarvelin, {AI} and Tekkedil, {MM} and Anders, S and Benes, V and Shi, Y and Elkon, R and Ugalde, {AP} and Agami, R and Ozsolak, F and Kapranov, P and Foissac, S and Kim, {SW} and Fishilevich, E and Monaghan, {AP} and Haenni, S and Ji, Z and Hoque, M and Rust, N and Sharpe, H and Eberhard, R and Hoque, M and Ji, Z and Zheng, D and Luo, W and Li, W and You, B and Stern-Ginossar, N and Weisburd, B and Michalski, A and Le, {VT} and Hein, {MY} and Huang, {SX} and Arias, C and Weisburd, B and Stern-Ginossar, N and Mercier, A and Madrid, {AS} and Bellare, P and Canny, {SP} and Reese, {TA} and Johnson, {LS} and Zhang, X and Kambal, A and Duan, E and Rutkowski, {AJ} and Erhard, F and L'Hernault, A and Bonfert, T and Schilhabel, M and Crump, C and Bonfert, T and Kirner, E and Csaba, G and Zimmer, R and Friedel, {CC} and Ng, P and Wei, {CL} and Sung, {WK} and Chiu, {KP} and Lipovich, L and Ang, {CC} and Birol, I and Raymond, A and Chiu, R and Nip, {KM} and Jackman, {SD} and Kreitzman, M and Beaudoing, E and Freier, S and Wyatt, {JR} and Claverie, {JM} and Gautheret, D and Fu, Y and Sun, Y and Li, Y and Li, J and Rao, X and Chen, C and Langmead, B and Trapnell, C and Pop, M and Salzberg, {SL} and Langmead, B and Salzberg, {SL} and Li, H and Durbin, R and Robertson, G and Schein, J and Chiu, R and Corbett, R and Field, M and Jackman, {SD} and Pauws, E and van Kampen, A and van de Graaf, S and de Vijlder, J and Ris-Stalpers, C and Liao, Y and Smyth, {GK} and Shi, W and Yates, A and Akanni, W and Amode, {MR} and Barrell, D and Billis, K and Carvalho-Silva, D and Graber, J and Cantor, C and Mohr, S and Smith, T and Proudfoot, {NJ} and Mignone, F and Pesole, G and Lindner, R and Friedel, {CC} and Boehmer, P and Lehman, I and Roizman, B and Knipe, {DM} and Wang, {QY} and Zhou, C and Johnson, {KE} and Colgrove, {RC} and Coen, {DM} and Knipe, {DM} and Xia, Z and Donehower, {LA} and Cooper, {TA} and Neilson, {JR} and Wheeler, {DA} and Wagner, {EJ}},
	editor = {Tian, Bin},
	date = {2017-01},
	file = {Attachment:/home/jlagarde/Zotero/storage/F3A75W5D/Bonfert et al. - 2017 - Prediction of Poly(A) Sites by Poly(A) Read Mapping.pdf:application/pdf}
}

@article{iyer_landscape_2015,
	title = {The landscape of long noncoding {RNAs} in the human transcriptome},
	volume = {47},
	issn = {1061-4036},
	url = {http://www.nature.com/doifinder/10.1038/ng.3192},
	doi = {10.1038/ng.3192},
	pages = {199--208},
	number = {3},
	journaltitle = {Nature Genetics},
	author = {Iyer, Matthew K and Niknafs, Yashar S and Malik, Rohit and Singhal, Udit and Sahu, Anirban and Hosono, Yasuyuki and Barrette, Terrence R and Prensner, John R and Evans, Joseph R and Zhao, Shuang and Poliakov, Anton and Cao, Xuhong and Dhanasekaran, Saravana M and Wu, Yi-Mi and Robinson, Dan R and Beer, David G and Feng, Felix Y and Iyer, Hariharan K and Chinnaiyan, Arul M},
	date = {2015-01}
}

@article{bornelov_different_2015,
	title = {Different distribution of histone modifications in genes with unidirectional and bidirectional transcription and a role of {CTCF} and cohesin in directing transcription},
	volume = {16},
	issn = {1471-2164},
	url = {http://www.biomedcentral.com/1471-2164/16/300},
	doi = {10.1186/s12864-015-1485-5},
	abstract = {Several post-translational histone modifications are mainly found in gene promoters and are associated with the promoter activity. It has been hypothesized that histone modifications regulate the transcription, as opposed to the traditional view with transcription factors as the key regulators. Promoters of most active genes do not only initiate transcription of the coding sequence, but also a substantial amount of transcription of the antisense strand upstream of the transcription start site ({TSS}). This promoter feature has generally not been considered in previous studies of histone modifications and transcription factor binding. We annotated protein-coding genes as bi- or unidirectional depending on their mode of transcription and compared histone modifications and transcription factor occurrences between them. We found that H3K4me3, H3K9ac, and H3K27ac were significantly more enriched upstream of the {TSS} in bidirectional genes compared with the unidirectional ones. In contrast, the downstream histone modification signals were similar, suggesting that the upstream histone modifications might be a consequence of transcription rather than a cause. Notably, we found well-positioned {CTCF} and {RAD}21 peaks approximately 60-80 bp upstream of the {TSS} in the unidirectional genes. The peak heights were related to the amount of antisense transcription and we hypothesized that {CTCF} and cohesin act as a barrier against antisense transcription. Our results provide insights into the distribution of histone modifications at promoters and suggest a novel role of {CTCF} and cohesin as regulators of transcriptional direction.},
	pages = {300},
	number = {1},
	journaltitle = {{BMC} Genomics},
	author = {Bornelöv, Susanne and Komorowski, Jan and Wadelius, Claes and Barski, A and Cuddapah, S and Cui, K and Roh, {TY} and Schones, {DE} and Wang, Z and Koch, {CM} and Andrews, {RM} and Flicek, P and Dillon, {SC} and Karaoz, U and Clelland, {GK} and Jenuwein, T and Allis, {CD} and Henikoff, S and Shilatifard, A and Kasowski, M and Kyriazopoulou-Panagiotopoulou, S and Grubert, F and Zaugg, {JB} and Kundaje, A and Liu, Y and {McVicker}, G and Geijn, B and Degner, {JF} and Cain, {CE} and Banovich, {NE} and Raj, A and Orphanides, G and Reinberg, D and Seila, {AC} and Calabrese, {JM} and Levine, {SS} and Yeo, {GW} and Rahl, {PB} and Flynn, {RA} and Core, {LJ} and Waterfall, {JJ} and Lis, {JT} and Wu, X and Sharp, {PA} and Trinklein, {ND} and Aldred, {SF} and Hartman, {SJ} and Schroeder, {DI} and Otillar, {RP} and Myers, {RM} and Adachi, N and Lieber, {MR} and Rada-Iglesias, A and Ameur, A and Kapranov, P and Enroth, S and Komorowski, J and Gingeras, {TR} and Cuddapah, S and Jothi, R and Schones, {DE} and Roh, {TY} and Cui, K and Zhao, K and Yan, J and Enge, M and Whitington, T and Dave, K and Liu, J and Sur, I and Wendt, {KS} and Yoshida, K and Itoh, T and Bando, M and Koch, B and Schirghuber, E and Ong, {CT} and Corces, {VG} and Hubbard, {TJ} and Aken, {BL} and Ayling, S and Ballester, B and Beal, K and Bragin, E and Derrien, T and Johnson, R and Bussotti, G and Tanzer, A and Djebali, S and Tilgner, H and Bernstein, {BE} and Birney, E and Dunham, I and Green, {ED} and Gunter, C and Li, G and Ruan, X and Auerbach, {RK} and Sandhu, {KS} and Zheng, M and Wang, P and Heintzman, {ND} and Stuart, {RK} and Hon, G and Fu, Y and Ching, {CW} and Hawkins, {RD} and Vermeulen, M and Mulder, {KW} and Denissov, S and Pijnappel, {WW} and Schaik, {FM} and Varier, {RA} and Yamaguchi, Y and Takagi, T and Wada, T and Yano, K and Furuya, A and Sugimoto, S and Zhou, Q and Li, T and Price, {DH} and Seila, {AC} and Core, {LJ} and Lis, {JT} and Sharp, {PA} and Wada, Y and Shukla, S and Kavak, E and Gregory, M and Imashimizu, M and Shutinoski, B and Kashlev, M and Nitzsche, A and Paszkowski-Rogacz, M and Matarese, F and Janssen-Megens, {EM} and Hubner, {NC} and Schulz, H and Tolstorukov, {MY} and Kharchenko, {PV} and Goldman, {JA} and Kingston, {RE} and Park, {PJ} and Hu, {GQ} and Cui, {KR} and Northrup, D and Liu, {CY} and Wang, {CC} and Tang, {QS} and Mavrich, {TN} and Jiang, {CZ} and Ioshikhes, {IP} and Li, {XY} and Venters, {BJ} and Zanton, {SJ} and Zilberman, D and Coleman-Derr, D and Ballinger, T and Henikoff, S and Lengronne, A and Katou, Y and Mori, S and Yokobayashi, S and Kelly, {GP} and Itoh, T and Wada, Y and Ohta, Y and Xu, M and Tsutsumi, S and Minami, T and Inoue, K and Motallebipour, M and Ameur, A and Bysani, {MS} Reddy and Patra, K and Wallerman, O and Mangion, J and Suzuki, H and Forrest, {AR} and Nimwegen, E and Daub, {CO} and Balwierz, {PJ} and Enroth, S and Andersson, R and Wadelius, C and Komorowski, J and Hinrichs, {AS} and Karolchik, D and Baertsch, R and Barber, {GP} and Bejerano, G and Clawson, H and Mathelier, A and Zhao, X and Zhang, {AW} and Parcy, F and Worsley-Hunt, R and Arenillas, {DJ} and Grant, {CE} and Bailey, {TL} and Noble, {WS} and Ye, T and Krebs, {AR} and Choukrallah, {MA} and Keime, C and Plewniak, F and Davidson, I},
	date = {2015-12},
	keywords = {Animal Genetics and Genomics, Microbial Genetics and Genomics, general, Proteomics, Life Sciences, Microarrays, Plant Genetics \& Genomics}
}

@article{sati_genome-wide_2012,
	title = {Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding {RNA} loci.},
	volume = {40},
	issn = {1362-4962},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22923516 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3488231},
	doi = {10.1093/nar/gks776},
	abstract = {A major fraction of the transcriptome of higher organisms comprised an extensive repertoire of long non-coding {RNA} ({lncRNA}) which express in a cell type and development stage-specific manner. While {lncRNAs} are a proven component of epigenetic gene expression modulation, epigenetic regulation of {lncRNA} itself remains poorly understood. Here we have analysed pan-genomic {DNA} methylation and histone modification marks (H3K4me3, H3K9me3, H3K27me3 and H3K36me3) associated with transcription start site ({TSS}) of {lncRNA} in four different cell types and three different tissue types representing various cellular stages. We observe that histone marks associated with active transcription H3K4me3 and H3K36me3 along with the repressive histone mark H3K27me3 have similar distribution pattern around {TSS} irrespective of cell types. Also, the density of these marks correlates well with expression of protein-coding and {lncRNA} genes. In contrast, the {lncRNA} genes harbour higher methylation density around {TSS} than protein-coding genes regardless of their expression status. Furthermore, we found that {DNA} methylation along with the other repressive histone mark H3K9me3 does not seem to play a role in {lncRNA} expression. Thus, our observation suggests that epigenetic regulation of {lncRNA} shares common features with {mRNA} except the role of {DNA} methylation which is markedly dissimilar.},
	pages = {10018--31},
	number = {20},
	journaltitle = {Nucleic acids research},
	author = {Sati, Satish and Ghosh, Sourav and Jain, Vaibhav and Scaria, Vinod and Sengupta, Shantanu},
	date = {2012-11},
	pmid = {22923516},
	file = {Attachment:/home/jlagarde/Zotero/storage/QQNCJHBL/Sati et al. - 2012 - Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA loci.pdf:application/pdf}
}

@article{barth_fast_2010,
	title = {Fast signals and slow marks: the dynamics of histone modifications},
	volume = {35},
	issn = {09680004},
	url = {http://linkinghub.elsevier.com/retrieve/pii/S0968000410000940},
	doi = {10.1016/j.tibs.2010.05.006},
	pages = {618--626},
	number = {11},
	journaltitle = {Trends in Biochemical Sciences},
	author = {Barth, Teresa K. and Imhof, Axel},
	date = {2010-11},
	file = {Attachment:/home/jlagarde/Zotero/storage/JT8832WQ/Barth, Imhof - 2010 - Fast signals and slow marks the dynamics of histone modifications.pdf:application/pdf}
}

@article{mele_chromatin_2016,
	title = {Chromatin environment, transcriptional regulation, and splicing distinguish {lincRNAs} and {mRNAs}.},
	issn = {1549-5469},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27927715},
	doi = {10.1101/gr.214205.116},
	abstract = {While long intergenic noncoding {RNAs} ({lincRNAs}) and {mRNAs} share similar biogenesis pathways, these transcript classes differ in many regards. {LincRNAs} are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre- and post-transcriptional regulation is different from that of {mRNAs}. Here, we perform an in-depth characterization of the features that contribute to {lincRNA} regulation in multiple human cell lines. We find that {lincRNA} promoters are depleted of transcription factor ({TF}) binding sites, yet enriched for some specific factors such as {GATA} and {FOS} relative to {mRNA} promoters. Surprisingly, we find that H3K9me3-a histone modification typically associated with transcriptional repression-is more enriched at the promoters of active {lincRNA} loci than at those of active {mRNAs}. Moreover, H3K9me3-marked {lincRNA} genes are more tissue-specific. The most discriminant differences between {lincRNAs} and {mRNAs} involve splicing. {LincRNAs} are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers but may be partially attributed to lower U2AF65 binding and weaker splicing-related motifs. Conversely, the stability of {lincRNAs} and {mRNAs} is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both {DNA} and {RNA} motifs and are enriched in {lincRNAs} that have been functionally characterized.},
	journaltitle = {Genome research},
	author = {Melé, Marta and Mattioli, Kaia and Mallard, William and Shechner, David M and Gerhardinger, Chiara and Rinn, John L},
	date = {2016-12},
	pmid = {27927715}
}

@article{core_nascent_2008,
	title = {Nascent {RNA} Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters},
	volume = {322},
	number = {5909},
	journaltitle = {Science},
	author = {Core, Leighton J. and Waterfall, Joshua J. and Lis, John T.},
	date = {2008}
}

@article{seila_divergent_2008,
	title = {Divergent Transcription from Active Promoters},
	volume = {322},
	number = {5909},
	journaltitle = {Science},
	author = {Seila, Amy C. and Calabrese, J. Mauro and Levine, Stuart S. and Yeo, Gene W. and Rahl, Peter B. and Flynn, Ryan A. and Young, Richard A. and Sharp, Phillip A.},
	date = {2008}
}

@article{engreitz_local_2016,
	title = {Local regulation of gene expression by {lncRNA} promoters, transcription and splicing},
	volume = {539},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature20149},
	doi = {10.1038/nature20149},
	pages = {452--455},
	number = {7629},
	journaltitle = {Nature},
	author = {Engreitz, Jesse M. and Haines, Jenna E. and Perez, Elizabeth M. and Munson, Glen and Chen, Jenny and Kane, Michael and {McDonel}, Patrick E. and Guttman, Mitchell and Lander, Eric S.},
	date = {2016-10},
	keywords = {Genomics, Animals, Conserved Sequence, Mice, {RNA} Splicing, Gene Expression Regulation, {RNA} Splice Sites, Cell Line, Female, Genes, Genetic Loci, Male, Evolution, Molecular, {RNA}, Long Noncoding, {RNA}, Messenger, Transcription, Genetic, Promoter Regions, Genetic, Mouse Embryonic Stem Cells},
	file = {Attachment:/home/jlagarde/Zotero/storage/M7EZZJED/Engreitz et al. - 2016 - Local regulation of gene expression by lncRNA promoters, transcription and splicing.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/IVQPIYLH/Engreitz et al. - 2016 - Local regulation of gene expression by lncRNA prom.pdf:application/pdf}
}

@article{fulco_systematic_2016,
	title = {Systematic mapping of functional enhancer-promoter connections with {CRISPR} interference},
	volume = {354},
	issn = {0036-8075},
	url = {http://www.sciencemag.org/cgi/doi/10.1126/science.aag2445},
	doi = {10.1126/science.aag2445},
	pages = {769--773},
	number = {6313},
	journaltitle = {Science},
	author = {Fulco, C. P. and Munschauer, M. and Anyoha, R. and Munson, G. and Grossman, S. R. and Perez, E. M. and Kane, M. and Cleary, B. and Lander, E. S. and Engreitz, J. M.},
	date = {2016-11}
}

@article{almada_promoter_2013,
	title = {Promoter directionality is controlled by U1 {snRNP} and polyadenylation signals},
	volume = {499},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature12349},
	doi = {10.1038/nature12349},
	pages = {360--363},
	number = {7458},
	journaltitle = {Nature},
	author = {Almada, Albert E. and Wu, Xuebing and Kriz, Andrea J. and Burge, Christopher B. and Sharp, Phillip A.},
	date = {2013-06},
	file = {Attachment:/home/jlagarde/Zotero/storage/JWTB4MEJ/Almada et al. - 2013 - Promoter directionality is controlled by U1 snRNP and polyadenylation signals.pdf:application/pdf}
}

@article{kim_architectural_2015,
	title = {Architectural and Functional Commonalities between Enhancers and Promoters.},
	volume = {162},
	issn = {1097-4172},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26317464 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4556168},
	doi = {10.1016/j.cell.2015.08.008},
	abstract = {With the explosion of genome-wide studies of regulated transcription, it has become clear that traditional definitions of enhancers and promoters need to be revisited. These control elements can now be characterized in terms of their local and regional architecture, their regulatory components, including histone modifications and associated binding factors, and their functional contribution to transcription. This Review discusses unifying themes between promoters and enhancers in transcriptional regulatory mechanisms.},
	pages = {948--59},
	number = {5},
	journaltitle = {Cell},
	author = {Kim, Tae-Kyung and Shiekhattar, Ramin and Adelman, K. and Lis, J.T. and Aerts, S. and Akbari, O.S. and Bae, E. and Johnsen, H. and Villaluz, A. and Wong, D. and Drewell, R.A. and Almada, A.E. and Wu, X. and Kriz, A.J. and Burge, C.B. and Sharp, P.A. and Andersson, R. and Gebhard, C. and Miguel-Escalada, I. and Hoof, I. and Bornholdt, J. and Boyd, M. and Chen, Y. and Zhao, X. and Schmidl, C. and Suzuki, T. and Consortium, {FANTOM} and Al, et and Arner, E. and Daub, C.O. and Vitting-Seerup, K. and Andersson, R. and Lilje, B. and Drabløs, F. and Lennartsson, A. and Rönnerblad, M. and Hrydziuszko, O. and Vitezic, M. and Consortium, {FANTOM} and Al, et and Ashe, H.L. and Monks, J. and Wijgerde, M. and Fraser, P. and Proudfoot, N.J. and Atchison, M.L. and Banerji, J. and Rusconi, S. and Schaffner, W. and Banerji, J. and Olson, L. and Schaffner, W. and Barrera, L.O. and Li, Z. and Smith, A.D. and Arden, K.C. and Cavenee, W.K. and Zhang, M.Q. and Green, R.D. and Ren, B. and Benoist, C. and Chambon, P. and Berg, M.G. and Singh, L.N. and Younis, I. and Liu, Q. and Pinto, A.M. and Kaida, D. and Zhang, Z. and Cho, S. and Sherrill-Mix, S. and Wan, L. and Dreyfuss, G. and Bernstein, B.E. and Mikkelsen, T.S. and Xie, X. and Kamal, M. and Huebert, D.J. and Cuff, J. and Fry, B. and Meissner, A. and Wernig, M. and Plath, K. and Al, et and Bienz, M. and Pelham, H.R. and Bohmann, D. and Keller, W. and Dale, T. and Schöler, H.R. and Tebb, G. and Mattaj, I.W. and Bonn, S. and Zinzen, R.P. and Girardot, C. and Gustafson, E.H. and Perez-Gonzalez, A. and Delhomme, N. and Ghavi-Helm, Y. and Wilczyński, B. and Riddell, A. and Furlong, E.E.M. and Boyle, A.P. and Davis, S. and Shulha, H.P. and Meltzer, P. and Margulies, E.H. and Weng, Z. and Furey, T.S. and Crawford, G.E. and Brodsky, A.S. and Meyer, C.A. and Swinburne, I.A. and Hall, G. and Keenan, B.J. and Liu, X.S. and Fox, E.A. and Silver, P.A. and Buenrostro, J.D. and Giresi, P.G. and Zaba, L.C. and Chang, H.Y. and Greenleaf, W.J. and Bulger, M. and Schübeler, D. and Bender, M.A. and Hamilton, J. and Farrell, C.M. and Hardison, R.C. and Groudine, M. and Carroll, J.S. and Meyer, C.A. and Song, J. and Li, W. and Geistlinger, T.R. and Eeckhoute, J. and Brodsky, A.S. and Keeton, E.K. and Fertuck, K.C. and Hall, G.F. and Al, et and Cho, H. and Orphanides, G. and Sun, X. and Yang, X.J. and Ogryzko, V. and Lees, E. and Nakatani, Y. and Reinberg, D. and Core, L.J. and Waterfall, J.J. and Lis, J.T. and Core, L.J. and Martins, A.L. and Danko, C.G. and Waters, C.T. and Siepel, A. and Lis, J.T. and Creyghton, M.P. and Cheng, A.W. and Welstead, G.G. and Kooistra, T. and Carey, B.W. and Steine, E.J. and Hanna, J. and Lodato, M.A. and Frampton, G.M. and Sharp, P.A. and Al, et and Santa, F. De and Barozzi, I. and Mietton, F. and Ghisletti, S. and Polletti, S. and Tusi, B.K. and Muller, H. and Ragoussis, J. and Wei, C.-L. and Natoli, G. and Derrien, T. and Johnson, R. and Bussotti, G. and Tanzer, A. and Djebali, S. and Tilgner, H. and Guernec, G. and Martin, D. and Merkel, A. and Knowles, D.G. and Al, et and Descostes, N. and Heidemann, M. and Spinelli, L. and Schüller, R. and Maqbool, M.A. and Fenouil, R. and Koch, F. and Innocenti, C. and Gut, M. and Gut, I. and Al, et and Djebali, S. and Davis, C.A. and Merkel, A. and Dobin, A. and Lassmann, T. and Mortazavi, A. and Tanzer, A. and Lagarde, J. and Lin, W. and Schlesinger, F. and Al, et and Duttke, S.H. and Lacadie, S.A. and Ibrahim, M.M. and Glass, C.K. and Corcoran, D.L. and Benner, C. and Heinz, S. and Kadonaga, J.T. and Ohler, U. and Birney, E. and Stamatoyannopoulos, J.A. and Dutta, A. and Guigo, R. and Gingeras, T.R. and Margulies, E.H. and Weng, Z. and Snyder, M. and Dermitzakis, E.T. and Consortium, {ENCODE} Project and Al, et and Consortium, {ENCODE} Project and Ernst, J. and Kheradpour, P. and Mikkelsen, T.S. and Shoresh, N. and Ward, L.D. and Epstein, C.B. and Zhang, X. and Wang, L. and Issner, R. and Coyne, M. and Al, et and Flynn, R.A. and Almada, A.E. and Zamudio, J.R. and Sharp, P.A. and Fromm, M. and Berg, P. and Fromm, M. and Berg, P. and Gerber, M. and Shilatifard, A. and Gillies, S.D. and Morrison, S.L. and Oi, V.T. and Tonegawa, S. and Giresi, P.G. and Kim, J. and {McDaniell}, R.M. and Iyer, V.R. and Lieb, J.D. and Goldberg, A.D. and Banaszynski, L.A. and Noh, K.M. and Lewis, P.W. and Elsaesser, S.J. and Stadler, S. and Dewell, S. and Law, M. and Guo, X. and Li, X. and Al, et and Gribnau, J. and Diderich, K. and Pruzina, S. and Calzolari, R. and Fraser, P. and Grosschedl, R. and Birnstiel, M.L. and Grosveld, F. and van Assendelft, G.B. and Greaves, D.R. and Kollias, G. and Guarente, L. and Hah, N. and Danko, C.G. and Core, L. and Waterfall, J.J. and Siepel, A. and Lis, J.T. and Kraus, W.L. and Hah, N. and Murakami, S. and Nagari, A. and Danko, C.G. and Kraus, W.L. and Hah, N. and Benner, C. and Chong, L.W. and Yu, R.T. and Downes, M. and Evans, R.M. and Harrow, J. and Frankish, A. and Gonzalez, J.M. and Tapanari, E. and Diekhans, M. and Kokocinski, F. and Aken, B.L. and Barrell, D. and Zadissa, A. and Searle, S. and Al, et and Heintzman, N.D. and Stuart, R.K. and Hon, G. and Fu, Y. and Ching, C.W. and Hawkins, R.D. and Barrera, L.O. and Calcar, S. Van and Qu, C. and Ching, K.A. and Al, et and Heintzman, N.D. and Hon, G.C. and Hawkins, R.D. and Kheradpour, P. and Stark, A. and Harp, L.F. and Ye, Z. and Lee, L.K. and Stuart, R.K. and Ching, C.W. and Al, et and Henikoff, S. and Henikoff, J.G. and Sakai, A. and Loeb, G.B. and Ahmad, K. and Hnisz, D. and Abraham, B.J. and Lee, T.I. and Lau, A. and Saint-André, V. and Sigova, A.A. and Hoke, H.A. and Young, R.A. and Hnisz, D. and Schuijers, J. and Lin, C.Y. and Weintraub, A.S. and Abraham, B.J. and Lee, T.I. and Bradner, J.E. and Young, R.A. and Ho, Y. and Elefant, F. and Liebhaber, S.A. and Cooke, N.E. and Hon, G. and Wang, W. and Ren, B. and Hsieh, C.L. and Fei, T. and Chen, Y. and Li, T. and Gao, Y. and Wang, X. and Sun, T. and Sweeney, C.J. and Lee, G.S. and Chen, S. and Al, et and Ilott, N.E. and Heward, J.A. and Roux, B. and Tsitsiou, E. and Fenwick, P.S. and Lenzi, L. and Goodhead, I. and Hertz-Fowler, C. and Heger, A. and Hall, N. and Al, et and Jin, C. and Zang, C. and Wei, G. and Cui, K. and Peng, W. and Zhao, K. and Felsenfeld, G. and Jin, Q. and Yu, L.R. and Wang, L. and Zhang, Z. and Kasper, L.H. and Lee, J.E. and Wang, C. and Brindle, P.K. and Dent, S.Y. and Ge, K. and Kagey, M.H. and Newman, J.J. and Bilodeau, S. and Zhan, Y. and Orlando, D.A. and van Berkum, N.L. and Ebmeier, C.C. and Goossens, J. and Rahl, P.B. and Levine, S.S. and Al, et and Kaida, D. and Berg, M.G. and Younis, I. and Kasim, M. and Singh, L.N. and Wan, L. and Dreyfuss, G. and Kaikkonen, M.U. and Spann, N.J. and Heinz, S. and Romanoski, C.E. and Allison, K.A. and Stender, J.D. and Chun, H.B. and Tough, D.F. and Prinjha, R.K. and Benner, C. and Glass, C.K. and Kellis, M. and Wold, B. and Snyder, M.P. and Bernstein, B.E. and Kundaje, A. and Marinov, G.K. and Ward, L.D. and Birney, E. and Crawford, G.E. and Dekker, J. and Al, et and Khoury, G. and Gruss, P. and Kim, T.K. and Hemberg, M. and Gray, J.M. and Costa, A.M. and Bear, D.M. and Wu, J. and Harmin, D.A. and Laptewicz, M. and Barbara-Haley, K. and Kuersten, S. and Al, et and Koch, F. and Fenouil, R. and Gut, M. and Cauchy, P. and Albert, T.K. and Zacarias-Cabeza, J. and Spicuglia, S. and de la Chapelle, A.L. and Heidemann, M. and Hintermair, C. and Al, et and Kohtz, J.D. and Kong, S. and Bohl, D. and Li, C. and Tuan, D. and Kowalczyk, M.S. and Hughes, J.R. and Garrick, D. and Lynch, M.D. and Sharpe, J.A. and Sloane-Stanley, J.A. and {McGowan}, S.J. and Gobbi, M. De and Hosseini, M. and Vernimmen, D. and Al, et and {LaCava}, J. and Houseley, J. and Saveanu, C. and Petfalski, E. and Thompson, E. and Jacquier, A. and Tollervey, D. and Lai, F. and Gardini, A. and Zhang, A. and Shiekhattar, R. and Lai, F. and Orom, U.A. and Cesaroni, M. and Beringer, M. and Taatjes, D.J. and Blobel, G.A. and Shiekhattar, R. and Lam, M.T. and Cho, H. and Lesch, H.P. and Gosselin, D. and Heinz, S. and Tanaka-Oishi, Y. and Benner, C. and Kaikkonen, M.U. and Kim, A.S. and Kosaka, M. and Al, et and Lam, M.T. and Li, W. and Rosenfeld, M.G. and Glass, C.K. and Levings, P.P. and Zhou, Z. and Vieira, K.F. and Crusselle-Davis, V.J. and Bungert, J. and Li, G. and Ruan, X. and Auerbach, R.K. and Sandhu, K.S. and Zheng, M. and Wang, P. and Poh, H.M. and Goh, Y. and Lim, J. and Zhang, J. and Al, et and Li, W. and Notani, D. and Ma, Q. and Tanasa, B. and Nunez, E. and Chen, A.Y. and Merkurjev, D. and Zhang, J. and Ohgi, K. and Song, X. and Al, et and Ling, J. and Ainol, L. and Zhang, L. and Yu, X. and Pi, W. and Tuan, D. and Ling, J. and Baibakov, B. and Pi, W. and Emerson, B.M. and Tuan, D. and Lovén, J. and Hoke, H.A. and Lin, C.Y. and Lau, A. and Orlando, D.A. and Vakoc, C.R. and Bradner, J.E. and Lee, T.I. and Young, R.A. and Maniatis, T. and Goodbourn, S. and Fischer, J.A. and Masternak, K. and Peyraud, N. and Krawczyk, M. and Barras, E. and Reith, W. and May, D. and Blow, M.J. and Kaplan, T. and {McCulley}, D.J. and Jensen, B.C. and Akiyama, J.A. and Holt, A. and Plajzer-Frick, I. and Shoukry, M. and Wright, C. and Al, et and Mayer, A. and di Iulio, J. and Maleri, S. and Eser, U. and Vierstra, J. and Reynolds, A. and Sandstrom, R. and Stamatoyannopoulos, J.A. and Churchman, L.S. and Melo, C.A. and Drost, J. and Wijchers, P.J. and van de Werken, H. and de Wit, E. and Vrielink, J.A.F.O. and Elkon, R. and Melo, S.A. and Léveillé, N. and Kalluri, R. and Al, et and Montavon, T. and Soshnikova, N. and Mascrez, B. and Joye, E. and Thevenet, L. and Splinter, E. and Laat, W. De and Spitz, F. and Duboule, D. and Moreau, P. and Hen, R. and Wasylyk, B. and Everett, R. and Gaub, M.P. and Chambon, P. and Mousavi, K. and Zare, H. and Dell'orso, S. and Grontved, L. and Gutierrez-Cruz, G. and Derfoul, A. and Hager, G.L. and Sartorelli, V. and Müller, M.M. and Gerster, T. and Schaffner, W. and Natoli, G. and Andrau, J.-C. and Neuberger, M.S. and Nowak, S.J. and Corces, V.G. and Ntini, E. and Järvelin, A.I. and Bornholdt, J. and Chen, Y. and Boyd, M. and Jørgensen, M. and Andersson, R. and Hoof, I. and Schein, A. and Andersen, P.R. and Al, et and Orkin, S.H. and Ørom, U.A. and Derrien, T. and Beringer, M. and Gumireddy, K. and Gardini, A. and Bussotti, G. and Lai, F. and Zytnicki, M. and Notredame, C. and Huang, Q. and Al, et and Parslow, T.G. and Jones, S.D. and Bond, B. and Yamamoto, K.R. and Pekowska, A. and Benoukraf, T. and Zacarias-Cabeza, J. and Belhocine, M. and Koch, F. and Holota, H. and Imbert, J. and Andrau, J.-C. and Ferrier, P. and Spicuglia, S. and Preker, P. and Nielsen, J. and Kammler, S. and Lykke-Andersen, S. and Christensen, M.S. and Mapendano, C.K. and Schierup, M.H. and Jensen, T.H. and Rada-Iglesias, A. and Bajpai, R. and Swigut, T. and Brugmann, S.A. and Flynn, R.A. and Wysocka, J. and Routledge, S.J. and Proudfoot, N.J. and Sanyal, A. and Lajoie, B.R. and Jain, G. and Dekker, J. and Schaukowitch, K. and Joo, J.Y. and Liu, X. and Watts, J.K. and Martinez, C. and Kim, T.K. and Scruggs, B.S. and Gilchrist, D.A. and Nechaev, S. and Muse, G.W. and Burkholder, A. and Fargo, D.C. and Adelman, K. and Seila, A.C. and Calabrese, J.M. and Levine, S.S. and Yeo, G.W. and Rahl, P.B. and Flynn, R.A. and Young, R.A. and Sharp, P.A. and Selth, L.A. and Sigurdsson, S. and Svejstrup, J.Q. and Serfling, E. and Lübbe, A. and Dorsch-Häsler, K. and Schaffner, W. and Shen, Y. and Yue, F. and {McCleary}, D.F. and Ye, Z. and Edsall, L. and Kuan, S. and Wagner, U. and Dixon, J. and Lee, L. and Lobanenkov, V.V. and Ren, B. and Smale, S.T. and Kadonaga, J.T. and Struhl, K. and Thurman, R.E. and Rynes, E. and Humbert, R. and Vierstra, J. and Maurano, M.T. and Haugen, E. and Sheffield, N.C. and Stergachis, A.B. and Wang, H. and Vernot, B. and Al, et and Tie, F. and Banerjee, R. and Stratton, C.A. and Prasad-Sinha, J. and Stepanik, V. and Zlobin, A. and Diaz, M.O. and Scacheri, P.C. and Harte, P.J. and Travers, A. and Trimarchi, T. and Bilal, E. and Ntziachristos, P. and Fabbri, G. and Dalla-Favera, R. and Tsirigos, A. and Aifantis, I. and Tuan, D. and Kong, S. and Hu, K. and Vernimmen, D. and Gobbi, M. De and Sloane-Stanley, J.A. and Wood, W.G. and Higgs, D.R. and Vieira, K.F. and Levings, P.P. and Hill, M.A. and Crusselle, V.J. and Kang, S.-H.L. and Engel, J.D. and Bungert, J. and Visel, A. and Blow, M.J. and Li, Z. and Zhang, T. and Akiyama, J.A. and Holt, A. and Plajzer-Frick, I. and Shoukry, M. and Wright, C. and Chen, F. and Al, et and Vučićević, D. and Corradin, O. and Ntini, E. and Scacheri, P.C. and Ørom, U.A. and Wang, Q. and Carroll, J.S. and Brown, M. and Wang, K.C. and Yang, Y.W. and Liu, B. and Sanyal, A. and Corces-Zimmerman, R. and Chen, Y. and Lajoie, B.R. and Protacio, A. and Flynn, R.A. and Gupta, R.A. and Al, et and Weingarten-Gabbay, S. and Segal, E. and Whyte, W.A. and Orlando, D.A. and Hnisz, D. and Abraham, B.J. and Lin, C.Y. and Kagey, M.H. and Rahl, P.B. and Lee, T.I. and Young, R.A. and Wyers, F. and Rougemaille, M. and Badis, G. and Rousselle, J.C. and Dufour, M.E. and Boulay, J. and Régnault, B. and Devaux, F. and Namane, A. and Séraphin, B. and Al, et and Yoo, E.J. and Cooke, N.E. and Liebhaber, S.A.},
	date = {2015-08},
	pmid = {26317464},
	file = {Attachment:/home/jlagarde/Zotero/storage/Y2DWAGJP/Kim et al. - 2015 - Architectural and Functional Commonalities between Enhancers and Promoters.pdf:application/pdf}
}

@article{uesaka_bidirectional_2014,
	title = {Bidirectional promoters are the major source of gene activation-associated non-coding {RNAs} in mammals},
	volume = {15},
	issn = {1471-2164},
	url = {http://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-15-35},
	doi = {10.1186/1471-2164-15-35},
	pages = {35},
	number = {1},
	journaltitle = {{BMC} Genomics},
	author = {Uesaka, Masahiro and Nishimura, Osamu and Go, Yasuhiro and Nakashima, Kinichi and Agata, Kiyokazu and Imamura, Takuya},
	date = {2014}
}

@article{kaida_u1_2010,
	title = {U1 {snRNP} protects pre-{mRNAs} from premature cleavage and polyadenylation.},
	volume = {468},
	issn = {1476-4687},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/20881964 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2996489},
	doi = {10.1038/nature09479},
	abstract = {In eukaryotes, U1 small nuclear ribonucleoprotein ({snRNP}) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 {snRNPs}; however, its abundance in human far exceeds that of the other {snRNPs}. Here we used antisense morpholino oligonucleotide to U1 {snRNA} to achieve functional U1 {snRNP} knockdown in {HeLa} cells, and identified accumulated unspliced pre-{mRNAs} by genomic tiling microarrays. In addition to inhibiting splicing, U1 {snRNP} knockdown caused premature cleavage and polyadenylation in numerous pre-{mRNAs} at cryptic polyadenylation signals, frequently in introns near ({\textbackslash}textless5 kilobases) the start of the transcript. This did not occur when splicing was inhibited with U2 {snRNA} antisense morpholino oligonucleotide or the U2-{snRNP}-inactivating drug spliceostatin A unless U1 antisense morpholino oligonucleotide was also included. We further show that U1 {snRNA}-pre-{mRNA} base pairing was required to suppress premature cleavage and polyadenylation from nearby cryptic polyadenylation signals located in introns. These findings reveal a critical splicing-independent function for U1 {snRNP} in protecting the transcriptome, which we propose explains its overabundance.},
	pages = {664--8},
	number = {7324},
	journaltitle = {Nature},
	author = {Kaida, Daisuke and Berg, Michael G and Younis, Ihab and Kasim, Mumtaz and Singh, Larry N and Wan, Lili and Dreyfuss, Gideon},
	date = {2010-12},
	pmid = {20881964}
}

@article{dutertre_recently_2014,
	title = {A recently evolved class of alternative 3'-terminal exons involved in cell cycle regulation by topoisomerase inhibitors.},
	volume = {5},
	issn = {2041-1723},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24577238},
	doi = {10.1038/ncomms4395},
	abstract = {Alternative 3'-terminal exons, which use intronic polyadenylation sites, are generally less conserved and expressed at lower levels than the last exon of genes. Here we discover a class of human genes, in which the last exon appeared recently during evolution, and the major gene product uses an alternative 3'-terminal exon corresponding to the ancestral last exon of the gene. This novel class of alternative 3'-terminal exons are downregulated on a large scale by doxorubicin, a cytostatic drug targeting topoisomerase {II}, and play a role in cell cycle regulation, including centromere-kinetochore assembly. The {RNA}-binding protein {HuR}/{ELAVL}1 is a major regulator of this specific set of alternative 3'-terminal exons. {HuR} binding to the alternative 3'-terminal exon in the pre-messenger {RNA} promotes its splicing, and is reduced by topoisomerase inhibitors. These findings provide new insights into the evolution, function and molecular regulation of alternative 3'-terminal exons.},
	pages = {3395},
	journaltitle = {Nature communications},
	author = {Dutertre, Martin and Chakrama, Fatima Zahra and Combe, Emmanuel and Desmet, François-Olivier and Mortada, Hussein and Polay Espinoza, Micaela and Gratadou, Lise and Auboeuf, Didier},
	date = {2014},
	pmid = {24577238}
}

@article{signal_computational_2016,
	title = {Computational Approaches for Functional Prediction and Characterisation of Long Noncoding {RNAs}},
	issn = {01689525},
	doi = {10.1016/j.tig.2016.08.004},
	abstract = {Although a considerable portion of eukaryotic genomes is transcribed as long noncoding {RNAs} ({lncRNAs}), the vast majority are functionally uncharacterised. The rapidly expanding catalogue of mechanistically investigated {lncRNAs} has provided evidence for distinct functional subclasses, which are now ripe for exploitation as a general model to predict functions for uncharacterised {lncRNAs}. By utilising publicly-available genome-wide datasets and computational methods, we present several developed and emerging in silico approaches to characterise and predict the functions of {lncRNAs}. We propose that the application of these techniques provides valuable functional and mechanistic insight into {lncRNAs}, and is a crucial step for informing subsequent functional studies.},
	journaltitle = {Trends in Genetics},
	author = {Signal, Bethany and Gloss, Brian S. and Dinger, Marcel E.},
	date = {2016},
	file = {Attachment:/home/jlagarde/Zotero/storage/YLH22QQX/Signal, Gloss, Dinger - 2016 - Computational Approaches for Functional Prediction and Characterisation of Long Noncoding RNAs.pdf:application/pdf}
}

@article{davidovich_recruitment_2015,
	title = {The recruitment of chromatin modifiers by long noncoding {RNAs}: lessons from {PRC}2},
	volume = {21},
	issn = {1355-8382},
	url = {http://rnajournal.cshlp.org/lookup/doi/10.1261/rna.053918.115},
	doi = {10.1261/rna.053918.115},
	pages = {2007--2022},
	number = {12},
	journaltitle = {{RNA}},
	author = {Davidovich, Chen and Cech, Thomas R.},
	date = {2015-12}
}

@article{kotzin_long_2016,
	title = {The long non-coding {RNA} Morrbid regulates Bim and short-lived myeloid cell lifespan},
	issn = {0028-0836},
	url = {http://www.nature.com/doifinder/10.1038/nature19346},
	doi = {10.1038/nature19346},
	journaltitle = {Nature},
	author = {Kotzin, Jonathan J. and Spencer, Sean P. and {McCright}, Sam J. and Kumar, , Dinesh B. Uthaya and Collet, Magalie A. and Mowel, Walter K. and Elliott, Ellen N. and Uyar, Asli and Makiya, Michelle A. and Dunagin, Margaret C. and Harman, Christian C. D. and Virtue, Anthony T. and Zhu, Stella and Bailis, Will and Stein, Judith and Hughes, Cynthia and Raj, Arjun and Wherry, E. John and Goff, Loyal A. and Klion, Amy D. and Rinn, John L. and Williams, Adam and Flavell, Richard A. and Henao-Mejia, Jorge},
	date = {2016-08}
}

@article{gruber_comprehensive_2016,
	title = {A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation.},
	volume = {26},
	issn = {1549-5469},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/27382025},
	doi = {10.1101/gr.202432.115},
	abstract = {Alternative polyadenylation ({APA}) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3' untranslated region (3' {UTR}) isoforms interact with different {RNA}-binding proteins ({RBPs}), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of pre-{mRNA} 3' end processing has been established with high-throughput approaches, the mechanisms that underlie systematic changes in 3' {UTR} lengths remain to be characterized. Through a uniform analysis of a large number of 3' end sequencing data sets, we have uncovered 18 signals, six of which are novel, whose positioning with respect to pre-{mRNA} cleavage sites indicates a role in pre-{mRNA} 3' end processing in both mouse and human. With 3' end sequencing we have demonstrated that the heterogeneous ribonucleoprotein C ({HNRNPC}), which binds the poly(U) motif whose frequency also peaks in the vicinity of polyadenylation (poly(A)) sites, has a genome-wide effect on poly(A) site usage. {HNRNPC}-regulated 3' {UTRs} are enriched in {ELAV}-like {RBP} 1 ({ELAVL}1) binding sites and include those of the {CD}47 gene, which participate in the recently discovered mechanism of 3' {UTR}-dependent protein localization ({UDPL}). Our study thus establishes an up-to-date, high-confidence catalog of 3' end processing sites and poly(A) signals, and it uncovers an important role of {HNRNPC} in regulating 3' end processing. It further suggests that U-rich elements mediate interactions with multiple {RBPs} that regulate different stages in a transcript's life cycle.},
	pages = {1145--59},
	number = {8},
	journaltitle = {Genome research},
	author = {Gruber, Andreas J and Schmidt, Ralf and Gruber, Andreas R and Martin, Georges and Ghosh, Souvik and Belmadani, Manuel and Keller, Walter and Zavolan, Mihaela},
	date = {2016-08},
	pmid = {27382025}
}

@article{ng_paired-end_2007,
	title = {Paired-end {diTagging} for transcriptome and genome analysis.},
	volume = {Chapter 21},
	issn = {1934-3647},
	doi = {10.1002/0471142727.mb2112s79},
	abstract = {The Paired-End {diTagging} ({PET}) procedure enables one to obtain sequence information from both termini of any contiguous {DNA} fragment. This is achieved by a series of enzymatic manipulations that introduce {MmeI} sites directly flanking each {DNA} insert during the construction of a plasmid library. Subsequent {MmeI} digestion and self-ligation results in the production of covalently-linked paired-end ditags ({PETs}) that can be extracted and then concatenated for efficient sequencing. By mapping the {PET} sequences to assembled genomes, the original {DNA} fragments from which the {PETs} were derived can be precisely localized. This unit details two applications of {PET} technology. In {GIS}-{PET}, ditagging of {mRNA} converted to full-length {cDNA} enables whole-transcriptome analysis, including novel gene identification, gene prediction validation, and gene expression studies. In {ChIP}-{PET}, ditagging of chromatin immunoprecipitation-enriched genomic {DNA} fragments enables the global mapping of transcription factor binding sites. A recent innovation (Multiplex Sequencing of Paired-End ditags; {MS}-{PET}) enables {PETs} to be sequenced using high-throughput 454 sequencing, greatly increasing the amount of data that can be collected in each run.},
	pages = {Unit 21.12},
	journaltitle = {Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.]},
	author = {Ng, Patrick and Wei, Chia-Lin and Ruan, Yijun},
	date = {2007-07},
	pmid = {18265396}
}

@article{bolisetty_determining_2015,
	title = {Determining exon connectivity in complex {mRNAs} by nanopore sequencing},
	volume = {16},
	issn = {1474-760X},
	doi = {10.1186/s13059-015-0777-z},
	abstract = {Short-read high-throughput {RNA} sequencing, though powerful, is limited in its ability to directly measure exon connectivity in {mRNAs} that contain multiple alternative exons located farther apart than the maximum read length. Here, we use the Oxford Nanopore {MinION} sequencer to identify 7,899 'full-length' isoforms expressed from four Drosophila genes, Dscam1, {MRP}, Mhc, and Rdl. These results demonstrate that nanopore sequencing can be used to deconvolute individual isoforms and that it has the potential to be a powerful method for comprehensive transcriptome characterization.},
	pages = {204},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Bolisetty, Mohan T. and Rajadinakaran, Gopinath and Graveley, Brenton R.},
	date = {2015-09},
	pmid = {26420219}
}

@article{li_enhancers_2016,
	title = {Enhancers as non-coding {RNA} transcription units: recent insights and future perspectives},
	volume = {17},
	issn = {1471-0056},
	url = {http://www.nature.com/nrg/journal/v17/n4/full/nrg.2016.4.html?WT.feed_name=subjects_transcription},
	doi = {10.1038/nrg.2016.4},
	pages = {207--223},
	number = {4},
	journaltitle = {Nature Reviews Genetics},
	author = {Li, Wenbo and Notani, Dimple and Rosenfeld, Michael G.},
	date = {2016-03},
	langid = {english}
}

@article{yang_widespread_2016,
	title = {Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.},
	volume = {164},
	issn = {1097-4172},
	url = {http://www.sciencedirect.com/science/article/pii/S0092867416300435},
	doi = {10.1016/j.cell.2016.01.029},
	abstract = {While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50\% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms").},
	pages = {805--817},
	number = {4},
	journaltitle = {Cell},
	author = {Yang, Xinping and Coulombe-Huntington, Jasmin and Kang, Shuli and Sheynkman, Gloria M and Hao, Tong and Richardson, Aaron and Sun, Song and Yang, Fan and Shen, Yun A and Murray, Ryan R and Spirohn, Kerstin and Begg, Bridget E and Duran-Frigola, Miquel and {MacWilliams}, Andrew and Pevzner, Samuel J and Zhong, Quan and Trigg, Shelly A and Tam, Stanley and Ghamsari, Lila and Sahni, Nidhi and Yi, Song and Rodriguez, Maria D and Balcha, Dawit and Tan, Guihong and Costanzo, Michael and Andrews, Brenda and Boone, Charles and Zhou, Xianghong J and Salehi-Ashtiani, Kourosh and Charloteaux, Benoit and Chen, Alyce A and Calderwood, Michael A and Aloy, Patrick and Roth, Frederick P and Hill, David E and Iakoucheva, Lilia M and Xia, Yu and Vidal, Marc},
	date = {2016-02},
	pmid = {26871637},
	file = {Attachment:/home/jlagarde/Zotero/storage/QVPX9T3V/Yang et al. - 2016 - Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.pdf:application/pdf}
}

@article{ji_transcriptional_2011,
	title = {Transcriptional activity regulates alternative cleavage and polyadenylation.},
	volume = {7},
	issn = {1744-4292},
	url = {http://msb.embopress.org/content/7/1/534.abstract},
	doi = {10.1038/msb.2011.69},
	abstract = {Genes containing multiple pre-{mRNA} cleavage and polyadenylation sites, or {polyA} sites, express {mRNA} isoforms with variable 3' untranslated regions ({UTRs}). By systematic analysis of human and mouse transcriptomes, we found that short 3'{UTR} isoforms are relatively more abundant when genes are highly expressed whereas long 3'{UTR} isoforms are relatively more abundant when genes are lowly expressed. Reporter assays indicated that {polyA} site choice can be modulated by transcriptional activity through the gene promoter. Using global and reporter-based nuclear run-on assays, we found that {RNA} polymerase {II} is more likely to pause at the {polyA} site of highly expressed genes than that of lowly expressed ones. Moreover, highly expressed genes tend to have a lower level of nucleosome but higher H3K4me3 and H3K36me3 levels at promoter-proximal {polyA} sites relative to distal ones. Taken together, our results indicate that {polyA} site usage is generally coupled to transcriptional activity, leading to regulation of alternative polyadenylation by transcription.},
	pages = {534},
	number = {1},
	journaltitle = {Molecular systems biology},
	author = {Ji, Zhe and Luo, Wenting and Li, Wencheng and Hoque, Mainul and Pan, Zhenhua and Zhao, Yun and Tian, Bin},
	date = {2011-01},
	langid = {english},
	pmid = {21952137},
	keywords = {Transcriptome, 3' Untranslated Regions, Animals, Genetic, Humans, Mice, {RNA}, Transcription, Gene Expression Regulation, Messenger, Messenger: genetics, Messenger: metabolism, Genes, Green Fluorescent Proteins, {HeLa} Cells, Histones, Histones: metabolism, Methylation, Poly A, Polyadenylation, Real-Time Polymerase Chain Reaction, Reporter, {RNA} Cleavage, {RNA} Precursors, {RNA} Precursors: genetics, Transcriptome: genetics, Poly A: genetics, Green Fluorescent Proteins: genetics, Green Fluorescent Proteins: metabolism, Nucleic Acid Probes, Nucleosomes, Nucleosomes: genetics, Nucleosomes: metabolism, Poly A: analysis, {RNA} Isoforms, {RNA} Isoforms: genetics, {RNA} Isoforms: metabolism, {RNA} Precursors: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/CYVE8CTI/Ji et al. - 2011 - Transcriptional activity regulates alternative cleavage and polyadenylation.pdf:application/pdf}
}

@article{xing_multiassembly_2004,
	title = {The multiassembly problem: reconstructing multiple transcript isoforms from {EST} fragment mixtures.},
	volume = {14},
	issn = {1088-9051},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=353230&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.1304504},
	abstract = {Recent evidence of abundant transcript variation (e.g., alternative splicing, alternative initiation, alternative polyadenylation) in complex genomes indicates that cataloging the complete set of transcripts from an organism is an important project. One challenge is the fact that most high-throughput experimental methods for characterizing transcripts (such as {EST} sequencing) give highly detailed information about short fragments of transcripts or protein products, instead of a complete characterization of a full-length form. We analyze this "multiassembly problem"-reconstructing the most likely set of full-length isoform sequences from a mixture of {EST} fragment data-and present a graph-based algorithm for solving it. In a variety of tests, we demonstrate that this algorithm deals appropriately with coupling of distinct alternative splicing events, increasing fragmentation of the input data and different types of transcript variation (such as alternative splicing, initiation, polyadenylation, and intron retention). To test the method's performance on pure fragment ({EST}) data, we removed all {mRNA} sequences, and found it produced no errors in 40 cases tested. Using this algorithm, we have constructed an Alternatively Spliced Proteins database ({ASP}) from analysis of human expressed and genomic sequences, consisting of 13,384 protein isoforms of 4422 genes, yielding an average of 3.0 protein isoforms per gene.},
	pages = {426--41},
	number = {3},
	journaltitle = {Genome research},
	author = {Xing, Yi and Resch, Alissa and Lee, Christopher},
	date = {2004-03},
	pmid = {14962984},
	keywords = {Genetic, Humans, Transcription, Computational Biology, Exons, Databases, Algorithms, Computational Biology: methods, Alternative Splicing, Exons: genetics, Expressed Sequence Tags, Genetic: genetics, Human Genome Project, Protein Biosynthesis, Protein Isoforms, Protein Isoforms: genetics, Alternative Splicing: genetics, Computational Biology: statistics \& numerical data, Genetic: statistics \& numerical data, Protein Biosynthesis: genetics, Transcobalamins, Transcobalamins: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/IDSHZCJG/Xing, Resch, Lee - 2004 - The multiassembly problem reconstructing multiple transcript isoforms from EST fragment mixtures.pdf:application/pdf}
}

@article{mourier_eukaryotic_2003,
	title = {Eukaryotic intron loss.},
	volume = {300},
	issn = {1095-9203},
	url = {http://science.sciencemag.org/content/300/5624/1393.abstract},
	doi = {10.1126/science.1080559},
	pages = {1393},
	number = {5624},
	journaltitle = {Science (New York, N.Y.)},
	author = {Mourier, Tobias and Jeffares, Daniel C},
	date = {2003-05},
	langid = {english},
	pmid = {12775832},
	keywords = {{DNA}, Animals, Complementary, Genetic, Humans, Mice, Caenorhabditis elegans, Introns, Complementary: genetics, Eukaryotic Cells, Rats, Recombination, Templates, Eukaryota, Eukaryota: genetics, Angiosperms, Angiosperms: genetics, Caenorhabditis elegans: genetics, Fungi, Fungi: genetics, Insects, Insects: genetics, Interspersed Repetitive Sequences, Plasmodium, Plasmodium: genetics, {RNA}-Directed {DNA} Polymerase, {RNA}-Directed {DNA} Polymerase: metabolism, Takifugu, Takifugu: genetics}
}

@article{nagalakshmi_transcriptional_2008,
	title = {The transcriptional landscape of the yeast genome defined by {RNA} sequencing.},
	volume = {320},
	issn = {1095-9203},
	url = {http://science.sciencemag.org/content/320/5881/1344.abstract},
	doi = {10.1126/science.1158441},
	abstract = {The identification of untranslated regions, introns, and coding regions within an organism remains challenging. We developed a quantitative sequencing-based method called {RNA}-Seq for mapping transcribed regions, in which complementary {DNA} fragments are subjected to high-throughput sequencing and mapped to the genome. We applied {RNA}-Seq to generate a high-resolution transcriptome map of the yeast genome and demonstrated that most (74.5\%) of the nonrepetitive sequence of the yeast genome is transcribed. We confirmed many known and predicted introns and demonstrated that others are not actively used. Alternative initiation codons and upstream open reading frames also were identified for many yeast genes. We also found unexpected 3'-end heterogeneity and the presence of many overlapping genes. These results indicate that the yeast transcriptome is more complex than previously appreciated.},
	pages = {1344--9},
	number = {5881},
	journaltitle = {Science (New York, N.Y.)},
	author = {Nagalakshmi, Ugrappa and Wang, Zhong and Waern, Karl and Shou, Chong and Raha, Debasish and Gerstein, Mark and Snyder, Michael},
	date = {2008-06},
	langid = {english},
	pmid = {18451266},
	keywords = {Genomics, {DNA}, Sequence Analysis, Complementary, Genetic, Genome, {RNA}, Transcription, Computational Biology, Gene Expression Profiling, Intergenic, Open Reading Frames, Algorithms, Introns, Codon, Fungal, Genes, Saccharomyces cerevisiae, Untranslated Regions, Fungal: genetics, Initiator, Saccharomyces cerevisiae: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/DXNZPQK8/Nagalakshmi et al. - 2008 - The transcriptional landscape of the yeast genome defined by RNA sequencing.pdf:application/pdf}
}

@article{weinstein_cancer_2013,
	title = {The Cancer Genome Atlas Pan-Cancer analysis project.},
	volume = {45},
	issn = {1546-1718},
	url = {http://dx.doi.org/10.1038/ng.2764},
	doi = {10.1038/ng.2764},
	shorttitle = {Nat Genet},
	abstract = {The Cancer Genome Atlas ({TCGA}) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the {DNA}, {RNA}, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by {TCGA}. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.},
	pages = {1113--20},
	number = {10},
	journaltitle = {Nature genetics},
	author = {Weinstein, John N and Collisson, Eric A and Mills, Gordon B and Shaw, Kenna R Mills and Ozenberger, Brad A and Ellrott, Kyle and Shmulevich, Ilya and Sander, Chris and Stuart, Joshua M},
	date = {2013-10},
	pmid = {24071849},
	keywords = {Genome, Humans, Gene Expression Profiling, Neoplasms, Neoplasms: genetics, Neoplasms: pathology},
	file = {Attachment:/home/jlagarde/Zotero/storage/B9D849K9/Weinstein et al. - 2013 - The Cancer Genome Atlas Pan-Cancer analysis project.pdf:application/pdf}
}

@article{auton_global_2015,
	title = {A global reference for human genetic variation},
	volume = {526},
	issn = {0028-0836},
	url = {http://dx.doi.org/10.1038/nature15393},
	doi = {10.1038/nature15393},
	shorttitle = {Nature},
	abstract = {The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms ({SNPs}), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes {\textbackslash}textgreater99\% of {SNP} variants with a frequency of {\textbackslash}textgreater1\% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.},
	pages = {68--74},
	number = {7571},
	journaltitle = {Nature},
	author = {Auton, Adam and Abecasis, Gonçalo R. and Altshuler, David M. and Durbin, Richard M. and Bentley, David R. and Chakravarti, Aravinda and Clark, Andrew G. and Donnelly, Peter and Eichler, Evan E. and Flicek, Paul and Gabriel, Stacey B. and Gibbs, Richard A. and Green, Eric D. and Hurles, Matthew E. and Knoppers, Bartha M. and Korbel, Jan O. and Lander, Eric S. and Lee, Charles and Lehrach, Hans and Mardis, Elaine R. and Marth, Gabor T. and {McVean}, Gil A. and Nickerson, Deborah A. and Schmidt, Jeanette P. and Sherry, Stephen T. and Wang, Jun and Wilson, Richard K. and Boerwinkle, Eric and Doddapaneni, Harsha and Han, Yi and Korchina, Viktoriya and Kovar, Christie and Lee, Sandra and Muzny, Donna and Reid, Jeffrey G. and Zhu, Yiming and Chang, Yuqi and Feng, Qiang and Fang, Xiaodong and Guo, Xiaosen and Jian, Min and Jiang, Hui and Jin, Xin and Lan, Tianming and Li, Guoqing and Li, Jingxiang and Li, Yingrui and Liu, Shengmao and Liu, Xiao and Lu, Yao and Ma, Xuedi and Tang, Meifang and Wang, Bo and Wang, Guangbiao and Wu, Honglong and Wu, Renhua and Xu, Xun and Yin, Ye and Zhang, Dandan and Zhang, Wenwei and Zhao, Jiao and Zhao, Meiru and Zheng, Xiaole and Gupta, Namrata and Gharani, Neda and Toji, Lorraine H. and Gerry, Norman P. and Resch, Alissa M. and Barker, Jonathan and Clarke, Laura and Gil, Laurent and Hunt, Sarah E. and Kelman, Gavin and Kulesha, Eugene and Leinonen, Rasko and {McLaren}, William M. and Radhakrishnan, Rajesh and Roa, Asier and Smirnov, Dmitriy and Smith, Richard E. and Streeter, Ian and Thormann, Anja and Toneva, Iliana and Vaughan, Brendan and Zheng-Bradley, Xiangqun and Grocock, Russell and Humphray, Sean and James, Terena and Kingsbury, Zoya and Sudbrak, Ralf and Albrecht, Marcus W. and Amstislavskiy, Vyacheslav S. and Borodina, Tatiana A. and Lienhard, Matthias and Mertes, Florian and Sultan, Marc and Timmermann, Bernd and Yaspo, Marie-Laure and Fulton, Lucinda and Fulton, Robert and Ananiev, Victor and Belaia, Zinaida and Beloslyudtsev, Dimitriy and Bouk, Nathan and Chen, Chao and Church, Deanna and Cohen, Robert and Cook, Charles and Garner, John and Hefferon, Timothy and Kimelman, Mikhail and Liu, Chunlei and Lopez, John and Meric, Peter and O'Sullivan, Chris and Ostapchuk, Yuri and Phan, Lon and Ponomarov, Sergiy and Schneider, Valerie and Shekhtman, Eugene and Sirotkin, Karl and Slotta, Douglas and Zhang, Hua and Balasubramaniam, Senduran and Burton, John and Danecek, Petr and Keane, Thomas M. and Kolb-Kokocinski, Anja and {McCarthy}, Shane and Stalker, James and Quail, Michael and Davies, Christopher J. and Gollub, Jeremy and Webster, Teresa and Wong, Brant and Zhan, Yiping and Campbell, Christopher L. and Kong, Yu and Marcketta, Anthony and Yu, Fuli and Antunes, Lilian and Bainbridge, Matthew and Sabo, Aniko and Huang, Zhuoyi and Coin, Lachlan J. M. and Fang, Lin and Li, Qibin and Li, Zhenyu and Lin, Haoxiang and Liu, Binghang and Luo, Ruibang and Shao, Haojing and Xie, Yinlong and Ye, Chen and Yu, Chang and Zhang, Fan and Zheng, Hancheng and Zhu, Hongmei and Alkan, Can and Dal, Elif and Kahveci, Fatma and Garrison, Erik P. and Kural, Deniz and Lee, Wan-Ping and Fung Leong, Wen and Stromberg, Michael and Ward, Alistair N. and Wu, Jiantao and Zhang, Mengyao and Daly, Mark J. and {DePristo}, Mark A. and Handsaker, Robert E. and Banks, Eric and Bhatia, Gaurav and del Angel, Guillermo and Genovese, Giulio and Li, Heng and Kashin, Seva and {McCarroll}, Steven A. and Nemesh, James C. and Poplin, Ryan E. and Yoon, Seungtai C. and Lihm, Jayon and Makarov, Vladimir and Gottipati, Srikanth and Keinan, Alon and Rodriguez-Flores, Juan L. and Rausch, Tobias and Fritz, Markus H. and Stütz, Adrian M. and Beal, Kathryn and Datta, Avik and Herrero, Javier and Ritchie, Graham R. S. and Zerbino, Daniel and Sabeti, Pardis C. and Shlyakhter, Ilya and Schaffner, Stephen F. and Vitti, Joseph and Cooper, David N. and Ball, Edward V. and Stenson, Peter D. and Barnes, Bret and Bauer, Markus and Keira Cheetham, R. and Cox, Anthony and Eberle, Michael and Kahn, Scott and Murray, Lisa and Peden, John and Shaw, Richard and Kenny, Eimear E. and Batzer, Mark A. and Konkel, Miriam K. and Walker, Jerilyn A. and {MacArthur}, Daniel G. and Lek, Monkol and Herwig, Ralf and Ding, Li and Koboldt, Daniel C. and Larson, David and Ye, Kai and Gravel, Simon and Swaroop, Anand and Chew, Emily and Lappalainen, Tuuli and Erlich, Yaniv and Gymrek, Melissa and Frederick Willems, Thomas and Simpson, Jared T. and Shriver, Mark D. and Rosenfeld, Jeffrey A. and Bustamante, Carlos D. and Montgomery, Stephen B. and De La Vega, Francisco M. and Byrnes, Jake K. and Carroll, Andrew W. and {DeGorter}, Marianne K. and Lacroute, Phil and Maples, Brian K. and Martin, Alicia R. and Moreno-Estrada, Andres and Shringarpure, Suyash S. and Zakharia, Fouad and Halperin, Eran and Baran, Yael and Cerveira, Eliza and Hwang, Jaeho and Malhotra, Ankit and Plewczynski, Dariusz and Radew, Kamen and Romanovitch, Mallory and Zhang, Chengsheng and Hyland, Fiona C. L. and Craig, David W. and Christoforides, Alexis and Homer, Nils and Izatt, Tyler and Kurdoglu, Ahmet A. and Sinari, Shripad A. and Squire, Kevin and Xiao, Chunlin and Sebat, Jonathan and Antaki, Danny and Gujral, Madhusudan and Noor, Amina and Ye, Kenny and Burchard, Esteban G. and Hernandez, Ryan D. and Gignoux, Christopher R. and Haussler, David and Katzman, Sol J. and James Kent, W. and Howie, Bryan and Ruiz-Linares, Andres and Dermitzakis, Emmanouil T. and Devine, Scott E. and Min Kang, Hyun and Kidd, Jeffrey M. and Blackwell, Tom and Caron, Sean and Chen, Wei and Emery, Sarah and Fritsche, Lars and Fuchsberger, Christian and Jun, Goo and Li, Bingshan and Lyons, Robert and Scheller, Chris and Sidore, Carlo and Song, Shiya and Sliwerska, Elzbieta and Taliun, Daniel and Tan, Adrian and Welch, Ryan and Kate Wing, Mary and Zhan, Xiaowei and Awadalla, Philip and Hodgkinson, Alan and Li, Yun and Shi, Xinghua and Quitadamo, Andrew and Lunter, Gerton and Marchini, Jonathan L. and Myers, Simon and Churchhouse, Claire and Delaneau, Olivier and Gupta-Hinch, Anjali and Kretzschmar, Warren and Iqbal, Zamin and Mathieson, Iain and Menelaou, Androniki and Rimmer, Andy and Xifara, Dionysia K. and Oleksyk, Taras K. and Fu, Yunxin and Liu, Xiaoming and Xiong, Momiao and Jorde, Lynn and Witherspoon, David and Xing, Jinchuan and Browning, Brian L. and Browning, Sharon R. and Hormozdiari, Fereydoun and Sudmant, Peter H. and Khurana, Ekta and Tyler-Smith, Chris and Albers, Cornelis A. and Ayub, Qasim and Chen, Yuan and Colonna, Vincenza and Jostins, Luke and Walter, Klaudia and Xue, Yali and Gerstein, Mark B. and Abyzov, Alexej and Balasubramanian, Suganthi and Chen, Jieming and Clarke, Declan and Fu, Yao and Harmanci, Arif O. and Jin, Mike and Lee, Donghoon and Liu, Jeremy and Jasmine Mu, Xinmeng and Zhang, Jing and Zhang, Yan and Hartl, Chris and Shakir, Khalid and Degenhardt, Jeremiah and Meiers, Sascha and Raeder, Benjamin and Paolo Casale, Francesco and Stegle, Oliver and Lameijer, Eric-Wubbo and Hall, Ira and Bafna, Vineet and Michaelson, Jacob and Gardner, Eugene J. and Mills, Ryan E. and Dayama, Gargi and Chen, Ken and Fan, Xian and Chong, Zechen and Chen, Tenghui and Chaisson, Mark J. and Huddleston, John and Malig, Maika and Nelson, Bradley J. and Parrish, Nicholas F. and Blackburne, Ben and Lindsay, Sarah J. and Ning, Zemin and Zhang, Yujun and Lam, Hugo and Sisu, Cristina and Challis, Danny and Evani, Uday S. and Lu, James and Nagaswamy, Uma and Yu, Jin and Li, Wangshen and Habegger, Lukas and Yu, Haiyuan and Cunningham, Fiona and Dunham, Ian and Lage, Kasper and Berg Jespersen, Jakob and Horn, Heiko and Kim, Donghoon and Desalle, Rob and Narechania, Apurva and Wilson Sayres, Melissa A. and Mendez, Fernando L. and David Poznik, G. and Underhill, Peter A. and Coin, Lachlan and Mittelman, David and Banerjee, Ruby and Cerezo, Maria and Fitzgerald, Thomas W. and Louzada, Sandra and Massaia, Andrea and Ritchie, Graham R. and Yang, Fengtang and Kalra, Divya and Hale, Walker and Dan, Xu and Barnes, Kathleen C. and Beiswanger, Christine and Cai, Hongyu and Cao, Hongzhi and Henn, Brenna and Jones, Danielle and Kaye, Jane S. and Kent, Alastair and Kerasidou, Angeliki and Mathias, Rasika and Ossorio, Pilar N. and Parker, Michael and Rotimi, Charles N. and Royal, Charmaine D. and Sandoval, Karla and Su, Yeyang and Tian, Zhongming and Tishkoff, Sarah and Via, Marc and Wang, Yuhong and Yang, Huanming and Yang, Ling and Zhu, Jiayong and Bodmer, Walter and Bedoya, Gabriel and Cai, Zhiming and Gao, Yang and Chu, Jiayou and Peltonen, Leena and Garcia-Montero, Andres and Orfao, Alberto and Dutil, Julie and Martinez-Cruzado, Juan C. and Mathias, Rasika A. and Hennis, Anselm and Watson, Harold and {McKenzie}, Colin and Qadri, Firdausi and {LaRocque}, Regina and Deng, Xiaoyan and Asogun, Danny and Folarin, Onikepe and Happi, Christian and Omoniwa, Omonwunmi and Stremlau, Matt and Tariyal, Ridhi and Jallow, Muminatou and Sisay Joof, Fatoumatta and Corrah, Tumani and Rockett, Kirk and Kwiatkowski, Dominic and Kooner, Jaspal and Tịnh Hiê`n, Trâ`n and Dunstan, Sarah J. and Thuy Hang, Nguyen and Fonnie, Richard and Garry, Robert and Kanneh, Lansana and Moses, Lina and Schieffelin, John and Grant, Donald S. and Gallo, Carla and Poletti, Giovanni and Saleheen, Danish and Rasheed, Asif and Brooks, Lisa D. and Felsenfeld, Adam L. and {McEwen}, Jean E. and Vaydylevich, Yekaterina and Duncanson, Audrey and Dunn, Michael and Schloss, Jeffery A.},
	date = {2015-09}
}

@article{olivarius_high-throughput_2009,
	title = {High-throughput verification of transcriptional starting sites by Deep-{RACE}.},
	volume = {46},
	issn = {0736-6205},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19317658},
	doi = {10.2144/000113066},
	abstract = {We present a high-throughput method for investigating the transcriptional starting sites of genes of interest, which we named Deep-{RACE} (Deep-rapid amplification of {cDNA} ends). Taking advantage of the latest sequencing technology, it allows the parallel analysis of multiple genes and is free of time-consuming cloning steps. In comparison to the sequencing of {RACE} {PCR} products, our approach is more precise and more cost-effective even for batches as small as 17.},
	pages = {130--2},
	number = {2},
	journaltitle = {{BioTechniques}},
	author = {Olivarius, Signe and Plessy, Charles and Carninci, Piero},
	date = {2009-02},
	pmid = {19317658},
	keywords = {{DNA}, Sequence Analysis, Base Sequence, Transcription Initiation Site, {DNA}: genetics, Molecular Sequence Data, Transcription Factors, Transcriptional Activation, Nucleic Acid Amplification Techniques, Nucleic Acid Amplification Techniques: methods, {DNA}: methods, Transcription Factors: genetics, Transcriptional Activation: genetics}
}

@article{neve_subcellular_2015,
	title = {Subcellular {RNA} profiling links splicing and nuclear {DICER}1 to alternative cleavage and polyadenylation.},
	volume = {26},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4691748&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.193995.115},
	abstract = {Alternative cleavage and polyadenylation ({APA}) plays a crucial role in the regulation of gene expression across eukaryotes. Although {APA} is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we used a rigorous subcellular fractionation approach to compare {APA} profiles of cytoplasmic and nuclear {RNA} fractions from human cell lines. This approach allowed us to extract {APA} isoforms that are subjected to differential regulation and provided us with a platform to interrogate the molecular regulatory pathways that shape {APA} profiles in different subcellular locations. Here, we show that {APA} isoforms with shorter 3' {UTRs} tend to be overrepresented in the cytoplasm and appear to be cell-type-specific events. Nuclear retention of longer {APA} isoforms occurs and is partly a result of incomplete splicing contributing to the observed cytoplasmic bias of transcripts with shorter 3' {UTRs}. We demonstrate that the endoribonuclease {III}, {DICER}1, contributes to the establishment of subcellular {APA} profiles not only by expected cytoplasmic {miRNA}-mediated destabilization of {APA} {mRNA} isoforms, but also by affecting polyadenylation site choice.},
	pages = {24--35},
	number = {1},
	journaltitle = {Genome research},
	author = {Neve, Jonathan and Burger, Kaspar and Li, Wencheng and Hoque, Mainul and Patel, Radhika and Tian, Bin and Gullerova, Monika and Furger, Andre},
	date = {2015-11},
	pmid = {26546131},
	file = {Attachment:/home/jlagarde/Zotero/storage/3TZLZ2X6/Neve et al. - 2015 - Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation.pdf:application/pdf}
}

@article{nunes_functional_2010,
	title = {A functional human Poly(A) site requires only a potent {DSE} and an A-rich upstream sequence.},
	volume = {29},
	issn = {1460-2075},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2876958&tool=pmcentrez&rendertype=abstract},
	doi = {10.1038/emboj.2010.42},
	abstract = {We have analysed the sequences required for cleavage and polyadenylation in the intronless melanocortin 4 receptor ({MC}4R) pre-{mRNA}. Unlike other intronless genes, 3'end processing of the {MC}4R primary transcript is independent of any auxiliary sequence elements and only requires the core poly(A) sequences. Mutation of the {AUUAAA} hexamer had little effect on {MC}4R 3'end processing but small changes in the short {DSE} severely reduced cleavage efficiency. The {MC}4R poly(A) site requires only the {DSE} and an A-rich upstream sequence to direct efficient cleavage and polyadenylation. Our observation may be highly relevant for the understanding of how human noncanonical poly(A) sites are recognised. This is supported by a genome-wide analysis of over 10 000 poly(A) sites where we show that many human noncanonical poly(A) signals contain A-rich upstream sequences and tend to have a higher frequency of U and {GU} nucleotides in their {DSE} compared with canonical poly(A) signals. The importance of A-rich elements for noncanonical poly(A) site recognition was confirmed by mutational analysis of the human {JUNB} gene, which contains an A-rich noncanonical poly(A) signal.},
	pages = {1523--36},
	number = {9},
	journaltitle = {The {EMBO} journal},
	author = {Nunes, Nuno Miguel and Li, Wencheng and Tian, Bin and Furger, André},
	date = {2010-05},
	pmid = {20339349},
	keywords = {3' Untranslated Regions, Base Sequence, Humans, Antigens, Cell Line, {DNA}-Binding Proteins, Molecular Sequence Data, Mutation, Neoplasm, Poly A, Receptor, {RNA} Precursors, {RNA} Precursors: genetics, Uridine, Poly A: genetics, 3' Flanking Region, Adenosine, Adenosine: chemistry, Adenosine: genetics, Melanocortin, Neoplasm Proteins, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-jun: genetics, Type 4, Type 4: genetics, Uridine: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/HM8UFTU7/Nunes et al. - 2010 - A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequence.pdf:application/pdf}
}

@article{lianoglou_ubiquitously_2013,
	title = {Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression.},
	volume = {27},
	issn = {1549-5477},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3828523&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gad.229328.113},
	abstract = {More than half of human genes use alternative cleavage and polyadenylation ({ApA}) to generate {mRNA} transcripts that differ in the lengths of their 3' untranslated regions ({UTRs}), thus altering the post-transcriptional fate of the message and likely the protein output. The extent of 3' {UTR} variation across tissues and the functional role of {ApA} remain poorly understood. We developed a sequencing method called 3'-seq to quantitatively map the 3' ends of the transcriptome of diverse human tissues and isogenic transformation systems. We found that cell type-specific gene expression is accomplished by two complementary programs. Tissue-restricted genes tend to have single 3' {UTRs}, whereas a majority of ubiquitously transcribed genes generate multiple 3' {UTRs}. During transformation and differentiation, single-{UTR} genes change their {mRNA} abundance levels, while multi-{UTR} genes mostly change 3' {UTR} isoform ratios to achieve tissue specificity. However, both regulation programs target genes that function in the same pathways and processes that characterize the new cell type. Instead of finding global shifts in 3' {UTR} length during transformation and differentiation, we identify tissue-specific groups of multi-{UTR} genes that change their 3' {UTR} ratios; these changes in 3' {UTR} length are largely independent from changes in {mRNA} abundance. Finally, tissue-specific usage of {ApA} sites appears to be a mechanism for changing the landscape targetable by ubiquitously expressed {microRNAs}.},
	pages = {2380--96},
	number = {21},
	journaltitle = {Genes \& development},
	author = {Lianoglou, Steve and Garg, Vidur and Yang, Julie L and Leslie, Christina S and Mayr, Christine},
	date = {2013-11},
	pmid = {24145798},
	keywords = {Human, 3' Untranslated Regions, Humans, {RNA}, Gene Expression Regulation, Gene Expression Profiling, Messenger, Messenger: genetics, Organ Specificity, Messenger: metabolism, 3' Untranslated Regions: genetics, Cell Differentiation, Cell Line, Cell Transformation, Developmental, Embryonic Stem Cells, {HEK}293 Cells, {HeLa} Cells, Herpesvirus 4, {MCF}-7 Cells, Messenger: chemistry, Molecular Sequence Data, Polyadenylation, Protein Isoforms, Tumor, Viral, Embryonic Stem Cells: metabolism, Human: physiology, Organ Specificity: genetics, Viral: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/5THXRC8R/Lianoglou et al. - 2013 - Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression.pdf:application/pdf}
}

@article{ulitsky_extensive_2012,
	title = {Extensive alternative polyadenylation during zebrafish development.},
	volume = {22},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3460199&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.139733.112},
	abstract = {The post-transcriptional fate of messenger {RNAs} ({mRNAs}) is largely dictated by their 3' untranslated regions (3' {UTRs}), which are defined by cleavage and polyadenylation ({CPA}) of pre-{mRNAs}. We used poly(A)-position profiling by sequencing (3P-seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-seq reads substantially increased and improved existing 3' {UTR} annotations, resulting in confidently identified 3' {UTRs} for {\textbackslash}textgreater79\% of the annotated protein-coding genes in zebrafish. {mRNAs} from most zebrafish genes undergo alternative {CPA}, with those from more than a thousand genes using different dominant 3' {UTRs} at different stages. These included one of the poly(A) polymerase genes, for which alternative {CPA} reinforces its repression in the ovary. 3' {UTRs} tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3' {UTRs} are highly expressed in the ovary, yet absent in the maternally contributed {RNAs} of the embryo, perhaps because their 3' {UTRs} are too short to accommodate a uridine-rich motif required for stability of the maternal {mRNA}. At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of {mRNA} degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3' {UTRs} provide a resource for studying gene regulation during vertebrate development.},
	pages = {2054--66},
	number = {10},
	journaltitle = {Genome research},
	author = {Ulitsky, Igor and Shkumatava, Alena and Jan, Calvin H and Subtelny, Alexander O and Koppstein, David and Bell, George W and Sive, Hazel and Bartel, David P},
	date = {2012-10},
	pmid = {22722342},
	keywords = {Genomics, 3' Untranslated Regions, Animals, Genetic, Humans, Transcription, Gene Expression Regulation, Developmental, Evolution, Female, Molecular, Molecular Sequence Annotation, Organogenesis, Organogenesis: genetics, Ovary, Ovary: embryology, Ovary: metabolism, Poly A, Polyadenylation, Zebrafish, Zebrafish: embryology, Zebrafish: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/BUA9IRFF/Ulitsky et al. - 2012 - Extensive alternative polyadenylation during zebrafish development.pdf:application/pdf}
}

@article{conesa_survey_2016,
	title = {A survey of best practices for {RNA}-seq data analysis},
	volume = {17},
	issn = {1474-760X},
	url = {http://genomebiology.com/2016/17/1/13},
	doi = {10.1186/s13059-016-0881-8},
	abstract = {{RNA}-sequencing ({RNA}-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in {RNA}-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and {eQTL} mapping. We highlight the challenges associated with each step. We discuss the analysis of small {RNAs} and the integration of {RNA}-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics.},
	pages = {13},
	number = {1},
	journaltitle = {Genome Biology},
	author = {Conesa, Ana and Madrigal, Pedro and Tarazona, Sonia and Gomez-Cabrero, David and Cervera, Alejandra and {McPherson}, Andrew and Szcześniak, Micha\{{\textbackslash}textbackslash\}l Wojciech and Gaffney, Daniel J. and Elo, Laura L. and Zhang, Xuegong and Mortazavi, Ali},
	date = {2016-01},
	langid = {english},
	file = {A survey of best practices for RNA-seq data analysis:/home/jlagarde/Zotero/storage/ADM9KRNE/conesa2016.pdf:application/pdf;Attachment:/home/jlagarde/Zotero/storage/87EKPRQB/Conesa et al. - 2016 - A survey of best practices for RNA-seq data analysis.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/I76WCYNM/Conesa et al. - 2016 - A survey of best practices for RNA-seq data analys.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/X7VX97G6/s13059-016-0881-8.html:text/html}
}

@article{yoon_genetics_2012,
	title = {Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells.},
	volume = {8},
	issn = {1553-7404},
	url = {http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002882},
	doi = {10.1371/journal.pgen.1002882},
	abstract = {Gene expression varies widely between individuals of a population, and regulatory change can underlie phenotypes of evolutionary and biomedical relevance. A key question in the field is how {DNA} sequence variants impact gene expression, with most mechanistic studies to date focused on the effects of genetic change on regulatory regions upstream of protein-coding sequence. By contrast, the role of {RNA} 3'-end processing in regulatory variation remains largely unknown, owing in part to the challenge of identifying functional elements in 3' untranslated regions. In this work, we conducted a genomic survey of transcript ends in lymphoblastoid cells from genetically distinct human individuals. Our analysis mapped the cis-regulatory architecture of 3' gene ends, finding that transcript end positions did not fall randomly in untranslated regions, but rather preferentially flanked the locations of 3' regulatory elements, including {miRNA} sites. The usage of these transcript length forms and motifs varied across human individuals, and polymorphisms in polyadenylation signals and other 3' motifs were significant predictors of expression levels of the genes in which they lay. Independent single-gene experiments confirmed the effects of polyadenylation variants on steady-state expression of their respective genes, and validated the regulatory function of 3' cis-regulatory sequence elements that mediated expression of these distinct {RNA} length forms. Focusing on the immune regulator {IRF}5, we established the effect of natural variation in {RNA} 3'-end processing on regulatory response to antigen stimulation. Our results underscore the importance of two mechanisms at play in the genetics of 3'-end variation: the usage of distinct 3'-end processing signals and the effects of 3' sequence elements that determine transcript fate. Our findings suggest that the strategy of integrating observed 3'-end positions with inferred 3' regulatory motifs will prove to be a critical tool in continued efforts to interpret human genome variation.},
	pages = {e1002882},
	number = {8},
	journaltitle = {{PLoS} genetics},
	author = {Yoon, Oh Kyu and Hsu, Tiffany Y and Im, Joo Hyun and Brem, Rachel B},
	date = {2012-01},
	pmid = {22916029},
	keywords = {Human, 3' Untranslated Regions, Genetic, Genome, Humans, Regulatory Sequences, Ribonucleic Acid, Open Reading Frames, 3' Untranslated Regions: genetics, Cell Line, Gene Expression, Polyadenylation, Polymorphism, B-Lymphocytes, B-Lymphocytes: cytology, B-Lymphocytes: metabolism, Interferon Regulatory Factors, Interferon Regulatory Factors: genetics, Ribonucleic Acid: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/5HBGFC2F/Yoon et al. - 2012 - Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells.pdf:application/pdf}
}

@article{tajnik_intergenic_2015,
	title = {Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends.},
	volume = {43},
	issn = {1362-4962},
	url = {http://nar.oxfordjournals.org/content/43/21/10492.full},
	doi = {10.1093/nar/gkv956},
	abstract = {The 3' untranslated regions (3' {UTRs}) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3' {UTRs}, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3' {UTRs} can alter {mRNA} stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3' {UTRs}.},
	pages = {10492--505},
	number = {21},
	journaltitle = {Nucleic acids research},
	author = {Tajnik, Mojca and Vigilante, Alessandra and Braun, Simon and Hänel, Heike and Luscombe, Nicholas M and Ule, Jernej and Zarnack, Kathi and König, Julian},
	date = {2015-12},
	pmid = {26400176},
	file = {Attachment:/home/jlagarde/Zotero/storage/UY6SMRKQ/Tajnik et al. - 2015 - Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends.pdf:application/pdf}
}

@article{chen_using_2009,
	title = {Using Alu elements as polyadenylation sites: A case of retroposon exaptation.},
	volume = {26},
	issn = {1537-1719},
	url = {http://mbe.oxfordjournals.org/content/26/2/327.short},
	doi = {10.1093/molbev/msn249},
	abstract = {Of the 1.1 million Alu retroposons in the human genome, about 10,000 are inserted in the 3' untranslated regions ({UTR}) of protein-coding genes and 1\% of these (107 events) are active as polyadenylation sites ({PASs}). Strikingly, although Alu's in 3' {UTR} are indifferently inserted in the forward or reverse direction, 99\% of polyadenylation-active Alu sequences are forward oriented. Consensus Alu+ sequences contain sites that can give rise to polyadenylation signals and enhancers through a few point mutations. We found that the strand bias of polyadenylation-active Alu's reflects a radical difference in the fitness of sense and antisense Alu's toward cleavage/polyadenylation activity. In contrast to previous beliefs, Alu inserts do not necessarily represent weak or cryptic {PASs}; instead, they often constitute the major or the unique {PAS} in a gene, adding to the growing list of Alu exaptations. Finally, some Alu-borne {PASs} are intronic and produce truncated transcripts that may impact gene function and/or contribute to gene remodeling.},
	pages = {327--34},
	number = {2},
	journaltitle = {Molecular biology and evolution},
	author = {Chen, Chongjian and Ara, Takeshi and Gautheret, Daniel},
	date = {2009-02},
	pmid = {18984903},
	keywords = {Animals, Base Sequence, Genetic, Humans, Mice, {RNA} Splice Sites, Enhancer Elements, Molecular Sequence Data, Polyadenylation, Alu Elements}
}

@article{proudfoot_ending_2011,
	title = {Ending the message: poly(A) signals then and now.},
	volume = {25},
	issn = {1549-5477},
	url = {http://genesdev.cshlp.org/content/25/17/1770.full},
	doi = {10.1101/gad.17268411},
	abstract = {Polyadenylation [poly(A)] signals ({PAS}) are a defining feature of eukaryotic protein-coding genes. The central sequence motif {AAUAAA} was identified in the mid-1970s and subsequently shown to require flanking, auxiliary elements for both 3'-end cleavage and polyadenylation of premessenger {RNA} (pre-{mRNA}) as well as to promote downstream transcriptional termination. More recent genomic analysis has established the generality of the {PAS} for eukaryotic {mRNA}. Evidence for the mechanism of {mRNA} 3'-end formation is outlined, as is the way this {RNA} processing reaction communicates with {RNA} polymerase {II} to terminate transcription. The widespread phenomenon of alternative poly(A) site usage and how this interrelates with pre-{mRNA} splicing is then reviewed. This shows that gene expression can be drastically affected by how the message is ended. A central theme of this review is that while genomic analysis provides generality for the importance of {PAS} selection, detailed mechanistic understanding still requires the direct analysis of specific genes by genetic and biochemical approaches.},
	pages = {1770--82},
	number = {17},
	journaltitle = {Genes \& development},
	author = {Proudfoot, Nick J},
	date = {2011-09},
	pmid = {21896654},
	keywords = {3' Untranslated Regions, Animals, Humans, {RNA}, {RNA} Splicing, Untranslated, Gene Expression Regulation, Untranslated: metabolism, 3' Untranslated Regions: genetics, {RNA} Precursors, {RNA} Precursors: metabolism, {RNA} 3' Polyadenylation Signals, {RNA} 3' Polyadenylation Signals: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/AHN452XI/Proudfoot - 2011 - Ending the message poly(A) signals then and now.pdf:application/pdf}
}

@article{quinlan_bedtools:_2014,
	title = {{BEDTools}: The Swiss-Army Tool for Genome Feature Analysis.},
	volume = {47},
	issn = {1934-340X},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4213956&tool=pmcentrez&rendertype=abstract},
	doi = {10.1002/0471250953.bi1112s47},
	abstract = {Technological advances have enabled the use of {DNA} sequencing as a flexible tool to characterize genetic variation and to measure the activity of diverse cellular phenomena such as gene isoform expression and transcription factor binding. Extracting biological insight from the experiments enabled by these advances demands the analysis of large, multi-dimensional datasets. This unit describes the use of the {BEDTools} toolkit for the exploration of high-throughput genomics datasets. Several protocols are presented for common genomic analyses, demonstrating how simple {BEDTools} operations may be combined to create bespoke pipelines addressing complex questions. Curr. Protoc. Bioinform. 47:11.12.1-11.12.34. © 2014 by John Wiley \& Sons, Inc.},
	pages = {11.12.1--11.12.34},
	journaltitle = {Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.]},
	author = {Quinlan, Aaron R},
	date = {2014-01},
	pmid = {25199790},
	file = {Attachment:/home/jlagarde/Zotero/storage/9YCR3224/Quinlan - 2014 - BEDTools The Swiss-Army Tool for Genome Feature Analysis.pdf:application/pdf}
}

@article{harrow_identifying_2009,
	title = {Identifying protein-coding genes in genomic sequences.},
	volume = {10},
	issn = {1474-760X},
	url = {http://genomebiology.com/2009/10/1/201},
	doi = {10.1186/gb-2009-10-1-201},
	abstract = {The vast majority of the biology of a newly sequenced genome is inferred from the set of encoded proteins. Predicting this set is therefore invariably the first step after the completion of the genome {DNA} sequence. Here we review the main computational pipelines used to generate the human reference protein-coding gene sets.},
	pages = {201},
	number = {1},
	journaltitle = {Genome biology},
	author = {Harrow, Jennifer and Nagy, Alinda and Reymond, Alexandre and Alioto, Tyler and Patthy, Laszlo and Antonarakis, Stylianos E and Guigó, Roderic},
	date = {2009-01},
	langid = {english},
	pmid = {19226436},
	keywords = {Animals, Base Sequence, Genome, Humans, Proteins, Proteins: genetics, Computational Biology, Computational Biology: methods, Genes, Genome: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/QIM5UIK7/Harrow et al. - 2009 - Identifying protein-coding genes in genomic sequences.pdf:application/pdf}
}

@article{clark_reality_2011,
	title = {The Reality of Pervasive Transcription},
	volume = {9},
	issn = {1545-7885},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3134446&tool=pmcentrez&rendertype=abstract},
	doi = {10.1371/journal.pbio.1000625},
	pages = {e1000625},
	number = {7},
	journaltitle = {{PLoS} Biology},
	author = {Clark, Michael B. and Amaral, Paulo P. and Schlesinger, Felix J. and Dinger, Marcel E. and Taft, Ryan J. and Rinn, John L. and Ponting, Chris P. and Stadler, Peter F. and Morris, Kevin V. and Morillon, Antonin and Rozowsky, Joel S. and Gerstein, Mark B. and Wahlestedt, Claes and Hayashizaki, Yoshihide and Carninci, Piero and Gingeras, Thomas R. and Mattick, John S.},
	editor = {Eisen, Michael B.},
	date = {2011-07},
	pmid = {21765801},
	keywords = {Epigenomics, {DNA}, Sequence Analysis, Animals, Complementary, Complementary: chemistry, Genetic, Genome, Humans, {RNA}, Transcription, Oligonucleotide Array Sequence Analysis, Databases, {RNA}: methods, Artifacts, Complementary: genetics, Expressed Sequence Tags, Mammals, Oligonucleotide Array Sequence Analysis: methods, Complementary: analysis, Expressed Sequence Tags: chemistry},
	file = {Attachment:/home/jlagarde/Zotero/storage/XJJ43R5P/Clark et al. - 2011 - The Reality of Pervasive Transcription.pdf:application/pdf}
}

@article{gorodkin_structure_2011,
	title = {From structure prediction to genomic screens for novel non-coding {RNAs}.},
	volume = {7},
	issn = {1553-7358},
	url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002100},
	doi = {10.1371/journal.pcbi.1002100},
	abstract = {Non-coding {RNAs} ({ncRNAs}) are receiving more and more attention not only as an abundant class of genes, but also as regulatory structural elements (some located in {mRNAs}). A key feature of {RNA} function is its structure. Computational methods were developed early for folding and prediction of {RNA} structure with the aim of assisting in functional analysis. With the discovery of more and more {ncRNAs}, it has become clear that a large fraction of these are highly structured. Interestingly, a large part of the structure is comprised of regular Watson-Crick and {GU} wobble base pairs. This and the increased amount of available genomes have made it possible to employ structure-based methods for genomic screens. The field has moved from folding prediction of single sequences to computational screens for {ncRNAs} in genomic sequence using the {RNA} structure as the main characteristic feature. Whereas early methods focused on energy-directed folding of single sequences, comparative analysis based on structure preserving changes of base pairs has been efficient in improving accuracy, and today this constitutes a key component in genomic screens. Here, we cover the basic principles of {RNA} folding and touch upon some of the concepts in current methods that have been applied in genomic screens for de novo {RNA} structures in searches for novel {ncRNA} genes and regulatory {RNA} structure on {mRNAs}. We discuss the strengths and weaknesses of the different strategies and how they can complement each other.},
	pages = {e1002100},
	number = {8},
	journaltitle = {{PLoS} computational biology},
	author = {Gorodkin, Jan and Hofacker, Ivo L},
	date = {2011-08},
	pmid = {21829340},
	keywords = {Base Sequence, {RNA}, Untranslated, Untranslated: chemistry, Computational Biology, Untranslated: genetics, Algorithms, Molecular Sequence Data, Nucleic Acid Conformation, {RNA} Folding, Biotechnology},
	file = {Attachment:/home/jlagarde/Zotero/storage/2VTBB5H4/Gorodkin, Hofacker - 2011 - From structure prediction to genomic screens for novel non-coding RNAs.pdf:application/pdf}
}

@article{kleene_possible_2001,
	title = {A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells},
	volume = {106},
	issn = {09254773},
	url = {http://www.sciencedirect.com/science/article/pii/S0925477301004130},
	doi = {10.1016/S0925-4773(01)00413-0},
	abstract = {This review focuses on the striking differences in the patterns of transcription and translation in somatic and spermatogenic cells in mammals. In early haploid cells, {mRNA} translation evidently functions to restrict the synthesis of certain proteins, notably protamines, to transcriptionally inert late haploid cells. However, this does not explain why a substantial proportion of virtually all {mRNA} species are sequestered in translationally inactive free-messenger ribonucleoprotein particles (free-{mRNPs}) in meiotic cells, since most {mRNAs} undergo little or no increase in translational activity in transcriptionally active early haploid cells. In addition, most {mRNAs} in meiotic cells appear to be overexpressed because they are never fully loaded on polysomes and the levels of the corresponding protein are often much lower than the {mRNA} and are sometimes undetectable. A large number of genes are expressed at grossly higher levels in meiotic and/or early haploid spermatogenic cells than in somatic cells, yet they too are translated inefficiently. Many genes utilize alternative promoters in somatic and spermatogenic cells. Some of the resulting spermatogenic cell-altered transcripts ({SCATs}) encode proteins with novel functions, while others contain features in their 5′-{UTRs}, secondary structure or upstream reading frames, that are predicted to inhibit translation. This review proposes that the transcriptional machinery is modified to provide access to specific {DNA} sequences during meiosis, which leads to {mRNA} overexpression and creates a need for translational fine-tuning to prevent deleterious consequences of overproducing proteins.},
	pages = {3--23},
	number = {1},
	journaltitle = {Mechanisms of Development},
	author = {Kleene, Kenneth C},
	date = {2001-08},
	keywords = {{ACE}, angiotensin converting enzyme, {CAT}, chloramphenicol acetyl transferase, {CREMt}, free-messenger ribonucleoprotein partic, free-{mRNP}, lactate dehydrogenase C, {LDH}-C, Meiosis, {PHGPx}, phospholipid hydroperoxide glutathione pero, {SCAT}, {SCS}, Spermatogenesis, spermatogenic cell-altered transcript, spermatogenic cell-specific, {TATA}-binding protein, {TBP}, testis-specific cyclic-{AMP} response modulat, Transcriptional promiscuity, Translational regulation},
	file = {Attachment:/home/jlagarde/Zotero/storage/JFMYMDW9/Kleene - 2001 - A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells.pdf:application/pdf}
}

@article{tilgner_comprehensive_2015,
	title = {Comprehensive transcriptome analysis using synthetic long-read sequencing reveals molecular co-association of distant splicing events},
	volume = {33},
	issn = {1087-0156},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25985263},
	doi = {10.1038/nbt.3242},
	abstract = {Alternative splicing shapes mammalian transcriptomes, with many {RNA} molecules undergoing multiple distant alternative splicing events. Comprehensive transcriptome analysis, including analysis of exon co-association in the same molecule, requires deep, long-read sequencing. Here we introduce an {RNA} sequencing method, synthetic long-read {RNA} sequencing ({SLR}-{RNA}-seq), in which small pools (≤1,000 molecules/pool, ≤1 molecule/gene for most genes) of full-length {cDNAs} are amplified, fragmented and short-read-sequenced. We demonstrate that these {RNA} sequences reconstructed from the short reads from each of the pools are mostly close to full length and contain few insertion and deletion errors. We report many previously undescribed isoforms (human brain: ∼13,800 affected genes, 14.5\% of molecules; mouse brain ∼8,600 genes, 18\% of molecules) and up to 165 human distant molecularly associated exon pairs ({dMAPs}) and distant molecularly and mutually exclusive pairs ({dMEPs}). Of 16 associated pairs detected in the mouse brain, 9 are conserved in human. Our results indicate conserved mechanisms that can produce distant but phased features on transcript and proteome isoforms.},
	pages = {736--42},
	number = {7},
	journaltitle = {Nature Biotechnology},
	author = {Tilgner, Hagen and Jahanbani, Fereshteh and Blauwkamp, Tim and Moshrefi, Ali and Jaeger, Erich and Chen, Feng and Harel, Itamar and Bustamante, Carlos D and Rasmussen, Morten and Snyder, Michael P},
	date = {2015-05},
	pmid = {25985263}
}

@article{mikheyev_first_2014,
	title = {A first look at the Oxford Nanopore {MinION} sequencer},
	volume = {14},
	issn = {1755098X},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25187008},
	doi = {10.1111/1755-0998.12324},
	abstract = {Oxford Nanopore's third-generation single-molecule sequencing platform promises to decrease costs for reagents and instrumentation. After a 2-year hiatus following the initial announcement, the first devices have been released as part of an early access program. We explore the performance of this platform by resequencing the lambda phage genome, and amplicons from a snake venom gland transcriptome. Although the handheld {MinION} sequencer can generate more than 150 megabases of raw data in one run, at most a quarter of the resulting reads map to the reference, with less than average 10\% identity. Much of the sequence consists of insertion/deletion errors, or is seemingly without similarity to the template. Using the lambda phage data as an example, although the reads are long, averaging 5 kb, at best 890 ± 1932 bases per mapped read could be matched to the reference without soft clipping. In the course of a 36 h run on the {MinION}, it was possible to resequence the 48 kb lambda phage reference at 16× coverage. Currently, substantially larger projects would not be feasible using the {MinION}. Without increases in accuracy, which would be required for applications such as genome scaffolding and phasing, the current utility of the {MinION} appears limited. Library preparation requires access to a molecular laboratory, and is of similar complexity and cost to that of other next-generation sequencing platforms. The {MinION} is an exciting step in a new direction for single-molecule sequencing, though it will require dramatic decreases in error rates before it lives up to its promise.},
	pages = {n/a--n/a},
	number = {6},
	journaltitle = {Molecular Ecology Resources},
	author = {Mikheyev, Alexander S. and Tin, Mandy M.Y.},
	date = {2014-09},
	pmid = {25187008},
	keywords = {Transcriptome, {DNA}, Sequence Analysis, Animals, High-Throughput Nucleotide Sequencing, Viral, {DNA}: methods, Bacteriophage lambda, Bacteriophage lambda: genetics, {DNA}: instrumentation, Exocrine Glands, Exocrine Glands: chemistry, High-Throughput Nucleotide Sequencing: instrumenta, High-Throughput Nucleotide Sequencing: methods, Snakes, Viral: chemistry, Viral: genetics}
}

@article{zhou_polyc-binding_2012,
	title = {Poly(C)-binding protein 1 ({PCBP}1) mediates housekeeping degradation of mitochondrial antiviral signaling ({MAVS}).},
	volume = {22},
	issn = {1748-7838},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3317556&tool=pmcentrez&rendertype=abstract},
	doi = {10.1038/cr.2011.184},
	abstract = {Mitochondrial antiviral signaling ({MAVS}) is a key adaptor in cellular antiviral innate immunity. We previously identified poly(C)-binding protein 2 ({PCBP}2) as a feedback inhibitor of {MAVS} that facilitates its degradation after viral infection, but little is known about the regulatory potential of poly(C)-binding protein 1 ({PCBP}1), which highly resembles {PCBP}2. Here we report that {PCBP}1 mediates housekeeping degradation of {MAVS} using the same mechanism as {PCBP}2 employs. Overexpression of {PCBP}1 impairs {MAVS}-mediated antiviral responses, while knockdown of {PCBP}1 exerts the opposite effect. The suppression is due to {PCBP}1-induced {MAVS} degradation. We observe that {PCBP}1 and {PCBP}2 show synergy in {MAVS} inhibition, but their expression patterns are distinct: {PCBP}1 is stably and abundantly expressed, while {PCBP}2 shows low basal expression with rapid induction after infection. Individual knockdown and subcellular fractionation analyses reveal that unlike the postinfection inhibitor {PCBP}2, {PCBP}1 continuously eliminates cellular {MAVS}. Our findings unravel a critical role of {PCBP}1 in regulating {MAVS} for both fine-tuning the antiviral immunity and preventing inflammation.},
	pages = {717--27},
	number = {4},
	journaltitle = {Cell research},
	author = {Zhou, Xiang and You, Fuping and Chen, Huihui and Jiang, Zhengfan},
	date = {2012-04},
	pmid = {22105485},
	keywords = {Humans, Gene Expression Regulation, Adaptor Proteins, Gene Knockdown Techniques, {HeLa} Cells, Heterogeneous-Nuclear Ribonucleoproteins, Proteolysis, {RNA} Interference, {RNA}-Binding Proteins, U937 Cells, Heterogeneous-Nuclear Ribonucleoproteins: genetics, Heterogeneous-Nuclear Ribonucleoproteins: metaboli, Infection, Infection: virology, Interferon Type I, Interferon Type I: metabolism, {RNA}-Binding Proteins: genetics, {RNA}-Binding Proteins: metabolism, Signal Transducing, Signal Transducing: genetics, Signal Transducing: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/GLVIC5S2/Zhou et al. - 2012 - Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS).pdf:application/pdf}
}

@article{danckwardt_3_2008,
	title = {3' end {mRNA} processing: molecular mechanisms and implications for health and disease.},
	volume = {27},
	issn = {1460-2075},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2241648&tool=pmcentrez&rendertype=abstract},
	doi = {10.1038/sj.emboj.7601932},
	abstract = {Recent advances in the understanding of the molecular mechanism of {mRNA} 3' end processing have uncovered a previously unanticipated integrated network of transcriptional and {RNA}-processing mechanisms. A variety of human diseases impressively reflect the importance of the precision of the complex 3' end-processing machinery and gene specific deregulation of 3' end processing can result from mutations of {RNA} sequence elements that bind key specific processing factors. Interestingly, more general deregulation of 3' end processing can be caused either by mutations of these processing factors or by the disturbance of the well-coordinated equilibrium between these factors. From a medical perspective, both loss of function and gain of function can be functionally relevant, and an increasing number of different disease entities exemplifies that inappropriate 3' end formation of human {mRNAs} can have a tremendous impact on health and disease. Here, we review the mechanistic hallmarks of {mRNA} 3' end processing, highlight the medical relevance of deregulation of this important step of {mRNA} maturation and illustrate the implications for diagnostic and therapeutic strategies.},
	pages = {482--98},
	number = {3},
	journaltitle = {The {EMBO} journal},
	author = {Danckwardt, Sven and Hentze, Matthias W and Kulozik, Andreas E},
	date = {2008-02},
	pmid = {18256699},
	keywords = {Animals, Genetic, Humans, {RNA}, Transcription, Messenger, Messenger: genetics, Immunity, Inflammation, Messenger: chemistry, Mutation, Neoplasms, Neoplasms: genetics, {RNA} 3' End Processing, Neoplasms: pathology, Genetic: physiology, Immunity: genetics, Inflammation: genetics, Inflammation: metabolism, Inflammation: pathology, Messenger: biosynthesis, Messenger: physiology, Neoplasms: chemistry, Neoplasms: metabolism, {RNA} 3' End Processing: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/5LN726MU/Danckwardt, Hentze, Kulozik - 2008 - 3' end mRNA processing molecular mechanisms and implications for health and disease.pdf:application/pdf}
}

@article{millevoi_interaction_2006,
	title = {An interaction between U2AF 65 and {CF} I(m) links the splicing and 3' end processing machineries.},
	volume = {25},
	issn = {0261-4189},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1618107&tool=pmcentrez&rendertype=abstract},
	doi = {10.1038/sj.emboj.7601331},
	abstract = {The protein factor U2 {snRNP} Auxiliary Factor (U2AF) 65 is an essential component required for splicing and involved in the coupling of splicing and 3' end processing of vertebrate pre-{mRNAs}. Here we have addressed the mechanisms by which U2AF 65 stimulates pre-{mRNA} 3' end processing. We identify an arginine/serine-rich region of U2AF 65 that mediates an interaction with an {RS}-like alternating charge domain of the 59 {kDa} subunit of the human cleavage factor I ({CF} I(m)), an essential 3' processing factor that functions at an early step in the recognition of the 3' end processing signal. Tethered functional analysis shows that the U2AF 65/{CF} I(m) 59 interaction stimulates in vitro 3' end cleavage and polyadenylation. These results therefore uncover a direct role of the U2AF 65/{CF} I(m) 59 interaction in the functional coordination of splicing and 3' end processing.},
	pages = {4854--64},
	number = {20},
	journaltitle = {The {EMBO} journal},
	author = {Millevoi, Stefania and Loulergue, Clarisse and Dettwiler, Sabine and Karaa, Sarah Zeïneb and Keller, Walter and Antoniou, Michael and Vagner, Stéphan},
	date = {2006-10},
	pmid = {17024186},
	keywords = {3' Untranslated Regions, Humans, {RNA} Splicing, Protein Binding, 3' Untranslated Regions: genetics, 3' Untranslated Regions: metabolism, Cell-Free System, Polyadenylation, Protein Structure, Ribonucleoproteins, Tertiary, Two-Hybrid System Techniques, Cell-Free System: metabolism, {mRNA} Cleavage and Polyadenylation Factors, {mRNA} Cleavage and Polyadenylation Factors: genetic, {mRNA} Cleavage and Polyadenylation Factors: metabol, Nuclear Proteins, Nuclear Proteins: genetics, Nuclear Proteins: metabolism, Polyadenylation: physiology, Protein Binding: genetics, Ribonucleoproteins: genetics, Ribonucleoproteins: metabolism, {RNA} Splicing: physiology, Tertiary: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/RQMJIQKE/Millevoi et al. - 2006 - An interaction between U2AF 65 and CF I(m) links the splicing and 3' end processing machineries.pdf:application/pdf}
}

@article{anderson_rna_2005,
	title = {{RNA} turnover: unexpected consequences of being tailed.},
	volume = {15},
	issn = {0960-9822},
	url = {http://www.cell.com/article/S0960982205008614/fulltext},
	doi = {10.1016/j.cub.2005.08.002},
	abstract = {In eukaryotic cells, the 3' poly(A) tails found on {mRNA} influence their stability and translation. The discovery of a second nuclear poly(A) polymerase complex has fueled a series of reports defining a new and unexpected role for 3' end poly(A) tails in the nuclear surveillance and turnover of noncoding {RNAs} and intergenic {mRNAs} of unknown function.},
	pages = {R635--8},
	number = {16},
	journaltitle = {Current biology : {CB}},
	author = {Anderson, James T},
	date = {2005-08},
	pmid = {16111937},
	keywords = {Genetic, {RNA}, Messenger, Messenger: genetics, Messenger: metabolism, Eukaryotic Cells, Models, Multiprotein Complexes, Post-Transcriptional, {RNA} Processing, {RNA} Stability, {RNA} 3' Polyadenylation Signals, {RNA} 3' Polyadenylation Signals: genetics, Eukaryotic Cells: physiology, Multiprotein Complexes: metabolism, Nucleotidyltransferases, Nucleotidyltransferases: metabolism, Post-Transcriptional: genetics, Post-Transcriptional: physiology, {RNA} 3' Polyadenylation Signals: physiology, {RNA} Stability: genetics, {RNA} Stability: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/XFLVJI3N/Anderson - 2005 - RNA turnover unexpected consequences of being tailed.pdf:application/pdf}
}

@article{altschul_basic_1990,
	title = {Basic local alignment search tool},
	volume = {215},
	issn = {0022-2836},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/2231712},
	doi = {10.1016/S0022-2836(05)80360-2},
	abstract = {A new approach to rapid sequence comparison, basic local alignment search tool ({BLAST}), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair ({MSP}) score. Recent mathematical results on the stochastic properties of {MSP} scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward {DNA} and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long {DNA} sequences. In addition to its flexibility and tractability to mathematical analysis, {BLAST} is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.},
	pages = {403--10},
	number = {3},
	journaltitle = {Journal of molecular biology},
	author = {Altschul, S F and Gish, W and Miller, W and Myers, E W and Lipman, D J},
	date = {1990-10},
	pmid = {2231712},
	keywords = {Base Sequence, Databases, Nucleic Acid, Algorithms, Software, Amino Acid Sequence, Factual, Mutation, Sensitivity and Specificity, Sequence Homology, Databases, Factual, Sequence Homology, Nucleic Acid}
}

@article{derti_quantitative_2012,
	title = {A quantitative atlas of polyadenylation in five mammals.},
	volume = {22},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3371698&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.132563.111},
	abstract = {We developed {PolyA}-seq, a strand-specific and quantitative method for high-throughput sequencing of 3' ends of polyadenylated transcripts, and used it to globally map polyadenylation ({polyA}) sites in 24 matched tissues in human, rhesus, dog, mouse, and rat. We show that {PolyA}-seq is as accurate as existing {RNA} sequencing ({RNA}-seq) approaches for digital gene expression ({DGE}), enabling simultaneous mapping of {polyA} sites and quantitative measurement of their usage. In human, we confirmed 158,533 known sites and discovered 280,857 novel sites ({FDR} {\textbackslash}textless 2.5\%). On average 10\% of novel human sites were also detected in matched tissues in other species. Most novel sites represent uncharacterized alternative {polyA} events and extensions of known transcripts in human and mouse, but primarily delineate novel transcripts in the other three species. A total of 69.1\% of known human genes that we detected have multiple {polyA} sites in their 3'{UTRs}, with 49.3\% having three or more. We also detected polyadenylation of noncoding and antisense transcripts, including constitutive and tissue-specific primary {microRNAs}. The canonical {polyA} signal was strongly enriched and positionally conserved in all species. In general, usage of {polyA} sites is more similar within the same tissues across different species than within a species. These quantitative maps of {polyA} usage in evolutionarily and functionally related samples constitute a resource for understanding the regulatory mechanisms underlying alternative polyadenylation.},
	pages = {1173--83},
	number = {6},
	journaltitle = {Genome research},
	author = {Derti, Adnan and Garrett-Engele, Philip and Macisaac, Kenzie D and Stevens, Richard C and Sriram, Shreedharan and Chen, Ronghua and Rohl, Carol A and Johnson, Jason M and Babak, Tomas},
	date = {2012-06},
	pmid = {22454233},
	keywords = {Transcriptome, 3' Untranslated Regions, Animals, Genetic, Humans, Mice, {RNA}, Untranslated, Dogs, Evolution, High-Throughput Nucleotide Sequencing, Macaca mulatta, Mammals, Mammals: genetics, {MicroRNAs}, {MicroRNAs}: genetics, Models, Molecular, Poly A, Polyadenylation, Rats, Poly A: genetics, High-Throughput Nucleotide Sequencing: methods, Chick Embryo, Macaca mulatta: genetics, Polyadenylation: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/45YAF4Y9/Derti et al. - 2012 - A quantitative atlas of polyadenylation in five mammals.pdf:application/pdf}
}

@article{murata_detecting_2014,
	title = {Detecting expressed genes using {CAGE}.},
	volume = {1164},
	issn = {1940-6029},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24927836},
	doi = {10.1007/978-1-4939-0805-9_7},
	abstract = {Cap analysis of gene expression ({CAGE}) provides accurate high-throughput measurement of {RNA} expression. By the large-scale analysis of 5' end of transcripts using {CAGE} method, it enables not only determination of the transcription start site but also prediction of promoter region. Here we provide a protocol for the construction of no-amplification non-tagging {CAGE} libraries for Illumina next-generation sequencers ({nAnT}-{iCAGE}). We have excluded the commonly used {PCR} amplification and cleavage of restriction enzyme to eliminate any potential biases. As a result, we achieved less biased simple preparation process.},
	pages = {67--85},
	journaltitle = {Methods in molecular biology (Clifton, N.J.)},
	author = {Murata, Mitsuyoshi and Nishiyori-Sueki, Hiromi and Kojima-Ishiyama, Miki and Carninci, Piero and Hayashizaki, Yoshihide and Itoh, Masayoshi},
	date = {2014-01},
	pmid = {24927836},
	keywords = {{DNA}, Animals, Base Sequence, Complementary, Genetic, Humans, Mice, Promoter Regions, {RNA}, Transcription Initiation Site, Gene Expression Profiling, Biotinylation, Complementary: genetics, Gene Expression Profiling: methods, Gene Library, High-Throughput Nucleotide Sequencing, Ribonuclease, {RNA}: genetics, High-Throughput Nucleotide Sequencing: methods, Alkaline Phosphatase, Alkaline Phosphatase: metabolism, Biotinylation: methods, Complementary: isolation \& purification, Complementary: metabolism, Exodeoxyribonucleases, Exodeoxyribonucleases: metabolism, Pancreatic, Pancreatic: metabolism, Reverse Transcription, {RNA}: metabolism}
}

@article{ardlie_genotype-tissue_2015,
	title = {The Genotype-Tissue Expression ({GTEx}) pilot analysis: Multitissue gene regulation in humans},
	volume = {348},
	issn = {0036-8075},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25954001},
	doi = {10.1126/science.1262110},
	abstract = {Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of {RNA} sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression ({GTEx}) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci ({eQTL}) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by {eQTLs}. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues.},
	pages = {648--660},
	number = {6235},
	journaltitle = {Science},
	author = {Ardlie, K. G. and Deluca, D. S. and Segre, A. V. and Sullivan, T. J. and Young, T. R. and Gelfand, E. T. and Trowbridge, C. A. and Maller, J. B. and Tukiainen, T. and Lek, M. and Ward, L. D. and Kheradpour, P. and Iriarte, B. and Meng, Y. and Palmer, C. D. and Esko, T. and Winckler, W. and Hirschhorn, J. N. and Kellis, M. and {MacArthur}, D. G. and Getz, G. and Shabalin, A. A. and Li, G. and Zhou, Y.-H. and Nobel, A. B. and Rusyn, I. and Wright, F. A. and Lappalainen, T. and Ferreira, P. G. and Ongen, H. and Rivas, M. A. and Battle, A. and Mostafavi, S. and Monlong, J. and Sammeth, M. and Mele, M. and Reverter, F. and Goldmann, J. M. and Koller, D. and Guigo, R. and {McCarthy}, M. I. and Dermitzakis, E. T. and Gamazon, E. R. and Im, H. K. and Konkashbaev, A. and Nicolae, D. L. and Cox, N. J. and Flutre, T. and Wen, X. and Stephens, M. and Pritchard, J. K. and Tu, Z. and Zhang, B. and Huang, T. and Long, Q. and Lin, L. and Yang, J. and Zhu, J. and Liu, J. and Brown, A. and Mestichelli, B. and Tidwell, D. and Lo, E. and Salvatore, M. and Shad, S. and Thomas, J. A. and Lonsdale, J. T. and Moser, M. T. and Gillard, B. M. and Karasik, E. and Ramsey, K. and Choi, C. and Foster, B. A. and Syron, J. and Fleming, J. and Magazine, H. and Hasz, R. and Walters, G. D. and Bridge, J. P. and Miklos, M. and Sullivan, S. and Barker, L. K. and Traino, H. M. and Mosavel, M. and Siminoff, L. A. and Valley, D. R. and Rohrer, D. C. and Jewell, S. D. and Branton, P. A. and Sobin, L. H. and Barcus, M. and Qi, L. and {McLean}, J. and Hariharan, P. and Um, K. S. and Wu, S. and Tabor, D. and Shive, C. and Smith, A. M. and Buia, S. A. and Undale, A. H. and Robinson, K. L. and Roche, N. and Valentino, K. M. and Britton, A. and Burges, R. and Bradbury, D. and Hambright, K. W. and Seleski, J. and Korzeniewski, G. E. and Erickson, K. and Marcus, Y. and Tejada, J. and Taherian, M. and Lu, C. and Basile, M. and Mash, D. C. and Volpi, S. and Struewing, J. P. and Temple, G. F. and Boyer, J. and Colantuoni, D. and Little, R. and Koester, S. and Carithers, L. J. and Moore, H. M. and Guan, P. and Compton, C. and Sawyer, S. J. and Demchok, J. P. and Vaught, J. B. and Rabiner, C. A. and Lockhart, N. C.},
	date = {2015-05},
	pmid = {25954001}
}

@article{clark_quantitative_2015,
	title = {Quantitative gene profiling of long noncoding {RNAs} with targeted {RNA} sequencing},
	volume = {12},
	issn = {1548-7091},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25751143},
	doi = {10.1038/nmeth.3321},
	abstract = {We compared quantitative {RT}-{PCR} ({qRT}-{PCR}), {RNA}-seq and capture sequencing ({CaptureSeq}) in terms of their ability to assemble and quantify long noncoding {RNAs} and novel coding exons across 20 human tissues. {CaptureSeq} was superior for the detection and quantification of genes with low expression, showed little technical variation and accurately measured differential expression. This approach expands and refines previous annotations and simultaneously generates an expression atlas.},
	pages = {339--42},
	number = {4},
	journaltitle = {Nature Methods},
	author = {Clark, Michael B and Mercer, Tim R and Bussotti, Giovanni and Leonardi, Tommaso and Haynes, Katelin R and Crawford, Joanna and Brunck, Marion E and Cao, Kim-Anh Lê and Thomas, Gethin P and Chen, Wendy Y and Taft, Ryan J and Nielsen, Lars K and Enright, Anton J and Mattick, John S and Dinger, Marcel E},
	date = {2015-03},
	pmid = {25751143},
	keywords = {Sequence Analysis, Humans, {RNA}, Gene Expression Profiling, K562 Cells, Polymerase Chain Reaction, {RNA}, Long Noncoding}
}

@article{kent_blatblast-like_2002,
	title = {{BLAT}–the {BLAST}-like alignment tool.},
	volume = {12},
	issn = {1088-9051},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=187518&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.229202. Article published online before March 2002},
	abstract = {Analyzing vertebrate genomes requires rapid {mRNA}/{DNA} and cross-species protein alignments. A new tool, {BLAT}, is more accurate and 500 times faster than popular existing tools for {mRNA}/{DNA} alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences. {BLAT}'s speed stems from an index of all nonoverlapping K-mers in the genome. This index fits inside the {RAM} of inexpensive computers, and need only be computed once for each genome assembly. {BLAT} has several major stages. It uses the index to find regions in the genome likely to be homologous to the query sequence. It performs an alignment between homologous regions. It stitches together these aligned regions (often exons) into larger alignments (typically genes). Finally, {BLAT} revisits small internal exons possibly missed at the first stage and adjusts large gap boundaries that have canonical splice sites where feasible. This paper describes how {BLAT} was optimized. Effects on speed and sensitivity are explored for various K-mer sizes, mismatch schemes, and number of required index matches. {BLAT} is compared with other alignment programs on various test sets and then used in several genome-wide applications. http://genome.ucsc.edu hosts a web-based {BLAT} server for the human genome.},
	pages = {656--64},
	number = {4},
	journaltitle = {Genome research},
	author = {Kent, W James},
	date = {2002-04},
	pmid = {11932250},
	keywords = {{DNA}, Animals, Humans, Mice, Proteins, {RNA}, Computational Biology, Messenger, Messenger: genetics, Computational Biology: methods, Software, {DNA}: genetics, Protein Biosynthesis, Sequence Alignment, Sequence Alignment: methods, Computational Biology: statistics \& numerical data, Proteins: chemistry, Sequence Alignment: statistics \& numerical data},
	file = {Attachment:/home/jlagarde/Zotero/storage/UF9WL5HG/Kent - 2002 - BLAT--the BLAST-like alignment tool.pdf:application/pdf}
}

@article{gregory_understanding_2008,
	title = {Understanding Evolutionary Trees},
	volume = {1},
	issn = {1936-6426},
	url = {http://link.springer.com/10.1007/s12052-008-0035-x},
	doi = {10.1007/s12052-008-0035-x},
	pages = {121--137},
	number = {2},
	journaltitle = {Evolution: Education and Outreach},
	author = {Gregory, T. Ryan},
	date = {2008-02},
	keywords = {and broken branches the, and covers, branch, clade, common ancestor, crust of the earth, dead, evolution, node, of life, phylogeny, sister taxa, topology, trend, which fills with its, with the great tree},
	file = {Attachment:/home/jlagarde/Zotero/storage/TEJXRIDD/Gregory - 2008 - Understanding Evolutionary Trees.pdf:application/pdf}
}

@article{deaton_cpg_2011,
	title = {{CpG} islands and the regulation of transcription.},
	volume = {25},
	issn = {1549-5477},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3093116&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gad.2037511},
	abstract = {Vertebrate {CpG} islands ({CGIs}) are short interspersed {DNA} sequences that deviate significantly from the average genomic pattern by being {GC}-rich, {CpG}-rich, and predominantly nonmethylated. Most, perhaps all, {CGIs} are sites of transcription initiation, including thousands that are remote from currently annotated promoters. Shared {DNA} sequence features adapt {CGIs} for promoter function by destabilizing nucleosomes and attracting proteins that create a transcriptionally permissive chromatin state. Silencing of {CGI} promoters is achieved through dense {CpG} methylation or polycomb recruitment, again using their distinctive {DNA} sequence composition. {CGIs} are therefore generically equipped to influence local chromatin structure and simplify regulation of gene activity.},
	pages = {1010--22},
	number = {10},
	journaltitle = {Genes \& development},
	author = {Deaton, Aimée M and Bird, Adrian},
	date = {2011-05},
	pmid = {21576262},
	keywords = {Animals, Genetic, Humans, Promoter Regions, Transcription Initiation Site, Gene Expression Regulation, Chromatin, {CpG} Islands, {DNA} Methylation, Gene Silencing, Genetic: genetics, Polycomb-Group Proteins, Chromatin: chemistry, {CpG} Islands: genetics, {CpG} Islands: physiology, Repressor Proteins, Repressor Proteins: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/S9XGZMY9/Deaton, Bird - 2011 - CpG islands and the regulation of transcription.pdf:application/pdf}
}

@article{wu_gmap:_2005,
	title = {{GMAP}: A genomic mapping and alignment program for {mRNA} and {EST} sequences},
	volume = {21},
	issn = {13674803},
	doi = {10.1093/bioinformatics/bti310},
	abstract = {{MOTIVATION}: We introduce {GMAP}, a standalone program for mapping and aligning {cDNA} sequences to a genome. The program maps and aligns a single sequence with minimal startup time and memory requirements, and provides fast batch processing of large sequence sets. The program generates accurate gene structures, even in the presence of substantial polymorphisms and sequence errors, without using probabilistic splice site models. Methodology underlying the program includes a minimal sampling strategy for genomic mapping, oligomer chaining for approximate alignment, sandwich {DP} for splice site detection, and microexon identification with statistical significance testing. {RESULTS}: On a set of human messenger {RNAs} with random mutations at a 1 and 3\% rate, {GMAP} identified all splice sites accurately in over 99.3\% of the sequences, which was one-tenth the error rate of existing programs. On a large set of human expressed sequence tags, {GMAP} provided higher-quality alignments more often than blat did. On a set of Arabidopsis {cDNAs}, {GMAP} performed comparably with {GeneSeqer}. In these experiments, {GMAP} demonstrated a several-fold increase in speed over existing programs. {AVAILABILITY}: Source code for gmap and associated programs is available at http://www.gene.com/share/gmap {SUPPLEMENTARY} {INFORMATION}: http://www.gene.com/share/gmap.},
	pages = {1859--1875},
	journaltitle = {Bioinformatics},
	author = {Wu, Thomas D. and Watanabe, Colin K.},
	date = {2005},
	pmid = {15728110}
}

@article{howald_combining_2012,
	title = {Combining {RT}-{PCR}-seq and {RNA}-seq to catalog all genic elements encoded in the human genome.},
	volume = {22},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3431487&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.134478.111},
	abstract = {Within the {ENCODE} Consortium, {GENCODE} aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon-exon junctions were evaluated by {RT}-{PCR} amplification followed by highly multiplexed sequencing readout, a method we called {RT}-{PCR}-seq. Seventy-nine percent of all assessed junctions are confirmed by this evaluation procedure, demonstrating the high quality of the {GENCODE} gene set. {RT}-{PCR}-seq was also efficient to screen gene models predicted using the Human Body Map ({HBM}) {RNA}-seq data. We validated 73\% of these predictions, thus confirming 1168 novel genes, mostly noncoding, which will further complement the {GENCODE} annotation. Our novel experimental validation pipeline is extremely sensitive, far more than unbiased transcriptome profiling through {RNA} sequencing, which is becoming the norm. For example, exon-exon junctions unique to {GENCODE} annotated transcripts are five times more likely to be corroborated with our targeted approach than with extensive large human transcriptome profiling. Data sets such as the {HBM} and {ENCODE} {RNA}-seq data fail sampling of low-expressed transcripts. Our {RT}-{PCR}-seq targeted approach also has the advantage of identifying novel exons of known genes, as we discovered unannotated exons in ∼11\% of assessed introns. We thus estimate that at least 18\% of known loci have yet-unannotated exons. Our work demonstrates that the cataloging of all of the genic elements encoded in the human genome will necessitate a coordinated effort between unbiased and targeted approaches, like {RNA}-seq and {RT}-{PCR}-seq.},
	pages = {1698--710},
	number = {9},
	journaltitle = {Genome research},
	author = {Howald, Cédric and Tanzer, Andrea and Chrast, Jacqueline and Kokocinski, Felix and Derrien, Thomas and Walters, Nathalie and Gonzalez, Jose M and Frankish, Adam and Aken, Bronwen L and Hourlier, Thibaut and Vogel, Jan-hinnerk and White, Simon and Searle, Stephen and Harrow, Jennifer and Hubbard, Tim J and Guigó, Roderic and Reymond, Alexandre},
	date = {2012-09},
	pmid = {22955982},
	keywords = {Transcriptome, Human, Genome, Humans, {RNA}, Computational Biology, Exons, Gene Expression Profiling, Messenger, Messenger: genetics, Reproducibility of Results, Open Reading Frames, Computational Biology: methods, Introns, Gene Expression Profiling: methods, High-Throughput Nucleotide Sequencing, Messenger: chemistry, Molecular Sequence Annotation, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, {RNA} Isoforms},
	file = {Attachment:/home/jlagarde/Zotero/storage/AHRIW6N7/Howald et al. - 2012 - Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome.pdf:application/pdf}
}

@article{kawaji_comparison_2014,
	title = {Comparison of {CAGE} and {RNA}-seq transcriptome profiling using clonally amplified and single-molecule next-generation sequencing.},
	volume = {24},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3975069&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.156232.113},
	abstract = {{CAGE} (cap analysis gene expression) and {RNA}-seq are two major technologies used to identify transcript abundances as well as structures. They measure expression by sequencing from either the 5' end of capped molecules ({CAGE}) or tags randomly distributed along the length of a transcript ({RNA}-seq). Library protocols for clonally amplified (Illumina, {SOLiD}, 454 Life Sciences [Roche], Ion Torrent), second-generation sequencing platforms typically employ {PCR} preamplification prior to clonal amplification, while third-generation, single-molecule sequencers can sequence unamplified libraries. Although these transcriptome profiling platforms have been demonstrated to be individually reproducible, no systematic comparison has been carried out between them. Here we compare {CAGE}, using both second- and third-generation sequencers, and {RNA}-seq, using a second-generation sequencer based on a panel of {RNA} mixtures from two human cell lines to examine power in the discrimination of biological states, detection of differentially expressed genes, linearity of measurements, and quantification reproducibility. We found that the quantified levels of gene expression are largely comparable across platforms and conclude that {CAGE} and {RNA}-seq are complementary technologies that can be used to improve incomplete gene models. We also found systematic bias in the second- and third-generation platforms, which is likely due to steps such as linker ligation, cleavage by restriction enzymes, and {PCR} amplification. This study provides a perspective on the performance of these platforms, which will be a baseline in the design of further experiments to tackle complex transcriptomes uncovered in a wide range of cell types.},
	pages = {708--17},
	number = {4},
	journaltitle = {Genome research},
	author = {Kawaji, Hideya and Lizio, Marina and Itoh, Masayoshi and Kanamori-Katayama, Mutsumi and Kaiho, Ai and Nishiyori-Sueki, Hiromi and Shin, Jay W and Kojima-Ishiyama, Miki and Kawano, Mitsuoki and Murata, Mitsuyoshi and Ninomiya-Fukuda, Noriko and Ishikawa-Kato, Sachi and Nagao-Sato, Sayaka and Noma, Shohei and Hayashizaki, Yoshihide and Forrest, Alistair R R and Carninci, Piero},
	date = {2014-04},
	pmid = {24676093},
	file = {Attachment:/home/jlagarde/Zotero/storage/WGDN47D4/Kawaji et al. - 2014 - Comparison of CAGE and RNA-seq transcriptome profiling using clonally amplified and single-molecule next-generati.pdf:application/pdf}
}

@article{yeku_rapid_2011,
	title = {Rapid amplification of {cDNA} ends ({RACE}).},
	volume = {703},
	issn = {1940-6029},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21125486},
	doi = {10.1007/978-1-59745-248-9_8},
	abstract = {Rapid Amplification of {cDNA} ends ({RACE}) provides an inexpensive and powerful tool to quickly obtain full-length {cDNA} when the sequence is only partially known. Starting with an {mRNA} mixture, gene-specific primers generated from the known regions of the gene and non-specific anchors, full-length sequences can be identified in as little as 3 days. {RACE} can also be used to identify alternative transcripts of a gene when the partial or complete sequence of only one transcript is known. In the following sections, we outline details for rapid amplification of 5(') and 3(') {cDNA} ends using the "new {RACE}" technique.},
	pages = {107--22},
	journaltitle = {Methods in molecular biology (Clifton, N.J.)},
	author = {Yeku, Oladapo and Frohman, Michael A},
	date = {2011-01},
	pmid = {21125486},
	keywords = {{DNA}, Complementary, {RNA}, Messenger, Messenger: genetics, Complementary: genetics, {DNA} Primers, Oligonucleotides, Nucleic Acid Amplification Techniques, Nucleic Acid Amplification Techniques: methods, {DNA} Primers: genetics, Oligonucleotides: genetics, {RNA}, Messenger, {DNA}, Complementary},
	file = {Attachment:/home/jlagarde/Zotero/storage/5FEAQTUN/Yeku, Frohman - 2011 - Rapid amplification of cDNA ends (RACE).pdf:application/pdf}
}

@article{tilgner_accurate_2013,
	title = {Accurate identification and analysis of human {mRNA} isoforms using deep long read sequencing.},
	volume = {3},
	issn = {2160-1836},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3583448&tool=pmcentrez&rendertype=abstract},
	doi = {10.1534/g3.112.004812},
	abstract = {Precise identification of {RNA}-coding regions and transcriptomes of eukaryotes is a significant problem in biology. Currently, eukaryote transcriptomes are analyzed using deep short-read sequencing experiments of complementary {DNAs}. The resulting short-reads are then aligned against a genome and annotated junctions to infer biological meaning. Here we use long-read complementary {DNA} datasets for the analysis of a eukaryotic transcriptome and generate two large datasets in the human K562 and {HeLa} S3 cell lines. Both data sets comprised at least 4 million reads and had median read lengths greater than 500 bp. We show that annotation-independent alignments of these reads provide partial gene structures that are very much in-line with annotated gene structures, 15\% of which have not been obtained in a previous de novo analysis of short reads. For long-noncoding {RNAs} (i.e., {lncRNA}) genes, however, we find an increased fraction of novel gene structures among our alignments. Other important aspects of transcriptome analysis, such as the description of cell type-specific splicing, can be performed in an accurate, reliable and completely annotation-free manner, making it ideal for the analysis of transcriptomes of newly sequenced genomes. Furthermore, we demonstrate that long read sequence can be assembled into full-length transcripts with considerable success. Our method is applicable to all long read sequencing technologies.},
	pages = {387--97},
	number = {3},
	journaltitle = {G3 (Bethesda, Md.)},
	author = {Tilgner, Hagen and Raha, Debasish and Habegger, Lukas and Mohiuddin, Mohammed and Gerstein, Mark and Snyder, Michael},
	date = {2013-03},
	pmid = {23450794},
	keywords = {Transcriptome, Human, {DNA}, Sequence Analysis, Complementary, Genome, Humans, {RNA}, Exons, Gene Expression Profiling, Reproducibility of Results, Long Noncoding, Long Noncoding: genetics, Introns, Alternative Splicing, Chromosome Mapping, Complementary: genetics, Gene Expression Profiling: methods, Gene Library, {HeLa} Cells, K562 Cells, Molecular Sequence Annotation, Sensitivity and Specificity, {RNA} Isoforms, {RNA} Isoforms: genetics, Complementary: analysis, Long Noncoding: analysis, Ribosomes, Ribosomes: genetics, {RNA} Isoforms: analysis},
	file = {Attachment:/home/jlagarde/Zotero/storage/FYJJTLED/Tilgner et al. - 2013 - Accurate identification and analysis of human mRNA isoforms using deep long read sequencing.pdf:application/pdf}
}

@article{pohl_bwtool:_2014,
	title = {bwtool: a tool for {bigWig} files.},
	volume = {30},
	issn = {1367-4811},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4029031&tool=pmcentrez&rendertype=abstract},
	doi = {10.1093/bioinformatics/btu056},
	abstract = {{UNLABELLED}: {BigWig} files are a compressed, indexed, binary format for genome-wide signal data for calculations (e.g. {GC} percent) or experiments (e.g. {ChIP}-seq/{RNA}-seq read depth). bwtool is a tool designed to read {bigWig} files rapidly and efficiently, providing functionality for extracting data and summarizing it in several ways, globally or at specific regions. Additionally, the tool enables the conversion of the positions of signal data from one genome assembly to another, also known as 'lifting'. We believe bwtool can be useful for the analyst frequently working with {bigWig} data, which is becoming a standard format to represent functional signals along genomes. The article includes supplementary examples of running the software. {AVAILABILITY} {AND} {IMPLEMENTATION}: The C source code is freely available under the {GNU} public license v3 at http://cromatina.crg.eu/bwtool.},
	pages = {1618--9},
	number = {11},
	journaltitle = {Bioinformatics (Oxford, England)},
	author = {Pohl, Andy and Beato, Miguel},
	date = {2014-06},
	pmid = {24489365},
	keywords = {Genomics, {DNA}, Sequence Analysis, {RNA}, Software, Chromatin Immunoprecipitation, Genomics: methods, Histones, Histones: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/U7I2M9HJ/Pohl, Beato - 2014 - bwtool a tool for bigWig files.pdf:application/pdf}
}

@article{mercer_targeted_2012,
	title = {Targeted {RNA} sequencing reveals the deep complexity of the human transcriptome.},
	volume = {30},
	issn = {1546-1696},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3710462&tool=pmcentrez&rendertype=abstract},
	doi = {10.1038/nbt.2024},
	abstract = {Transcriptomic analyses have revealed an unexpected complexity to the human transcriptome, whose breadth and depth exceeds current {RNA} sequencing capability. Using tiling arrays to target and sequence select portions of the transcriptome, we identify and characterize unannotated transcripts whose rare or transient expression is below the detection limits of conventional sequencing approaches. We use the unprecedented depth of coverage afforded by this technique to reach the deepest limits of the human transcriptome, exposing widespread, regulated and remarkably complex noncoding transcription in intergenic regions, as well as unannotated exons and splicing patterns in even intensively studied protein-coding loci such as p53 and {HOX}. The data also show that intermittent sequenced reads observed in conventional {RNA} sequencing data sets, previously dismissed as noise, are in fact indicative of unassembled rare transcripts. Collectively, these results reveal the range, depth and complexity of a human transcriptome that is far from fully characterized.},
	pages = {99--104},
	number = {1},
	journaltitle = {Nature biotechnology},
	author = {Mercer, Tim R and Gerhardt, Daniel J and Dinger, Marcel E and Crawford, Joanna and Trapnell, Cole and Jeddeloh, Jeffrey a and Mattick, John S and Rinn, John L},
	date = {2012-01},
	pmid = {22081020},
	keywords = {Transcriptome, {DNA}, Sequence Analysis, Humans, {RNA}, Untranslated, Exons, Intergenic, Untranslated: genetics, Open Reading Frames, {RNA}: methods, Exons: genetics, Gene Expression, Intergenic: genetics, Molecular Sequence Annotation, Open Reading Frames: genetics, Transcriptome: genetics},
	file = {Attachment:/home/jlagarde/Zotero/storage/FDN4PBYF/Mercer et al. - 2012 - Targeted RNA sequencing reveals the deep complexity of the human transcriptome.pdf:application/pdf}
}

@article{brosius_waste_2005,
	title = {Waste not, want not–transcript excess in multicellular eukaryotes},
	volume = {21},
	url = {http://www.sciencedirect.com/science/article/pii/S0168952505000600},
	doi = {10.1038/nature03016},
	pages = {26--27},
	number = {5},
	journaltitle = {{TRENDS} in Genetics},
	author = {Brosius, J},
	date = {2005},
	file = {Attachment:/home/jlagarde/Zotero/storage/A3X5DWN7/Brosius - 2005 - Waste not, want not--transcript excess in multicellular eukaryotes.pdf:application/pdf}
}

@article{korf_genomics:_2013,
	title = {Genomics: the state of the art in {RNA}-seq analysis.},
	volume = {10},
	issn = {1548-7105},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24296473},
	doi = {10.1038/nmeth.2735},
	abstract = {{RNA}-seq is a recent and immensely popular technology for cataloging and comparing gene expression. Two papers from the international {RGASP} consortium report on large-scale competitions to identify the best algorithms for {RNA}-seq analysis, with surprising variability in the results.},
	pages = {1165--6},
	journaltitle = {Nature Methods},
	author = {Korf, Ian},
	date = {2013},
	pmid = {24296473},
	keywords = {Sequence Analysis, Animals, Humans, {RNA}, {RNA} Splicing, Computational Biology, Computational Biology: methods, {RNA}: methods, Sequence Alignment, Sequence Alignment: methods}
}

@article{adams_rapid_1993,
	title = {Rapid {cDNA} sequencing (expressed sequence tags) from a directionally cloned human infant brain {cDNA} library.},
	volume = {4},
	issn = {1061-4036},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8401585},
	doi = {10.1038/ng0893-373},
	abstract = {A human infant brain {cDNA} library, made specifically for production of expressed sequence tags ({ESTs}) was evaluated by partial sequencing of over 1,600 clones. Advantages of this library, constructed for {EST} sequencing, include the use of directional cloning, size selection, very low numbers of mitochondrial and ribosomal transcripts, short {polyA} tails, few non-recombinants and a broad representation of transcripts. 37\% of the clones were identified, based on matches to over 320 different genes in the public databases. Of these, two proteins similar to the Alzheimer's disease amyloid precursor protein were identified.},
	pages = {373--80},
	number = {4},
	journaltitle = {Nature genetics},
	author = {Adams, M D and Soares, M B and Kerlavage, A R and Fields, C and Venter, J C},
	date = {1993-08},
	pmid = {8401585},
	keywords = {{DNA}, Base Sequence, Complementary, Complementary: chemistry, Humans, Proteins, Proteins: genetics, Amino Acid, Amino Acid Sequence, Brain, Cloning, Complementary: genetics, Gene Expression, Gene Library, Infant, Molecular, Molecular Sequence Data, Oligodeoxyribonucleotides, Sequence Homology, Proteins: chemistry, Amyloid beta-Protein Precursor, Amyloid beta-Protein Precursor: chemistry, Amyloid beta-Protein Precursor: genetics, Brain: metabolism}
}

@article{mudge_functional_2013,
	title = {Functional transcriptomics in the post-{ENCODE} era.},
	volume = {23},
	issn = {1549-5469},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3847767&tool=pmcentrez&rendertype=abstract},
	doi = {10.1101/gr.161315.113},
	abstract = {The last decade has seen tremendous effort committed to the annotation of the human genome sequence, most notably perhaps in the form of the {ENCODE} project. One of the major findings of {ENCODE}, and other genome analysis projects, is that the human transcriptome is far larger and more complex than previously thought. This complexity manifests, for example, as alternative splicing within protein-coding genes, as well as in the discovery of thousands of long noncoding {RNAs}. It is also possible that significant numbers of human transcripts have not yet been described by annotation projects, while existing transcript models are frequently incomplete. The question as to what proportion of this complexity is truly functional remains open, however, and this ambiguity presents a serious challenge to genome scientists. In this article, we will discuss the current state of human transcriptome annotation, drawing on our experience gained in generating the {GENCODE} gene annotation set. We highlight the gaps in our knowledge of transcript functionality that remain, and consider the potential computational and experimental strategies that can be used to help close them. We propose that an understanding of the true overlap between transcriptional complexity and functionality will not be gained in the short term. However, significant steps toward obtaining this knowledge can now be taken by using an integrated strategy, combining all of the experimental resources at our disposal.},
	pages = {1961--73},
	number = {12},
	journaltitle = {Genome research},
	author = {Mudge, Jonathan M and Frankish, Adam and Harrow, Jennifer},
	date = {2013-12},
	pmid = {24172201},
	keywords = {Transcriptome, Human, Genomics, Animals, Genetic, Genome, Humans, Proteins, Proteins: genetics, {RNA}, Databases, Long Noncoding, Alternative Splicing, Evolution, Genomics: methods, Molecular, Molecular Sequence Annotation, Proteomics, Sequence Alignment},
	file = {Attachment:/home/jlagarde/Zotero/storage/CQ9ADQL7/Mudge, Frankish, Harrow - 2013 - Functional transcriptomics in the post-ENCODE era.pdf:application/pdf}
}

@article{boley_genome-guided_2014,
	title = {Genome-guided transcript assembly by integrative analysis of {RNA} sequence data.},
	volume = {32},
	issn = {1546-1696},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24633242},
	doi = {10.1038/nbt.2850},
	abstract = {The identification of full length transcripts entirely from short-read {RNA} sequencing data ({RNA}-seq) remains a challenge in the annotation of genomes. Here we describe an automated pipeline for genome annotation that integrates {RNA}-seq and gene-boundary data sets, which we call Generalized {RNA} Integration Tool, or {GRIT}. Applying {GRIT} to Drosophila melanogaster short-read {RNA}-seq, cap analysis of gene expression ({CAGE}) and poly(A)-site-seq data collected for the {modENCODE} project, we recovered the vast majority of previously annotated transcripts and doubled the total number of transcripts cataloged. We found that 20\% of protein coding genes encode multiple protein-localization signals and that, in 20-d-old adult fly heads, genes with multiple polyadenylation sites are more common than genes with alternative splicing or alternative promoters. {GRIT} demonstrates 30\% higher precision and recall than the most widely used transcript assembly tools. {GRIT} will facilitate the automated generation of high-quality genome annotations without the need for extensive manual annotation.},
	pages = {341--6},
	number = {4},
	journaltitle = {Nature biotechnology},
	author = {Boley, Nathan and Stoiber, Marcus H and Booth, Benjamin W and Wan, Kenneth H and Hoskins, Roger A and Bickel, Peter J and Celniker, Susan E and Brown, James B},
	date = {2014-04},
	pmid = {24633242}
}

@article{blanco_computational_2009,
	title = {Computational gene annotation in new genome assemblies using {GeneID}},
	volume = {537},
	issn = {1064-3745},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/19378148},
	doi = {10.1007/978-1-59745-251-9_12},
	abstract = {The sequence of many eukaryotic genomes is nowadays available from a personal computer to any researcher in the world-wide scientific community. However, the sequences are worthless without the adequate annotation of the biological meaningful elements. The annotation of the genes, in particular, is a challenging task that can not be tackled without the aid of specific bioinformatics tools. We present in this chapter a simple protocol mainly based on the combination of the program {GeneID} and other computational tools to annotate the location of a gene, which was previously annotated in D. melanogaster, in the recently assembled genome of D. yakuba.},
	pages = {243--61},
	journaltitle = {Methods in molecular biology (Clifton, N.J.)},
	author = {Blanco, Enrique and Abril, Josep F},
	date = {2009-01},
	pmid = {19378148},
	keywords = {Genomics, Base Sequence, Genetic, Genome, Databases, Software, Amino Acid Sequence, Genes, Genomics: methods, Molecular Sequence Data, Sequence Alignment, Sequence Alignment: methods}
}

@article{keller_novel_2011,
	title = {A novel hybrid gene prediction method employing protein multiple sequence alignments.},
	volume = {27},
	issn = {1367-4811},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/21216780},
	doi = {10.1093/bioinformatics/btr010},
	abstract = {{MOTIVATION}: As improved {DNA} sequencing techniques have increased enormously the speed of producing new eukaryotic genome assemblies, the further development of automated gene prediction methods continues to be essential. While the classification of proteins into families is a task heavily relying on correct gene predictions, it can at the same time provide a source of additional information for the prediction, complementary to those presently used. {RESULTS}: We extended the gene prediction software {AUGUSTUS} by a method that employs block profiles generated from multiple sequence alignments as a protein signature to improve the accuracy of the prediction. Equipped with profiles modelling human dynein heavy chain ({DHC}) proteins and other families, {AUGUSTUS} was run on the genomic sequences known to contain members of these families. Compared with {AUGUSTUS}' ab initio version, the rate of genes predicted with high accuracy showed a dramatic increase. {AVAILABILITY}: The {AUGUSTUS} project web page is located at http://augustus.gobics.de, with the executable program as well as the source code available for download.},
	pages = {757--63},
	number = {6},
	journaltitle = {Bioinformatics (Oxford, England)},
	author = {Keller, Oliver and Kollmar, Martin and Stanke, Mario and Waack, Stephan},
	date = {2011-03},
	pmid = {21216780},
	keywords = {Sequence Analysis, Animals, Genetic, Humans, Computational Biology, Exons, Algorithms, Computational Biology: methods, Software, Amino Acid Sequence, Models, Multigene Family, Protein, Sequence Alignment, Automatic Data Processing, Automatic Data Processing: methods, Dyneins, Dyneins: genetics, Protein: methods}
}

@article{ravasi_atlas_2010,
	title = {An atlas of combinatorial transcriptional regulation in mouse and man.},
	volume = {140},
	issn = {1097-4172},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2836267&tool=pmcentrez&rendertype=abstract},
	doi = {10.1016/j.cell.2010.01.044},
	abstract = {Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse {DNA}-binding transcription factors ({TFs}). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected {TFs} are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of {TF} combinations for determining cell fate, and they lead to the identification of a {SMAD}3/{FLI}1 complex expressed during development of immunity. The availability of large {TF} combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.},
	pages = {744--52},
	number = {5},
	journaltitle = {Cell},
	author = {Ravasi, Timothy and Suzuki, Harukazu and Cannistraci, Carlo Vittorio and Katayama, Shintaro and Bajic, Vladimir B and Tan, Kai and Akalin, Altuna and Schmeier, Sebastian and Kanamori-Katayama, Mutsumi and Bertin, Nicolas and Carninci, Piero and Daub, Carsten O and Forrest, Alistair R R and Gough, Julian and Grimmond, Sean and Han, Jung-Hoon and Hashimoto, Takehiro and Hide, Winston and Hofmann, Oliver and Kamburov, Atanas and Kaur, Mandeep and Kawaji, Hideya and Kubosaki, Atsutaka and Lassmann, Timo and van Nimwegen, Erik and {MacPherson}, Cameron Ross and Ogawa, Chihiro and Radovanovic, Aleksandar and Schwartz, Ariel and Teasdale, Rohan D and Tegnér, Jesper and Lenhard, Boris and Teichmann, Sarah A and Arakawa, Takahiro and Ninomiya, Noriko and Murakami, Kayoko and Tagami, Michihira and Fukuda, Shiro and Imamura, Kengo and Kai, Chikatoshi and Ishihara, Ryoko and Kitazume, Yayoi and Kawai, Jun and Hume, David A and Ideker, Trey and Hayashizaki, Yoshihide},
	date = {2010-03},
	pmid = {20211142},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, Organ Specificity, Cell Differentiation, Evolution, Gene Regulatory Networks, Molecular, Transcription Factors, Transcription Factors: metabolism, Monocytes, Monocytes: cytology, Smad3 Protein, Smad3 Protein: metabolism, Trans-Activators, Trans-Activators: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/FSRMMV3P/Ravasi et al. - 2010 - An atlas of combinatorial transcriptional regulation in mouse and man.pdf:application/pdf}
}

@article{andersson_atlas_2014,
	title = {An atlas of active enhancers across human cell types and tissues.},
	volume = {507},
	issn = {1476-4687},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24670763},
	doi = {10.1038/nature12787},
	abstract = {Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the {FANTOM}5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with {CpG}-poor messenger {RNA} promoters but produce bidirectional, exosome-sensitive, relatively short unspliced {RNAs}, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online {FANTOM}5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.},
	pages = {455--61},
	number = {7493},
	journaltitle = {Nature},
	author = {Andersson, Robin and Gebhard, Claudia and Miguel-Escalada, Irene and Hoof, Ilka and Bornholdt, Jette and Boyd, Mette and Chen, Yun and Zhao, Xiaobei and Schmidl, Christian and Suzuki, Takahiro and Ntini, Evgenia and Arner, Erik and Valen, Eivind and Li, Kang and Schwarzfischer, Lucia and Glatz, Dagmar and Raithel, Johanna and Lilje, Berit and Rapin, Nicolas and Bagger, Frederik Otzen and Jørgensen, Mette and Andersen, Peter Refsing and Bertin, Nicolas and Rackham, Owen and Burroughs, A Maxwell and Baillie, J Kenneth and Ishizu, Yuri and Shimizu, Yuri and Furuhata, Erina and Maeda, Shiori and Negishi, Yutaka and Mungall, Christopher J and Meehan, Terrence F and Lassmann, Timo and Itoh, Masayoshi and Kawaji, Hideya and Kondo, Naoto and Kawai, Jun and Lennartsson, Andreas and Daub, Carsten O and Heutink, Peter and Hume, David A and Jensen, Torben Heick and Suzuki, Harukazu and Hayashizaki, Yoshihide and Müller, Ferenc and Forrest, Alistair R R and Carninci, Piero and Rehli, Michael and Sandelin, Albin},
	date = {2014-03},
	pmid = {24670763},
	keywords = {Genetic, Humans, Promoter Regions, {RNA}, Transcription Initiation Site, Gene Expression Regulation, Messenger, Messenger: genetics, Organ Specificity, Cells, Cultured, Atlases as Topic, Cell Line, Cluster Analysis, Enhancer Elements, Gene Expression Regulation: genetics, Genetic Predisposition to Disease, Genetic Predisposition to Disease: genetics, Genetic: genetics, {HeLa} Cells, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Single Nucleotide: genetics, Messenger: biosynthesis, Transcription Initiation},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/XH24U4D6/Andersson et al. - 2014 - An atlas of active enhancers across human cell typ.pdf:application/pdf}
}

@article{huttenhofer_non-coding_2005,
	title = {Non-coding {RNAs}: hope or hype?},
	volume = {21},
	issn = {0168-9525},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15851066},
	doi = {10.1016/j.tig.2005.03.007},
	abstract = {The past four years have seen an explosion in the number of detected {RNA} transcripts with no apparent protein-coding potential. This has led to speculation that non-protein-coding {RNAs} ({ncRNAs}) might be as important as proteins in the regulation of vital cellular functions. However, there has been significantly less progress in actually demonstrating the functions of these transcripts. In this article, we review the results of recent experiments that show that transcription of non-protein-coding {RNA} is far more widespread than was previously anticipated. Although some {ncRNAs} act as molecular switches that regulate gene expression, the function of many {ncRNAs} is unknown. New experimental and computational approaches are emerging that will help determine whether these newly identified transcription products are evidence of important new biochemical pathways or are merely 'junk' {RNA} generated by the cell as a by-product of its functional activities.},
	pages = {289--97},
	number = {5},
	journaltitle = {Trends in genetics : {TIG}},
	author = {Hüttenhofer, Alexander and Schattner, Peter and Polacek, Norbert},
	date = {2005-05},
	pmid = {15851066},
	keywords = {Animals, Genetic, Genome, Humans, {RNA}, Transcription, Untranslated, Gene Expression Regulation, Untranslated: genetics, Untranslated: metabolism, Forecasting, Gene Expression Regulation: genetics, Genetic: genetics}
}

@article{brosius_waste_2005-1,
	title = {Waste not, want not–transcript excess in multicellular eukaryotes.},
	volume = {21},
	issn = {0168-9525},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/15851065},
	doi = {10.1016/j.tig.2005.02.014},
	abstract = {There is growing evidence that mammalian genomes produce thousands of transcripts that do not encode proteins, and this {RNA} class might even rival the complexity of {mRNAs}. There is no doubt that a number of these non-protein-coding {RNAs} have important regulatory functions in the cell. However, do all transcripts have a function or are many of them products of fortuitous transcription with no function? The second scenario is mirrored by numerous alternative-splicing events that lead to truncated proteins. Nevertheless, analogous to 'superfluous' genomic {DNA}, aberrant transcripts or processing products embody evolutionary potential and provide novel {RNAs} that natural selection can act on.},
	pages = {287--8},
	number = {5},
	journaltitle = {Trends in genetics : {TIG}},
	author = {Brosius, Jürgen},
	date = {2005-05},
	pmid = {15851065},
	keywords = {Animals, Genetic, Genome, Humans, {RNA}, Transcription, Untranslated, Gene Expression Regulation, Messenger, Messenger: genetics, Alternative Splicing, Eukaryotic Cells, Evolution, Gene Expression Regulation: genetics, Molecular, {RNA} Precursors, {RNA} Precursors: genetics, Selection, Untranslated: physiology, Alternative Splicing: genetics, Eukaryotic Cells: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/WT3EAIWJ/Brosius - 2005 - Waste not, want not--transcript excess in multicellular eukaryotes.pdf:application/pdf}
}

@article{struhl_transcriptional_2007,
	title = {Transcriptional noise and the fidelity of initiation by {RNA} polymerase {II}},
	volume = {14},
	issn = {1545-9993},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/17277804},
	doi = {10.1038/nsmb0207-103},
	abstract = {Eukaryotes transcribe much of their genomes, but little is known about the fidelity of transcriptional initiation by {RNA} polymerase {II} in vivo. I suggest that 90\% of Pol {II} initiation events in yeast represent transcriptional noise, and that the specificity of initiation is comparable to that of {DNA}-binding proteins and other biological processes. This emphasizes the need to develop criteria that distinguish transcriptional noise from transcription with a biological function.},
	pages = {103--5},
	number = {2},
	journaltitle = {Nature structural \& molecular biology},
	author = {Struhl, Kevin},
	date = {2007-02},
	pmid = {17277804},
	keywords = {Genetic, Genome, {RNA}, Transcription, Messenger, Fungal, Saccharomyces cerevisiae, Saccharomyces cerevisiae: genetics, Messenger: biosynthesis, Fungal: biosynthesis, {RNA} Polymerase {II}, {RNA} Polymerase {II}: physiology, Saccharomyces cerevisiae: metabolism}
}

@article{zhang_long_2013,
	title = {Long non-coding {RNA}: a new player in cancer.},
	volume = {6},
	issn = {1756-8722},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3693878&tool=pmcentrez&rendertype=abstract},
	doi = {10.1186/1756-8722-6-37},
	abstract = {Emerging evidence showed that long non-coding {RNAs} ({lncRNAs}) play important roles in a wide range of biological processes and dysregulated {lncRNAs} are involved in many complex human diseases, including cancer. Although a few {lncRNAs}' functions in cancer have been characterized, the detailed regulatory mechanisms of majority of {lncRNAs} in cancer initiation and progression remain largely unknown. In this review, we summarized recent progress on the mechanisms and functions of {lncRNAs} in cancer, especially focusing on the oncogenic and tumor suppressive roles of the newly identified {lncRNAs}, and the pathways these novel molecules might be involved in. Their potentials as biomarkers for diagnosis and prognosis in cancer are also discussed in this paper.},
	pages = {37},
	journaltitle = {Journal of hematology \& oncology},
	author = {Zhang, Hua and Chen, Zhenhua and Wang, Xinxin and Huang, Zunnan and He, Zhiwei and Chen, Yueqin},
	date = {2013-01},
	pmid = {23725405},
	keywords = {Humans, {RNA}, Gene Expression Regulation, Long Noncoding, Long Noncoding: genetics, Long Noncoding: metabolism, Alternative Splicing, Neoplasms, Neoplasms: genetics, Neoplastic, Prognosis, Signal Transduction, Neoplasms: metabolism},
	file = {Attachment:/home/jlagarde/Zotero/storage/M5YRI6U2/Zhang et al. - 2013 - Long non-coding RNA a new player in cancer.pdf:application/pdf}
}

@article{ulitsky_lincrnas:_2013,
	title = {{lincRNAs}: genomics, evolution, and mechanisms.},
	volume = {154},
	issn = {1097-4172},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3924787&tool=pmcentrez&rendertype=abstract},
	doi = {10.1016/j.cell.2013.06.020},
	abstract = {Long intervening noncoding {RNAs} ({lincRNAs}) are transcribed from thousands of loci in mammalian genomes and might play widespread roles in gene regulation and other cellular processes. This Review outlines the emerging understanding of {lincRNAs} in vertebrate animals, with emphases on how they are being identified and current conclusions and questions regarding their genomics, evolution and mechanisms of action.},
	pages = {26--46},
	number = {1},
	journaltitle = {Cell},
	author = {Ulitsky, Igor and Bartel, David P},
	date = {2013-07},
	pmid = {23827673},
	keywords = {Animals, Genetic, Humans, {RNA}, Transcription, Gene Expression Regulation, Long Noncoding, Long Noncoding: chemistry, Long Noncoding: genetics, Long Noncoding: metabolism, Biological Evolution, Evolution, Molecular, Long Noncoding: isolation \& purification},
	file = {Attachment:/home/jlagarde/Zotero/storage/DDD66LJT/Ulitsky, Bartel - 2013 - lincRNAs genomics, evolution, and mechanisms.pdf:application/pdf}
}

@article{bardou_long_2014,
	title = {Long Noncoding {RNA} Modulates Alternative Splicing Regulators in Arabidopsis},
	volume = {30},
	issn = {15345807},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25073154},
	doi = {10.1016/j.devcel.2014.06.017},
	abstract = {Alternative splicing ({AS}) of pre-{mRNA} represents a major mechanism underlying increased transcriptome and proteome complexity. Here, we show that the nuclear speckle {RNA}-binding protein ({NSR}) and the {AS} competitor long noncoding {RNA} (or {ASCO}-{lncRNA}) constitute an {AS} regulatory module. {AtNSR}-{GFP} translational fusions are expressed in primary and lateral root ({LR}) meristems. Double Atnsr mutants and {ASCO} overexpressors exhibit an altered ability to form {LRs} after auxin treatment. Interestingly, auxin induces a major change in {AS} patterns of many genes, a response largely dependent on {NSRs}. {RNA} immunoprecipitation assays demonstrate that {AtNSRs} interact not only with their alternatively spliced {mRNA} targets but also with the {ASCO}-{RNA} in vivo. The {ASCO}-{RNA} displaces an {AS} target from an {NSR}-containing complex in vitro. Expression of {ASCO}-{RNA} in Arabidopsis affects the splicing patterns of several {NSR}-regulated {mRNA} targets. Hence, {lncRNA} can hijack nuclear {AS} regulators to modulate {AS} patterns during development.},
	pages = {166--176},
	number = {2},
	journaltitle = {Developmental Cell},
	author = {Bardou, Florian and Ariel, Federico and Simpson, Craig G. and Romero-Barrios, Natali and Laporte, Philippe and Balzergue, Sandrine and Brown, John W.S. and Crespi, Martin},
	date = {2014-07},
	pmid = {25073154}
}

@article{johnsson_evolutionary_2014,
	title = {Evolutionary conservation of long non-coding {RNAs}; sequence, structure, function.},
	volume = {1840},
	issn = {0006-3002},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24184936},
	doi = {10.1016/j.bbagen.2013.10.035},
	abstract = {{BACKGROUND}: Recent advances in genomewide studies have revealed the abundance of long non-coding {RNAs} ({lncRNAs}) in mammalian transcriptomes. The {ENCODE} Consortium has elucidated the prevalence of human {lncRNA} genes, which are as numerous as protein-coding genes. Surprisingly, many {lncRNAs} do not show the same pattern of high interspecies conservation as protein-coding genes. The absence of functional studies and the frequent lack of sequence conservation therefore make functional interpretation of these newly discovered transcripts challenging. Many investigators have suggested the presence and importance of secondary structural elements within {lncRNAs}, but mammalian {lncRNA} secondary structure remains poorly understood. It is intriguing to speculate that in this group of genes, {RNA} secondary structures might be preserved throughout evolution and that this might explain the lack of sequence conservation among many {lncRNAs}. {SCOPE} {OF} {REVIEW}: Here, we review the extent of interspecies conservation among different {lncRNAs}, with a focus on a subset of {lncRNAs} that have been functionally investigated. The function of {lncRNAs} is widespread and we investigate whether different forms of functionalities may be conserved. {MAJOR} {CONCLUSIONS}: Lack of conservation does not imbue a lack of function. We highlight several examples of {lncRNAs} where {RNA} structure appears to be the main functional unit and evolutionary constraint. We survey existing genomewide studies of mammalian {lncRNA} conservation and summarize their limitations. We further review specific human {lncRNAs} which lack evolutionary conservation beyond primates but have proven to be both functional and therapeutically relevant. {GENERAL} {SIGNIFICANCE}: Pioneering studies highlight a role in {lncRNAs} for secondary structures, and possibly the presence of functional "modules", which are interspersed with longer and less conserved stretches of nucleotide sequences. Taken together, high-throughput analysis of conservation and functional composition of the still-mysterious {lncRNA} genes is only now becoming feasible.},
	pages = {1063--71},
	number = {3},
	journaltitle = {Biochimica et biophysica acta},
	author = {Johnsson, Per and Lipovich, Leonard and Grandér, Dan and Morris, Kevin V},
	date = {2014-03},
	pmid = {24184936},
	keywords = {Animals, Conserved Sequence, Humans, {RNA}, Long Noncoding, Long Noncoding: chemistry, Long Noncoding: genetics, Antisense, Evolution, Molecular, Antisense: chemistry, Antisense: physiology, Long Noncoding: physiology}
}

@article{fatica_long_2014,
	title = {Long non-coding {RNAs}: new players in cell differentiation and development.},
	volume = {15},
	issn = {1471-0064},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24296535},
	doi = {10.1038/nrg3606},
	abstract = {Genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding {RNAs} ({ncRNAs}). Long {ncRNAs} ({lncRNAs}) belong to a novel heterogeneous class of {ncRNAs} that includes thousands of different species. {lncRNAs} have crucial roles in gene expression control during both developmental and differentiation processes, and the number of {lncRNA} species increases in genomes of developmentally complex organisms, which highlights the importance of {RNA}-based levels of control in the evolution of multicellular organisms. In this Review, we describe the function of {lncRNAs} in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.},
	pages = {7--21},
	number = {1},
	journaltitle = {Nature reviews. Genetics},
	author = {Fatica, Alessandro and Bozzoni, Irene},
	date = {2014-01},
	pmid = {24296535},
	keywords = {Animals, Genetic, {RNA}, Gene Expression Regulation, Long Noncoding, Long Noncoding: genetics, Cell Differentiation, Cell Differentiation: genetics, Cell Differentiation: physiology, Cytoplasm, Cytoplasm: genetics, Developmental, Developmental: genetic, Dosage Compensation, Genetic: genetics, Genomic Imprinting, Genomic Imprinting: genetics, Mammals, Mammals: genetics, Mammals: growth \& development, Models, Molecular, Muscles, Muscles: physiology, Organogenesis, Organogenesis: genetics, Species Specificity}
}

@article{kung_long_2013,
	title = {Long noncoding {RNAs}: past, present, and future.},
	volume = {193},
	issn = {1943-2631},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3583990&tool=pmcentrez&rendertype=abstract},
	doi = {10.1534/genetics.112.146704},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. {lncRNAs} of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied {lncRNAs} have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the {lncRNA} field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of {lncRNAs}. We also reflect on how the recent interest in {lncRNAs} is deeply rooted in biology's longstanding concern with the evolution and function of genomes.},
	pages = {651--69},
	number = {3},
	journaltitle = {Genetics},
	author = {Kung, Johnny T Y and Colognori, David and Lee, Jeannie T},
	date = {2013-03},
	pmid = {23463798},
	keywords = {Animals, Genetic, Humans, {RNA}, Transcription, Long Noncoding, Long Noncoding: genetics, Long Noncoding: metabolism, Epigenesis, Evolution, Molecular, Post-Transcriptional, {RNA} Processing},
	file = {Attachment:/home/jlagarde/Zotero/storage/65MNSKWN/Kung, Colognori, Lee - 2013 - Long noncoding RNAs past, present, and future.pdf:application/pdf}
}

@article{kutter_rapid_2012,
	title = {Rapid turnover of long noncoding {RNAs} and the evolution of gene expression.},
	volume = {8},
	issn = {1553-7404},
	url = {http://dx.plos.org/10.1371/journal.pgen.1002841},
	doi = {10.1371/journal.pgen.1002841},
	abstract = {A large proportion of functional sequence within mammalian genomes falls outside protein-coding exons and can be transcribed into long {RNAs}. However, the roles in mammalian biology of long noncoding {RNA} ({lncRNA}) are not well understood. Few {lncRNAs} have experimentally determined roles, with some of these being lineage-specific. Determining the extent by which transcription of {lncRNA} loci is retained or lost across multiple evolutionary lineages is essential if we are to understand their contribution to mammalian biology and to lineage-specific traits. Here, we experimentally investigated the conservation of {lncRNA} expression among closely related rodent species, allowing the evolution of {DNA} sequence to be uncoupled from evolution of transcript expression. We generated total {RNA} ({RNAseq}) and H3K4me3-bound ({ChIPseq}) {DNA} data, and combined both to construct catalogues of transcripts expressed in the adult liver of Mus musculus domesticus (C57BL/6J), Mus musculus castaneus, and Rattus norvegicus. We estimated the rate of transcriptional turnover of {lncRNAs} and investigated the effects of their lineage-specific birth or death. {LncRNA} transcription showed considerably greater gain and loss during rodent evolution, compared with protein-coding genes. Nucleotide substitution rates were found to mirror the in vivo transcriptional conservation of intergenic {lncRNAs} between rodents: only the sequences of noncoding loci with conserved transcription were constrained. Finally, we found that lineage-specific intergenic {lncRNAs} appear to be associated with modestly elevated expression of genomically neighbouring protein-coding genes. Our findings show that nearly half of intergenic {lncRNA} loci have been gained or lost since the last common ancestor of mouse and rat, and they predict that such rapid transcriptional turnover contributes to the evolution of tissue- and lineage-specific gene expression.},
	pages = {e1002841},
	number = {7},
	journaltitle = {{PLoS} genetics},
	author = {Kutter, Claudia and Watt, Stephen and Stefflova, Klara and Wilson, Michael D and Goncalves, Angela and Ponting, Chris P and Odom, Duncan T and Marques, Ana C},
	editor = {Bartel, David P.},
	date = {2012-01},
	pmid = {22844254},
	keywords = {Animals, Conserved Sequence, Genetic, Mice, {RNA}, Transcription, Untranslated, Untranslated: genetics, Untranslated: metabolism, Open Reading Frames, Conserved Sequence: genetics, Evolution, Gene Expression, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Liver, Liver: metabolism, Microarray Analysis, Molecular, Open Reading Frames: genetics, Rats},
	file = {Attachment:/home/jlagarde/Zotero/storage/ENJTHE6Y/Kutter et al. - 2012 - Rapid turnover of long noncoding RNAs and the evolution of gene expression.pdf:application/pdf}
}

@article{necsulea_evolution_2014,
	title = {The evolution of {lncRNA} repertoires and expression patterns in tetrapods.},
	volume = {505},
	issn = {1476-4687},
	url = {http://dx.doi.org/10.1038/nature12943},
	doi = {10.1038/nature12943},
	shorttitle = {Nature},
	abstract = {Only a very small fraction of long noncoding {RNAs} ({lncRNAs}) are well characterized. The evolutionary history of {lncRNAs} can provide insights into their functionality, but the absence of {lncRNA} annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of {lncRNA} repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific {lncRNAs} and 2,500 highly conserved {lncRNAs}, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that {lncRNAs}, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most {lncRNAs} evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous {lncRNA} and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for {lncRNAs} in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through {microRNA} production.},
	pages = {635--40},
	number = {7485},
	journaltitle = {Nature},
	author = {Necsulea, Anamaria and Soumillon, Magali and Warnefors, Maria and Liechti, Angélica and Daish, Tasman and Zeller, Ulrich and Baker, Julie C and Grützner, Frank and Kaessmann, Henrik},
	date = {2014-01},
	pmid = {24463510},
	keywords = {Transcriptome, Genomics, Animals, Conserved Sequence, Humans, Mice, Proteins, Proteins: genetics, {RNA}, Gene Expression Regulation, Long Noncoding, Long Noncoding: genetics, Anura, Anura: genetics, Chickens, Chickens: genetics, Conserved Sequence: genetics, Developmental, Developmental: genetic, Evolution, {MicroRNAs}, {MicroRNAs}: genetics, Molecular, Multigene Family, Primates, Primates: genetics, {RNA} Precursors, {RNA} Precursors: genetics}
}

@article{mattick_non-coding_2001,
	title = {Non-coding {RNAs}: the architects of eukaryotic complexity.},
	volume = {2},
	issn = {1469-221X},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1084129&tool=pmcentrez&rendertype=abstract},
	doi = {10.1093/embo-reports/kve230},
	abstract = {Around 98\% of all transcriptional output in humans is non-coding {RNA}. {RNA}-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like {RNA} interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to {RNA} signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding {RNAs} have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting {RNAs} that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, {RNA}-{DNA}, {RNA}-{RNA} and {RNA}-protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.},
	pages = {986--91},
	number = {11},
	journaltitle = {{EMBO} reports},
	author = {Mattick, J S},
	date = {2001-11},
	pmid = {11713189},
	keywords = {Animals, Genetic, Genome, Humans, {RNA}, Transcription, Introns, Chromatin, Chromatin: metabolism, Eukaryotic Cells, Gene Expression, Phenotype, Transcriptional Activation, {RNA}: genetics, {RNA}: metabolism, Eukaryotic Cells: metabolism, {RNA}: physiology},
	file = {Attachment:/home/jlagarde/Zotero/storage/XUJPA7V2/Mattick - 2001 - Non-coding RNAs the architects of eukaryotic complexity.pdf:application/pdf}
}

@article{guttman_ribosome_2013,
	title = {Ribosome profiling provides evidence that large noncoding {RNAs} do not encode proteins.},
	volume = {154},
	issn = {1097-4172},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3756563&tool=pmcentrez&rendertype=abstract},
	doi = {10.1016/j.cell.2013.06.009},
	abstract = {Large noncoding {RNAs} are emerging as an important component in cellular regulation. Considerable evidence indicates that these transcripts act directly as functional {RNAs} rather than through an encoded protein product. However, a recent study of ribosome occupancy reported that many large intergenic {ncRNAs} ({lincRNAs}) are bound by ribosomes, raising the possibility that they are translated into proteins. Here, we show that classical noncoding {RNAs} and 5' {UTRs} show the same ribosome occupancy as {lincRNAs}, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding. Instead, we define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon. We show that this metric accurately discriminates between protein-coding transcripts and all classes of known noncoding transcripts, including {lincRNAs}. Taken together, these results argue that the large majority of {lincRNAs} do not function through encoded proteins.},
	pages = {240--51},
	number = {1},
	journaltitle = {Cell},
	author = {Guttman, Mitchell and Russell, Pamela and Ingolia, Nicholas T and Weissman, Jonathan S and Lander, Eric S},
	date = {2013-07},
	pmid = {23810193},
	keywords = {3' Untranslated Regions, Animals, Mice, {RNA}, Untranslated, Untranslated: metabolism, Long Noncoding, Long Noncoding: chemistry, Long Noncoding: genetics, Long Noncoding: metabolism, 5' Untranslated Regions, Embryo, Mammalian, Protein Biosynthesis, Ribosomes, Mammalian: metabolism, Ribosomes: metabolism, {RNA}, Long Noncoding, {RNA}, Untranslated, Embryo, Mammalian},
	file = {Attachment:/home/jlagarde/Zotero/storage/YL5X5V5S/Guttman et al. - 2013 - Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/33DXC4QW/Guttman et al. - 2013 - Ribosome profiling provides evidence that large no.pdf:application/pdf}
}

@article{mercer_targeted_2014,
	title = {Targeted sequencing for gene discovery and quantification using {RNA} {CaptureSeq}.},
	volume = {9},
	issn = {1750-2799},
	url = {http://dx.doi.org/10.1038/nprot.2014.058},
	doi = {10.1038/nprot.2014.058},
	shorttitle = {Nat. Protocols},
	abstract = {{RNA} sequencing ({RNAseq}) samples the majority of expressed genes infrequently, owing to the large size, complex splicing and wide dynamic range of eukaryotic transcriptomes. This results in sparse sequencing coverage that can hinder robust isoform assembly and quantification. {RNA} capture sequencing ({CaptureSeq}) addresses this challenge by using oligonucleotide probes to capture selected genes or regions of interest for targeted sequencing. Targeted {RNAseq} provides enhanced coverage for sensitive gene discovery, robust transcript assembly and accurate gene quantification. Here we describe a detailed protocol for all stages of {RNA} {CaptureSeq}, from initial probe design considerations and capture of targeted genes to final assembly and quantification of captured transcripts. Initial probe design and final analysis can take less than 1 d, whereas the central experimental capture stage requires ∼7 d.},
	pages = {989--1009},
	number = {5},
	journaltitle = {Nature protocols},
	author = {Mercer, Tim R and Clark, Michael B and Crawford, Joanna and Brunck, Marion E and Gerhardt, Daniel J and Taft, Ryan J and Nielsen, Lars K and Dinger, Marcel E and Mattick, John S},
	date = {2014-05},
	pmid = {24705597},
	file = {Attachment:/home/jlagarde/Zotero/storage/YBUBA8KN/Mercer et al. - 2014 - Targeted sequencing for gene discovery and quantification using RNA CaptureSeq.pdf:application/pdf}
}

@article{nesterova_loss_2001,
	title = {Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos.},
	volume = {235},
	issn = {0012-1606},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11437441},
	doi = {10.1006/dbio.2001.0295},
	abstract = {We have analysed Xist expression patterns in parthenogenetic and control fertilised preimplantation embryos by using {RNA} {FISH}. In normal {XX} embryos, maternally derived Xist alleles are repressed throughout preimplantation development. Paternal alleles are expressed as early as the 2-cell stage. In parthenogenetic embryos, we observed Xist {RNA} expression and accumulation from the morula stage onwards, indicating loss of maternal imprinting. In the majority of cells, expression was from a single allele, indicating that X chromosome counting occurs to establish appropriate monoallelic Xist expression. We discuss these data in the context of models for regulation of imprinted and random X inactivation.},
	pages = {343--50},
	number = {2},
	journaltitle = {Developmental biology},
	author = {Nesterova, T B and Barton, S C and Surani, M A and Brockdorff, N},
	date = {2001-07},
	pmid = {11437441},
	keywords = {{DNA}, Animals, Genetic, Mice, {RNA}, Alleles, Blastocyst, Female, Fluorescence, Genomic Imprinting, In Situ Hybridization, Inbred C57BL, Inbred {CBA}, Male, Models, Phenotype, Time Factors, X Chromosome, {RNA}: metabolism, Blastocyst: metabolism, {DNA}: metabolism, Fathers, Mothers, X Chromosome: genetics}
}

@article{herzing_xist_1997,
	title = {Xist has properties of the X-chromosome inactivation centre.},
	volume = {386},
	issn = {0028-0836},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9069284},
	doi = {10.1038/386272a0},
	abstract = {X-chromosome inactivation is the process by which female mammals (with two X chromosomes) achieve expression of X-chromosomal genes equivalent to that of males (one X and one Y chromosome). This results in the transcriptional silencing of virtually all genes on one of the X chromosomes in female somatic cells. X-chromosome inactivation has been shown to act in cis and to initiate and spread from a single site on the X chromosome known as the X-inactivation centre (Xic). The Xic has been localized to a 450-kilobase region of the mouse X chromosome. The Xist gene also maps to this region and is expressed exclusively from the inactive X chromosome. Xist is unusual in that it appears not to code for a protein but produces a nuclear {RNA} which colocalizes with the inactive X chromosome. The creation of a null allele of Xist in embryonic stem cells has demonstrated that this gene is required for X inactivation to occur in cis. Here we show that Xist, introduced onto an autosome, is sufficient by itself for inactivation in cis and that Xist {RNA} becomes localized close to the autosome into which the gene is integrated. In addition, the presence of autosomal Xist copies leads to activation of the endogeneous Xist gene in some cells, suggesting that elements required for some aspects of chromosome counting are contained within the construct. Thus the Xist gene exhibits properties of the X-inactivation centre.},
	pages = {272--5},
	number = {6622},
	journaltitle = {Nature},
	author = {Herzing, L B and Romer, J T and Horn, J M and Ashworth, A},
	date = {1997-03},
	pmid = {9069284},
	keywords = {Animals, Genetic, Mice, {RNA}, Untranslated, Long Noncoding, Cell Line, Dosage Compensation, Female, Fluorescence, Genes, In Situ Hybridization, Inbred C57BL, Male, Reporter, Stem Cells, Transcription Factors, Transfection, X Chromosome, Transcription Factors: genetics, {RNA}: metabolism, Cosmids}
}

@article{li_genome-wide_2014,
	title = {Genome-Wide Identification and Characterization of Long Intergenic Non-Coding {RNAs} in Ganoderma lucidum.},
	volume = {9},
	issn = {1932-6203},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4059649&tool=pmcentrez&rendertype=abstract},
	doi = {10.1371/journal.pone.0099442},
	abstract = {Ganoderma lucidum is a white-rot fungus best-known for its medicinal activities. We have previously sequenced its genome and annotated the protein coding genes. However, long non-coding {RNAs} in G. lucidum genome have not been analyzed. In this study, we have identified and characterized long intergenic non-coding {RNAs} ({lincRNA}) in G. lucidum systematically. We developed a computational pipeline, which was used to analyze {RNA}-Seq data derived from G. lucidum samples collected from three developmental stages. A total of 402 {lincRNA} candidates were identified, with an average length of 609 bp. Analysis of their adjacent protein-coding genes ({apcGenes}) revealed that 46 {apcGenes} belong to the pathways of triterpenoid biosynthesis and lignin degradation, or families of cytochrome P450, mating type B genes, and carbohydrate-active enzymes. To determine if {lincRNAs} and these {apcGenes} have any interactions, the corresponding pairs of {lincRNAs} and {apcGenes} were analyzed in detail. We developed a modified 3' {RACE} method to analyze the transcriptional direction of a transcript. Among the 46 {lincRNAs}, 37 were found unidirectionally transcribed, and 9 were found bidirectionally transcribed. The expression profiles of 16 of these 37 {lincRNAs} were found to be highly correlated with those of the {apcGenes} across the three developmental stages. Among them, 11 are positively correlated (r{\textbackslash}textgreater0.8) and 5 are negatively correlated (r{\textbackslash}textless-0.8). The co-localization and co-expression of {lincRNAs} and those {apcGenes} playing important functions is consistent with the notion that {lincRNAs} might be important regulators for cellular processes. In summary, this represents the very first study to identify and characterize {lincRNAs} in the genomes of basidiomycetes. The results obtained here have laid the foundation for study of potential {lincRNA}-mediated expression regulation of genes in G. lucidum.},
	pages = {e99442},
	number = {6},
	journaltitle = {{PloS} one},
	author = {Li, Jianqin and Wu, Bin and Xu, Jiang and Liu, Chang},
	date = {2014-01},
	pmid = {24932683},
	file = {Attachment:/home/jlagarde/Zotero/storage/SPPBWXPX/Li et al. - 2014 - Genome-Wide Identification and Characterization of Long Intergenic Non-Coding RNAs in Ganoderma lucidum.pdf:application/pdf}
}

@article{derrien_long_2011,
	title = {The Long Non-Coding {RNAs}: A New (P)layer in the "Dark Matter".},
	volume = {2},
	issn = {1664-8021},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3266617&tool=pmcentrez&rendertype=abstract},
	doi = {10.3389/fgene.2011.00107},
	abstract = {The transcriptome of a cell is represented by a myriad of different {RNA} molecules with and without protein-coding capacities. In recent years, advances in sequencing technologies have allowed researchers to more fully appreciate the complexity of whole transcriptomes, showing that the vast majority of the genome is transcribed, producing a diverse population of non-protein coding {RNAs} ({ncRNAs}). Thus, the biological significance of non-coding {RNAs} ({ncRNAs}) have been largely underestimated. Amongst these multiple classes of {ncRNAs}, the long non-coding {RNAs} ({lncRNAs}) are apparently the most numerous and functionally diverse. A small but growing number of {lncRNAs} have been experimentally studied, and a view is emerging that these are key regulators of epigenetic gene regulation in mammalian cells. {LncRNAs} have already been implicated in human diseases such as cancer and neurodegeneration, highlighting the importance of this emergent field. In this article, we review the catalogs of annotated {lncRNAs} and the latest advances in our understanding of {lncRNAs}.},
	pages = {107},
	journaltitle = {Frontiers in genetics},
	author = {Derrien, Thomas and Guigó, Roderic and Johnson, Rory},
	date = {2011-01},
	pmid = {22303401}
}

@article{johnson_ridl_2014,
	title = {The {RIDL} hypothesis: transposable elements as functional domains of long noncoding {RNAs}.},
	volume = {20},
	issn = {1469-9001},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24850885},
	doi = {10.1261/rna.044560.114},
	abstract = {Our genome contains tens of thousands of long noncoding {RNAs} ({lncRNAs}), many of which are likely to have genetic regulatory functions. It has been proposed that {lncRNA} are organized into combinations of discrete functional domains, but the nature of these and their identification remain elusive. One class of sequence elements that is enriched in {lncRNA} is represented by transposable elements ({TEs}), repetitive mobile genetic sequences that have contributed widely to genome evolution through a process termed exaptation. Here, we link these two concepts by proposing that exonic {TEs} act as {RNA} domains that are essential for {lncRNA} function. We term such elements Repeat Insertion Domains of {LncRNAs} ({RIDLs}). A growing number of {RIDLs} have been experimentally defined, where {TE}-derived fragments of {lncRNA} act as {RNA}-, {DNA}-, and protein-binding domains. We propose that these reflect a more general phenomenon of exaptation during {lncRNA} evolution, where inserted {TE} sequences are repurposed as recognition sites for both protein and nucleic acids. We discuss a series of genomic screens that may be used in the future to systematically discover {RIDLs}. The {RIDL} hypothesis has the potential to explain how functional evolution can keep pace with the rapid gene evolution observed in {lncRNA}. More practically, {TE} maps may in the future be used to predict {lncRNA} function.},
	pages = {959--76},
	number = {7},
	journaltitle = {{RNA} (New York, N.Y.)},
	author = {Johnson, Rory and Guigó, Roderic},
	date = {2014-07},
	pmid = {24850885}
}

@article{vikram_functional_2014,
	title = {Functional significance of long non-coding {RNAs} in breast cancer.},
	issn = {1880-4233},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25038622},
	doi = {10.1007/s12282-014-0554-y},
	abstract = {Most of the genome is transcribed to transcripts of no protein-coding potential. However, these transcripts do not represent transcriptional 'noise', rather they play an important role in cellular metabolism and development. Non-coding transcripts of 200 bases to 100 kb length are termed as long non-coding {RNAs}, majority of which are yet to be characterised thoroughly. Long non-coding {RNAs} ({lncRNAs}) play a significant role in cellular process ranging from transcriptional to post-transcriptional regulation. In this review, we highlight the recent efforts to characterise the major functions of {lncRNAs} in breast cancer. {lncRNA} expression is altered in several cancer types. Further, the aberrant regulation of {lncRNAs} promotes tumour development as they are involved in several cancer-associated pathways.},
	journaltitle = {Breast cancer (Tokyo, Japan)},
	author = {Vikram, Rajeev and Ramachandran, Rahul and Abdul, Khaja Shameem Mohammed},
	date = {2014-07},
	pmid = {25038622}
}

@article{jensen_arrayprospector:_2004,
	title = {{ArrayProspector}: A web resource of functional associations inferred from microarray expression data},
	volume = {32},
	abstract = {{DNA} microarray experiments have provided vast amounts of data which can be used for inferring gene function. However, most methods for predicting functional associations between genes from expression data are not suited to simultaneous analysis of multiple datasets, and a comprehensive resource of coexpression-based predictions is currently lacking. Here, we present an interactive web resource of gene associations predicted by applying a novel algorithm to all expression data in the Stanford Microarray Database. The underlying pre-computed database currently contains more than 200 000 high-confidence gene associations in 12 different species sampled from a broad taxonomic range. The resource allows every association to be inspected visually and can be accessed at http://www.bork.embl.de/{ArrayProspector}.},
	issue = {{WEB} {SERVER} {ISS}.},
	journaltitle = {Nucleic Acids Research},
	author = {Jensen, Lars Juhl and Lagarde, Julien and von Mering, Christian and Bork, Peer},
	date = {2004},
	file = {Attachment:/home/jlagarde/Zotero/storage/FJQ64PTW/Jensen et al. - 2004 - ArrayProspector A web resource of functional associations inferred from microarray expression data.pdf:application/pdf}
}

@article{mortazavi_mapping_2008,
	title = {Mapping and quantifying mammalian transcriptomes by {RNA}-Seq.},
	volume = {5},
	issn = {1548-7091},
	doi = {10.1038/nmeth.1226},
	abstract = {We have mapped and quantified mouse transcriptomes by deeply sequencing them and recording how frequently each gene is represented in the sequence sample ({RNA}-Seq). This provides a digital measure of the presence and prevalence of transcripts from known and previously unknown genes. We report reference measurements composed of 41-52 million mapped 25-base-pair reads for poly(A)-selected {RNA} from adult mouse brain, liver and skeletal muscle tissues. We used {RNA} standards to quantify transcript prevalence and to test the linear range of transcript detection, which spanned five orders of magnitude. Although {\textbackslash}textgreater90\% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3' untranscribed regions, as well as new candidate {microRNA} precursors. {RNA} splice events, which are not readily measured by standard gene expression microarray or serial analysis of gene expression methods, were detected directly by mapping splice-crossing sequence reads. We observed 1.45 x 10(5) distinct splices, and alternative splices were prominent, with 3,500 different genes expressing one or more alternate internal splices.},
	pages = {621--628},
	number = {7},
	journaltitle = {Nature methods},
	author = {Mortazavi, Ali and Williams, Brian A and {McCue}, Kenneth and Schaeffer, Lorian and Wold, Barbara},
	date = {2008},
	pmid = {18516045}
}

@article{mensh_ten_2017,
	title = {Ten simple rules for structuring papers},
	volume = {13},
	issn = {1553-7358},
	url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005619},
	doi = {10.1371/journal.pcbi.1005619},
	pages = {e1005619},
	number = {9},
	journaltitle = {{PLOS} Computational Biology},
	shortjournal = {{PLOS} Computational Biology},
	author = {Mensh, Brett and Kording, Konrad},
	urldate = {2018-08-23},
	date = {2017-09-28},
	langid = {english},
	keywords = {Careers, Cell differentiation, Communications, Crystals, Experimental design, Patient advocacy, Scientists, Syntax},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/R3CRFNSU/Mensh and Kording - 2017 - Ten simple rules for structuring papers.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TSRZ2W3E/article.html:text/html}
}

@article{derrien_gencode_2012,
	title = {The {GENCODE} v7 catalog of human long noncoding {RNAs}: analysis of their gene structure, evolution, and expression},
	volume = {22},
	issn = {1549-5469},
	doi = {10.1101/gr.132159.111},
	shorttitle = {The {GENCODE} v7 catalog of human long noncoding {RNAs}},
	abstract = {The human genome contains many thousands of long noncoding {RNAs} ({lncRNAs}). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive {lncRNA} annotation. Here, we present and analyze the most complete human {lncRNA} annotation to date, produced by the {GENCODE} consortium within the framework of the {ENCODE} project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that {lncRNAs} are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, {lncRNAs} display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small {RNAs}. They are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that {lncRNAs} are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific {lncRNAs} expressed in the brain. Expression correlation analysis indicates that {lncRNAs} show particularly striking positive correlation with the expression of antisense coding genes. This {GENCODE} annotation represents a valuable resource for future studies of {lncRNAs}.},
	pages = {1775--1789},
	number = {9},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Derrien, Thomas and Johnson, Rory and Bussotti, Giovanni and Tanzer, Andrea and Djebali, Sarah and Tilgner, Hagen and Guernec, Gregory and Martin, David and Merkel, Angelika and Knowles, David G. and Lagarde, Julien and Veeravalli, Lavanya and Ruan, Xiaoan and Ruan, Yijun and Lassmann, Timo and Carninci, Piero and Brown, James B. and Lipovich, Leonard and Gonzalez, Jose M. and Thomas, Mark and Davis, Carrie A. and Shiekhattar, Ramin and Gingeras, Thomas R. and Hubbard, Tim J. and Notredame, Cedric and Harrow, Jennifer and Guigó, Roderic},
	date = {2012-09},
	pmid = {22955988},
	pmcid = {PMC3431493},
	keywords = {Animals, Genetic, Humans, {RNA}, Transcription, Gene Expression Regulation, Exons, Gene Expression Profiling, Messenger, Messenger: genetics, Organ Specificity, Databases, Open Reading Frames, Cell Nucleus, Cell Nucleus: genetics, Long Noncoding, Long Noncoding: genetics, {RNA} Splice Sites, Alternative Splicing, Cluster Analysis, Evolution, Histones, Histones: metabolism, Molecular, Molecular Sequence Annotation, Post-Transcriptional, Primates, Primates: genetics, {RNA} Processing, Selection, Organ Specificity: genetics, Cell Nucleus: metabolism, Databases, Genetic, Evolution, Molecular, {RNA} Processing, Post-Transcriptional, {RNA}, Long Noncoding, {RNA}, Messenger, Selection, Genetic, Transcription, Genetic},
	file = {Attachment:/home/jlagarde/Zotero/storage/VEE3HRZA/Derrien et al. - 2012 - The GENCODE v7 catalog of human long noncoding RNAs analysis of their gene structure, evolution, and expression.pdf:application/pdf}
}

@article{wang_compendium_2018,
	title = {A compendium of conserved cleavage and polyadenylation events in mammalian genes},
	issn = {1549-5469},
	doi = {10.1101/gr.237826.118},
	abstract = {Cleavage and polyadenylation is essential for 3' end processing of almost all eukaryotic {mRNAs}. Recent studies have shown widespread alternative cleavage and polyadenylation ({APA}) events leading to {mRNA} isoforms with different 3' {UTRs} and/or coding sequences. Here we present a compendium of conserved cleavage and polyadenylation sites ({PASs}) in mammalian genes, based on {\textasciitilde}1.2 billion 3' end sequencing reads from over 360 human, mouse and rat samples. We show that {\textasciitilde}80\% of mammalian {mRNA} genes contain at least one conserved {PAS}, and {\textasciitilde}50\% have conserved {APA} events. {PAS} conservation generally reduces promiscuous 3' end processing, stabilizing gene expression levels across species. Conservation of {APA} correlates with gene age, gene expression features, and gene functions. Genes with certain functions, such as cell morphology, cell proliferation, and {mRNA} metabolism, are particularly enriched with conserved {APA} events. While tissue-specific genes typically have a low {APA} rate, brain-specific genes tend to evolve {APA}. In addition, we show enrichment of {mRNA} destabilizing motifs in alternative 3' {UTR} sequences, leading to substantial differences in {mRNA} stability between 3' {UTR} isoforms. Using conserved {PASs}, we reveal sequence motifs surrounding {APA} sites and a preference of adenosine at the cleavage site. Furthermore, we show that mutations of U-rich motifs around the {PAS} often accompany {APA} profile differences between species. Analysis of {lncRNA} {PASs} indicates a mechanism of {PAS} fixation through evolution of A-rich motifs. Taken together, our results present a comprehensive view of {PAS} evolution in mammals, and a phylogenic perspective on {APA} functions.},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Wang, Ruijia and Zheng, Dinghai and Yehia, Ghassan and Tian, Bin},
	date = {2018-08-24},
	pmid = {30143597}
}

@article{salmela_lordec:_2014,
	title = {{LoRDEC}: accurate and efficient long read error correction},
	volume = {30},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/btu538},
	shorttitle = {{LoRDEC}},
	abstract = {{MOTIVATION}: {PacBio} single molecule real-time sequencing is a third-generation sequencing technique producing long reads, with comparatively lower throughput and higher error rate. Errors include numerous indels and complicate downstream analysis like mapping or de novo assembly. A hybrid strategy that takes advantage of the high accuracy of second-generation short reads has been proposed for correcting long reads. Mapping of short reads on long reads provides sufficient coverage to eliminate up to 99\% of errors, however, at the expense of prohibitive running times and considerable amounts of disk and memory space.
{RESULTS}: We present {LoRDEC}, a hybrid error correction method that builds a succinct de Bruijn graph representing the short reads, and seeks a corrective sequence for each erroneous region in the long reads by traversing chosen paths in the graph. In comparison, {LoRDEC} is at least six times faster and requires at least 93\% less memory or disk space than available tools, while achieving comparable accuracy. Availability and implementaion: {LoRDEC} is written in C++, tested on Linux platforms and freely available at http://atgc.lirmm.fr/lordec.},
	pages = {3506--3514},
	number = {24},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Salmela, Leena and Rivals, Eric},
	date = {2014-12-15},
	pmid = {25165095},
	pmcid = {PMC4253826},
	keywords = {Genomics, Animals, Algorithms, Software, High-Throughput Nucleotide Sequencing, Escherichia coli, Parrots, Yeasts}
}

@article{chen_long_2017,
	title = {Long non-coding {RNAs} and complex diseases: from experimental results to computational models},
	volume = {18},
	issn = {1477-4054},
	doi = {10.1093/bib/bbw060},
	shorttitle = {Long non-coding {RNAs} and complex diseases},
	abstract = {{LncRNAs} have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of {lncRNA} have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that {lncRNAs} are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of {lncRNAs} would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of {lncRNAs}, five important {lncRNA}-related diseases, five critical disease-related {lncRNAs} and some important publicly available {lncRNA}-related databases about sequence, expression, function, etc. Nowadays, only a limited number of {lncRNAs} have been experimentally reported to be related to human diseases. Therefore, analyzing available {lncRNA}-disease associations and predicting potential human {lncRNA}-disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at {lncRNA} level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related {lncRNAs} on a large scale and select the most promising disease-related {lncRNAs} for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for {lncRNA} research.},
	pages = {558--576},
	number = {4},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief. Bioinformatics},
	author = {Chen, Xing and Yan, Chenggang Clarence and Zhang, Xu and You, Zhu-Hong},
	date = {2017},
	pmid = {27345524},
	pmcid = {PMC5862301},
	keywords = {Humans, Computational Biology, Algorithms, Computer Simulation, {RNA}, Long Noncoding, biological network, complex disease, computational model, {lncRNA}–disease association prediction, long non-coding {RNA}, machine learning}
}

@article{munschauer_norad_2018,
	title = {The {NORAD} {lncRNA} assembles a topoisomerase complex critical for genome stability},
	rights = {2018 Springer Nature Limited},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/s41586-018-0453-z},
	doi = {10.1038/s41586-018-0453-z},
	abstract = {The long non-coding {RNA} {NORAD} interacts with proteins involved in {DNA} replication and repair, and controls the ability of {RBMX} to form a ribonucleoprotein complex that helps to maintain genomic stability.},
	pages = {1},
	journaltitle = {Nature},
	author = {Munschauer, Mathias and Nguyen, Celina T. and Sirokman, Klara and Hartigan, Christina R. and Hogstrom, Larson and Engreitz, Jesse M. and Ulirsch, Jacob C. and Fulco, Charles P. and Subramanian, Vidya and Chen, Jenny and Schenone, Monica and Guttman, Mitchell and Carr, Steven A. and Lander, Eric S.},
	urldate = {2018-08-29},
	date = {2018-08-27},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/KU4FWDRG/s41586-018-0453-z.html:text/html;The NORAD lncRNA assembles a topoisomerase complex critical for genome stability:/home/jlagarde/Zotero/storage/4J699IUV/10.1038@s41586-018-0453-z.pdf:application/pdf}
}

@article{li_minimap2:_2018,
	title = {Minimap2: pairwise alignment for nucleotide sequences},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/bty191},
	shorttitle = {Minimap2},
	abstract = {Motivation: Recent advances in sequencing technologies promise ultra-long reads of ∼100 kilo bases (kb) in average, full-length {mRNA} or {cDNA} reads in high throughput and genomic contigs over 100 mega bases (Mb) in length. Existing alignment programs are unable or inefficient to process such data at scale, which presses for the development of new alignment algorithms.
Results: Minimap2 is a general-purpose alignment program to map {DNA} or long {mRNA} sequences against a large reference database. It works with accurate short reads of ≥ 100bp in length, ≥1kb genomic reads at error rate ∼15\%, full-length noisy Direct {RNA} or {cDNA} reads, and assembly contigs or closely related full chromosomes of hundreds of megabases in length. Minimap2 does split-read alignment, employs concave gap cost for long insertions and deletions ({INDELs}) and introduces new heuristics to reduce spurious alignments. It is 3-4 times as fast as mainstream short-read mappers at comparable accuracy, and is ≥30 times faster than long-read genomic or {cDNA} mappers at higher accuracy, surpassing most aligners specialized in one type of alignment.
Availability and implementation: https://github.com/lh3/minimap2.
Contact: hengli@broadinstitute.org.},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Li, Heng},
	date = {2018-05-10},
	pmid = {29750242},
	file = {Minimap2\: pairwise alignment for nucleotide sequences:/home/jlagarde/Zotero/storage/T6UATN9B/li2018.pdf:application/pdf}
}

@article{blanco_using_2007,
	title = {Using geneid to identify genes},
	volume = {Chapter 4},
	issn = {1934-340X},
	doi = {10.1002/0471250953.bi0403s18},
	abstract = {This unit describes the usage of geneid, an efficient gene-finding program that allows for the analysis of large genomic sequences, including whole mammalian chromosomes. These sequences can be partially annotated, and geneid can be used to refine this initial annotation. Training geneid is relatively easy, and parameter configurations exist for a number of eukaryotic species. Geneid produces output in a variety of standard formats. The results, thus, can be processed by a variety of software tools, including visualization programs. Geneid software is in the public domain, and it is undergoing constant development. It is easy to install and use. Exhaustive benchmark evaluations show that geneid compares favorably with other existing gene finding tools.},
	pages = {Unit 4.3},
	journaltitle = {Current Protocols in Bioinformatics},
	shortjournal = {Curr Protoc Bioinformatics},
	author = {Blanco, Enrique and Parra, Genís and Guigo, Roderic},
	date = {2007-06},
	pmid = {18428791},
	keywords = {Base Sequence, Algorithms, Chromosome Mapping, Genes, Molecular Sequence Data, Sequence Alignment, Sequence Analysis, {DNA}},
	file = {Using geneid to identify genes:/home/jlagarde/Zotero/storage/IJ296GAX/blanco2007.pdf:application/pdf}
}

@article{fantom_consortium_and_the_riken_pmi_and_clst_dgt_promoter-level_2014,
	title = {A promoter-level mammalian expression atlas},
	volume = {507},
	issn = {1476-4687},
	doi = {10.1038/nature13182},
	abstract = {Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule {cDNA} sequencing, we mapped transcription start sites ({TSSs}) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated {TSSs}, with independent cell-type-specific expression profiles. {TSSs} specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 ({FANTOM}5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.},
	pages = {462--470},
	number = {7493},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {{FANTOM Consortium and the RIKEN PMI and CLST (DGT)} and Forrest, Alistair R. R. and Kawaji, Hideya and Rehli, Michael and Baillie, J. Kenneth and de Hoon, Michiel J. L. and Haberle, Vanja and Lassmann, Timo and Kulakovskiy, Ivan V. and Lizio, Marina and Itoh, Masayoshi and Andersson, Robin and Mungall, Christopher J. and Meehan, Terrence F. and Schmeier, Sebastian and Bertin, Nicolas and Jørgensen, Mette and Dimont, Emmanuel and Arner, Erik and Schmidl, Christian and Schaefer, Ulf and Medvedeva, Yulia A. and Plessy, Charles and Vitezic, Morana and Severin, Jessica and Semple, Colin A. and Ishizu, Yuri and Young, Robert S. and Francescatto, Margherita and Alam, Intikhab and Albanese, Davide and Altschuler, Gabriel M. and Arakawa, Takahiro and Archer, John A. C. and Arner, Peter and Babina, Magda and Rennie, Sarah and Balwierz, Piotr J. and Beckhouse, Anthony G. and Pradhan-Bhatt, Swati and Blake, Judith A. and Blumenthal, Antje and Bodega, Beatrice and Bonetti, Alessandro and Briggs, James and Brombacher, Frank and Burroughs, A. Maxwell and Califano, Andrea and Cannistraci, Carlo V. and Carbajo, Daniel and Chen, Yun and Chierici, Marco and Ciani, Yari and Clevers, Hans C. and Dalla, Emiliano and Davis, Carrie A. and Detmar, Michael and Diehl, Alexander D. and Dohi, Taeko and Drabløs, Finn and Edge, Albert S. B. and Edinger, Matthias and Ekwall, Karl and Endoh, Mitsuhiro and Enomoto, Hideki and Fagiolini, Michela and Fairbairn, Lynsey and Fang, Hai and Farach-Carson, Mary C. and Faulkner, Geoffrey J. and Favorov, Alexander V. and Fisher, Malcolm E. and Frith, Martin C. and Fujita, Rie and Fukuda, Shiro and Furlanello, Cesare and Furino, Masaaki and Furusawa, Jun-ichi and Geijtenbeek, Teunis B. and Gibson, Andrew P. and Gingeras, Thomas and Goldowitz, Daniel and Gough, Julian and Guhl, Sven and Guler, Reto and Gustincich, Stefano and Ha, Thomas J. and Hamaguchi, Masahide and Hara, Mitsuko and Harbers, Matthias and Harshbarger, Jayson and Hasegawa, Akira and Hasegawa, Yuki and Hashimoto, Takehiro and Herlyn, Meenhard and Hitchens, Kelly J. and Ho Sui, Shannan J. and Hofmann, Oliver M. and Hoof, Ilka and Hori, Furni and Huminiecki, Lukasz and Iida, Kei and Ikawa, Tomokatsu and Jankovic, Boris R. and Jia, Hui and Joshi, Anagha and Jurman, Giuseppe and Kaczkowski, Bogumil and Kai, Chieko and Kaida, Kaoru and Kaiho, Ai and Kajiyama, Kazuhiro and Kanamori-Katayama, Mutsumi and Kasianov, Artem S. and Kasukawa, Takeya and Katayama, Shintaro and Kato, Sachi and Kawaguchi, Shuji and Kawamoto, Hiroshi and Kawamura, Yuki I. and Kawashima, Tsugumi and Kempfle, Judith S. and Kenna, Tony J. and Kere, Juha and Khachigian, Levon M. and Kitamura, Toshio and Klinken, S. Peter and Knox, Alan J. and Kojima, Miki and Kojima, Soichi and Kondo, Naoto and Koseki, Haruhiko and Koyasu, Shigeo and Krampitz, Sarah and Kubosaki, Atsutaka and Kwon, Andrew T. and Laros, Jeroen F. J. and Lee, Weonju and Lennartsson, Andreas and Li, Kang and Lilje, Berit and Lipovich, Leonard and Mackay-Sim, Alan and Manabe, Ri-ichiroh and Mar, Jessica C. and Marchand, Benoit and Mathelier, Anthony and Mejhert, Niklas and Meynert, Alison and Mizuno, Yosuke and de Lima Morais, David A. and Morikawa, Hiromasa and Morimoto, Mitsuru and Moro, Kazuyo and Motakis, Efthymios and Motohashi, Hozumi and Mummery, Christine L. and Murata, Mitsuyoshi and Nagao-Sato, Sayaka and Nakachi, Yutaka and Nakahara, Fumio and Nakamura, Toshiyuki and Nakamura, Yukio and Nakazato, Kenichi and van Nimwegen, Erik and Ninomiya, Noriko and Nishiyori, Hiromi and Noma, Shohei and Noma, Shohei and Noazaki, Tadasuke and Ogishima, Soichi and Ohkura, Naganari and Ohimiya, Hiroko and Ohno, Hiroshi and Ohshima, Mitsuhiro and Okada-Hatakeyama, Mariko and Okazaki, Yasushi and Orlando, Valerio and Ovchinnikov, Dmitry A. and Pain, Arnab and Passier, Robert and Patrikakis, Margaret and Persson, Helena and Piazza, Silvano and Prendergast, James G. D. and Rackham, Owen J. L. and Ramilowski, Jordan A. and Rashid, Mamoon and Ravasi, Timothy and Rizzu, Patrizia and Roncador, Marco and Roy, Sugata and Rye, Morten B. and Saijyo, Eri and Sajantila, Antti and Saka, Akiko and Sakaguchi, Shimon and Sakai, Mizuho and Sato, Hiroki and Savvi, Suzana and Saxena, Alka and Schneider, Claudio and Schultes, Erik A. and Schulze-Tanzil, Gundula G. and Schwegmann, Anita and Sengstag, Thierry and Sheng, Guojun and Shimoji, Hisashi and Shimoni, Yishai and Shin, Jay W. and Simon, Christophe and Sugiyama, Daisuke and Sugiyama, Takaai and Suzuki, Masanori and Suzuki, Naoko and Swoboda, Rolf K. and 't Hoen, Peter A. C. and Tagami, Michihira and Takahashi, Naoko and Takai, Jun and Tanaka, Hiroshi and Tatsukawa, Hideki and Tatum, Zuotian and Thompson, Mark and Toyodo, Hiroo and Toyoda, Tetsuro and Valen, Elvind and van de Wetering, Marc and van den Berg, Linda M. and Verado, Roberto and Vijayan, Dipti and Vorontsov, Ilya E. and Wasserman, Wyeth W. and Watanabe, Shoko and Wells, Christine A. and Winteringham, Louise N. and Wolvetang, Ernst and Wood, Emily J. and Yamaguchi, Yoko and Yamamoto, Masayuki and Yoneda, Misako and Yonekura, Yohei and Yoshida, Shigehiro and Zabierowski, Susan E. and Zhang, Peter G. and Zhao, Xiaobei and Zucchelli, Silvia and Summers, Kim M. and Suzuki, Harukazu and Daub, Carsten O. and Kawai, Jun and Heutink, Peter and Hide, Winston and Freeman, Tom C. and Lenhard, Boris and Bajic, Vladimir B. and Taylor, Martin S. and Makeev, Vsevolod J. and Sandelin, Albin and Hume, David A. and Carninci, Piero and Hayashizaki, Yoshihide},
	date = {2014-03-27},
	pmid = {24670764},
	pmcid = {PMC4529748},
	keywords = {Transcriptome, Animals, Conserved Sequence, Genome, Humans, Mice, Transcription Initiation Site, Gene Expression Regulation, Organ Specificity, Open Reading Frames, Atlases as Topic, Cell Line, Cluster Analysis, Gene Regulatory Networks, Molecular Sequence Annotation, Transcription Factors, {RNA}, Messenger, Transcription, Genetic, Cells, Cultured, Genes, Essential, Promoter Regions, Genetic},
	file = {A promoter-level mammalian expression atlas:/home/jlagarde/Zotero/storage/FK3JWQ5G/forrest2014.pdf:application/pdf;Accepted Version:/home/jlagarde/Zotero/storage/VWX4ENFP/FANTOM Consortium and the RIKEN PMI and CLST (DGT) et al. - 2014 - A promoter-level mammalian expression atlas.pdf:application/pdf}
}

@article{kaiser_amid_2018,
	title = {Amid fears of idea theft, {NIH} targets foreign funding links},
	volume = {361},
	rights = {Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works},
	issn = {0036-8075, 1095-9203},
	url = {http://science.sciencemag.org/content/361/6405/834},
	doi = {10.1126/science.361.6405.834},
	abstract = {Fears that foreign governments are tapping U.S.-funded research for valuable information have reached the nation's largest research funder, the National Institutes of Health ({NIH}) in Bethesda, Maryland. Last week, {NIH} sent a letter to more than 10,000 research institutions, urging them to ensure that {NIH} grantees are properly reporting their foreign ties. The agency also said it is investigating about a half-dozen cases in which {NIH}-funded investigators may have broken reporting rules, and it reminded researchers who review grant applications that they should not share proposal information with outsiders. At a Senate committee hearing on {NIH} oversight last week, {NIH} Director Francis Collins said risks to the integrity of biomedical research are increasing. He announced a new advisory group to help the agency tighten procedures.
Agency reminds applicants to report all grant sources, warns against violating confidentiality of peer review.
Agency reminds applicants to report all grant sources, warns against violating confidentiality of peer review.},
	pages = {834--834},
	number = {6405},
	journaltitle = {Science},
	author = {Kaiser, Jocelyn and Malakoff, David},
	urldate = {2018-08-31},
	date = {2018-08-31},
	langid = {english},
	file = {Amid fears of idea theft, NIH targets foreign funding links:/home/jlagarde/Zotero/storage/WQRT4U7F/10.1126@science.361.6405.834.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/MNEX9NMC/834.html:text/html}
}

@article{koster_snakemake-scalable_2018,
	title = {Snakemake-a scalable bioinformatics workflow engine},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/bty350},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Köster, Johannes and Rahmann, Sven},
	date = {2018-05-16},
	pmid = {29788404},
	file = {Snakemake-a scalable bioinformatics workflow engine:/home/jlagarde/Zotero/storage/RJH3R47P/kster2018.pdf:application/pdf}
}

@article{herzel_long-read_2018,
	title = {Long-read sequencing of nascent {RNA} reveals coupling among {RNA} processing events},
	volume = {28},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/28/7/1008},
	doi = {10.1101/gr.232025.117},
	abstract = {Pre-{mRNA} splicing is accomplished by the spliceosome, a megadalton complex that assembles de novo on each intron. Because spliceosome assembly and catalysis occur cotranscriptionally, we hypothesized that introns are removed in the order of their transcription in genomes dominated by constitutive splicing. Remarkably little is known about splicing order and the regulatory potential of nascent transcript remodeling by splicing, due to the limitations of existing methods that focus on analysis of mature splicing products ({mRNAs}) rather than substrates and intermediates. Here, we overcome this obstacle through long-read {RNA} sequencing of nascent, multi-intron transcripts in the fission yeast Schizosaccharomyces pombe. Most multi-intron transcripts were fully spliced, consistent with rapid cotranscriptional splicing. However, an unexpectedly high proportion of transcripts were either fully spliced or fully unspliced, suggesting that splicing of any given intron is dependent on the splicing status of other introns in the transcript. Supporting this, mild inhibition of splicing by a temperature-sensitive mutation in prp2, the homolog of vertebrate U2AF65, increased the frequency of fully unspliced transcripts. Importantly, fully unspliced transcripts displayed transcriptional read-through at the {polyA} site and were degraded cotranscriptionally by the nuclear exosome. Finally, we show that cellular {mRNA} levels were reduced in genes with a high number of unspliced nascent transcripts during caffeine treatment, showing regulatory significance of cotranscriptional splicing. Therefore, overall splicing of individual nascent transcripts, 3′ end formation, and {mRNA} half-life depend on the splicing status of neighboring introns, suggesting crosstalk among spliceosomes and the {polyA} cleavage machinery during transcription elongation.},
	pages = {1008--1019},
	number = {7},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Herzel, Lydia and Straube, Korinna and Neugebauer, Karla M.},
	urldate = {2018-09-04},
	date = {2018-07-01},
	langid = {english},
	pmid = {29903723},
	file = {Long-read sequencing of nascent RNA reveals coupling among RNA processing events:/home/jlagarde/Zotero/storage/55D7JMX5/herzel2018.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/ZLMMTPWV/1008.html:text/html}
}

@article{ibrahim_ribothrypsis_2018,
	title = {Ribothrypsis, a novel process of canonical {mRNA} decay, mediates ribosome-phased {mRNA} endonucleolysis},
	volume = {25},
	issn = {1545-9985},
	doi = {10.1038/s41594-018-0042-8},
	abstract = {{mRNAs} transmit the genetic information that dictates protein production and are a nexus for numerous pathways that regulate gene expression. The prevailing view of canonical {mRNA} decay is that it is mediated by deadenylation and decapping followed by exonucleolysis from the 3' and 5' ends. By developing Akron-seq, a novel approach that captures the native 3' and 5' ends of capped and polyadenylated {RNAs}, respectively, we show that canonical human {mRNAs} are subject to repeated cotranslational and ribosome-phased endonucleolytic cuts at the exit site of the {mRNA} ribosome channel, in a process that we term ribothrypsis. We uncovered {RNA} G quadruplexes among likely ribothrypsis triggers and show that ribothrypsis is a conserved process. Strikingly, we found that {mRNA} fragments are abundant in living cells and thus have important implications for the interpretation of experiments, such as {RNA}-seq, that rely on the assumption that {mRNAs} exist largely as full-length molecules in vivo.},
	pages = {302--310},
	number = {4},
	journaltitle = {Nature Structural \& Molecular Biology},
	shortjournal = {Nat. Struct. Mol. Biol.},
	author = {Ibrahim, Fadia and Maragkakis, Manolis and Alexiou, Panagiotis and Mourelatos, Zissimos},
	date = {2018-04},
	pmid = {29507394},
	pmcid = {PMC5889319},
	file = {Ribothrypsis, a novel process of canonical mRNA decay, mediates ribosome-phased mRNA endonucleolysis:/home/jlagarde/Zotero/storage/YN9A75QB/ibrahim2018.pdf:application/pdf}
}

@article{yeo_maximum_2004,
	title = {Maximum entropy modeling of short sequence motifs with applications to {RNA} splicing signals},
	volume = {11},
	issn = {1066-5277},
	doi = {10.1089/1066527041410418},
	abstract = {We propose a framework for modeling sequence motifs based on the maximum entropy principle ({MEP}). We recommend approximating short sequence motif distributions with the maximum entropy distribution ({MED}) consistent with low-order marginal constraints estimated from available data, which may include dependencies between nonadjacent as well as adjacent positions. Many maximum entropy models ({MEMs}) are specified by simply changing the set of constraints. Such models can be utilized to discriminate between signals and decoys. Classification performance using different {MEMs} gives insight into the relative importance of dependencies between different positions. We apply our framework to large datasets of {RNA} splicing signals. Our best models out-perform previous probabilistic models in the discrimination of human 5' (donor) and 3' (acceptor) splice sites from decoys. Finally, we discuss mechanistically motivated ways of comparing models.},
	pages = {377--394},
	number = {2},
	journaltitle = {Journal of Computational Biology: A Journal of Computational Molecular Cell Biology},
	shortjournal = {J. Comput. Biol.},
	author = {Yeo, Gene and Burge, Christopher B.},
	date = {2004},
	pmid = {15285897},
	keywords = {Base Sequence, Computational Biology, Introns, {RNA} Splice Sites, Consensus Sequence, Phylogeny, {ROC} Curve, Markov Chains, Models, Genetic},
	file = {Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals:/home/jlagarde/Zotero/storage/ZSBVMMA4/yeo2004.pdf:application/pdf}
}

@article{isoda_non-coding_2017,
	title = {Non-coding Transcription Instructs Chromatin Folding and Compartmentalization to Dictate Enhancer-Promoter Communication and T Cell Fate},
	volume = {171},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2017.09.001},
	abstract = {It is now established that Bcl11b specifies T cell fate. Here, we show that in developing T cells, the Bcl11b enhancer repositioned from the lamina to the nuclear interior. Our search for factors that relocalized the Bcl11b enhancer identified a non-coding {RNA} named {ThymoD} (thymocyte differentiation factor). {ThymoD}-deficient mice displayed a block at the onset of T cell development and developed lymphoid malignancies. We found that {ThymoD} transcription promoted demethylation at {CTCF} bound sites and activated cohesin-dependent looping to reposition the Bcl11b enhancer from the lamina to the nuclear interior and to juxtapose the Bcl11b enhancer and promoter into a single-loop domain. These large-scale changes in nuclear architecture were associated with the deposition of activating epigenetic marks across the loop domain, plausibly facilitating phase separation. These data indicate how, during developmental progression and tumor suppression, non-coding transcription orchestrates chromatin folding and compartmentalization to direct with high precision enhancer-promoter communication.},
	pages = {103--119.e18},
	number = {1},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Isoda, Takeshi and Moore, Amanda J. and He, Zhaoren and Chandra, Vivek and Aida, Masatoshi and Denholtz, Matthew and Piet van Hamburg, Jan and Fisch, Kathleen M. and Chang, Aaron N. and Fahl, Shawn P. and Wiest, David L. and Murre, Cornelis},
	date = {2017-09-21},
	pmid = {28938112},
	pmcid = {PMC5621651},
	keywords = {Animals, Mice, Chromatin, Leukemia, Lymphoma, Tumor Suppressor Proteins, Repressor Proteins, Transcription, Genetic, Promoter Regions, Genetic, {CCCTC}-Binding Factor, cohesin, compartmentalization, {CTCF}, Enhancer Elements, Genetic, leukemia, Locus Control Region, loop extrusion, lymphoma, Non-coding transcription, Nuclear Lamina, phase separation, {RNA}, Untranslated, single-loop domain, T cell development, T-Lymphocytes, Thymus Gland},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/T4TN5UPS/Isoda et al. - 2017 - Non-coding Transcription Instructs Chromatin Foldi.pdf:application/pdf;Non-coding Transcription Instructs Chromatin Folding and Compartmentalization to Dictate Enhancer-Promoter Communication and T Cell Fate:/home/jlagarde/Zotero/storage/YBTU5292/isoda2017.pdf:application/pdf;Non-coding Transcription Instructs Chromatin Folding and Compartmentalization to Dictate Enhancer-Promoter Communication and T Cell Fate:/home/jlagarde/Zotero/storage/37FPTBKG/isoda2017.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TEQA6UCX/S0092-8674(17)31050-4.html:text/html}
}

@article{kirk_functional_2018,
	title = {Functional classification of long non-coding {RNAs} by k -mer content},
	rights = {2018 The Author(s), under exclusive licence to Springer Nature America, Inc.},
	issn = {1546-1718},
	url = {https://www.nature.com/articles/s41588-018-0207-8},
	doi = {10.1038/s41588-018-0207-8},
	abstract = {{SEEKR} is a method that deconstructs linear sequence relationships between {lncRNAs} and evaluates similarity on the basis of abundance of short motifs called k-mers. {LncRNAs} of related function often have similar k-mer profiles despite lacking linear homology.},
	pages = {1},
	journaltitle = {Nature Genetics},
	author = {Kirk, Jessime M. and Kim, Susan O. and Inoue, Kaoru and Smola, Matthew J. and Lee, David M. and Schertzer, Megan D. and Wooten, Joshua S. and Baker, Allison R. and Sprague, Daniel and Collins, David W. and Horning, Christopher R. and Wang, Shuo and Chen, Qidi and Weeks, Kevin M. and Mucha, Peter J. and Calabrese, J. Mauro},
	urldate = {2018-09-26},
	date = {2018-09-17},
	langid = {english},
	file = {Functional classification of long non-coding RNAs by k -mer content:/home/jlagarde/Zotero/storage/VUMBYW98/10.1038@s41588-018-0207-8.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/5JHFYL87/s41588-018-0207-8.html:text/html}
}

@article{mele_cats_2016,
	title = {“Cat’s Cradling” the 3D Genome by the Act of {LncRNA} Transcription},
	volume = {62},
	issn = {1097-2765},
	url = {http://www.sciencedirect.com/science/article/pii/S1097276516301484},
	doi = {10.1016/j.molcel.2016.05.011},
	abstract = {There is growing evidence that transcription and nuclear organization are tightly linked. Yet, whether transcription of thousands of long noncoding {RNAs} ({lncRNAs}) could play a role in this packaging process remains elusive. Although some {lncRNAs} have been found to have clear roles in nuclear architecture (e.g., {FIRRE}, {NEAT}1, {XIST}, and others), the vast majority remain poorly understood. In this Perspective, we highlight how the act of transcription can affect nuclear architecture. We synthesize several recent findings into a proposed model where the transcription of {lncRNAs} can serve as guide-posts for shaping genome organization. This model is similar to the game “cat’s cradle,” where the shape of a string is successively changed by opening up new sites for finger placement. Analogously, transcription of {lncRNAs} could serve as “grip holds” for nuclear proteins to pull the genome into new positions. This model could explain general {lncRNA} properties such as low abundance and tissue specificity. Overall, we propose a general framework for how the act of {lncRNA} transcription could play a role in organizing the 3D genome.},
	pages = {657--664},
	number = {5},
	journaltitle = {Molecular Cell},
	shortjournal = {Molecular Cell},
	author = {Melé, Marta and Rinn, John L.},
	urldate = {2018-09-26},
	date = {2016-06-02},
	file = {“Cat’s Cradling” the 3D Genome by the Act of LncRNA Transcription:/home/jlagarde/Zotero/storage/F7JWBNMF/mel2016.pdf:application/pdf;ScienceDirect Full Text PDF:/home/jlagarde/Zotero/storage/RRBXCRYU/Melé and Rinn - 2016 - “Cat’s Cradling” the 3D Genome by the Act of LncRN.pdf:application/pdf;ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/GBKTIAAZ/S1097276516301484.html:text/html}
}

@article{schlackow_distinctive_2017,
	title = {Distinctive Patterns of Transcription and {RNA} Processing for Human {lincRNAs}},
	volume = {65},
	issn = {1097-2765},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222723/},
	doi = {10.1016/j.molcel.2016.11.029},
	abstract = {Numerous long intervening noncoding {RNAs} ({lincRNAs}) are generated from the mammalian genome by {RNA} polymerase {II} (Pol {II}) transcription. Although multiple functions have been ascribed to {lincRNAs}, their synthesis and turnover remain poorly characterized. Here, we define systematic differences in transcription and {RNA} processing between protein-coding and {lincRNA} genes in human {HeLa} cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing ({mNET}-seq). Notably, {mNET}-seq patterns specific for different Pol {II} {CTD} phosphorylation states reveal weak co-transcriptional splicing and poly(A) signal-independent Pol {II} termination of {lincRNAs} as compared to pre-{mRNAs}. In addition, {lincRNAs} are mostly restricted to chromatin, since they are rapidly degraded by the {RNA} exosome. We also show that a {lincRNA}-specific co-transcriptional {RNA} cleavage mechanism acts to induce premature termination. In effect, functional {lincRNAs} must escape from this targeted nuclear surveillance process., 
          
            
              •
              {lincRNAs} and pre-{mRNAs} are transcribed by different Pol {II} phospho-{CTD} isoforms
            
            
              •
              {lincRNAs} are rarely spliced and mainly non-polyadenylated
            
            
              •
              {lincRNAs} are stabilized in the nucleoplasm following exosome inactivation
            
            
              •
              {lincRNAs} are co-transcriptionally cleaved
            
          
        , Schlackow and Nojima et al. show that mammalian pre-{mRNAs} and long intergenic noncoding (linc) {RNAs} employ radically different transcription and {RNA}-processing strategies. Pre-{mRNAs} are transcribed by defined {RNA} polymerase (Pol) {II} isoforms reflecting co-transcriptional splicing and polyadenylation. Instead, {lincRNAs} are mainly transcribed by deregulated Pol {II} and simultaneously degraded.},
	pages = {25--38},
	number = {1},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol Cell},
	author = {Schlackow, Margarita and Nojima, Takayuki and Gomes, Tomas and Dhir, Ashish and Carmo-Fonseca, Maria and Proudfoot, Nick J.},
	urldate = {2018-10-04},
	date = {2017-01-05},
	pmid = {28017589},
	pmcid = {PMC5222723},
	file = {Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs:/home/jlagarde/Zotero/storage/DK83HFH3/schlackow2017.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/I334U6J6/Schlackow et al. - 2017 - Distinctive Patterns of Transcription and RNA Proc.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/9U6GHQ97/Schlackow et al. - 2017 - Distinctive Patterns of Transcription and RNA Proc.html:text/html}
}

@article{laumont_noncoding_2018,
	title = {Noncoding regions are the main source of targetable tumor-specific antigens},
	volume = {10},
	rights = {Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. http://www.sciencemag.org/about/science-licenses-journal-article-{reuseThis} is an article distributed under the terms of the Science Journals Default License.},
	issn = {1946-6234, 1946-6242},
	url = {http://stm.sciencemag.org/content/10/470/eaau5516},
	doi = {10.1126/scitranslmed.aau5516},
	abstract = {Expanding the landscape of immunotherapy targets
Most searches for druggable tumor-specific antigens ({TSAs}) start with an examination of peptides derived from protein-coding exons. Laumont et al. took a different approach and found numerous {TSAs} aberrantly expressed from noncoding sequences in murine cell lines and in B-lineage acute lymphoblastic leukemia and lung cancer patient samples, but not in cells responsible for T cell selection. The authors validated the immunogenicity and efficacy of {TSA} vaccination for select antigens in mouse models of cancer. The finding that noncoding regions are a potentially rich source of {TSAs} could greatly expand the number of targetable antigens across different cancers, including those with low mutational burdens.
Tumor-specific antigens ({TSAs}) represent ideal targets for cancer immunotherapy, but few have been identified thus far. We therefore developed a proteogenomic approach to enable the high-throughput discovery of {TSAs} coded by potentially all genomic regions. In two murine cancer cell lines and seven human primary tumors, we identified a total of 40 {TSAs}, about 90\% of which derived from allegedly noncoding regions and would have been missed by standard exome-based approaches. Moreover, most of these {TSAs} derived from nonmutated yet aberrantly expressed transcripts (such as endogenous retroelements) that could be shared by multiple tumor types. Last, we demonstrated that, in mice, the strength of antitumor responses after {TSA} vaccination was influenced by two parameters that can be estimated in humans and could serve for {TSA} prioritization in clinical studies: {TSA} expression and the frequency of {TSA}-responsive T cells in the preimmune repertoire. In conclusion, the strategy reported herein could considerably facilitate the identification and prioritization of actionable human {TSAs}.
A proteogenomic method identifies potentially actionable tumor-specific antigens and shows that most of them are not coded by classic exons.
A proteogenomic method identifies potentially actionable tumor-specific antigens and shows that most of them are not coded by classic exons.},
	pages = {eaau5516},
	number = {470},
	journaltitle = {Science Translational Medicine},
	author = {Laumont, Céline M. and Vincent, Krystel and Hesnard, Leslie and Audemard, Éric and Bonneil, Éric and Laverdure, Jean-Philippe and Gendron, Patrick and Courcelles, Mathieu and Hardy, Marie-Pierre and Côté, Caroline and Durette, Chantal and St-Pierre, Charles and Benhammadi, Mohamed and Lanoix, Joël and Vobecky, Suzanne and Haddad, Elie and Lemieux, Sébastien and Thibault, Pierre and Perreault, Claude},
	urldate = {2018-12-09},
	date = {2018-12-05},
	langid = {english},
	pmid = {30518613},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/Z2CHVP2V/Laumont et al. - 2018 - Noncoding regions are the main source of targetabl.pdf:application/pdf;Noncoding regions are the main source of targetable tumor-specific antigens:/home/jlagarde/Zotero/storage/M937T6XB/10.1126@scitranslmed.aau5516.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/DQBURXBB/Laumont et al. - 2018 - Noncoding regions are the main source of targetabl.html:text/html}
}

@article{tang_full-length_2018,
	title = {Full-length transcript characterization of {SF}3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/early/2018/09/06/410183},
	doi = {10.1101/410183},
	abstract = {{SF}3B1 is one of the most frequently mutated genes in chronic lymphocytic leukemia ({CLL}) and is associated with poor patient prognosis. While alternative splicing patterns caused by mutations in {SF}3B1 have been identified with short-read {RNA} sequencing, a critical barrier in understanding the functional consequences of these splicing changes is that we lack the full transcript context in which these changes are occurring. Using nanopore sequencing technology, we have resequenced full-length {cDNA} from {CLL} samples with and without the hotspot {SF}3B1 K700E mutation, and a normal B cell. We have developed a workflow called {FLAIR} (Full-Length Alternative Isoform analysis of {RNA}), leveraging the full-length transcript sequencing data that nanopore affords. We report results from nanopore sequencing that are concordant with known {SF}3B1 biology from short read sequencing as well as altered intron retention events more confidently observed using long reads. Splicing analysis of nanopore reads between the {SF}3B1WT and {SF}3B1K700E samples identifies alternative upstream 3' splice sites associated with {SF}3B1K700E. We also find downregulation of intron retention events in {SF}3B1K700E relative to {SF}3B1WT and no difference between {CLL} {SF}3B1MUT and B cell, suggesting an aberrant intron retention landscape in {CLL} samples lacking {SF}3B1 mutation. With full-length isoforms, we are able to better estimate the abundance of {RNA} transcripts that are productive and will likely be translated versus those that are unproductive. Validation from short-read data also reveals a strong branch point sequence in these downregulated intron retention events, consistent with previously reported branch points associated with mutated {SF}3B1. As nanopore sequencing has yet to become a routine tool for characterization of the transcriptome, our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.},
	pages = {410183},
	journaltitle = {{bioRxiv}},
	author = {Tang, Alison D. and Soulette, Cameron M. and Baren, Marijke J. van and Hart, Kevyn and Hrabeta-Robinson, Eva and Wu, Catherine J. and Brooks, Angela N.},
	urldate = {2018-12-07},
	date = {2018-09-06},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/KI9N83GT/Tang et al. - 2018 - Full-length transcript characterization of SF3B1 m.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/M3UE7Z95/Tang et al. - 2018 - Full-length transcript characterization of SF3B1 m.html:text/html}
}

@article{paralkar_unlinking_2016,
	title = {Unlinking an {lncRNA} from Its Associated cis Element},
	volume = {62},
	issn = {1097-2765},
	url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(16)00140-4},
	doi = {10.1016/j.molcel.2016.02.029},
	pages = {104--110},
	number = {1},
	journaltitle = {Molecular Cell},
	shortjournal = {Molecular Cell},
	author = {Paralkar, Vikram R. and Taborda, Cristian C. and Huang, Peng and Yao, Yu and Kossenkov, Andrew V. and Prasad, Rishi and Luan, Jing and Davies, James O. J. and Hughes, Jim R. and Hardison, Ross C. and Blobel, Gerd A. and Weiss, Mitchell J.},
	urldate = {2018-12-06},
	date = {2016-04-07},
	pmid = {27041223},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/AGE6N2H6/Paralkar et al. - 2016 - Unlinking an lncRNA from Its Associated cis Elemen.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/PSGXPFT8/Paralkar et al. - 2016 - Unlinking an lncRNA from Its Associated cis Elemen.html:text/html}
}

@article{mattioli_high-throughput_2018,
	title = {High-throughput functional analysis of {lncRNA} core promoters elucidates rules governing tissue-specificity},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/early/2018/11/29/482232},
	doi = {10.1101/482232},
	abstract = {Transcription initiates at both coding and non-coding genomic elements, including {mRNA} and long non-coding {RNA} ({lncRNA}) core promoters and enhancer {RNAs} ({eRNAs}). However, each class has different expression profiles with {lncRNAs} and {eRNAs} being the most tissue-specific. How these complex differences in expression profiles and tissue-specificities are encoded in a single {DNA} sequence, however, remains unresolved. Here, we address this question using computational approaches and massively parallel reporter assays ({MPRA}) surveying hundreds of promoters and enhancers. We find that both divergent {lncRNA} and {mRNA} core promoters have higher capacities to drive transcription than non-divergent {lncRNA} and {mRNA} core promoters, respectively. Conversely, {lincRNAs} and {eRNAs} have lower capacities to drive transcription and are more tissue-specific than divergent genes. This higher tissue-specificity is strongly associated with having less complex {TF} motif profiles at the core promoter. We experimentally validated these findings by testing both engineered single-nucleotide deletions and human single-nucleotide polymorphisms ({SNPs}) in {MPRA}. In both cases, we observe that single nucleotides associated with many motifs are important drivers of promoter activity. Thus, we suggest that high {TF} motif density serves as a robust mechanism to increase promoter activity at the expense of tissue-specificity. Moreover, we find that 22\% of common {SNPs} in core promoter regions have significant regulatory effects. Collectively, our findings show that high {TF} motif density provides redundancy and increases promoter activity at the expense of tissue specificity, suggesting that specificity of expression may be regulated by simplicity of motif usage.},
	pages = {482232},
	journaltitle = {{bioRxiv}},
	author = {Mattioli, Kaia and Volders, Pieter-Jan and Gerhardinger, Chiara and Lee, James C. and Maass, Philipp G. and Mele, Marta and Rinn, John L.},
	urldate = {2018-12-04},
	date = {2018-11-29},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/R9VI7HZ2/Mattioli et al. - 2018 - High-throughput functional analysis of lncRNA core.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/86GDAWBC/Mattioli et al. - 2018 - High-throughput functional analysis of lncRNA core.html:text/html}
}

@article{lima_comparative_2018,
	title = {Comparative assessment of long-read error-correction software applied to {RNA}-sequencing data},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/early/2018/11/23/476622},
	doi = {10.1101/476622},
	abstract = {Long-read sequencing technologies offer promising alternatives to high-throughput short read sequencing, especially in the context of {RNA}-sequencing. However these technologies are currently hindered by high error rates that affect analyses such as the identification of isoforms, exon boundaries, open reading frames, and the creation of gene catalogues. Due to the novelty of such data, computational methods are still actively being developed and options for the error-correction of {RNA}-sequencing long reads remain limited. In this article, we evaluate the extent to which existing long-read {DNA} error correction methods are capable of correcting {cDNA} Nanopore reads. We provide an automatic and extensive benchmark tool that not only reports classical error-correction metrics but also the effect of correction on gene families, isoform diversity, bias toward the major isoform, and splice site detection. We find that long read error-correction tools that were originally developed for {DNA} are also suitable for the correction of {RNA}-sequencing data, especially in terms of increasing base-pair accuracy. Yet investigators should be warned that the correction process perturbs gene family sizes and isoform diversity. This work provides guidelines on which (or whether) error-correction tools should be used, depending on the application type. Benchmarking software: https://gitlab.com/leoisl/{LR}\_EC\_analyser},
	pages = {476622},
	journaltitle = {{bioRxiv}},
	author = {Lima, Leandro Ishi Soares de and Marchet, Camille and Caboche, Segolene and Silva, Corinne Da and Istace, Benjamin and Aury, Jean-Marc and Touzet, Helene and Chikhi, Rayan},
	urldate = {2018-12-02},
	date = {2018-11-23},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/5H8FX6QN/Lima et al. - 2018 - Comparative assessment of long-read error-correcti.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/NRMVD6CP/Lima et al. - 2018 - Comparative assessment of long-read error-correcti.html:text/html}
}

@article{gu_transcription-coupled_2018,
	title = {Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements},
	volume = {359},
	rights = {Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. http://www.sciencemag.org/about/science-licenses-journal-article-{reuseThis} is an article distributed under the terms of the Science Journals Default License.},
	issn = {0036-8075, 1095-9203},
	url = {http://science.sciencemag.org/content/359/6379/1050},
	doi = {10.1126/science.aao3136},
	abstract = {Tracking regulatory {DNA} in action
Cis-regulatory {DNA} elements such as enhancers and promoters are critical for transcription regulation. Little is known about the relationship between these elements' transcriptional activity and their mobility within the nucleus in living cells. Gu et al. developed a strategy to deliver multiple {RNAs} to guide inactive Cas9 to label these elements. Quantitative measurement of their movement during stem cell differentiation revealed that increased {DNA} loci mobility correlated with transcriptional activation.
Science, this issue p. 1050
To achieve guide {RNA} ({gRNA}) multiplexing and an efficient delivery of tens of distinct {gRNAs} into single cells, we developed a molecular assembly strategy termed chimeric array of {gRNA} oligonucleotides ({CARGO}). We coupled {CARGO} with {dCas}9 (catalytically dead Cas9) imaging to quantitatively measure the movement of enhancers and promoters that undergo differentiation-associated activity changes in live embryonic stem cells. Whereas all examined functional elements exhibited subdiffusive behavior, their relative mobility increased concurrently with transcriptional activation. Furthermore, acute perturbation of {RNA} polymerase {II} activity can reverse these activity-linked increases in loci mobility. Through quantitative {CARGO}-{dCas}9 imaging, we provide direct measurements of cis-regulatory element dynamics in living cells and distinct cellular and activity states and uncover an intrinsic connection between cis-regulatory element mobility and transcription.
Live-cell imaging of cis-regulatory {DNA} elements reveals an intrinsic connection between their transcriptional activity and nuclear mobility.
Live-cell imaging of cis-regulatory {DNA} elements reveals an intrinsic connection between their transcriptional activity and nuclear mobility.},
	pages = {1050--1055},
	number = {6379},
	journaltitle = {Science},
	author = {Gu, Bo and Swigut, Tomek and Spencley, Andrew and Bauer, Matthew R. and Chung, Mingyu and Meyer, Tobias and Wysocka, Joanna},
	urldate = {2018-11-19},
	date = {2018-03-02},
	langid = {english},
	pmid = {29371426},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/BT2NIUJC/Gu et al. - 2018 - Transcription-coupled changes in nuclear mobility .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/M27QDWMD/Gu et al. - 2018 - Transcription-coupled changes in nuclear mobility .html:text/html;Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements:/home/jlagarde/Zotero/storage/HRXKYXUS/gu2018.pdf:application/pdf}
}

@article{workman_nanopore_2018,
	title = {Nanopore native {RNA} sequencing of a human poly(A) transcriptome},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/early/2018/11/09/459529},
	doi = {10.1101/459529},
	abstract = {High throughput {RNA} sequencing technologies have dramatically advanced our understanding of transcriptome complexity and regulation. However, these {cDNA}-based methods lose information contained in biological {RNA} because the copied reads are short or because modifications are not carried forward in {cDNA}. Here we address these limitations using a native poly(A) {RNA} sequencing strategy developed by Oxford Nanopore Technologies ({ONT}). Our study focused on poly(A) {RNA} isolated from the human cell line {GM}12878, from which we sequenced approximately 9.9 million individual aligned strands. These native {RNA} sequence reads had an N50 length of 1334 bases, and a maximum length of 22,000 bases. A total of 78,199 high-confidence isoforms were identified by combining long nanopore reads with short higher accuracy Illumina reads. Among these isoforms, over 50\% are not present in {GENCODE} v24. We describe strategies for assessing 3'poly(A) tail length, base modifications and transcript haplotypes using this single molecule technology. Together, these nanopore-based techniques are poised to deliver new insights into {RNA} biology.},
	pages = {459529},
	journaltitle = {{bioRxiv}},
	author = {Workman, Rachael E. and Tang, Alison and Tang, Paul S. and Jain, Miten and Tyson, John R. and Zuzarte, Philip C. and Gilpatrick, Timothy and Razaghi, Roham and Quick, Joshua and Sadowski, Norah and Holmes, Nadine and Jesus, Jaqueline Goes de and Jones, Karen and Snutch, Terrance P. and Loman, Nicholas James and Paten, Benedict and Loose, Matthew W. and Simpson, Jared T. and Olsen, Hugh E. and Brooks, Angela N. and Akeson, Mark and Timp, Winston},
	urldate = {2018-11-14},
	date = {2018-11-09},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/WMT5MA95/Workman et al. - 2018 - Nanopore native RNA sequencing of a human poly(A) .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/GMIV4NAF/Workman et al. - 2018 - Nanopore native RNA sequencing of a human poly(A) .html:text/html}
}

@article{kuo_normalized_2017,
	title = {Normalized long read {RNA} sequencing in chicken reveals transcriptome complexity similar to human},
	volume = {18},
	issn = {1471-2164},
	doi = {10.1186/s12864-017-3691-9},
	abstract = {{BACKGROUND}: Despite the significance of chicken as a model organism, our understanding of the chicken transcriptome is limited compared to human. This issue is common to all non-human vertebrate annotations due to the difficulty in transcript identification from short read {RNAseq} data. While previous studies have used single molecule long read sequencing for transcript discovery, they did not perform {RNA} normalization and 5'-cap selection which may have resulted in lower transcriptome coverage and truncated transcript sequences.
{RESULTS}: We sequenced normalised chicken brain and embryo {RNA} libraries with Pacific Bioscience Iso-Seq. 5' cap selection was performed on the embryo library to provide methodological comparison. From these Iso-Seq sequencing projects, we have identified 60 k transcripts and 29 k genes within the chicken transcriptome. Of these, more than 20 k are novel {lncRNA} transcripts with {\textasciitilde}3 k classified as sense exonic overlapping {lncRNA}, which is a class that is underrepresented in many vertebrate annotations. The relative proportion of alternative transcription events revealed striking similarities between the chicken and human transcriptomes while also providing explanations for previously observed genomic differences.
{CONCLUSIONS}: Our results indicate that the chicken transcriptome is similar in complexity compared to human, and provide insights into other vertebrate biology. Our methodology demonstrates the potential of Iso-Seq sequencing to rapidly expand our knowledge of transcriptomics.},
	pages = {323},
	number = {1},
	journaltitle = {{BMC} genomics},
	shortjournal = {{BMC} Genomics},
	author = {Kuo, Richard I. and Tseng, Elizabeth and Eory, Lel and Paton, Ian R. and Archibald, Alan L. and Burt, David W.},
	date = {2017},
	pmid = {28438136},
	pmcid = {PMC5404281},
	keywords = {{PacBio}, Genomics, Animals, Humans, Gene Expression Profiling, Organ Specificity, {RNA} Splice Sites, Chickens, Molecular Sequence Annotation, Phylogeny, Species Specificity, Avian, Chicken, Coding {RNA}, Gallus gallus, Genome annotation, Iso-Seq, Non-coding {RNA}, {RNAseq}, Sequence Analysis, {RNA}, Single molecule long read sequencing, Transcriptome sequencing}
}

@article{sheynkman_orf_2019,
	title = {{ORF} Capture-Seq: a versatile method for targeted identification of full-length isoforms},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NonCommercial}-{NoDerivs} 4.0 International), {CC} {BY}-{NC}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/604157v1},
	doi = {10.1101/604157},
	shorttitle = {{ORF} Capture-Seq},
	abstract = {{\textless}p{\textgreater}Most human protein-coding genes are expressed as multiple isoforms. This in turn greatly expands the functional repertoire of the encoded proteome. While at least one reliable open reading frame ({ORF}) model has been assigned for every gene, the majority of alternative isoforms remains uncharacterized experimentally. This is primarily due to: i) vast differences of overall levels between different isoforms expressed from common genes, and ii) the difficulty of obtaining contiguous full-length {ORF} sequences. Here, we present {ORF} Capture-Seq ({OCS}), a flexible and cost-effective method that addresses both challenges for targeted full-length isoform sequencing applications using collections of cloned {ORFs} as probes. As proof-of-concept, we show that an {OCS} pipeline focused on genes coding for transcription factors increases isoform detection by an order of magnitude, compared to unenriched sample. In short, {OCS} enables rapid discovery of isoforms from custom-selected genes and will allow mapping of the full set of human isoforms at reasonable cost.{\textless}/p{\textgreater}},
	pages = {604157},
	journaltitle = {{bioRxiv}},
	author = {Sheynkman, Gloria M. and Tuttle, Katharine S. and Tseng, Elizabeth and Underwood, Jason G. and Yu, Liang and Dong, Da and Smith, Melissa L. and Sebra, Robert and Hao, Tong and Calderwood, Michael A. and Hill, David E. and Vidal, Marc},
	urldate = {2019-04-16},
	date = {2019-04-11},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/EH9SXTUZ/Sheynkman et al. - 2019 - ORF Capture-Seq\: a versatile method for targeted i.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/E6QN6KTW/Sheynkman et al. - 2019 - ORF Capture-Seq\: a versatile method for targeted i.html:text/html}
}

@article{roach_full-length_2019,
	title = {The full-length transcriptome of C. elegans using direct {RNA} sequencing},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/598763v2},
	doi = {10.1101/598763},
	abstract = {{\textless}p{\textgreater}Current transcriptome annotations have largely relied on short read lengths intrinsic to most widely used high-throughput {cDNA} sequencing technologies. For example, in the annotation of the Caenorhabditis elegans transcriptome, more than half of the transcript isoforms lack full-length support and instead rely on inference from short reads that do not span the full length of the isoform. We applied nanopore-based direct {RNA} sequencing to characterize the developmental polyadenylated transcriptome of C. elegans. Taking advantage of long reads spanning the full length of {mRNA} transcripts, we provide support for 20,902 splice isoforms across 14,115 genes, without the need for computational reconstruction of gene models. Of the isoforms identified, 2,188 are novel splice isoforms not present in the Wormbase {WS}265 annotation. Furthermore, we identified 16,325 39 untranslated region (39UTR) isoforms, 2,304 of which are novel and do not fall within 10 bp of existing 39UTR datasets and annotations. Combining 39UTRs and splice isoforms we identified 25,944 full-length isoforms. We also determined that poly(A) tail lengths of transcripts vary across development, as do the strengths of previously reported correlations between poly(A) tail length and expression level, and poly(A) tail length and 39UTR length. Finally, we have formatted this data as a publically accessible track hub, enabling researchers to explore this dataset easily in a genome browser.{\textless}/p{\textgreater}},
	pages = {598763},
	journaltitle = {{bioRxiv}},
	author = {Roach, Nathan P. and Sadowski, Norah and Alessi, Amelia F. and Timp, Winston and Taylor, James and Kim, John K.},
	urldate = {2019-04-15},
	date = {2019-04-09},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/Q99HHSB2/Roach et al. - 2019 - The full-length transcriptome of C. elegans using .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/KBGG8D3U/Roach et al. - 2019 - The full-length transcriptome of C. elegans using .html:text/html}
}

@article{saudemont_fitness_2017,
	title = {The fitness cost of mis-splicing is the main determinant of alternative splicing patterns},
	volume = {18},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-017-1344-6},
	doi = {10.1186/s13059-017-1344-6},
	abstract = {Most eukaryotic genes are subject to alternative splicing ({AS}), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger {RNA} ({mRNA}) decay ({NMD}). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated.},
	pages = {208},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Saudemont, Baptiste and Popa, Alexandra and Parmley, Joanna L. and Rocher, Vincent and Blugeon, Corinne and Necsulea, Anamaria and Meyer, Eric and Duret, Laurent},
	urldate = {2019-04-04},
	date = {2017-10-30},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/U9SW5ZV4/Saudemont et al. - 2017 - The fitness cost of mis-splicing is the main deter.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/MQT4U34U/Saudemont et al. - 2017 - The fitness cost of mis-splicing is the main deter.html:text/html}
}

@article{xu_evidence_2019,
	title = {Evidence that alternative transcriptional initiation is largely nonadaptive},
	volume = {17},
	issn = {1545-7885},
	url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000197},
	doi = {10.1371/journal.pbio.3000197},
	abstract = {Alternative transcriptional initiation ({ATI}) refers to the frequent observation that one gene has multiple transcription start sites ({TSSs}). Although this phenomenon is thought to be adaptive, the specific advantage is rarely known. Here, we propose that each gene has one optimal {TSS} and that {ATI} arises primarily from imprecise transcriptional initiation that could be deleterious. This error hypothesis predicts that (i) the {TSS} diversity of a gene reduces with its expression level; (ii) the fractional use of the major {TSS} increases, but that of each minor {TSS} decreases, with the gene expression level; and (iii) cis-elements for major {TSSs} are selectively constrained, while those for minor {TSSs} are not. By contrast, the adaptive hypothesis does not make these predictions a priori. Our analysis of human and mouse transcriptomes confirms each of the three predictions. These and other findings strongly suggest that {ATI} predominantly results from molecular errors, requiring a major revision of our understanding of the precision and regulation of transcription.},
	pages = {e3000197},
	number = {3},
	journaltitle = {{PLOS} Biology},
	shortjournal = {{PLOS} Biology},
	author = {Xu, Chuan and Park, Joong-Ki and Zhang, Jianzhi},
	urldate = {2019-03-30},
	date = {2019-03-18},
	langid = {english},
	keywords = {{RNA} sequencing, {DNA} transcription, Gene expression, Gene sequencing, Natural selection, Shannon index, Simpson index, Transcriptional control},
	file = {Evidence that alternative transcriptional initiation is largely nonadaptive:/home/jlagarde/Zotero/storage/CRQ7QKB9/xu2019.pdf:application/pdf;Evidence that alternative transcriptional initiation is largely nonadaptive:/home/jlagarde/Zotero/storage/KQEDUQ6C/xu2019.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/7R76D83K/Xu et al. - 2019 - Evidence that alternative transcriptional initiati.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/K5FV3NMG/Xu et al. - 2019 - Evidence that alternative transcriptional initiati.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/JQ355TZR/Xu et al. - 2019 - Evidence that alternative transcriptional initiati.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/9BTJSFG4/Xu et al. - 2019 - Evidence that alternative transcriptional initiati.html:text/html}
}

@online{noauthor_whole-genome_nodate,
	title = {Whole-genome and {RNA} sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex {\textbar} {bioRxiv}},
	url = {https://www.biorxiv.org/content/10.1101/585430v1?rss=1&utm_source=dlvr.it&utm_medium=twitter},
	urldate = {2019-03-25}
}

@article{liu_crispri-based_2017,
	title = {{CRISPRi}-based genome-scale identification of functional long noncoding {RNA} loci in human cells},
	volume = {355},
	rights = {Copyright © 2017, American Association for the Advancement of Science},
	issn = {0036-8075, 1095-9203},
	url = {http://science.sciencemag.org/content/355/6320/eaah7111},
	doi = {10.1126/science.aah7111},
	abstract = {A very focused function for {lncRNAs}
The human genome generates many thousands of long noncoding {RNAs} ({lncRNAs}). A very small number of {lncRNAs} have been shown to be functional. Liu et al. carried out a large-scale {CRISPR}-based screen to assess the function of ∼17,000 {lncRNAs} in seven different human cell lines. A considerable number (∼500) of the tested {lncRNAs} influenced cell growth, suggesting biological function. In almost all cases, though, the function was highly cell type—specific, often limited to just one cell type.
Science, this issue p. 10.1126/science.aah7111
Structured Abstract
{INTRODUCTIONThe} human genome contains tens of thousands of loci that produce long noncoding {RNAs} ({lncRNAs}), transcripts that have no apparent protein-coding potential. A subset of {lncRNAs} have been found to play critical roles in cellular processes, organismal development, and disease. Although these examples are suggestive of the importance and diversity of {lncRNAs}, the vast majority of {lncRNA} genes have not been functionally tested.
{RATIONALEBecause} it is currently not possible to predict which {lncRNA} loci are functional or what function they perform, there is a need for large-scale, systematic approaches to interrogating the functional contribution of {lncRNA} loci. We therefore developed a genome-scale screening platform based on {CRISPR}-mediated interference ({CRISPRi}), which uses a catalytically inactive {CRISPR} effector protein, (d)Cas9, fused to a repressive {KRAB} domain and targeted by a single guide {RNA} ({sgRNA}), to inhibit gene expression. By catalyzing repressive chromatin modifications around the transcription start site ({TSS}) and serving as a transcriptional roadblock, {CRISPRi} tests a broad range of {lncRNA} gene functions, including the production of cis- and trans-acting {RNA} transcripts, cis-mediated regulation related to {lncRNA} transcription itself, and enhancer-like function of some {lncRNA} loci.
{RESULTSWe} designed a {CRISPRi} Non-Coding Library ({CRiNCL}), which targets 16,401 {lncRNA} genes each with 10 {sgRNAs} per {TSS}, and applied this pooled screening approach to identify {lncRNA} genes that modify robust cell growth. We screened seven human cell lines, including six transformed cell lines and induced pluripotent stem cells ({iPSCs}), and identified 499 {lncRNA} loci that modified cell growth upon {CRISPRi} targeting; 372 and 299 of these loci were distal from any protein coding gene or mapped enhancer, respectively. Extensive validation confirmed the screen results and demonstrated the robust and specific performance of {CRISPRi} for repressing {lncRNA} transcription. Remarkably, 89\% of the {lncRNA} gene hits modified growth in just one of the cell lines tested, and no hits were common to all seven cell lines. Although nearly all of the hit genes were expressed in the cell line in which they exhibited a growth phenotype, expression alone was insufficient to explain the cell type specificity of their function. Transcriptional profiling revealed extensive gene expression changes upon {CRISPRi} targeting of {lncRNA} loci in the cells in which they modified growth, whereas targeting the same {lncRNA} locus in other cell lines resulted in minimal changes to the transcriptome beyond depletion of the targeted {lncRNA} transcript itself.
{CONCLUSIONOur} study considerably increases the number of known functional {lncRNA} loci. More broadly, our {CRISPRi} approach enables mechanistic studies of specific {lncRNA} functions and, when applied systematically, supports the global exploration of the complex biology contained in the {lncRNA}-expressing genome. Finally, in contrast to recent studies that found that essential protein-coding genes typically are required across a broad range of cell types, we show that {lncRNA} function is highly cell type–specific, a finding that has important implications for their involvement in both normal biology and disease. {\textless}img class="fragment-image" aria-describedby="F1-caption" src="http://science.sciencemag.org/content/sci/355/6320/eaah7111/F1.medium.gif"/{\textgreater} Download high-res image Open in new tab Download Powerpoint {CRISPRi} screening of {lncRNAs} in human cells.{CRISPRi} can precisely repress transcription of {lncRNAs}. The {CRISPRi} Non-Coding Library ({CRiNCL}) was generated to interrogate the function of thousands of long noncoding {RNAs} in seven different cell lines. Validation studies confirmed the exquisite cell type–specific function of {lncRNAs}.
The human genome produces thousands of long noncoding {RNAs} ({lncRNAs})—transcripts {\textgreater}200 nucleotides long that do not encode proteins. Although critical roles in normal biology and disease have been revealed for a subset of {lncRNAs}, the function of the vast majority remains untested. We developed a {CRISPR} interference ({CRISPRi}) platform targeting 16,401 {lncRNA} loci in seven diverse cell lines, including six transformed cell lines and human induced pluripotent stem cells ({iPSCs}). Large-scale screening identified 499 {lncRNA} loci required for robust cellular growth, of which 89\% showed growth-modifying function exclusively in one cell type. We further found that {lncRNA} knockdown can perturb complex transcriptional networks in a cell type–specific manner. These data underscore the functional importance and cell type specificity of many {lncRNAs}.
A considerable fraction of long noncoding {RNAs} have highly cell type–specific biological functions.
A considerable fraction of long noncoding {RNAs} have highly cell type–specific biological functions.},
	pages = {eaah7111},
	number = {6320},
	journaltitle = {Science},
	author = {Liu, S. John and Horlbeck, Max A. and Cho, Seung Woo and Birk, Harjus S. and Malatesta, Martina and He, Daniel and Attenello, Frank J. and Villalta, Jacqueline E. and Cho, Min Y. and Chen, Yuwen and Mandegar, Mohammad A. and Olvera, Michael P. and Gilbert, Luke A. and Conklin, Bruce R. and Chang, Howard Y. and Weissman, Jonathan S. and Lim, Daniel A.},
	urldate = {2019-03-13},
	date = {2017-01-06},
	langid = {english},
	pmid = {27980086},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/RGDGAQJA/Liu et al. - 2017 - CRISPRi-based genome-scale identification of funct.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/NRIHVR87/Liu et al. - 2017 - CRISPRi-based genome-scale identification of funct.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TP4SMAMM/Liu et al. - 2017 - CRISPRi-based genome-scale identification of funct.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/Q49IPIW4/eaah7111.html:text/html}
}

@article{cocquet_reverse_2006,
	title = {Reverse transcriptase template switching and false alternative transcripts},
	volume = {88},
	issn = {0888-7543},
	doi = {10.1016/j.ygeno.2005.12.013},
	abstract = {Reverse transcriptase ({RT}) can switch from one template to another in a homology-dependent manner. In the study of eukaryotic transcripts, this propensity of {RT} can produce an artificially deleted {cDNA}, which can be wrongly interpreted as an alternative transcript. Here, we have investigated the presence of such template-switching artifacts in {cDNA} databases, by scanning a collection of human splice sites (Information for the Coordinates of Exons, {ICE} database). We have confirmed several cases at the experimental level. Artifacts represent a significant portion of apparently spliced sequences using noncanonical splice signals but are rare in the context of the whole database. However, care should be taken in the annotation of alternative transcripts, especially when the {RT} used is poorly thermostable and when the putative intron is flanked by direct repeats, which are the substrate for template switching.},
	pages = {127--131},
	number = {1},
	journaltitle = {Genomics},
	shortjournal = {Genomics},
	author = {Cocquet, Julie and Chong, Allen and Zhang, Guanglan and Veitia, Reiner A.},
	date = {2006-07},
	pmid = {16457984},
	keywords = {Base Sequence, Humans, Alternative Splicing, Forkhead Transcription Factors, Gene Library, Molecular Sequence Data, Nucleic Acid Conformation, Reverse Transcriptase Polymerase Chain Reaction, {RNA}-Directed {DNA} Polymerase, Artifact, {cDNA} library, {EST} database, {FOXL}2, Reverse transcriptase, {RT}-{PCR}, Splice isoforms, Template switching, Forkhead Box Protein L2, Templates, Genetic},
	file = {Attachment:/home/jlagarde/Zotero/storage/95S6NEE5/Cocquet et al. - 2006 - Reverse transcriptase template switching and false alternative transcripts.pdf:application/pdf}
}

@article{hardwick_targeted_2019,
	title = {Targeted, High-Resolution {RNA} Sequencing Of Non-Coding Genomic Regions Associated With Neuropsychiatric Functions},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NonCommercial}-{NoDerivs} 4.0 International), {CC} {BY}-{NC}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/539882v1},
	doi = {10.1101/539882},
	abstract = {{\textless}p{\textgreater}The human brain is one of the last frontiers of biomedical research. Genome-wide association studies ({GWAS}) have succeeded in identifying thousands of haplotype blocks associated with a range of neuropsychiatric traits, including disorders such as schizophrenia, Alzheimer9s and Parkinson9s disease. However, the majority of single nucleotide polymorphisms ({SNPs}) that mark these haplotype blocks fall within non-coding regions of the genome, hindering their functional validation. While some of these {GWAS} loci may contain cis-acting regulatory {DNA} elements such as enhancers, we hypothesized that many are also transcribed into non-coding {RNAs} that are missing from publicly available transcriptome annotations. Here, we use targeted {RNA} capture (9RNA {CaptureSeq}9) in combination with nanopore long-read {cDNA} sequencing to transcriptionally profile 1,023 haplotype blocks across the genome containing non-coding {GWAS} {SNPs} associated with neuropsychiatric traits, using post-mortem human brain tissue from three neurologically healthy donors. We find that the majority (62\%) of targeted haplotype blocks, including 13\% of intergenic blocks, are transcribed into novel, multi-exonic {RNAs}, most of which are not yet recorded in {GENCODE} annotations. We validated our findings with short-read {RNA}-seq, providing orthogonal confirmation of novel splice junctions and enabling a quantitative assessment of the long-read assemblies. Many novel transcripts are supported by independent evidence of transcription including cap analysis of gene expression ({CAGE}) data and epigenetic marks, and some show signs of potential functional roles. We present these transcriptomes as a preliminary atlas of non-coding transcription in human brain that can be used to connect neurological phenotypes with gene expression.{\textless}/p{\textgreater}},
	pages = {539882},
	journaltitle = {{bioRxiv}},
	author = {Hardwick, Simon A. and Bassett, Samuel D. and Kaczorowski, Dominik and Blackburn, James and Barton, Kirston and Bartonicek, Nenad and Carswell, Shaun L. and Tilgner, Hagen U. and Loy, Clement and Halliday, Glenda and Mercer, Tim R. and Smith, Martin A. and Mattick, John S.},
	urldate = {2019-02-05},
	date = {2019-02-04},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/FIZ5GIZZ/Hardwick et al. - 2019 - Targeted, High-Resolution RNA Sequencing Of Non-Co.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/4RRDW3GI/Hardwick et al. - 2019 - Targeted, High-Resolution RNA Sequencing Of Non-Co.html:text/html}
}

@article{herbert_cross-site_2018,
	title = {Cross-site comparison of ribosomal depletion kits for Illumina {RNAseq} library construction},
	volume = {19},
	issn = {1471-2164},
	url = {https://doi.org/10.1186/s12864-018-4585-1},
	doi = {10.1186/s12864-018-4585-1},
	abstract = {Ribosomal {RNA} ({rRNA}) comprises at least 90\% of total {RNA} extracted from mammalian tissue or cell line samples. Informative transcriptional profiling using massively parallel sequencing technologies requires either enrichment of mature poly-adenylated transcripts or targeted depletion of the {rRNA} fraction. The latter method is of particular interest because it is compatible with degraded samples such as those extracted from {FFPE} and also captures transcripts that are not poly-adenylated such as some non-coding {RNAs}. Here we provide a cross-site study that evaluates the performance of ribosomal {RNA} removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded {RNA} samples.},
	pages = {199},
	number = {1},
	journaltitle = {{BMC} Genomics},
	shortjournal = {{BMC} Genomics},
	author = {Herbert, Zachary T. and Kershner, Jamie P. and Butty, Vincent L. and Thimmapuram, Jyothi and Choudhari, Sulbha and Alekseyev, Yuriy O. and Fan, Jun and Podnar, Jessica W. and Wilcox, Edward and Gipson, Jenny and Gillaspy, Allison and Jepsen, Kristen and {BonDurant}, Sandra Splinter and Morris, Krystalynne and Berkeley, Maura and {LeClerc}, Ashley and Simpson, Stephen D. and Sommerville, Gary and Grimmett, Leslie and Adams, Marie and Levine, Stuart S.},
	urldate = {2019-05-17},
	date = {2018-03-15},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/JJ6UT5CF/Herbert et al. - 2018 - Cross-site comparison of ribosomal depletion kits .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/C6T4IP75/Herbert et al. - 2018 - Cross-site comparison of ribosomal depletion kits .html:text/html}
}

@article{ransohoff_functions_2018,
	title = {The functions and unique features of long intergenic non-coding {RNA}},
	volume = {19},
	issn = {1471-0072},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889127/},
	doi = {10.1038/nrm.2017.104},
	abstract = {Long intergenic non-coding {RNA} ({lincRNA}) genes have diverse features that distinguish them from {mRNA}-encoding genes and exercise functions such as remodelling chromatin and genome architecture, {RNA} stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding {lincRNAs} include small open reading frames ({smORFs}) and encode functional peptides and thus may be more properly classified as coding {RNAs}. {lincRNAs} may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome.},
	pages = {143--157},
	number = {3},
	journaltitle = {Nature reviews. Molecular cell biology},
	shortjournal = {Nat Rev Mol Cell Biol},
	author = {Ransohoff, Julia D. and Wei, Yuning and Khavari, Paul A.},
	urldate = {2019-05-22},
	date = {2018-03},
	pmid = {29138516},
	pmcid = {PMC5889127},
	keywords = {coding {RNAs}, Gene regulation, Long non, Open reading frames},
	file = {Attachment:/home/jlagarde/Zotero/storage/CHR3WRUX/Ransohoff, Wei, Khavari - 2017 - The functions and unique features of long intergenic non-coding RNA.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/8EDCI75Z/Ransohoff et al. - 2018 - The functions and unique features of long intergen.pdf:application/pdf}
}

@article{rozowsky_alleleseq:_2011,
	title = {{AlleleSeq}: analysis of allele-specific expression and binding in a network framework},
	volume = {7},
	issn = {1744-4292},
	doi = {10.1038/msb.2011.54},
	shorttitle = {{AlleleSeq}},
	abstract = {To study allele-specific expression ({ASE}) and binding ({ASB}), that is, differences between the maternally and paternally derived alleles, we have developed a computational pipeline ({AlleleSeq}). Our pipeline initially constructs a diploid personal genome sequence (and corresponding personalized gene annotation) using genomic sequence variants ({SNPs}, indels, and structural variants), and then identifies allele-specific events with significant differences in the number of mapped reads between maternal and paternal alleles. There are many technical challenges in the construction and alignment of reads to a personal diploid genome sequence that we address, for example, bias of reads mapping to the reference allele. We have applied {AlleleSeq} to variation data for {NA}12878 from the 1000 Genomes Project as well as matched, deeply sequenced {RNA}-Seq and {ChIP}-Seq data sets generated for this purpose. In addition to observing fairly widespread allele-specific behavior within individual functional genomic data sets (including results consistent with X-chromosome inactivation), we can study the interaction between {ASE} and {ASB}. Furthermore, we investigate the coordination between {ASE} and {ASB} from multiple transcription factors events using a regulatory network framework. Correlation analyses and network motifs show mostly coordinated {ASB} and {ASE}.},
	pages = {522},
	journaltitle = {Molecular Systems Biology},
	shortjournal = {Mol. Syst. Biol.},
	author = {Rozowsky, Joel and Abyzov, Alexej and Wang, Jing and Alves, Pedro and Raha, Debasish and Harmanci, Arif and Leng, Jing and Bjornson, Robert and Kong, Yong and Kitabayashi, Naoki and Bhardwaj, Nitin and Rubin, Mark and Snyder, Michael and Gerstein, Mark},
	date = {2011-08-02},
	pmid = {21811232},
	pmcid = {PMC3208341},
	keywords = {Humans, Gene Expression Regulation, Oligonucleotide Array Sequence Analysis, Alleles, Cell Line, Chromosome Mapping, {DNA}-Binding Proteins, Gene Regulatory Networks, Molecular Sequence Annotation, Transcription Factors, Databases, Genetic, Sequence Analysis, {RNA}, Chromosomes, Human, X, Chromosomes, Human, Y, Genome, Human, Polymorphism, Single Nucleotide}
}

@article{frankish_gencode_2019,
	title = {{GENCODE} reference annotation for the human and mouse genomes},
	volume = {47},
	issn = {0305-1048},
	url = {https://academic.oup.com/nar/article/47/D1/D766/5144133},
	doi = {10.1093/nar/gky955},
	abstract = {Abstract.  The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of dat},
	pages = {D766--D773},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Frankish, Adam and Diekhans, Mark and Ferreira, Anne-Maud and Johnson, Rory and Jungreis, Irwin and Loveland, Jane and Mudge, Jonathan M. and Sisu, Cristina and Wright, James and Armstrong, Joel and Barnes, If and Berry, Andrew and Bignell, Alexandra and Carbonell Sala, Silvia and Chrast, Jacqueline and Cunningham, Fiona and Di Domenico, Tomás and Donaldson, Sarah and Fiddes, Ian T. and García Girón, Carlos and Gonzalez, Jose Manuel and Grego, Tiago and Hardy, Matthew and Hourlier, Thibaut and Hunt, Toby and Izuogu, Osagie G. and Lagarde, Julien and Martin, Fergal J. and Martínez, Laura and Mohanan, Shamika and Muir, Paul and Navarro, Fabio C. P. and Parker, Anne and Pei, Baikang and Pozo, Fernando and Ruffier, Magali and Schmitt, Bianca M. and Stapleton, Eloise and Suner, Marie-Marthe and Sycheva, Irina and Uszczynska-Ratajczak, Barbara and Xu, Jinuri and Yates, Andrew and Zerbino, Daniel and Zhang, Yan and Aken, Bronwen and Choudhary, Jyoti S. and Gerstein, Mark and Guigó, Roderic and Hubbard, Tim J. P. and Kellis, Manolis and Paten, Benedict and Reymond, Alexandre and Tress, Michael L. and Flicek, Paul},
	urldate = {2019-05-28},
	date = {2019-01-08},
	langid = {english},
	file = {Frankish et al. - 2019 - GENCODE reference annotation for the human and mou.pdf:/home/jlagarde/Zotero/storage/87LK7BYD/Frankish et al. - 2019 - GENCODE reference annotation for the human and mou.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/6VW75M4A/5144133.html:text/html}
}

@article{lowe_genomic_2015,
	title = {Genomic approaches for understanding the genetics of complex disease},
	volume = {25},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579328/},
	doi = {10.1101/gr.190603.115},
	abstract = {There are thousands of known associations between genetic variants and complex human phenotypes, and the rate of novel discoveries is rapidly increasing. Translating those associations into knowledge of disease mechanisms remains a fundamental challenge because the associated variants are overwhelmingly in noncoding regions of the genome where we have few guiding principles to predict their function. Intersecting the compendium of identified genetic associations with maps of regulatory activity across the human genome has revealed that phenotype-associated variants are highly enriched in candidate regulatory elements. Allele-specific analyses of gene regulation can further prioritize variants that likely have a functional effect on disease mechanisms; and emerging high-throughput assays to quantify the activity of candidate regulatory elements are a promising next step in that direction. Together, these technologies have created the ability to systematically and empirically test hypotheses about the function of noncoding variants and haplotypes at the scale needed for comprehensive and systematic follow-up of genetic association studies. Major coordinated efforts to quantify regulatory mechanisms across genetically diverse populations in increasingly realistic cell models would be highly beneficial to realize that potential.},
	pages = {1432--1441},
	number = {10},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Lowe, William L. and Reddy, Timothy E.},
	urldate = {2019-05-28},
	date = {2015-10},
	pmid = {26430153},
	pmcid = {PMC4579328},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/AHFSHTDS/Lowe and Reddy - 2015 - Genomic approaches for understanding the genetics .pdf:application/pdf}
}

@article{li_rna_2016,
	title = {{RNA} splicing is a primary link between genetic variation and disease},
	volume = {352},
	issn = {0036-8075},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5182069/},
	doi = {10.1126/science.aad9417},
	abstract = {Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines ({LCLs}). About {\textasciitilde}65\% of expression quantitative trait loci ({eQTLs}) have primary effects on chromatin, whereas the remaining {eQTLs} are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing {QTLs}, most of which have little or no effect on gene-level expression. These splicing {QTLs} are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.},
	pages = {600--604},
	number = {6285},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Li, Yang I. and van de Geijn, Bryce and Raj, Anil and Knowles, David A. and Petti, Allegra A. and Golan, David and Gilad, Yoav and Pritchard, Jonathan K.},
	urldate = {2019-05-28},
	date = {2016-04-29},
	pmid = {27126046},
	pmcid = {PMC5182069},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/MMUBDFP5/Li et al. - 2016 - RNA splicing is a primary link between genetic var.pdf:application/pdf}
}

@article{macarthur_systematic_2012,
	title = {A systematic survey of loss-of-function variants in human protein-coding genes},
	volume = {335},
	issn = {1095-9203},
	doi = {10.1126/science.1215040},
	abstract = {Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function ({LoF}) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative {LoF} variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain {\textasciitilde}100 genuine {LoF} variants with {\textasciitilde}20 genes completely inactivated. We identify rare and likely deleterious {LoF} alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common {LoF} variants in nonessential genes. We describe functional and evolutionary differences between {LoF}-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.},
	pages = {823--828},
	number = {6070},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {MacArthur, Daniel G. and Balasubramanian, Suganthi and Frankish, Adam and Huang, Ni and Morris, James and Walter, Klaudia and Jostins, Luke and Habegger, Lukas and Pickrell, Joseph K. and Montgomery, Stephen B. and Albers, Cornelis A. and Zhang, Zhengdong D. and Conrad, Donald F. and Lunter, Gerton and Zheng, Hancheng and Ayub, Qasim and DePristo, Mark A. and Banks, Eric and Hu, Min and Handsaker, Robert E. and Rosenfeld, Jeffrey A. and Fromer, Menachem and Jin, Mike and Mu, Xinmeng Jasmine and Khurana, Ekta and Ye, Kai and Kay, Mike and Saunders, Gary Ian and Suner, Marie-Marthe and Hunt, Toby and Barnes, If H. A. and Amid, Clara and Carvalho-Silva, Denise R. and Bignell, Alexandra H. and Snow, Catherine and Yngvadottir, Bryndis and Bumpstead, Suzannah and Cooper, David N. and Xue, Yali and Romero, Irene Gallego and {1000 Genomes Project Consortium} and Wang, Jun and Li, Yingrui and Gibbs, Richard A. and McCarroll, Steven A. and Dermitzakis, Emmanouil T. and Pritchard, Jonathan K. and Barrett, Jeffrey C. and Harrow, Jennifer and Hurles, Matthew E. and Gerstein, Mark B. and Tyler-Smith, Chris},
	date = {2012-02-17},
	pmid = {22344438},
	pmcid = {PMC3299548},
	keywords = {Humans, Proteins, Disease, Gene Expression, Gene Frequency, Genetic Variation, Phenotype, Selection, Genetic, Genome, Human, Polymorphism, Single Nucleotide},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/SR7MYPS2/MacArthur et al. - 2012 - A systematic survey of loss-of-function variants i.pdf:application/pdf}
}

@article{sudmant_integrated_2015,
	title = {An integrated map of structural variation in 2,504 human genomes},
	volume = {526},
	rights = {2015 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature15394},
	doi = {10.1038/nature15394},
	abstract = {Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read {DNA} sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.},
	pages = {75--81},
	number = {7571},
	journaltitle = {Nature},
	author = {Sudmant, Peter H. and Rausch, Tobias and Gardner, Eugene J. and Handsaker, Robert E. and Abyzov, Alexej and Huddleston, John and Zhang, Yan and Ye, Kai and Jun, Goo and Hsi-Yang Fritz, Markus and Konkel, Miriam K. and Malhotra, Ankit and Stütz, Adrian M. and Shi, Xinghua and Paolo Casale, Francesco and Chen, Jieming and Hormozdiari, Fereydoun and Dayama, Gargi and Chen, Ken and Malig, Maika and Chaisson, Mark J. P. and Walter, Klaudia and Meiers, Sascha and Kashin, Seva and Garrison, Erik and Auton, Adam and Lam, Hugo Y. K. and Jasmine Mu, Xinmeng and Alkan, Can and Antaki, Danny and Bae, Taejeong and Cerveira, Eliza and Chines, Peter and Chong, Zechen and Clarke, Laura and Dal, Elif and Ding, Li and Emery, Sarah and Fan, Xian and Gujral, Madhusudan and Kahveci, Fatma and Kidd, Jeffrey M. and Kong, Yu and Lameijer, Eric-Wubbo and McCarthy, Shane and Flicek, Paul and Gibbs, Richard A. and Marth, Gabor and Mason, Christopher E. and Menelaou, Androniki and Muzny, Donna M. and Nelson, Bradley J. and Noor, Amina and Parrish, Nicholas F. and Pendleton, Matthew and Quitadamo, Andrew and Raeder, Benjamin and Schadt, Eric E. and Romanovitch, Mallory and Schlattl, Andreas and Sebra, Robert and Shabalin, Andrey A. and Untergasser, Andreas and Walker, Jerilyn A. and Wang, Min and Yu, Fuli and Zhang, Chengsheng and Zhang, Jing and Zheng-Bradley, Xiangqun and Zhou, Wanding and Zichner, Thomas and Sebat, Jonathan and Batzer, Mark A. and McCarroll, Steven A. and {The 1000 Genomes Project Consortium} and Mills, Ryan E. and Gerstein, Mark B. and Bashir, Ali and Stegle, Oliver and Devine, Scott E. and Lee, Charles and Eichler, Evan E. and Korbel, Jan O.},
	urldate = {2019-05-28},
	date = {2015-10},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/4BC7WB6Q/Sudmant et al. - 2015 - An integrated map of structural variation in 2,504.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/UFN6FPSX/nature15394.html:text/html}
}

@article{manzoni_genome_2016,
	title = {Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences},
	volume = {19},
	issn = {1467-5463},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018996/},
	doi = {10.1093/bib/bbw114},
	shorttitle = {Genome, transcriptome and proteome},
	abstract = {Advances in the technologies and informatics used to generate and process large biological data sets (omics data) are promoting a critical shift in the study of biomedical sciences. While genomics, transcriptomics and proteinomics, coupled with bioinformatics and biostatistics, are gaining momentum, they are still, for the most part, assessed individually with distinct approaches generating monothematic rather than integrated knowledge. As other areas of biomedical sciences, including metabolomics, epigenomics and pharmacogenomics, are moving towards the omics scale, we are witnessing the rise of inter-disciplinary data integration strategies to support a better understanding of biological systems and eventually the development of successful precision medicine. This review cuts across the boundaries between genomics, transcriptomics and proteomics, summarizing how omics data are generated, analysed and shared, and provides an overview of the current strengths and weaknesses of this global approach. This work intends to target students and researchers seeking knowledge outside of their field of expertise and fosters a leap from the reductionist to the global-integrative analytical approach in research.},
	pages = {286--302},
	number = {2},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief Bioinform},
	author = {Manzoni, Claudia and Kia, Demis A and Vandrovcova, Jana and Hardy, John and Wood, Nicholas W and Lewis, Patrick A and Ferrari, Raffaele},
	urldate = {2019-05-28},
	date = {2016-11-22},
	pmid = {27881428},
	pmcid = {PMC6018996},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/QPRE3GCN/Manzoni et al. - 2016 - Genome, transcriptome and proteome the rise of om.pdf:application/pdf}
}

@article{ashley_precision_2015,
	title = {The precision medicine initiative: a new national effort},
	volume = {313},
	issn = {1538-3598},
	doi = {10.1001/jama.2015.3595},
	shorttitle = {The precision medicine initiative},
	pages = {2119--2120},
	number = {21},
	journaltitle = {{JAMA}},
	shortjournal = {{JAMA}},
	author = {Ashley, Euan A.},
	date = {2015-06-02},
	pmid = {25928209},
	keywords = {Humans, Biological Specimen Banks, Genetic Diseases, Inborn, Government Regulation, Information Dissemination, Precision Medicine, United States}
}

@article{marx_dna_2015,
	title = {The {DNA} of a nation},
	volume = {524},
	issn = {1476-4687},
	doi = {10.1038/524503a},
	pages = {503--505},
	number = {7566},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Marx, Vivien},
	date = {2015-08-27},
	pmid = {26310768},
	keywords = {Genomics, Humans, Software, {DNA} Mutational Analysis, Genetic Predisposition to Disease, Genetic Variation, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Genome, Human, Precision Medicine, Databases, Factual, Genetic Testing, Genetics, Medical, Genetics, Population, Internationality, United Kingdom},
	file = {The DNA of a nation:/home/jlagarde/Zotero/storage/L8CDU8MU/marx2015.pdf:application/pdf}
}

@article{salzberg_next-generation_2019,
	title = {Next-generation genome annotation: we still struggle to get it right},
	volume = {20},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-019-1715-2},
	doi = {10.1186/s13059-019-1715-2},
	shorttitle = {Next-generation genome annotation},
	abstract = {While the genome sequencing revolution has led to the sequencing and assembly of many thousands of new genomes, genome annotation still uses very nearly the same technology that we have used for the past two decades. The sheer number of genomes necessitates the use of fully automated procedures for annotation, but errors in annotation are just as prevalent as they were in the past, if not more so. How are we to solve this growing problem?},
	pages = {92},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Salzberg, Steven L.},
	urldate = {2019-07-08},
	date = {2019-05-16},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/Z4HH7ZHG/Salzberg - 2019 - Next-generation genome annotation\: we still strugg.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TC3C8HT6/Salzberg - 2019 - Next-generation genome annotation\: we still strugg.html:text/html}
}

@article{gruber_alternative_2019,
	title = {Alternative cleavage and polyadenylation in health and disease},
	rights = {2019 Springer Nature Limited},
	issn = {1471-0064},
	url = {https://www.nature.com/articles/s41576-019-0145-z},
	doi = {10.1038/s41576-019-0145-z},
	abstract = {In most human genes, {RNA} 3ʹ end cleavage and polyadenylation can occur at multiple, alternative sites, enabling the expression of distinct transcripts. Novel techniques to sequence {RNA} 3ʹ ends, coupled with innovative computational methods for studying the list of polyadenylation sites that they generate, have uncovered the roles of alternative cleavage and polyadenylation in both health and disease.},
	pages = {1},
	journaltitle = {Nature Reviews Genetics},
	author = {Gruber, Andreas J. and Zavolan, Mihaela},
	urldate = {2019-07-04},
	date = {2019-07-02},
	file = {Snapshot:/home/jlagarde/Zotero/storage/NV7PPZH2/Gruber and Zavolan - 2019 - Alternative cleavage and polyadenylation in health.html:text/html}
}

@article{cook_long_2017,
	title = {Long Read Annotation ({LoReAn}): automated eukaryotic genome annotation based on long-read {cDNA} sequencing},
	rights = {© 2017, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/10.1101/230359v1},
	doi = {10.1101/230359},
	shorttitle = {Long Read Annotation ({LoReAn})},
	abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}p{\textgreater}Single-molecule full-length {cDNA} sequencing can aid genome annotation by revealing transcript structure and alternative splice-forms, yet current annotation pipelines do not incorporate such information. Here we present {LoReAn} (Long Read Annotation) software, an automated annotation pipeline utilizing short- and long-read {cDNA} sequencing, protein evidence, and \textit{ab initio} prediction to generate accurate genome annotations. Based on annotations of two fungal and two plant genomes, we show that {LoReAn} outperforms popular annotation pipelines by integrating single-molecule {cDNA} sequencing data generated from either the {PacBio} or {MinION} sequencing platforms, and correctly predicting gene structure and capturing genes missed by other annotation pipelines.{\textless}/p{\textgreater}},
	pages = {230359},
	journaltitle = {{bioRxiv}},
	author = {Cook, David E. and Valle-Inclan, Jose Espejo and Pajoro, Alije and Rovenich, Hanna and Thomma, Bart {PHJ} and Faino, Luigi},
	urldate = {2019-07-01},
	date = {2017-12-08},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/3P8ZTUT5/Cook et al. - 2017 - Long Read Annotation (LoReAn)\: automated eukaryoti.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/7DVHEDV3/Cook et al. - 2017 - Long Read Annotation (LoReAn)\: automated eukaryoti.html:text/html}
}

@article{lima_comparative_nodate,
	title = {Comparative assessment of long-read error correction software applied to Nanopore {RNA}-sequencing data},
	url = {https://academic.oup.com/bib/advance-article/doi/10.1093/bib/bbz058/5512144},
	doi = {10.1093/bib/bbz058},
	abstract = {{AbstractMotivation}.  Nanopore long-read sequencing technology offers promising alternatives to high-throughput short read sequencing, especially in the context},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief Bioinform},
	author = {Lima, Leandro and Marchet, Camille and Caboche, Ségolène and Da Silva, Corinne and Istace, Benjamin and Aury, Jean-Marc and Touzet, Hélène and Chikhi, Rayan},
	urldate = {2019-07-01},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/RZUEQEAZ/Lima et al. - Comparative assessment of long-read error correcti.html:text/html}
}

@article{carithers_novel_2015,
	title = {A Novel Approach to High-Quality Postmortem Tissue Procurement: The {GTEx} Project},
	volume = {13},
	issn = {1947-5535},
	url = {https://www.liebertpub.com/doi/full/10.1089/bio.2015.0032},
	doi = {10.1089/bio.2015.0032},
	shorttitle = {A Novel Approach to High-Quality Postmortem Tissue Procurement},
	abstract = {The Genotype-Tissue Expression ({GTEx}) project, sponsored by the {NIH} Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the {GTEx} project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the {GTEx} project are available to the research community.},
	pages = {311--319},
	number = {5},
	journaltitle = {Biopreservation and Biobanking},
	shortjournal = {Biopreservation and Biobanking},
	author = {Carithers, Latarsha J. and Ardlie, Kristin and Barcus, Mary and Branton, Philip A. and Britton, Angela and Buia, Stephen A. and Compton, Carolyn C. and {DeLuca}, David S. and Peter-Demchok, Joanne and Gelfand, Ellen T. and Guan, Ping and Korzeniewski, Greg E. and Lockhart, Nicole C. and Rabiner, Chana A. and Rao, Abhi K. and Robinson, Karna L. and Roche, Nancy V. and Sawyer, Sherilyn J. and Segrè, Ayellet V. and Shive, Charles E. and Smith, Anna M. and Sobin, Leslie H. and Undale, Anita H. and Valentino, Kimberly M. and Vaught, Jim and Young, Taylor R. and Moore, Helen M.},
	urldate = {2019-06-26},
	date = {2015-10-01},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/I6KFCMXZ/Carithers et al. - 2015 - A Novel Approach to High-Quality Postmortem Tissue.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/US27C36J/Carithers et al. - 2015 - A Novel Approach to High-Quality Postmortem Tissue.html:text/html}
}

@article{wick_performance_2019,
	title = {Performance of neural network basecalling tools for Oxford Nanopore sequencing},
	volume = {20},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-019-1727-y},
	doi = {10.1186/s13059-019-1727-y},
	abstract = {Basecalling, the computational process of translating raw electrical signal to nucleotide sequence, is of critical importance to the sequencing platforms produced by Oxford Nanopore Technologies ({ONT}). Here, we examine the performance of different basecalling tools, looking at accuracy at the level of bases within individual reads and at majority-rule consensus basecalls in an assembly. We also investigate some additional aspects of basecalling: training using a taxon-specific dataset, using a larger neural network model and improving consensus basecalls in an assembly by additional signal-level analysis with Nanopolish.},
	pages = {129},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Wick, Ryan R. and Judd, Louise M. and Holt, Kathryn E.},
	urldate = {2019-06-26},
	date = {2019-06-24},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/W3GWE452/Wick et al. - 2019 - Performance of neural network basecalling tools fo.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/D3ZV8F9B/Wick et al. - 2019 - Performance of neural network basecalling tools fo.html:text/html}
}

@online{noauthor_open_nodate,
	title = {Open collaborative writing with Manubot},
	url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007128},
	urldate = {2019-06-26}
}

@article{sessegolo_transcriptome_2019,
	title = {Transcriptome profiling of mouse samples using nanopore sequencing of {cDNA} and {RNA} molecules},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/575142v1},
	doi = {10.1101/575142},
	abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}h3{\textgreater}Background{\textless}/h3{\textgreater} {\textless}p{\textgreater}Our vision of {DNA} transcription and splicing has changed dramatically with the intro-duction of short-read sequencing. These high-throughput sequencing technologies promised to unravel the complexity of any transcriptome. Generally gene expression levels are well-captured using these technologies, but there are still remaining caveats due to the limited read length and the fact that {RNA} molecules had to be reverse transcribed before sequencing. Oxford Nanopore Technologies has recently launched a portable sequencer which offers the possibility of sequencing long reads and most importantly {RNA} molecules.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Results{\textless}/h3{\textgreater} {\textless}p{\textgreater}Here we generated a full mouse transcriptome from brain and liver using the Oxford Nanopore device. As a comparison, we sequenced {RNA} ({RNA}-Seq) and {cDNA} ({cDNA}-Seq) molecules using both long and short reads technologies. In addition, we tested the {TeloPrime} preparation kit, dedicated to the enrichment of full-length transcripts.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Conclusions{\textless}/h3{\textgreater} {\textless}p{\textgreater}Using spike-in data, we confirmed that expression levels are efficiently captured by {cDNA}-Seq using short reads. More importantly, Oxford Nanopore {RNA}-Seq tends to be more efficient, while {cDNA}-Seq appears to be more biased. We further show that the {cDNA} library preparation of the Nanopore protocol induces read truncation for transcripts containing stretches of A’s. Furthermore, bioinformatics challenges remain ahead for quantifying at the transcript level, especially when reads are not full-length. Accurate quantification of processed pseudogenes also remains difficult, and we show that current mapping protocols which map reads to the genome largely over-estimate their expression, at the expense of their parent gene.{\textless}/p{\textgreater}},
	pages = {575142},
	journaltitle = {{bioRxiv}},
	author = {Sessegolo, Camille and Cruaud, Corinne and Silva, Corinne Da and Dubarry, Marion and Derrien, Thomas and Lacroix, Vincent and Aury, Jean-Marc},
	urldate = {2019-06-12},
	date = {2019-03-12},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/Q9VSDBVI/Sessegolo et al. - 2019 - Transcriptome profiling of mouse samples using nan.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/R9U6DF58/Sessegolo et al. - 2019 - Transcriptome profiling of mouse samples using nan.html:text/html}
}

@article{morillon_bridging_2019,
	title = {Bridging the gap between reference and real transcriptomes},
	volume = {20},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-019-1710-7},
	doi = {10.1186/s13059-019-1710-7},
	abstract = {Genetic, transcriptional, and post-transcriptional variations shape the transcriptome of individual cells, rendering establishing an exhaustive set of reference {RNAs} a complicated matter. Current reference transcriptomes, which are based on carefully curated transcripts, are lagging behind the extensive {RNA} variation revealed by massively parallel sequencing. Much may be missed by ignoring this unreferenced {RNA} diversity. There is plentiful evidence for non-reference transcripts with important phenotypic effects. Although reference transcriptomes are inestimable for gene expression analysis, they may turn limiting in important medical applications. We discuss computational strategies for retrieving hidden transcript diversity.},
	pages = {112},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Morillon, Antonin and Gautheret, Daniel},
	urldate = {2019-06-12},
	date = {2019-06-03},
	file = {Full Text:/home/jlagarde/Zotero/storage/LD56WX9C/Morillon and Gautheret - 2019 - Bridging the gap between reference and real transc.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/A368JM8I/Morillon and Gautheret - 2019 - Bridging the gap between reference and real transc.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/4GASR88G/Morillon and Gautheret - 2019 - Bridging the gap between reference and real transc.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/9B3GDWKS/s13059-019-1710-7.html:text/html}
}

@article{szczesniak_towards_2019,
	title = {Towards a deeper annotation of human {lncRNAs}},
	issn = {1874-9399},
	url = {http://www.sciencedirect.com/science/article/pii/S187493991830525X},
	doi = {10.1016/j.bbagrm.2019.05.003},
	abstract = {A substantial fraction of the human transcriptome is composed of the so-called long noncoding {RNAs} ({lncRNAs}), yet the available catalogs of known {lncRNAs} are far from complete. Moreover, functional studies of these {RNAs} are challenged by several factors, such as their tissue-specific expression and functional heterogeneity, resulting in only ca. 1\% of them being well characterized. Here, we describe a set of 41,400 novel {lncRNAs} discovered with {RNA}-Seq data from 1463 samples encompassing diverse tissues and cell lines. We utilized publicly available transcriptomic and genomic data to provide their characteristics, such as tissue specificity, cellular abundance, {polyA} status, cellular localization, evolutionary conservation and transcript stability, which allowed us to speculate on their possible biological roles. We also pinpointed 24 novel {lncRNAs} as candidates for breast cancer biomarkers. The results bring us closer to a comprehensive annotation of human {lncRNAs}, though vast amounts of further work are needed to validate the predictions and fully decipher their biology. This article is part of a Special Issue entitled: {ncRNA} in control of gene expression edited by Kotb Abdelmohsen.},
	journaltitle = {Biochimica et Biophysica Acta ({BBA}) - Gene Regulatory Mechanisms},
	shortjournal = {Biochimica et Biophysica Acta ({BBA}) - Gene Regulatory Mechanisms},
	author = {Szcześniak, Michał Wojciech and Wanowska, Elżbieta and Mukherjee, Neelanjan and Ohler, Uwe and Makałowska, Izabela},
	urldate = {2019-06-11},
	date = {2019-05-22},
	keywords = {Polyadenylation, Antisense {RNAs}, Cancer biomarkers, Long noncoding {RNAs}, {RNA}-Seq, {RNA}:{RNA} interactions},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/7RIF6IHT/Szcześniak et al. - 2019 - Towards a deeper annotation of human lncRNAs.html:text/html}
}

@article{griffith_significance_1928,
	title = {The Significance of Pneumococcal Types},
	volume = {27},
	issn = {0022-1724},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2167760/},
	pages = {113--159},
	number = {2},
	journaltitle = {The Journal of Hygiene},
	shortjournal = {J Hyg (Lond)},
	author = {Griffith, Fred.},
	urldate = {2019-07-08},
	date = {1928-01},
	pmid = {20474956},
	pmcid = {PMC2167760},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/LBNPZ4QA/Griffith - 1928 - The Significance of Pneumococcal Types.pdf:application/pdf}
}

@article{avery_studies_1944,
	title = {Studies on the chemical nature of the substance inducing transformation of pneumococcal types},
	volume = {79},
	issn = {0022-1007},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445/},
	abstract = {1. From Type {III} pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type {II} into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered. 2. Methods for the isolation and purification of the active transforming material are described. 3. The data obtained by chemical, enzymatic, and serological analyses together with the results of preliminary studies by electrophoresis, ultracentrifugation, and ultraviolet spectroscopy indicate that, within the limits of the methods, the active fraction contains no demonstrable protein, unbound lipid, or serologically reactive polysaccharide and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid. 4. Evidence is presented that the chemically induced alterations in cellular structure and function are predictable, type-specific, and transmissible in series. The various hypotheses that have been advanced concerning the nature of these changes are reviewed.},
	pages = {137--158},
	number = {2},
	journaltitle = {The Journal of Experimental Medicine},
	shortjournal = {J Exp Med},
	author = {Avery, Oswald T. and {MacLeod}, Colin M. and {McCarty}, Maclyn},
	urldate = {2019-07-08},
	date = {1944-02-01},
	pmid = {19871359},
	pmcid = {PMC2135445},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/WEKFND9N/Avery et al. - 1944 - STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE IN.pdf:application/pdf}
}

@article{kovaka_transcriptome_2019,
	title = {Transcriptome assembly from long-read {RNA}-seq alignments with {StringTie}2},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/694554v1},
	doi = {10.1101/694554},
	abstract = {{\textless}p{\textgreater}{RNA} sequencing using the latest single-molecule sequencing instruments produces reads that are thousands of nucleotides long. The ability to assemble these long reads can greatly improve the sensitivity of long-read analyses. Here we present {StringTie}2, a reference-guided transcriptome assembler that works with both short and long reads. {StringTie}2 includes new computational methods to handle the high error rate of long-read sequencing technology, which previous assemblers could not tolerate. It also offers the ability to work with full-length super-reads assembled from short reads, which further improves the quality of assemblies. On 33 short-read datasets from humans and two plant species, {StringTie}2 is 47.3\% more precise and 3.9\% more sensitive than Scallop. On multiple long read datasets, {StringTie}2 on average correctly assembles 8.3 and 2.6 times as many transcripts as {FLAIR} and Traphlor, respectively, with substantially higher precision. {StringTie}2 is also faster and has a smaller memory footprint than all comparable tools.{\textless}/p{\textgreater}},
	pages = {694554},
	journaltitle = {{bioRxiv}},
	author = {Kovaka, Sam and Zimin, Aleksey V. and Pertea, Geo M. and Razaghi, Roham and Salzberg, Steven L. and Pertea, Mihaela},
	urldate = {2019-07-09},
	date = {2019-07-08},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/JS7FUULE/Kovaka et al. - 2019 - Transcriptome assembly from long-read RNA-seq alig.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/SW3CQVPP/694554v1.html:text/html}
}

@article{sutton_chromosomes_1903,
	title = {The chromosomes in heredity},
	volume = {4},
	pages = {231--251},
	journaltitle = {Biological Bulletin},
	shortjournal = {Biol Bull},
	author = {Sutton, {WS}},
	date = {1903},
	file = {Sutton - 1903 - The chromosomes in heredity.pdf:/home/jlagarde/Zotero/storage/6FAKPV3J/Sutton - 1903 - The chromosomes in heredity.pdf:application/pdf}
}

@article{boveri_ergebnisse_1904,
	title = {Ergebnisse über die Konstitution der chromatischen Substanz des Zelkerns},
	journaltitle = {Jena, G. Fischer},
	author = {Boveri, {TH}},
	date = {1904}
}

@article{johannsen_elemente_1909,
	title = {Elemente der exakten Erblichkeitslehre},
	journaltitle = {Jena, G. Fischer},
	author = {Johannsen, W},
	date = {1909}
}

@article{fleischmann_whole-genome_1995,
	title = {Whole-genome random sequencing and assembly of Haemophilus influenzae Rd},
	volume = {269},
	rights = {© 1995},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/269/5223/496},
	doi = {10.1126/science.7542800},
	abstract = {An approach for genome analysis based on sequencing and assembly of unselected pieces of {DNA} from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence {DataBase} accession number L42023) represents the only complete genome sequence from a free-living organism.},
	pages = {496--512},
	number = {5223},
	journaltitle = {Science},
	author = {Fleischmann, R. D. and Adams, M. D. and White, O. and Clayton, R. A. and Kirkness, E. F. and Kerlavage, A. R. and Bult, C. J. and Tomb, J. F. and Dougherty, B. A. and Merrick, J. M. and Al, Et},
	urldate = {2019-07-09},
	date = {1995-07-28},
	langid = {english},
	pmid = {7542800},
	file = {Snapshot:/home/jlagarde/Zotero/storage/8RTQK8H7/496.html:text/html}
}

@article{yan_recappable_2019,
	title = {{ReCappable} Seq: Comprehensive Determination of Transcription Start Sites derived from all {RNA} polymerases.},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NoDerivs} 4.0 International), {CC} {BY}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/696559v1},
	doi = {10.1101/696559},
	shorttitle = {{ReCappable} Seq},
	abstract = {{\textless}p{\textgreater}Methodologies for determining eukaryotic Transcription Start Sites ({TSS}) rely on the selection of the 5 prime canonical cap structure of Pol-{II} transcripts and are consequently ignoring entire classes of {TSS} derived from other {RNA} polymerases which play critical roles in various cell functions. To overcome this limitation, we developed {ReCappable}-seq and identified {TSS} from Pol-{lI} and non-Pol-{II} transcripts at nucleotide resolution. Applied to the human transcriptome, {ReCappable}-seq identifies Pol-{II} {TSS} with higher specificity than {CAGE} and reveals a rich landscape of {TSS} associated notably with Pol-{III} transcripts which have been previously not possible to study on a genome-wide scale. Novel {TSS} consistent with non-Pol-{II} transcripts can be found in the nuclear and mitochondrial genomes. By identifying {TSS} derived from all {RNA}-polymerases, {ReCappable}-seq reveals distinct epigenetic marks among Pol-{lI} and non-Pol-{II} {TSS} and provides a unique opportunity to concurrently interrogate the regulatory landscape of coding and non-coding {RNA}.{\textless}/p{\textgreater}},
	pages = {696559},
	journaltitle = {{bioRxiv}},
	author = {Yan, Bo and Tzertzinis, George and Schildkraut, Ira and Ettwiller, Laurence M.},
	urldate = {2019-07-10},
	date = {2019-07-09},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/27QL93NK/Yan et al. - 2019 - ReCappable Seq Comprehensive Determination of Tra.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/HRCBKDV9/696559v1.html:text/html}
}

@article{sutton_morphology_1902,
	title = {On the morphology of the chromosome group in Brachystola magna},
	volume = {4},
	pages = {24--39},
	journaltitle = {Biological Bulletin},
	shortjournal = {Biol Bull},
	author = {Sutton, {WS}},
	date = {1902}
}

@article{mendel_versuche_1865,
	title = {Versuche über Pflanzenhybriden},
	volume = {{IV}},
	pages = {3--47},
	journaltitle = {Verhandlungen des naturforschenden Vereines in Brünn},
	author = {Mendel, Gregor},
	date = {1865}
}

@book{henig_monk_2000,
	title = {The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics},
	isbn = {978-0-395-97765-1},
	publisher = {Boston: Houghton Mifflin},
	author = {Henig, Robin Marantz},
	date = {2000}
}

@article{crow_100_2002,
	title = {100 Years Ago: Walter Sutton and the Chromosome Theory of Heredity},
	volume = {160},
	rights = {Copyright © 2002 by the Genetics Society of America},
	issn = {0016-6731, 1943-2631},
	url = {https://www.genetics.org/content/160/1/1},
	shorttitle = {100 Years Ago},
	abstract = {{EVERY} student of elementary genetics learns of Walter Sutton (1877–1916). Sutton was the first to point out that chromosomes obey Mendel's rules—the first clear argument for the chromosome theory of heredity. This year marks the centennial of Sutton's ([1902][1]) historic paper, surely the most},
	pages = {1--4},
	number = {1},
	journaltitle = {Genetics},
	author = {Crow, Ernest W. and Crow, James F.},
	urldate = {2019-07-10},
	date = {2002-01-01},
	langid = {english},
	pmid = {11805039},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/VH2EK5K4/Crow and Crow - 2002 - 100 Years Ago Walter Sutton and the Chromosome Th.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/AK73BV69/1.html:text/html}
}

@article{carothers_mendelian_1913,
	title = {The mendelian ratio in relation to certain orthopteran chromosomes},
	volume = {24},
	rights = {Copyright © 1913 Wiley‐Liss, Inc.},
	issn = {1097-4687},
	url = {https://www.onlinelibrary.wiley.com/doi/abs/10.1002/jmor.1050240403},
	doi = {10.1002/jmor.1050240403},
	pages = {487--511},
	number = {4},
	journaltitle = {Journal of Morphology},
	author = {Carothers, E. Eleanor},
	urldate = {2019-07-10},
	date = {1913},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/ANUF2EV6/jmor.html:text/html;Submitted Version:/home/jlagarde/Zotero/storage/XKX3BX7L/Carothers - 1913 - The mendelian ratio in relation to certain orthopt.pdf:application/pdf}
}

@book{morgan_mechanism_1915,
	title = {The mechanism of Mendelian heredity},
	publisher = {New York : H. Holt and company},
	author = {Morgan, T. H. and Sturtevant, A. H. and Muller, H.J. and Bridges, C.B.},
	date = {1915},
	keywords = {Mendel's law}
}

@article{sturtevant_linear_1913,
	title = {The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association},
	volume = {14},
	rights = {Copyright © 1913 Wiley‐Liss, Inc., A Wiley Company},
	issn = {1097-010X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jez.1400140104},
	doi = {10.1002/jez.1400140104},
	pages = {43--59},
	number = {1},
	journaltitle = {Journal of Experimental Zoology},
	author = {Sturtevant, A. H.},
	urldate = {2019-07-11},
	date = {1913},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/DBWTGLIY/jez.html:text/html}
}

@article{kossel_weitere_1886,
	title = {Weitere Beiträge zur Chemie des Zellkerns.},
	volume = {10},
	pages = {148--264},
	journaltitle = {Zeitschrift für Physiologische Chemie},
	author = {Kossel, Albrecht},
	date = {1886}
}

@article{hershey_independent_1952,
	title = {Independent functions of viral protein and nucleic acid in growth of bacteriophage},
	volume = {36},
	issn = {0022-1295},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147348/},
	abstract = {1. Osmotic shock disrupts particles of phage T2 into material containing nearly all the phage sulfur in a form precipitable by antiphage serum, and capable of specific adsorption to bacteria. It releases into solution nearly all the phage {DNA} in a form not precipitable by antiserum and not adsorbable to bacteria. The sulfur-containing protein of the phage particle evidently makes up a membrane that protects the phage {DNA} from {DNase}, comprises the sole or principal antigenic material, and is responsible for attachment of the virus to bacteria. 2. Adsorption of T2 to heat-killed bacteria, and heating or alternate freezing and thawing of infected cells, sensitize the {DNA} of the adsorbed phage to {DNase}. These treatments have little or no sensitizing effect on unadsorbed phage. Neither heating nor freezing and thawing releases the phage {DNA} from infected cells, although other cell constituents can be extracted by these methods. These facts suggest that the phage {DNA} forms part of an organized intracellular structure throughout the period of phage growth. 3. Adsorption of phage T2 to bacterial debris causes part of the phage {DNA} to appear in solution, leaving the phage sulfur attached to the debris. Another part of the phage {DNA}, corresponding roughly to the remaining half of the {DNA} of the inactivated phage, remains attached to the debris but can be separated from it by {DNase}. Phage T4 behaves similarly, although the two phages can be shown to attach to different combining sites. The inactivation of phage by bacterial debris is evidently accompanied by the rupture of the viral membrane. 4. Suspensions of infected cells agitated in a Waring blendor release 75 per cent of the phage sulfur and only 15 per cent of the phage phosphorus to the solution as a result of the applied shearing force. The cells remain capable of yielding phage progeny. 5. The facts stated show that most of the phage sulfur remains at the cell surface and most of the phage {DNA} enters the cell on infection. Whether sulfur-free material other than {DNA} enters the cell has not been determined. The properties of the sulfur-containing residue identify it as essentially unchanged membranes of the phage particles. All types of evidence show that the passage of phage {DNA} into the cell occurs in non-nutrient medium under conditions in which other known steps in viral growth do not occur. 6. The phage progeny yielded by bacteria infected with phage labeled with radioactive sulfur contain less than 1 per cent of the parental radioactivity. The progeny of phage particles labeled with radioactive phosphorus contain 30 per cent or more of the parental phosphorus. 7. Phage inactivated by dilute formaldehyde is capable of adsorbing to bacteria, but does not release its {DNA} to the cell. This shows that the interaction between phage and bacterium resulting in release of the phage {DNA} from its protective membrane depends on labile components of the phage particle. By contrast, the components of the bacterium essential to this interaction are remarkably stable. The nature of the interaction is otherwise unknown. 8. The sulfur-containing protein of resting phage particles is confined to a protective coat that is responsible for the adsorption to bacteria, and functions as an instrument for the injection of the phage {DNA} into the cell. This protein probably has no function in the growth of intracellular phage. The {DNA} has some function. Further chemical inferences should not be drawn from the experiments presented.},
	pages = {39--56},
	number = {1},
	journaltitle = {The Journal of General Physiology},
	shortjournal = {J Gen Physiol},
	author = {Hershey, A. D. and Chase, Martha},
	urldate = {2019-07-12},
	date = {1952-09-20},
	pmid = {12981234},
	pmcid = {PMC2147348},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/M3MU7NKP/Hershey and Chase - 1952 - INDEPENDENT FUNCTIONS OF VIRAL PROTEIN AND NUCLEIC.pdf:application/pdf}
}

@article{watson_molecular_1953,
	title = {Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid},
	volume = {171},
	rights = {1953 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/171737a0},
	doi = {10.1038/171737a0},
	shorttitle = {Molecular Structure of Nucleic Acids},
	abstract = {Article},
	pages = {737},
	number = {4356},
	journaltitle = {Nature},
	author = {Watson, J. D. and Crick, F. H. C.},
	urldate = {2019-07-12},
	date = {1953-04},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/875B2GZL/Watson and Crick - 1953 - Molecular Structure of Nucleic Acids A Structure .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/2YB2RSYJ/171737a0.html:text/html}
}

@article{sanger_dna_1977,
	title = {{DNA} sequencing with chain-terminating inhibitors},
	volume = {74},
	issn = {0027-8424},
	doi = {10.1073/pnas.74.12.5463},
	abstract = {A new method for determining nucleotide sequences in {DNA} is described. It is similar to the "plus and minus" method [Sanger, F. \& Coulson, A. R. (1975) J. Mol. Biol. 94, 441-448] but makes use of the 2',3'-dideoxy and arabinonucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of {DNA} polymerase. The technique has been applied to the {DNA} of bacteriophage {varphiX}174 and is more rapid and more accurate than either the plus or the minus method.},
	pages = {5463--5467},
	number = {12},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Sanger, F. and Nicklen, S. and Coulson, A. R.},
	date = {1977-12},
	pmid = {271968},
	pmcid = {PMC431765},
	keywords = {Base Sequence, {DNA} Restriction Enzymes, Methods, Coliphages, Deoxyribonucleotides, {DNA} Polymerase I, {DNA}, Viral},
	file = {Full Text:/home/jlagarde/Zotero/storage/3B27J644/Sanger et al. - 1977 - DNA sequencing with chain-terminating inhibitors.pdf:application/pdf}
}

@article{maxam_new_1977,
	title = {A new method for sequencing {DNA}},
	volume = {74},
	issn = {0027-8424},
	doi = {10.1073/pnas.74.2.560},
	abstract = {{DNA} can be sequenced by a chemical procedure that breaks a terminally labeled {DNA} molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave {DNA} preferentially at guanines, at adenines, at cytosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by electrophoresis on a polyacrylamide gel, the {DNA} sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of labeling.},
	pages = {560--564},
	number = {2},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Maxam, A. M. and Gilbert, W.},
	date = {1977-02},
	pmid = {265521},
	pmcid = {PMC392330},
	keywords = {{DNA}, Base Sequence, {DNA} Restriction Enzymes, Methods, Nucleic Acid Hybridization, Guanine, Adenine, Biochemical Phenomena, Biochemistry, Cytosine, Hydrazines, Thymine},
	file = {Full Text:/home/jlagarde/Zotero/storage/ZX5TW2BQ/Maxam and Gilbert - 1977 - A new method for sequencing DNA.pdf:application/pdf}
}

@article{sanger_nucleotide_1977,
	title = {Nucleotide sequence of bacteriophage phi X174 {DNA}},
	volume = {265},
	issn = {0028-0836},
	doi = {10.1038/265687a0},
	abstract = {A {DNA} sequence for the genome of bacteriophage phi X174 of approximately 5,375 nucleotides has been determined using the rapid and simple 'plus and minus' method. The sequence identifies many of the features responsible for the production of the proteins of the nine known genes of the organism, including initiation and termination sites for the proteins and {RNAs}. Two pairs of genes are coded by the same region of {DNA} using different reading frames.},
	pages = {687--695},
	number = {5596},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Sanger, F. and Air, G. M. and Barrell, B. G. and Brown, N. L. and Coulson, A. R. and Fiddes, C. A. and Hutchison, C. A. and Slocombe, P. M. and Smith, M.},
	date = {1977-02-24},
	pmid = {870828},
	keywords = {Base Sequence, Binding Sites, Codon, {DNA} Replication, {DNA} Restriction Enzymes, Genes, Molecular Sequence Data, Ribosomes, Coliphages, {RNA}, Messenger, Transcription, Genetic, Templates, Genetic, {DNA}, Viral, Genes, Regulator, Peptide Chain Initiation, Translational, {RNA}, Viral, Viral Proteins}
}

@article{heather_sequence_2016,
	title = {The sequence of sequencers: The history of sequencing {DNA}},
	volume = {107},
	issn = {0888-7543},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727787/},
	doi = {10.1016/j.ygeno.2015.11.003},
	shorttitle = {The sequence of sequencers},
	abstract = {Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and technologies to facilitate this feat, sequencing {DNA} and {RNA} molecules. This time-scale has witnessed tremendous changes, moving from sequencing short oligonucleotides to millions of bases, from struggling towards the deduction of the coding sequence of a single gene to rapid and widely available whole genome sequencing. This article traverses those years, iterating through the different generations of sequencing technology, highlighting some of the key discoveries, researchers, and sequences along the way., 
          
            
              •
              We review the drastic changes to {DNA} sequencing technology over the last 50 years.
            
            
              •
              First-generation methods enabled sequencing of clonal {DNA} populations.
            
            
              •
              The second-generation massively increased throughput by parallelizing many reactions.
            
            
              •
              Third-generation methods allow direct sequencing of single {DNA} molecules.},
	pages = {1--8},
	number = {1},
	journaltitle = {Genomics},
	shortjournal = {Genomics},
	author = {Heather, James M. and Chain, Benjamin},
	urldate = {2019-07-14},
	date = {2016-01},
	pmid = {26554401},
	pmcid = {PMC4727787}
}

@article{sanger_rapid_1975,
	title = {A rapid method for determining sequences in {DNA} by primed synthesis with {DNA} polymerase},
	volume = {94},
	issn = {0022-2836},
	url = {http://www.sciencedirect.com/science/article/pii/0022283675902132},
	doi = {10.1016/0022-2836(75)90213-2},
	abstract = {A simple and rapid method for determining nucleotide sequences in single-stranded {DNA} by primed synthesis with {DNA} polymerase is described. It depends on the use of Escherichia coli {DNA} polymerase I and {DNA} polymerase from bacteriophage T4 under conditions of different limiting nucleoside triphosphates and concurrent fractionation of the products according to size by ionophoresis on acrylamide gels. The method was used to determine two sequences in bacteriophage φX174 {DNA} using the synthetic decanucleotide A-G-A-A-A-T-A-A-A-A and a restriction enzyme digestion product as primers.},
	pages = {441--448},
	number = {3},
	journaltitle = {Journal of Molecular Biology},
	shortjournal = {Journal of Molecular Biology},
	author = {Sanger, F. and Coulson, A. R.},
	urldate = {2019-07-14},
	date = {1975-05-25},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/SZDNRP7S/0022283675902132.html:text/html}
}

@article{stein_genome_2001,
	title = {Genome annotation: from sequence to biology},
	volume = {2},
	issn = {1471-0056},
	doi = {10.1038/35080529},
	shorttitle = {Genome annotation},
	abstract = {The genome sequence of an organism is an information resource unlike any that biologists have previously had access to. But the value of the genome is only as good as its annotation. It is the annotation that bridges the gap from the sequence to the biology of the organism. The aim of high-quality annotation is to identify the key features of the genome - in particular, the genes and their products. The tools and resources for annotation are developing rapidly, and the scientific community is becoming increasingly reliant on this information for all aspects of biological research.},
	pages = {493--503},
	number = {7},
	journaltitle = {Nature Reviews Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Stein, L.},
	date = {2001-07},
	pmid = {11433356},
	keywords = {Base Sequence, Humans, Sequence Analysis, {DNA}, Genome, Human, Databases, Factual, Biology},
	file = {Stein - 2001 - Genome annotation from sequence to biology.pdf:/home/jlagarde/Zotero/storage/YAQAAZVH/Stein - 2001 - Genome annotation from sequence to biology.pdf:application/pdf}
}

@article{fiers_complete_1976,
	title = {Complete nucleotide sequence of bacteriophage {MS}2 {RNA}: primary and secondary structure of the replicase gene},
	volume = {260},
	issn = {0028-0836},
	doi = {10.1038/260500a0},
	shorttitle = {Complete nucleotide sequence of bacteriophage {MS}2 {RNA}},
	abstract = {Bacteriophage {MS}2 {RNA} is 3,569 nucleotides long. The nucleotide sequence has been established for the third and last gene, which codes for the replicase protein. A secondary structure model has also been proposed. Biological properties, such as ribosome binding and codon interactions can now be discussed on a molecular basis. As the sequences for the other regions of this {RNA} have been published already, the complete, primary chemical structure of a viral genome has now been established.},
	pages = {500--507},
	number = {5551},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Fiers, W. and Contreras, R. and Duerinck, F. and Haegeman, G. and Iserentant, D. and Merregaert, J. and Min Jou, W. and Molemans, F. and Raeymaekers, A. and Van den Berghe, A. and Volckaert, G. and Ysebaert, M.},
	date = {1976-04-08},
	pmid = {1264203},
	keywords = {Base Sequence, Codon, Nucleic Acid Conformation, Protein Biosynthesis, Coliphages, {RNA}, Viral, Viral Proteins}
}

@article{goffeau_life_1996,
	title = {Life with 6000 genes},
	volume = {274},
	issn = {0036-8075},
	doi = {10.1126/science.274.5287.546},
	abstract = {The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal {RNA}, 40 genes for small nuclear {RNA} molecules, and 275 transfer {RNA} genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.},
	pages = {546, 563--567},
	number = {5287},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Goffeau, A. and Barrell, B. G. and Bussey, H. and Davis, R. W. and Dujon, B. and Feldmann, H. and Galibert, F. and Hoheisel, J. D. and Jacq, C. and Johnston, M. and Louis, E. J. and Mewes, H. W. and Murakami, Y. and Philippsen, P. and Tettelin, H. and Oliver, S. G.},
	date = {1996-10-25},
	pmid = {8849441},
	keywords = {Base Sequence, Open Reading Frames, Amino Acid Sequence, Chromosome Mapping, Gene Library, International Cooperation, Multigene Family, Saccharomyces cerevisiae, Evolution, Molecular, Sequence Analysis, {DNA}, Chromosomes, Fungal, Computer Communication Networks, {DNA}, Fungal, Fungal Proteins, Genes, Fungal, Genome, Fungal, {RNA}, Fungal}
}

@article{adams_genome_2000,
	title = {The genome sequence of Drosophila melanogaster},
	volume = {287},
	issn = {0036-8075},
	doi = {10.1126/science.287.5461.2185},
	abstract = {The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.},
	pages = {2185--2195},
	number = {5461},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Adams, M. D. and Celniker, S. E. and Holt, R. A. and Evans, C. A. and Gocayne, J. D. and Amanatides, P. G. and Scherer, S. E. and Li, P. W. and Hoskins, R. A. and Galle, R. F. and George, R. A. and Lewis, S. E. and Richards, S. and Ashburner, M. and Henderson, S. N. and Sutton, G. G. and Wortman, J. R. and Yandell, M. D. and Zhang, Q. and Chen, L. X. and Brandon, R. C. and Rogers, Y. H. and Blazej, R. G. and Champe, M. and Pfeiffer, B. D. and Wan, K. H. and Doyle, C. and Baxter, E. G. and Helt, G. and Nelson, C. R. and Gabor, G. L. and Abril, J. F. and Agbayani, A. and An, H. J. and Andrews-Pfannkoch, C. and Baldwin, D. and Ballew, R. M. and Basu, A. and Baxendale, J. and Bayraktaroglu, L. and Beasley, E. M. and Beeson, K. Y. and Benos, P. V. and Berman, B. P. and Bhandari, D. and Bolshakov, S. and Borkova, D. and Botchan, M. R. and Bouck, J. and Brokstein, P. and Brottier, P. and Burtis, K. C. and Busam, D. A. and Butler, H. and Cadieu, E. and Center, A. and Chandra, I. and Cherry, J. M. and Cawley, S. and Dahlke, C. and Davenport, L. B. and Davies, P. and de Pablos, B. and Delcher, A. and Deng, Z. and Mays, A. D. and Dew, I. and Dietz, S. M. and Dodson, K. and Doup, L. E. and Downes, M. and Dugan-Rocha, S. and Dunkov, B. C. and Dunn, P. and Durbin, K. J. and Evangelista, C. C. and Ferraz, C. and Ferriera, S. and Fleischmann, W. and Fosler, C. and Gabrielian, A. E. and Garg, N. S. and Gelbart, W. M. and Glasser, K. and Glodek, A. and Gong, F. and Gorrell, J. H. and Gu, Z. and Guan, P. and Harris, M. and Harris, N. L. and Harvey, D. and Heiman, T. J. and Hernandez, J. R. and Houck, J. and Hostin, D. and Houston, K. A. and Howland, T. J. and Wei, M. H. and Ibegwam, C. and Jalali, M. and Kalush, F. and Karpen, G. H. and Ke, Z. and Kennison, J. A. and Ketchum, K. A. and Kimmel, B. E. and Kodira, C. D. and Kraft, C. and Kravitz, S. and Kulp, D. and Lai, Z. and Lasko, P. and Lei, Y. and Levitsky, A. A. and Li, J. and Li, Z. and Liang, Y. and Lin, X. and Liu, X. and Mattei, B. and {McIntosh}, T. C. and {McLeod}, M. P. and {McPherson}, D. and Merkulov, G. and Milshina, N. V. and Mobarry, C. and Morris, J. and Moshrefi, A. and Mount, S. M. and Moy, M. and Murphy, B. and Murphy, L. and Muzny, D. M. and Nelson, D. L. and Nelson, D. R. and Nelson, K. A. and Nixon, K. and Nusskern, D. R. and Pacleb, J. M. and Palazzolo, M. and Pittman, G. S. and Pan, S. and Pollard, J. and Puri, V. and Reese, M. G. and Reinert, K. and Remington, K. and Saunders, R. D. and Scheeler, F. and Shen, H. and Shue, B. C. and Sidén-Kiamos, I. and Simpson, M. and Skupski, M. P. and Smith, T. and Spier, E. and Spradling, A. C. and Stapleton, M. and Strong, R. and Sun, E. and Svirskas, R. and Tector, C. and Turner, R. and Venter, E. and Wang, A. H. and Wang, X. and Wang, Z. Y. and Wassarman, D. A. and Weinstock, G. M. and Weissenbach, J. and Williams, S. M. and {WoodageT}, null and Worley, K. C. and Wu, D. and Yang, S. and Yao, Q. A. and Ye, J. and Yeh, R. F. and Zaveri, J. S. and Zhan, M. and Zhang, G. and Zhao, Q. and Zheng, L. and Zheng, X. H. and Zhong, F. N. and Zhong, W. and Zhou, X. and Zhu, S. and Zhu, X. and Smith, H. O. and Gibbs, R. A. and Myers, E. W. and Rubin, G. M. and Venter, J. C.},
	date = {2000-03-24},
	pmid = {10731132},
	keywords = {Animals, Genome, Computational Biology, Drosophila melanogaster, Biological Transport, Chromatin, {DNA} Repair, {DNA} Replication, Gene Library, Protein Biosynthesis, Nuclear Proteins, Transcription, Genetic, Sequence Analysis, {DNA}, Cloning, Molecular, Contig Mapping, Cytochrome P-450 Enzyme System, Euchromatin, Genes, Insect, Heterochromatin, Insect Proteins}
}

@article{lander_initial_2001,
	title = {Initial sequencing and analysis of the human genome},
	volume = {409},
	issn = {0028-0836},
	doi = {10.1038/35057062},
	abstract = {The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.},
	pages = {860--921},
	number = {6822},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Lander, E. S. and Linton, L. M. and Birren, B. and Nusbaum, C. and Zody, M. C. and Baldwin, J. and Devon, K. and Dewar, K. and Doyle, M. and FitzHugh, W. and Funke, R. and Gage, D. and Harris, K. and Heaford, A. and Howland, J. and Kann, L. and Lehoczky, J. and LeVine, R. and McEwan, P. and McKernan, K. and Meldrim, J. and Mesirov, J. P. and Miranda, C. and Morris, W. and Naylor, J. and Raymond, C. and Rosetti, M. and Santos, R. and Sheridan, A. and Sougnez, C. and Stange-Thomann, Y. and Stojanovic, N. and Subramanian, A. and Wyman, D. and Rogers, J. and Sulston, J. and Ainscough, R. and Beck, S. and Bentley, D. and Burton, J. and Clee, C. and Carter, N. and Coulson, A. and Deadman, R. and Deloukas, P. and Dunham, A. and Dunham, I. and Durbin, R. and French, L. and Grafham, D. and Gregory, S. and Hubbard, T. and Humphray, S. and Hunt, A. and Jones, M. and Lloyd, C. and McMurray, A. and Matthews, L. and Mercer, S. and Milne, S. and Mullikin, J. C. and Mungall, A. and Plumb, R. and Ross, M. and Shownkeen, R. and Sims, S. and Waterston, R. H. and Wilson, R. K. and Hillier, L. W. and McPherson, J. D. and Marra, M. A. and Mardis, E. R. and Fulton, L. A. and Chinwalla, A. T. and Pepin, K. H. and Gish, W. R. and Chissoe, S. L. and Wendl, M. C. and Delehaunty, K. D. and Miner, T. L. and Delehaunty, A. and Kramer, J. B. and Cook, L. L. and Fulton, R. S. and Johnson, D. L. and Minx, P. J. and Clifton, S. W. and Hawkins, T. and Branscomb, E. and Predki, P. and Richardson, P. and Wenning, S. and Slezak, T. and Doggett, N. and Cheng, J. F. and Olsen, A. and Lucas, S. and Elkin, C. and Uberbacher, E. and Frazier, M. and Gibbs, R. A. and Muzny, D. M. and Scherer, S. E. and Bouck, J. B. and Sodergren, E. J. and Worley, K. C. and Rives, C. M. and Gorrell, J. H. and Metzker, M. L. and Naylor, S. L. and Kucherlapati, R. S. and Nelson, D. L. and Weinstock, G. M. and Sakaki, Y. and Fujiyama, A. and Hattori, M. and Yada, T. and Toyoda, A. and Itoh, T. and Kawagoe, C. and Watanabe, H. and Totoki, Y. and Taylor, T. and Weissenbach, J. and Heilig, R. and Saurin, W. and Artiguenave, F. and Brottier, P. and Bruls, T. and Pelletier, E. and Robert, C. and Wincker, P. and Smith, D. R. and Doucette-Stamm, L. and Rubenfield, M. and Weinstock, K. and Lee, H. M. and Dubois, J. and Rosenthal, A. and Platzer, M. and Nyakatura, G. and Taudien, S. and Rump, A. and Yang, H. and Yu, J. and Wang, J. and Huang, G. and Gu, J. and Hood, L. and Rowen, L. and Madan, A. and Qin, S. and Davis, R. W. and Federspiel, N. A. and Abola, A. P. and Proctor, M. J. and Myers, R. M. and Schmutz, J. and Dickson, M. and Grimwood, J. and Cox, D. R. and Olson, M. V. and Kaul, R. and Raymond, C. and Shimizu, N. and Kawasaki, K. and Minoshima, S. and Evans, G. A. and Athanasiou, M. and Schultz, R. and Roe, B. A. and Chen, F. and Pan, H. and Ramser, J. and Lehrach, H. and Reinhardt, R. and McCombie, W. R. and de la Bastide, M. and Dedhia, N. and Blöcker, H. and Hornischer, K. and Nordsiek, G. and Agarwala, R. and Aravind, L. and Bailey, J. A. and Bateman, A. and Batzoglou, S. and Birney, E. and Bork, P. and Brown, D. G. and Burge, C. B. and Cerutti, L. and Chen, H. C. and Church, D. and Clamp, M. and Copley, R. R. and Doerks, T. and Eddy, S. R. and Eichler, E. E. and Furey, T. S. and Galagan, J. and Gilbert, J. G. and Harmon, C. and Hayashizaki, Y. and Haussler, D. and Hermjakob, H. and Hokamp, K. and Jang, W. and Johnson, L. S. and Jones, T. A. and Kasif, S. and Kaspryzk, A. and Kennedy, S. and Kent, W. J. and Kitts, P. and Koonin, E. V. and Korf, I. and Kulp, D. and Lancet, D. and Lowe, T. M. and McLysaght, A. and Mikkelsen, T. and Moran, J. V. and Mulder, N. and Pollara, V. J. and Ponting, C. P. and Schuler, G. and Schultz, J. and Slater, G. and Smit, A. F. and Stupka, E. and Szustakowki, J. and Thierry-Mieg, D. and Thierry-Mieg, J. and Wagner, L. and Wallis, J. and Wheeler, R. and Williams, A. and Wolf, Y. I. and Wolfe, K. H. and Yang, S. P. and Yeh, R. F. and Collins, F. and Guyer, M. S. and Peterson, J. and Felsenfeld, A. and Wetterstrand, K. A. and Patrinos, A. and Morgan, M. J. and de Jong, P. and Catanese, J. J. and Osoegawa, K. and Shizuya, H. and Choi, S. and Chen, Y. J. and Szustakowki, J. and {International Human Genome Sequencing Consortium}},
	date = {2001-02-15},
	pmid = {11237011},
	keywords = {Human, Animals, Conserved Sequence, Humans, Proteins, {RNA}, Proteins/genetics, *Genome, Databases, Nucleic Acid, *Human Genome Project, *Sequence Analysis, Chromosome Mapping, {CpG} Islands, {DNA} Transposable Elements, {DNA}/methods, Drug Industry, Evolution, Factual, Forecasting, {GC} Rich Sequence, Gene Duplication, Genes, Genetic Diseases, Genetics, Human Genome Project, Inborn, Medical, Molecular, Mutation, Private Sector, Proteome, Public Sector, Repetitive Sequences, {RNA}/genetics, Species Specificity, Evolution, Molecular, Sequence Analysis, {DNA}, Genome, Human, Genetic Diseases, Inborn, Databases, Factual, Genetics, Medical, Repetitive Sequences, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/Y4MGU6KA/Lander et al. - 2001 - Initial sequencing and analysis of the human genom.pdf:application/pdf}
}

@article{venter_sequence_2001,
	title = {The Sequence of the Human Genome},
	volume = {291},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/291/5507/1304},
	doi = {10.1126/science.1058040},
	abstract = {A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp {DNA} sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the {DNA} of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90\% of the genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1\% of the genome is spanned by exons, whereas 24\% is in introns, with 75\% of the genome being intergenic {DNA}. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. {DNA} sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms ({SNPs}). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1\% of all {SNPs} resulted in variation in proteins, but the task of determining which {SNPs} have functional consequences remains an open challenge.},
	pages = {1304--1351},
	number = {5507},
	journaltitle = {Science},
	author = {Venter, J. Craig and Adams, Mark D. and Myers, Eugene W. and Li, Peter W. and Mural, Richard J. and Sutton, Granger G. and Smith, Hamilton O. and Yandell, Mark and Evans, Cheryl A. and Holt, Robert A. and Gocayne, Jeannine D. and Amanatides, Peter and Ballew, Richard M. and Huson, Daniel H. and Wortman, Jennifer Russo and Zhang, Qing and Kodira, Chinnappa D. and Zheng, Xiangqun H. and Chen, Lin and Skupski, Marian and Subramanian, Gangadharan and Thomas, Paul D. and Zhang, Jinghui and Miklos, George L. Gabor and Nelson, Catherine and Broder, Samuel and Clark, Andrew G. and Nadeau, Joe and {McKusick}, Victor A. and Zinder, Norton and Levine, Arnold J. and Roberts, Richard J. and Simon, Mel and Slayman, Carolyn and Hunkapiller, Michael and Bolanos, Randall and Delcher, Arthur and Dew, Ian and Fasulo, Daniel and Flanigan, Michael and Florea, Liliana and Halpern, Aaron and Hannenhalli, Sridhar and Kravitz, Saul and Levy, Samuel and Mobarry, Clark and Reinert, Knut and Remington, Karin and Abu-Threideh, Jane and Beasley, Ellen and Biddick, Kendra and Bonazzi, Vivien and Brandon, Rhonda and Cargill, Michele and Chandramouliswaran, Ishwar and Charlab, Rosane and Chaturvedi, Kabir and Deng, Zuoming and Francesco, Valentina Di and Dunn, Patrick and Eilbeck, Karen and Evangelista, Carlos and Gabrielian, Andrei E. and Gan, Weiniu and Ge, Wangmao and Gong, Fangcheng and Gu, Zhiping and Guan, Ping and Heiman, Thomas J. and Higgins, Maureen E. and Ji, Rui-Ru and Ke, Zhaoxi and Ketchum, Karen A. and Lai, Zhongwu and Lei, Yiding and Li, Zhenya and Li, Jiayin and Liang, Yong and Lin, Xiaoying and Lu, Fu and Merkulov, Gennady V. and Milshina, Natalia and Moore, Helen M. and Naik, Ashwinikumar K. and Narayan, Vaibhav A. and Neelam, Beena and Nusskern, Deborah and Rusch, Douglas B. and Salzberg, Steven and Shao, Wei and Shue, Bixiong and Sun, Jingtao and Wang, Zhen Yuan and Wang, Aihui and Wang, Xin and Wang, Jian and Wei, Ming-Hui and Wides, Ron and Xiao, Chunlin and Yan, Chunhua and Yao, Alison and Ye, Jane and Zhan, Ming and Zhang, Weiqing and Zhang, Hongyu and Zhao, Qi and Zheng, Liansheng and Zhong, Fei and Zhong, Wenyan and Zhu, Shiaoping C. and Zhao, Shaying and Gilbert, Dennis and Baumhueter, Suzanna and Spier, Gene and Carter, Christine and Cravchik, Anibal and Woodage, Trevor and Ali, Feroze and An, Huijin and Awe, Aderonke and Baldwin, Danita and Baden, Holly and Barnstead, Mary and Barrow, Ian and Beeson, Karen and Busam, Dana and Carver, Amy and Center, Angela and Cheng, Ming Lai and Curry, Liz and Danaher, Steve and Davenport, Lionel and Desilets, Raymond and Dietz, Susanne and Dodson, Kristina and Doup, Lisa and Ferriera, Steven and Garg, Neha and Gluecksmann, Andres and Hart, Brit and Haynes, Jason and Haynes, Charles and Heiner, Cheryl and Hladun, Suzanne and Hostin, Damon and Houck, Jarrett and Howland, Timothy and Ibegwam, Chinyere and Johnson, Jeffery and Kalush, Francis and Kline, Lesley and Koduru, Shashi and Love, Amy and Mann, Felecia and May, David and {McCawley}, Steven and {McIntosh}, Tina and {McMullen}, Ivy and Moy, Mee and Moy, Linda and Murphy, Brian and Nelson, Keith and Pfannkoch, Cynthia and Pratts, Eric and Puri, Vinita and Qureshi, Hina and Reardon, Matthew and Rodriguez, Robert and Rogers, Yu-Hui and Romblad, Deanna and Ruhfel, Bob and Scott, Richard and Sitter, Cynthia and Smallwood, Michelle and Stewart, Erin and Strong, Renee and Suh, Ellen and Thomas, Reginald and Tint, Ni Ni and Tse, Sukyee and Vech, Claire and Wang, Gary and Wetter, Jeremy and Williams, Sherita and Williams, Monica and Windsor, Sandra and Winn-Deen, Emily and Wolfe, Keriellen and Zaveri, Jayshree and Zaveri, Karena and Abril, Josep F. and Guigó, Roderic and Campbell, Michael J. and Sjolander, Kimmen V. and Karlak, Brian and Kejariwal, Anish and Mi, Huaiyu and Lazareva, Betty and Hatton, Thomas and Narechania, Apurva and Diemer, Karen and Muruganujan, Anushya and Guo, Nan and Sato, Shinji and Bafna, Vineet and Istrail, Sorin and Lippert, Ross and Schwartz, Russell and Walenz, Brian and Yooseph, Shibu and Allen, David and Basu, Anand and Baxendale, James and Blick, Louis and Caminha, Marcelo and Carnes-Stine, John and Caulk, Parris and Chiang, Yen-Hui and Coyne, My and Dahlke, Carl and Mays, Anne Deslattes and Dombroski, Maria and Donnelly, Michael and Ely, Dale and Esparham, Shiva and Fosler, Carl and Gire, Harold and Glanowski, Stephen and Glasser, Kenneth and Glodek, Anna and Gorokhov, Mark and Graham, Ken and Gropman, Barry and Harris, Michael and Heil, Jeremy and Henderson, Scott and Hoover, Jeffrey and Jennings, Donald and Jordan, Catherine and Jordan, James and Kasha, John and Kagan, Leonid and Kraft, Cheryl and Levitsky, Alexander and Lewis, Mark and Liu, Xiangjun and Lopez, John and Ma, Daniel and Majoros, William and {McDaniel}, Joe and Murphy, Sean and Newman, Matthew and Nguyen, Trung and Nguyen, Ngoc and Nodell, Marc and Pan, Sue and Peck, Jim and Peterson, Marshall and Rowe, William and Sanders, Robert and Scott, John and Simpson, Michael and Smith, Thomas and Sprague, Arlan and Stockwell, Timothy and Turner, Russell and Venter, Eli and Wang, Mei and Wen, Meiyuan and Wu, David and Wu, Mitchell and Xia, Ashley and Zandieh, Ali and Zhu, Xiaohong},
	urldate = {2019-07-14},
	date = {2001-02-16},
	langid = {english},
	pmid = {11181995},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/PHV84BN6/Venter et al. - 2001 - The Sequence of the Human Genome.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/E4TETRZJ/1304.html:text/html}
}

@article{mouse_genome_sequencing_consortium_initial_2002,
	title = {Initial sequencing and comparative analysis of the mouse genome},
	volume = {420},
	issn = {0028-0836},
	doi = {10.1038/nature01262},
	abstract = {The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.},
	pages = {520--562},
	number = {6915},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {{Mouse Genome Sequencing Consortium} and Waterston, Robert H. and Lindblad-Toh, Kerstin and Birney, Ewan and Rogers, Jane and Abril, Josep F. and Agarwal, Pankaj and Agarwala, Richa and Ainscough, Rachel and Alexandersson, Marina and An, Peter and Antonarakis, Stylianos E. and Attwood, John and Baertsch, Robert and Bailey, Jonathon and Barlow, Karen and Beck, Stephan and Berry, Eric and Birren, Bruce and Bloom, Toby and Bork, Peer and Botcherby, Marc and Bray, Nicolas and Brent, Michael R. and Brown, Daniel G. and Brown, Stephen D. and Bult, Carol and Burton, John and Butler, Jonathan and Campbell, Robert D. and Carninci, Piero and Cawley, Simon and Chiaromonte, Francesca and Chinwalla, Asif T. and Church, Deanna M. and Clamp, Michele and Clee, Christopher and Collins, Francis S. and Cook, Lisa L. and Copley, Richard R. and Coulson, Alan and Couronne, Olivier and Cuff, James and Curwen, Val and Cutts, Tim and Daly, Mark and David, Robert and Davies, Joy and Delehaunty, Kimberly D. and Deri, Justin and Dermitzakis, Emmanouil T. and Dewey, Colin and Dickens, Nicholas J. and Diekhans, Mark and Dodge, Sheila and Dubchak, Inna and Dunn, Diane M. and Eddy, Sean R. and Elnitski, Laura and Emes, Richard D. and Eswara, Pallavi and Eyras, Eduardo and Felsenfeld, Adam and Fewell, Ginger A. and Flicek, Paul and Foley, Karen and Frankel, Wayne N. and Fulton, Lucinda A. and Fulton, Robert S. and Furey, Terrence S. and Gage, Diane and Gibbs, Richard A. and Glusman, Gustavo and Gnerre, Sante and Goldman, Nick and Goodstadt, Leo and Grafham, Darren and Graves, Tina A. and Green, Eric D. and Gregory, Simon and Guigó, Roderic and Guyer, Mark and Hardison, Ross C. and Haussler, David and Hayashizaki, Yoshihide and Hillier, LaDeana W. and Hinrichs, Angela and Hlavina, Wratko and Holzer, Timothy and Hsu, Fan and Hua, Axin and Hubbard, Tim and Hunt, Adrienne and Jackson, Ian and Jaffe, David B. and Johnson, L. Steven and Jones, Matthew and Jones, Thomas A. and Joy, Ann and Kamal, Michael and Karlsson, Elinor K. and Karolchik, Donna and Kasprzyk, Arkadiusz and Kawai, Jun and Keibler, Evan and Kells, Cristyn and Kent, W. James and Kirby, Andrew and Kolbe, Diana L. and Korf, Ian and Kucherlapati, Raju S. and Kulbokas, Edward J. and Kulp, David and Landers, Tom and Leger, J. P. and Leonard, Steven and Letunic, Ivica and Levine, Rosie and Li, Jia and Li, Ming and Lloyd, Christine and Lucas, Susan and Ma, Bin and Maglott, Donna R. and Mardis, Elaine R. and Matthews, Lucy and Mauceli, Evan and Mayer, John H. and McCarthy, Megan and McCombie, W. Richard and McLaren, Stuart and McLay, Kirsten and McPherson, John D. and Meldrim, Jim and Meredith, Beverley and Mesirov, Jill P. and Miller, Webb and Miner, Tracie L. and Mongin, Emmanuel and Montgomery, Kate T. and Morgan, Michael and Mott, Richard and Mullikin, James C. and Muzny, Donna M. and Nash, William E. and Nelson, Joanne O. and Nhan, Michael N. and Nicol, Robert and Ning, Zemin and Nusbaum, Chad and O'Connor, Michael J. and Okazaki, Yasushi and Oliver, Karen and Overton-Larty, Emma and Pachter, Lior and Parra, Genís and Pepin, Kymberlie H. and Peterson, Jane and Pevzner, Pavel and Plumb, Robert and Pohl, Craig S. and Poliakov, Alex and Ponce, Tracy C. and Ponting, Chris P. and Potter, Simon and Quail, Michael and Reymond, Alexandre and Roe, Bruce A. and Roskin, Krishna M. and Rubin, Edward M. and Rust, Alistair G. and Santos, Ralph and Sapojnikov, Victor and Schultz, Brian and Schultz, Jörg and Schwartz, Matthias S. and Schwartz, Scott and Scott, Carol and Seaman, Steven and Searle, Steve and Sharpe, Ted and Sheridan, Andrew and Shownkeen, Ratna and Sims, Sarah and Singer, Jonathan B. and Slater, Guy and Smit, Arian and Smith, Douglas R. and Spencer, Brian and Stabenau, Arne and Stange-Thomann, Nicole and Sugnet, Charles and Suyama, Mikita and Tesler, Glenn and Thompson, Johanna and Torrents, David and Trevaskis, Evanne and Tromp, John and Ucla, Catherine and Ureta-Vidal, Abel and Vinson, Jade P. and Von Niederhausern, Andrew C. and Wade, Claire M. and Wall, Melanie and Weber, Ryan J. and Weiss, Robert B. and Wendl, Michael C. and West, Anthony P. and Wetterstrand, Kris and Wheeler, Raymond and Whelan, Simon and Wierzbowski, Jamey and Willey, David and Williams, Sophie and Wilson, Richard K. and Winter, Eitan and Worley, Kim C. and Wyman, Dudley and Yang, Shan and Yang, Shiaw-Pyng and Zdobnov, Evgeny M. and Zody, Michael C. and Lander, Eric S.},
	date = {2002-12-05},
	pmid = {12466850},
	keywords = {Human, Genomics, {DNA}, Sequence Analysis, Animals, Conserved Sequence, Genetic, Genome, Humans, Mice, {RNA}, Gene Expression Regulation, *Genome, *Evolution, *Physical Chromosome Mapping, Animal, Base Composition, Chromosomes, Conserved Sequence/genetics, {CpG} Islands, {CpG} Islands/genetics, Genes, Genes/genetics, Genetic Variation, Genetic Variation/genetics, Knockout, Mammalian/*genetics, Mice/classification/*genetics, Models, Molecular, Multigene Family, Multigene Family/genetics, Mutagenesis, Neoplasms, Neoplasms/genetics, Nucleic Acid/genetics, Proteome, Proteome/genetics, Pseudogenes, Pseudogenes/genetics, Quantitative Trait Loci, Quantitative Trait Loci/genetics, Repetitive Sequences, Selection, Sex Chromosomes/genetics, Species Specificity, Synteny, Transgenic, Untranslated/genetics, Evolution, Molecular, Selection, Genetic, Sequence Analysis, {DNA}, {RNA}, Untranslated, Genome, Human, Repetitive Sequences, Nucleic Acid, Chromosomes, Mammalian, Mice, Knockout, Mice, Transgenic, Models, Animal, Physical Chromosome Mapping, Sex Chromosomes},
	file = {Full Text:/home/jlagarde/Zotero/storage/MWHPDKTJ/Mouse Genome Sequencing Consortium et al. - 2002 - Initial sequencing and comparative analysis of the.pdf:application/pdf}
}

@article{c._elegans_sequencing_consortium_genome_1998,
	title = {Genome sequence of the nematode C. elegans: a platform for investigating biology},
	volume = {282},
	issn = {0036-8075},
	doi = {10.1126/science.282.5396.2012},
	shorttitle = {Genome sequence of the nematode C. elegans},
	abstract = {The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and highly conserved genes provides evidence for a regional organization of the chromosomes.},
	pages = {2012--2018},
	number = {5396},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {{C. elegans Sequencing Consortium}},
	date = {1998-12-11},
	pmid = {9851916},
	keywords = {Animals, Genome, Caenorhabditis elegans, Chromosomes, Molecular Sequence Data, Evolution, Molecular, Sequence Analysis, {DNA}, Repetitive Sequences, Nucleic Acid, Physical Chromosome Mapping, {DNA}, Helminth, Genes, Helminth, Helminth Proteins, {RNA}, Helminth}
}

@article{staden_strategy_1979,
	title = {A strategy of {DNA} sequencing employing computer programs},
	volume = {6},
	issn = {0305-1048},
	doi = {10.1093/nar/6.7.2601},
	abstract = {With modern fast sequencing techniques and suitable computer programs it is now possible to sequence whole genomes without the need of restriction maps. This paper describes computer programs that can be used to order both sequence gel readings and clones. A method of coding for uncertainties in gel readings is described. These programs are available on request.},
	pages = {2601--2610},
	number = {7},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res.},
	author = {Staden, R.},
	date = {1979-06-11},
	pmid = {461197},
	pmcid = {PMC327874},
	keywords = {{DNA}, Base Sequence, Computers, Oligodeoxyribonucleotides, {DNA}, Recombinant},
	file = {Full Text:/home/jlagarde/Zotero/storage/VT6BC9FV/Staden - 1979 - A strategy of DNA sequencing employing computer pr.pdf:application/pdf}
}

@article{perbal_case_2015,
	title = {The case of the gene},
	volume = {16},
	issn = {1469-3178},
	url = {https://www.embopress.org/doi/abs/10.15252/embr.201540179},
	doi = {10.15252/embr.201540179},
	pages = {777--781},
	number = {7},
	journaltitle = {{EMBO} reports},
	author = {Perbal, Laurence},
	urldate = {2019-07-15},
	date = {2015-07-01},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/AG7TFMG3/Perbal - 2015 - The case of the gene.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/ISJWQB72/embr.html:text/html}
}

@article{jacob_genetic_1961,
	title = {Genetic regulatory mechanisms in the synthesis of proteins},
	volume = {3},
	issn = {0022-2836},
	doi = {10.1016/s0022-2836(61)80072-7},
	pages = {318--356},
	journaltitle = {Journal of Molecular Biology},
	shortjournal = {J. Mol. Biol.},
	author = {Jacob, F. and Monod, J.},
	date = {1961-06},
	pmid = {13718526},
	keywords = {Proteins, Chromosomes, {CHROMOSOMES}, Enzymes, {ENZYMES}/metabolism, {PROTEINS}/metabolism}
}

@article{mayr_cause_1961,
	title = {Cause and Effect in Biology: Kinds of causes, predictability, and teleology are viewed by a practicing biologist},
	volume = {134},
	rights = {1961 by the American Association for the Advancement of Science},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/134/3489/1501},
	doi = {10.1126/science.134.3489.1501},
	shorttitle = {Cause and Effect in Biology},
	pages = {1501--1506},
	number = {3489},
	journaltitle = {Science},
	author = {Mayr, Ernst},
	urldate = {2019-07-15},
	date = {1961-11-10},
	langid = {english},
	pmid = {14471768},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/FBLR4CKQ/Mayr - 1961 - Cause and Effect in Biology Kinds of causes, pred.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/I2BP9JQI/1501.html:text/html}
}

@article{blattner_complete_1997,
	title = {The complete genome sequence of Escherichia coli K-12},
	volume = {277},
	issn = {0036-8075},
	doi = {10.1126/science.277.5331.1453},
	abstract = {The 4,639,221-base pair sequence of Escherichia coli K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 {ABC} transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence ({IS}) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.},
	pages = {1453--1462},
	number = {5331},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Blattner, F. R. and Plunkett, G. and Bloch, C. A. and Perna, N. T. and Burland, V. and Riley, M. and Collado-Vides, J. and Glasner, J. D. and Rode, C. K. and Mayhew, G. F. and Gregor, J. and Davis, N. W. and Kirkpatrick, H. A. and Goeden, M. A. and Rose, D. J. and Mau, B. and Shao, Y.},
	date = {1997-09-05},
	pmid = {9278503},
	keywords = {Binding Sites, Base Composition, Chromosome Mapping, {DNA} Replication, {DNA} Transposable Elements, Molecular Sequence Data, Mutation, Operon, Bacteriophage lambda, Escherichia coli, Sequence Analysis, {DNA}, Repetitive Sequences, Nucleic Acid, Bacterial Proteins, {DNA}, Bacterial, Genes, Bacterial, Genome, Bacterial, Recombination, Genetic, Regulatory Sequences, Nucleic Acid, {RNA}, Bacterial, {RNA}, Transfer, Sequence Homology, Amino Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/KC7ENPJC/Blattner et al. - 1997 - The complete genome sequence of Escherichia coli K.pdf:application/pdf}
}

@article{ramilowski_functional_2019,
	title = {Functional Annotation of Human Long Non-Coding {RNAs} via Molecular Phenotyping},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/10.1101/700864v1},
	doi = {10.1101/700864},
	abstract = {{\textless}p{\textgreater}Long non-coding {RNAs} ({lncRNAs}) constitute the majority of transcripts in mammalian genomes and yet, their functions remain largely unknown. We systematically suppressed 285 {lncRNAs} in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression ({CAGE}). The resulting transcriptomic profiles recapitulated the observed cellular phenotypes, yielding specific roles for over 40\% of analyzed {lncRNAs} in regulating distinct biological pathways, transcriptional machinery, alternative promoter activity and architecture usage. Overall, combining cellular and molecular profiling provided a powerful approach to unravel the distinct functions of {lncRNAs}, which we highlight with specific functional roles for {ZNF}213-{AS}1 and lnc-{KHDC}3L-2.{\textless}/p{\textgreater}},
	pages = {700864},
	journaltitle = {{bioRxiv}},
	author = {Ramilowski, Jordan and Yip, Chi Wai and Agrawal, Saumya and Chang, Jen-Chien and Ciani, Yari and Kulakovskiy, Ivan V. and Mendez, Mickael and Ooi, Jasmine Li Ching and Ouyang, John F. and Parkinson, Nick and Petri, Andreas and Roos, Leonie and Severin, Jessica and Yasuzawa, Kayoko and Abugessaisa, Imad and Akalin, Altuna and Antonov, Ivan and Arner, Erik and Bonetti, Alessandro and Bono, Hidemasa and Borsari, Beatrice and Brombacher, Frank and Cannistraci, Carlo Vittorio and Cardenas, Ryan and Cardon, Melissa and Chang, Howard and Dostie, Josée and Ducoli, Luca and Favorov, Alexander and Fort, Alexandre and Garrido, Diego and Gil, Noa and Gimenez, Juliette and Guler, Reto and Handoko, Lusy and Harshbarger, Jayson and Hasegawa, Akira and Hasegawa, Yuki and Hashimoto, Kosuke and Hayatsu, Norihito and Heutink, Peter and Hirose, Tetsuro and Imada, Eddie L. and Itoh, Masayoshi and Kaczkowski, Bogumil and Kanhere, Aditi and Kawabata, Emily and Kawaji, Hideya and Kawashima, Tsugumi and Kelly, Tom and Kojima, Miki and Kondo, Naoto and Koseki, Haruhiko and Kouno, Tsukasa and Kratz, Anton and Kurowska-Stolarska, Mariola and Kwon, Andrew Tae Jun and Leek, Jeffrey and Lennartsson, Andreas and Lizio, Marina and Lopez, Fernando and Luginbühl, Joachim and Maeda, Shiori and Makeev, Vsevolod and Marchionni, Luigi and Medvedeva, Yulia A. and Minoda, Aki and Müller, Ferenc and Aguirre, Manuel Munoz and Murata, Mitsuyoshi and Nishiyori, Hiromi and Nitta, Kazuhiro and Noguchi, Shuhei and Noro, Yukihiko and Nurtdinov, Ramil and Okazaki, Yasushi and Orlando, Valerio and Paquette, Denis and Parr, Callum and Rackham, Owen {JL} and Rizzu, Patrizia and Sanchez, Diego Fernando and Sandelin, Albin and Sanjana, Pillay and Semple, Colin {AM} and Sharma, Harshita and Shibayama, Youtaro and Sivaraman, Divya and Suzuki, Takahiro and Szumowski, Suzannah and Tagami, Michihira and Taylor, Martin S. and Terao, Chikashi and Thodberg, Malte and Thongjuea, Supat and Tripathi, Vidisha and Ulitsky, Igor and Verardo, Roberto and Vorontsov, Ilya and Yamamoto, Chinatsu and Young, Robert S. and Baillie, J. Kenneth and Forrest, Alistair {RR} and Guigó, Roderic and Hoffman, Michael M. and Hon, Chung Chau and Kasukawa, Takeya and Kauppinen, Sakari and Kere, Juha and Lenhard, Boris and Schneider, Claudio and Suzuki, Harukazu and Yagi, Ken and Consortium, Fantom and Hoon, Michiel de and Shin, Jay W. and Carninci, Piero},
	urldate = {2019-07-17},
	date = {2019-07-14},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/ZNSA2C52/Ramilowski et al. - 2019 - Functional Annotation of Human Long Non-Coding RNA.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/SK7PKRBZ/Ramilowski et al. - 2019 - Functional Annotation of Human Long Non-Coding RNA.html:text/html}
}

@article{burge_finding_1998,
	title = {Finding the genes in genomic {DNA}},
	volume = {8},
	issn = {0959-440X},
	url = {http://www.sciencedirect.com/science/article/pii/S0959440X98800699},
	doi = {10.1016/S0959-440X(98)80069-9},
	abstract = {Genome sequencing efforts will soon generate hundreds of millions of bases of human genomic {DNA} containing thousands of novel genes. In the past year, the accuracy of computational gene-finding methods has improved significantly, to the point where a reasonable approximation of the gene structures within an extended genomic region can often be predicted in advance of more detailed experimental studies.},
	pages = {346--354},
	number = {3},
	journaltitle = {Current Opinion in Structural Biology},
	shortjournal = {Current Opinion in Structural Biology},
	author = {Burge, Christopher B and Karlin, Samuel},
	urldate = {2019-07-18},
	date = {1998-06-01},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/A9TMCY6B/S0959440X98800699.html:text/html}
}

@article{yandell_beginners_2012,
	title = {A beginner's guide to eukaryotic genome annotation},
	volume = {13},
	rights = {2012 Nature Publishing Group},
	issn = {1471-0064},
	url = {https://www.nature.com/articles/nrg3174},
	doi = {10.1038/nrg3174},
	abstract = {The falling cost of genome sequencing is having a marked impact on the research community with respect to which genomes are sequenced and how and where they are annotated. Genome annotation projects have generally become small-scale affairs that are often carried out by an individual laboratory. Although annotating a eukaryotic genome assembly is now within the reach of non-experts, it remains a challenging task. Here we provide an overview of the genome annotation process and the available tools and describe some best-practice approaches.},
	pages = {329--342},
	number = {5},
	journaltitle = {Nature Reviews Genetics},
	author = {Yandell, Mark and Ence, Daniel},
	urldate = {2019-07-19},
	date = {2012-05},
	langid = {english},
	keywords = {Genomics, Base Sequence, Genetic, Genome, Humans, {RNA}, Exons, Databases, Introns, Software, Molecular Sequence Annotation, Molecular Sequence Data, Quality Control, Sequence Alignment, {RNA}: genetics, Eukaryota, Eukaryota: genetics, Molecular Sequence Annotation: methods, Molecular Sequence Annotation: standards},
	file = {Attachment:/home/jlagarde/Zotero/storage/64WL5GVJ/Yandell, Ence - 2012 - A beginner's guide to eukaryotic genome annotation.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/AAUJVJ3Y/nrg3174.html:text/html}
}

@article{guigo_egasp:_2006,
	title = {{EGASP}: the human {ENCODE} Genome Annotation Assessment Project},
	volume = {7},
	issn = {1465-6906},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810551/},
	doi = {10.1186/gb-2006-7-s1-s2},
	shorttitle = {{EGASP}},
	abstract = {Background
We present the results of {EGASP}, a community experiment to assess the state-of-the-art in genome annotation within the {ENCODE} regions, which span 1\% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the {ENCODE} regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the {GENCODE} project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment.

Results
The best methods had at least one gene transcript correctly predicted for close to 70\% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40\% to 50\% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90\% in both sensitivity and specificity. Programs relying on {mRNA} and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2\%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified.

Conclusion
This is the first such experiment in human {DNA}, and we have followed the standards established in a similar experiment, {GASP}1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.},
	pages = {S2},
	issue = {Suppl 1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol},
	author = {Guigó, Roderic and Flicek, Paul and Abril, Josep F and Reymond, Alexandre and Lagarde, Julien and Denoeud, France and Antonarakis, Stylianos and Ashburner, Michael and Bajic, Vladimir B and Birney, Ewan and Castelo, Robert and Eyras, Eduardo and Ucla, Catherine and Gingeras, Thomas R and Harrow, Jennifer and Hubbard, Tim and Lewis, Suzanna E and Reese, Martin G},
	urldate = {2019-07-20},
	date = {2006},
	pmid = {16925836},
	pmcid = {PMC1810551},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/5MDNHUHX/Guigó et al. - 2006 - EGASP the human ENCODE Genome Annotation Assessme.pdf:application/pdf}
}

@article{brent_genome_2005,
	title = {Genome annotation past, present, and future: How to define an {ORF} at each locus},
	volume = {15},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/15/12/1777},
	doi = {10.1101/gr.3866105},
	shorttitle = {Genome annotation past, present, and future},
	abstract = {Driven by competition, automation, and technology, the genomics community has far exceeded its ambition to sequence the human genome by 2005. By analyzing mammalian genomes, we have shed light on the history of our {DNA} sequence, determined that alternatively spliced {RNAs} and retroposed pseudogenes are incredibly abundant, and glimpsed the apparently huge number of non-coding {RNAs} that play significant roles in gene regulation. Ultimately, genome science is likely to provide comprehensive catalogs of these elements. However, the methods we have been using for most of the last 10 years will not yield even one complete open reading frame ({ORF}) for every gene—the first plateau on the long climb toward a comprehensive catalog. These strategies—sequencing randomly selected {cDNA} clones, aligning protein sequences identified in other organisms, sequencing more genomes, and manual curation—will have to be supplemented by large-scale amplification and sequencing of specific predicted {mRNAs}. The steady improvements in gene prediction that have occurred over the last 10 years have increased the efficacy of this approach and decreased its cost. In this Perspective, I review the state of gene prediction roughly 10 years ago, summarize the progress that has been made since, argue that the primary {ORF} identification methods we have relied on so far are inadequate, and recommend a path toward completing the Catalog of Protein Coding Genes, Version 1.0.},
	pages = {1777--1786},
	number = {12},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Brent, Michael R.},
	urldate = {2019-07-20},
	date = {2005-12-01},
	langid = {english},
	pmid = {16339376},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/UP9QC8GV/Brent - 2005 - Genome annotation past, present, and future How t.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/C9Y3AJW7/1777.html:text/html}
}

@article{brent_recent_2004,
	title = {Recent advances in gene structure prediction},
	volume = {14},
	issn = {0959-440X},
	url = {http://www.sciencedirect.com/science/article/pii/S0959440X04000818},
	doi = {10.1016/j.sbi.2004.05.007},
	abstract = {De novo gene predictors are programs that predict the exon-intron structures of genes using the sequences of one or more genomes as their only input. In the past two years, dual-genome de novo predictors, which exploit local rates and patterns of mutation inferred from alignments between two genomes, have led to significant improvements in accuracy. Systems that exploit more than two genomes simultaneously have only recently begun to appear and are not yet competitive on practical tasks, but offer the greatest hope for near-term improvements. Dual-genome de novo prediction for compact eukaryotic genomes such as those of Arabidopsis thaliana and Caenorhabditis elegans is already quite accurate. Although mammalian gene prediction lags behind in accuracy, it is yielding ever more useful results. Coupled with significant improvements in pseudogene detection methods, which have eliminated many false positives, we have reached the point where de novo gene predictions are being used as hypotheses to drive experimental annotation via systematic {RT}-{PCR} and sequencing.},
	pages = {264--272},
	number = {3},
	journaltitle = {Current Opinion in Structural Biology},
	shortjournal = {Current Opinion in Structural Biology},
	author = {Brent, Michael R and Guigó, Roderic},
	urldate = {2019-07-20},
	date = {2004-06-01},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/CB4Q2QIQ/S0959440X04000818.html:text/html}
}

@article{brent_steady_2008,
	title = {Steady progress and recent breakthroughs in the accuracy of automated genome annotation},
	volume = {9},
	issn = {1471-0064},
	doi = {10.1038/nrg2220},
	abstract = {The sequencing of large, complex genomes has become routine, but understanding how sequences relate to biological function is less straightforward. Although much attention is focused on how to annotate genomic features such as developmental enhancers and non-coding {RNAs}, there is still no higher eukaryote for which we know the correct exon-intron structure of at least one {ORF} for each gene. Despite this uncomfortable truth, genome annotation has made remarkable progress since the first drafts of the human genome were analysed. By combining several computational and experimental methods, we are now closer to producing complete and accurate gene catalogues than ever before.},
	pages = {62--73},
	number = {1},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Brent, Michael R.},
	date = {2008-01},
	pmid = {18087260},
	keywords = {Genome, Exons, Open Reading Frames, Introns, Automation, Sequence Analysis, {DNA}, {RNA}, Untranslated}
}

@article{barash_deciphering_2010,
	title = {Deciphering the splicing code},
	volume = {465},
	rights = {2010 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature09000},
	doi = {10.1038/nature09000},
	abstract = {Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of {RNA} features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger {RNA} decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.},
	pages = {53--59},
	number = {7294},
	journaltitle = {Nature},
	author = {Barash, Yoseph and Calarco, John A. and Gao, Weijun and Pan, Qun and Wang, Xinchen and Shai, Ofer and Blencowe, Benjamin J. and Frey, Brendan J.},
	urldate = {2019-07-21},
	date = {2010-05},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/LZHBPI95/nature09000.html:text/html}
}

@article{wang_alternative_2008,
	title = {Alternative isoform regulation in human tissue transcriptomes},
	volume = {456},
	rights = {2008 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature07509},
	doi = {10.1038/nature07509},
	abstract = {Through alternative processing of pre-messenger {RNAs}, individual mammalian genes often produce multiple {mRNA} and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary {DNA} fragments, yielding a digital inventory of gene and {mRNA} isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94\% of human genes undergo alternative splicing, ∼86\% with a minor isoform frequency of 15\% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or ‘switch-like’ regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3′ untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.},
	pages = {470--476},
	number = {7221},
	journaltitle = {Nature},
	author = {Wang, Eric T. and Sandberg, Rickard and Luo, Shujun and Khrebtukova, Irina and Zhang, Lu and Mayr, Christine and Kingsmore, Stephen F. and Schroth, Gary P. and Burge, Christopher B.},
	urldate = {2019-07-21},
	date = {2008-11},
	langid = {english},
	keywords = {Base Sequence, Humans, Exons, Gene Expression Profiling, Organ Specificity, Open Reading Frames, Alternative Splicing, Cell Line, Polyadenylation, Protein Isoforms, {RNA}-Binding Proteins, Repressor Proteins, {RNA}, Messenger, {RNA} Splicing Factors},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/BJNLKCDF/Wang et al. - 2008 - Alternative isoform regulation in human tissue tra.pdf:application/pdf;Accepted Version:/home/jlagarde/Zotero/storage/SZT9NQT6/Wang et al. - 2008 - Alternative isoform regulation in human tissue tra.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/WID96JZI/nature07509.html:text/html}
}

@article{kim_different_2007,
	title = {Different levels of alternative splicing among eukaryotes},
	volume = {35},
	issn = {0305-1048},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1802581/},
	doi = {10.1093/nar/gkl924},
	abstract = {Alternative splicing increases transcriptome and proteome diversification. Previous analyses aiming at comparing the rate of alternative splicing between different organisms provided contradicting results. These contradicting results were attributed to the fact that both analyses were dependent on the expressed sequence tag ({EST}) coverage, which varies greatly between the tested organisms. In this study we compare the level of alternative splicing among eight different organisms. By employing an {EST} independent approach we reveal that the percentage of genes and exons undergoing alternative splicing is higher in vertebrates compared with invertebrates. We also find that alternative exons of the skipping type are flanked by longer introns compared to constitutive ones, whereas alternative 5′ and 3′ splice sites events are generally not. In addition, although the regulation of alternative splicing and sizes of introns and exons have changed during metazoan evolution, intron retention remained the rarest type of alternative splicing, whereas exon skipping is more prevalent and exhibits a slight increase, from invertebrates to vertebrates. The difference in the level of alternative splicing suggests that alternative splicing may contribute greatly to the mammal higher level of phenotypic complexity, and that accumulation of introns confers an evolutionary advantage as it allows increasing the number of alternative splicing forms.},
	pages = {125--131},
	number = {1},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Kim, Eddo and Magen, Alon and Ast, Gil},
	urldate = {2019-07-21},
	date = {2007-01},
	pmid = {17158149},
	pmcid = {PMC1802581},
	keywords = {Animals, Humans, Mice, Algorithms, Introns, {RNA} Splice Sites, Alternative Splicing, Chickens, Expressed Sequence Tags, Rats, Vertebrates, Evolution, Molecular, Sequence Analysis, {DNA}, Databases, Nucleic Acid, Invertebrates},
	file = {Full Text:/home/jlagarde/Zotero/storage/EWVG6N6A/Kim et al. - 2007 - Different levels of alternative splicing among euk.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/YPS34UXL/Kim et al. - 2007 - Different levels of alternative splicing among euk.pdf:application/pdf}
}

@article{baralle_splicing_2018,
	title = {The splicing code},
	volume = {164},
	issn = {0303-2647},
	url = {http://www.sciencedirect.com/science/article/pii/S0303264717303210},
	doi = {10.1016/j.biosystems.2017.11.002},
	series = {Code Biology},
	abstract = {This issue dedicated to the code of life tackles very challenging and open questions in Biology. The genetic code, brilliantly uncovered over 50 years ago is an example of a univocal biological code. In fact, except for very few and marginal variations, it is the same from bacteria to man, the {RNA} stretch: 5′ {GUGUUC} 3′ reads as the dipeptide: Val-Phe in bacteria, in yeast, in Arabidopsis, in zebra fish, in mouse and in human. A degree of ambiguity is possible if mutations are introduced in the {tRNAs} in a way that the anticodon reads one amino acid but the aminoacyl-transferase attaches a different one onto the {tRNA}. These were the very useful suppressor genes that aided greatly the study of bacterial genetics. Other biological codes however, are more akin to social codes and are less amenable to an unambiguous deciphering. Legal and ethical codes, weather we like it or not, are flexible and depend on the structure and history of the society that has produced them, as well as a specific point in time. The codes that govern {RNA} splicing have similar characteristics. In fact, the splicing code depends on a myriad of different factors that in part are influenced by the background in which they are read such as different cells, tissues or developmental stages. Given the complexity of the splicing process, the construction of an algorithm that can define exons or their fate with certainty has not yet been achieved. However a substantial amount of information towards the deciphering of the splicing code has been gathered and in this manuscript we summarize the point reached.},
	pages = {39--48},
	journaltitle = {Biosystems},
	shortjournal = {Biosystems},
	author = {Baralle, Marco and Baralle, Francisco Ernesto},
	urldate = {2019-07-21},
	date = {2018-02-01},
	keywords = {Alternative splicing, Aplicing regulators, {RNA} binding proteins, Splicing code, Splicing regulatory elements},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/9GDW7RES/S0303264717303210.html:text/html}
}

@article{leppek_functional_2018,
	title = {Functional 5' {UTR} {mRNA} structures in eukaryotic translation regulation and how to find them},
	volume = {19},
	rights = {2017 Nature Publishing Group},
	issn = {1471-0080},
	url = {https://www.nature.com/articles/nrm.2017.103},
	doi = {10.1038/nrm.2017.103},
	abstract = {{RNA} molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5′ untranslated regions ({UTRs}) of eukaryotic {mRNAs} and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of {RNA} structures and higher-order {RNA} interactions, as well as cap-independent translation initiation through internal ribosome entry sites ({IRESs}), {mRNA} modifications and other specialized translation pathways. We discuss known 5′ {UTR} {RNA} structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured {RNA} elements that shape post-transcriptional control of gene expression and the development of multicellular organisms.},
	pages = {158--174},
	number = {3},
	journaltitle = {Nature Reviews Molecular Cell Biology},
	author = {Leppek, Kathrin and Das, Rhiju and Barna, Maria},
	urldate = {2019-07-21},
	date = {2018-03},
	langid = {english},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/5ZNR7RI9/Leppek et al. - 2018 - Functional 5′ UTR mRNA structures in eukaryotic tr.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/ZYRCY33R/nrm.2017.html:text/html}
}

@article{mayr_regulation_2017,
	title = {Regulation by 3'-Untranslated Regions},
	volume = {51},
	url = {https://doi.org/10.1146/annurev-genet-120116-024704},
	doi = {10.1146/annurev-genet-120116-024704},
	abstract = {3'-untranslated regions (3'-{UTRs}) are the noncoding parts of {mRNAs}. Compared to yeast, in humans, median 3'-{UTR} length has expanded approximately tenfold alongside an increased generation of alternative 3'-{UTR} isoforms. In contrast, the number of coding genes, as well as coding region length, has remained similar. This suggests an important role for 3′-{UTRs} in the biology of higher organisms. 3′-{UTRs} are best known to regulate diverse fates of {mRNAs}, including degradation, translation, and localization, but they can also function like long noncoding or small {RNAs}, as has been shown for whole 3′-{UTRs} as well as for cleaved fragments. Furthermore, 3′-{UTRs} determine the fate of proteins through the regulation of protein–protein interactions. They facilitate cotranslational protein complex formation, which establishes a role for 3′-{UTRs} as evolved eukaryotic operons. Whereas bacterial operons promote the interaction of two subunits, 3′-{UTRs} enable the formation of protein complexes with diverse compositions. All of these 3′-{UTR} functions are accomplished by effector proteins that are recruited by {RNA}-binding proteins that bind to 3′-{UTR} cis-elements. In summary, 3′-{UTRs} seem to be major players in gene regulation that enable local functions, compartmentalization, and cooperativity, which makes them important tools for the regulation of phenotypic diversity of higher organisms.},
	pages = {171--194},
	number = {1},
	journaltitle = {Annual Review of Genetics},
	author = {Mayr, Christine},
	urldate = {2019-07-21},
	date = {2017},
	pmid = {28853924}
}

@article{mignone_untranslated_2002,
	title = {Untranslated regions of {mRNAs}},
	volume = {3},
	issn = {1465-6906},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139023/},
	abstract = {Gene expression is finely regulated at the post-transcriptional level. Features of the untranslated regions of {mRNAs} that control their translation, degradation and localization include stem-loop structures, upstream initiation codons and open reading frames, internal ribosome entry sites and various cis-acting elements that are bound by {RNA}-binding proteins.},
	pages = {reviews0004.1--reviews0004.10},
	number = {3},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol},
	author = {Mignone, Flavio and Gissi, Carmela and Liuni, Sabino and Pesole, Graziano},
	urldate = {2019-07-21},
	date = {2002},
	pmid = {11897027},
	pmcid = {PMC139023},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/GLT4M7N5/Mignone et al. - 2002 - Untranslated regions of mRNAs.pdf:application/pdf}
}

@article{du_plessis_what_2011,
	title = {The what, where, how and why of gene ontology—a primer for bioinformaticians},
	volume = {12},
	issn = {1467-5463},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220872/},
	doi = {10.1093/bib/bbr002},
	abstract = {With high-throughput technologies providing vast amounts of data, it has become more important to provide systematic, quality annotations. The Gene Ontology ({GO}) project is the largest resource for cataloguing gene function. Nonetheless, its use is not yet ubiquitous and is still fraught with pitfalls. In this review, we provide a short primer to the {GO} for bioinformaticians. We summarize important aspects of the structure of the ontology, describe sources and types of functional annotations, survey measures of {GO} annotation similarity, review typical uses of {GO} and discuss other important considerations pertaining to the use of {GO} in bioinformatics applications.},
	pages = {723--735},
	number = {6},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief Bioinform},
	author = {du Plessis, Louis and Škunca, Nives and Dessimoz, Christophe},
	urldate = {2019-07-23},
	date = {2011-11},
	pmid = {21330331},
	pmcid = {PMC3220872},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/JPMF4FST/du Plessis et al. - 2011 - The what, where, how and why of gene ontology—a pr.pdf:application/pdf}
}

@article{gabaldon_prediction_2004,
	title = {Prediction of protein function and pathways in the genome era},
	volume = {61},
	issn = {1420-682X},
	doi = {10.1007/s00018-003-3387-y},
	abstract = {The growing number of completely sequenced genomes adds new dimensions to the use of sequence analysis to predict protein function. Compared with the classical knowledge transfer from one protein to a similar sequence (homology-based function prediction), knowledge about the corresponding genes in other genomes (orthology-based function prediction) provides more specific information about the protein's function, while the analysis of the sequence in its genomic context (context-based function prediction) provides information about its functional context. Whereas homology-based methods predict the molecular function of a protein, genomic context methods predict the biological process in which it plays a role. These complementary approaches can be combined to elucidate complete functional networks and biochemical pathways from the genome sequence of an organism. Here we review recent advances in the field of genomic-context based methods of protein function prediction. Techniques are highlighted with examples, including an analysis that combines information from genomic-context with homology to predict a role of the {RNase} L inhibitor in the maturation of ribosomal {RNA}.},
	pages = {930--944},
	number = {7},
	journaltitle = {Cellular and molecular life sciences: {CMLS}},
	shortjournal = {Cell. Mol. Life Sci.},
	author = {Gabaldón, T. and Huynen, M. A.},
	date = {2004-04},
	pmid = {15095013},
	keywords = {Genomics, Animals, Base Sequence, Genome, Humans, Proteins, Amino Acid Sequence, Chromosomes, Molecular Sequence Data, Phylogeny, Sequence Alignment, Evolution, Molecular, Artificial Gene Fusion, {ATP}-Binding Cassette Transporters, Chaperonins, {RNA}, Ribosomal}
}

@article{rost_automatic_2003,
	title = {Automatic prediction of protein function},
	volume = {60},
	issn = {1420-682X},
	doi = {10.1007/s00018-003-3114-8},
	abstract = {Most methods annotating protein function utilise sequence homology to proteins of experimentally known function. Such a homology-based annotation transfer is problematic and limited in scope. Therefore, computational biologists have begun to develop ab initio methods that predict aspects of function, including subcellular localization, post-translational modifications, functional type and protein-protein interactions. For the first two cases, the most accurate approaches rely on identifying short signalling motifs, while the most general methods utilise tools of artificial intelligence. An outstanding new method predicts classes of cellular function directly from sequence. Similarly, promising methods have been developed predicting protein-protein interaction partners at acceptable levels of accuracy for some pairs in entire proteomes. No matter how difficult the task, successes over the last few years have clearly paved the way for ab initio prediction of protein function.},
	pages = {2637--2650},
	number = {12},
	journaltitle = {Cellular and molecular life sciences: {CMLS}},
	shortjournal = {Cell. Mol. Life Sci.},
	author = {Rost, B. and Liu, J. and Nair, R. and Wrzeszczynski, K. O. and Ofran, Y.},
	date = {2003-12},
	pmid = {14685688},
	keywords = {Proteins, Computational Biology, Sequence Homology, Structure-Activity Relationship, Databases, Protein, Protein Processing, Post-Translational}
}

@article{dominguez_beyond_2016,
	title = {Beyond editing: repurposing {CRISPR}–Cas9 for precision genome regulation and interrogation},
	volume = {17},
	issn = {1471-0072},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922510/},
	doi = {10.1038/nrm.2015.2},
	shorttitle = {Beyond editing},
	abstract = {The bacterial {CRISPR}–Cas9 system has emerged as a multifunctional platform for sequence-specific regulation of gene expression. This Review describes the development of technologies based on nuclease-deactivated Cas9, termed {dCas}9, for {RNA}-guided genomic transcription regulation, both by repression through {CRISPR} interference ({CRISPRi}) and by activation through {CRISPR} activation ({CRISPRa}). We highlight different uses in diverse organisms, including bacterial and eukaryotic cells, and summarize current applications of harnessing {CRISPR}–{dCas}9 for multiplexed, inducible gene regulation, genome-wide screens and cell fate engineering. We also provide a perspective on future developments of the technology and its applications in biomedical research and clinical studies.},
	pages = {5--15},
	number = {1},
	journaltitle = {Nature reviews. Molecular cell biology},
	shortjournal = {Nat Rev Mol Cell Biol},
	author = {Dominguez, Antonia A. and Lim, Wendell A. and Qi, Lei S.},
	urldate = {2019-07-23},
	date = {2016-01},
	pmid = {26670017},
	pmcid = {PMC4922510},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/AVWFBS68/Dominguez et al. - 2016 - Beyond editing repurposing CRISPR–Cas9 for precis.pdf:application/pdf}
}

@incollection{golshirazi_antisense_2018,
	location = {New York, {NY}},
	title = {Antisense Oligonucleotide Targeting of 3’-{UTR} of {mRNA} for Expression Knockdown},
	isbn = {978-1-4939-8651-4},
	url = {https://doi.org/10.1007/978-1-4939-8651-4_6},
	series = {Methods in Molecular Biology},
	abstract = {With the recent conditional approval of an antisense oligonucleotide ({AON}) that restores the reading frame of {DMD} transcript in a subset of Duchenne muscular dystrophy patients, it has been established that {AONs} sharing similar chemistry have clear clinical potential. Genetic diseases, such as facioscapulohumeral dystrophy ({FSHD}), can be the result of gain-of-function mutations. Since {mRNA} processing in terms of termination of transcription, its transport from the nucleus to the cytoplasm, its stability and translation efficiency are dependent on key 3’{UTR} elements, it follows that targeting these elements with {AONs} have the potential to induce gene silencing. Aberrant expression of the Double homeobox 4 ({DUX}4) transcription factor and the downstream consequences of such expression is the hallmark of {FSHD}. Here we describe the bioinformatic strategies behind the design of {AONs} targeting polyadenylation signals and the methodologies relevant to their in vitro screening for efficacy and safety, including analysis of expression at the transcript and protein level of the specific target and downstream genes, and measurement of the effect on the fusion index of myotubes. The targeting of permissive {DUX}4 and {MSTN} are used as examples. {MSTN} encodes for myostatin, a negative regulator of myogenesis; the downregulation of {MSTN} expression has the potential to address the muscular atrophy associated with muscular dystrophies, sarcopenia, cancer and acquired immunodeficiency syndrome.},
	pages = {91--124},
	booktitle = {Exon Skipping and Inclusion Therapies: Methods and Protocols},
	publisher = {Springer New York},
	author = {Golshirazi, Golnoush and Ciszewski, Lukasz and Lu-Nguyen, Ngoc and Popplewell, Linda},
	editor = {Yokota, Toshifumi and Maruyama, Rika},
	urldate = {2019-07-23},
	date = {2018},
	langid = {english},
	doi = {10.1007/978-1-4939-8651-4_6},
	keywords = {Myostatin, Antisense oligonucleotides, {DUX}4, Facioscapulohumeral dystrophy, Polyadenylation signal}
}

@article{van_bakel_most_2010,
	title = {Most "dark matter" transcripts are associated with known genes},
	volume = {8},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.1000371},
	abstract = {A series of reports over the last few years have indicated that a much larger portion of the mammalian genome is transcribed than can be accounted for by currently annotated genes, but the quantity and nature of these additional transcripts remains unclear. Here, we have used data from single- and paired-end {RNA}-Seq and tiling arrays to assess the quantity and composition of transcripts in {PolyA}+ {RNA} from human and mouse tissues. Relative to tiling arrays, {RNA}-Seq identifies many fewer transcribed regions ("seqfrags") outside known exons and {ncRNAs}. Most nonexonic seqfrags are in introns, raising the possibility that they are fragments of pre-{mRNAs}. The chromosomal locations of the majority of intergenic seqfrags in {RNA}-Seq data are near known genes, consistent with alternative cleavage and polyadenylation site usage, promoter- and terminator-associated transcripts, or new alternative exons; indeed, reads that bridge splice sites identified 4,544 new exons, affecting 3,554 genes. Most of the remaining seqfrags correspond to either single reads that display characteristics of random sampling from a low-level background or several thousand small transcripts (median length = 111 bp) present at higher levels, which also tend to display sequence conservation and originate from regions with open chromatin. We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known exons, and the genome is not as pervasively transcribed as previously reported.},
	pages = {e1000371},
	number = {5},
	journaltitle = {{PLoS} biology},
	shortjournal = {{PLoS} Biol.},
	author = {van Bakel, Harm and Nislow, Corey and Blencowe, Benjamin J. and Hughes, Timothy R.},
	date = {2010-05-18},
	pmid = {20502517},
	pmcid = {PMC2872640},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Genetic, Genome, Humans, Mice, {RNA}, Transcription, Untranslated, Messenger/genetics, *{DNA}, *Genome, *Transcription, Computational Biology, Exons, Gene Expression Profiling, Intergenic, Messenger, Messenger: genetics, Oligonucleotide Array Sequence Analysis, Organ Specificity, Untranslated: genetics, Untranslated: metabolism, Untranslated/genetics/metabolism, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated, Sequence Analysis, {RNA}, Genome, Human, {DNA}, Intergenic},
	file = {Attachment:/home/jlagarde/Zotero/storage/WMYQZRP5/van Bakel et al. - 2010 - Most dark matter transcripts are associated with known genes.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/39V5DML3/van Bakel et al. - 2010 - Most dark matter transcripts are associated with.pdf:application/pdf}
}

@article{meyer_practical_2007,
	title = {A practical guide to the art of {RNA} gene prediction},
	volume = {8},
	issn = {1467-5463},
	url = {https://academic.oup.com/bib/article/8/6/396/249003},
	doi = {10.1093/bib/bbm011},
	abstract = {Abstract.  This review introduces the different strategies and computational methods that can be used in order to predict {RNA} genes. It discusses our current vi},
	pages = {396--414},
	number = {6},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief Bioinform},
	author = {Meyer, Irmtraud M.},
	urldate = {2019-07-24},
	date = {2007-11-01},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/PM8Q3PU8/Meyer - 2007 - A practical guide to the art of RNA gene predictio.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/6NQV8XW9/249003.html:text/html}
}

@article{panwar_prediction_2014,
	title = {Prediction and classification of {ncRNAs} using structural information},
	volume = {15},
	issn = {1471-2164},
	url = {https://doi.org/10.1186/1471-2164-15-127},
	doi = {10.1186/1471-2164-15-127},
	abstract = {Evidence is accumulating that non-coding transcripts, previously thought to be functionally inert, play important roles in various cellular activities. High throughput techniques like next generation sequencing have resulted in the generation of vast amounts of sequence data. It is therefore desirable, not only to discriminate coding and non-coding transcripts, but also to assign the noncoding {RNA} ({ncRNA}) transcripts into respective classes (families). Although there are several algorithms available for this task, their classification performance remains a major concern. Acknowledging the crucial role that non-coding transcripts play in cellular processes, it is required to develop algorithms that are able to precisely classify {ncRNA} transcripts.},
	pages = {127},
	number = {1},
	journaltitle = {{BMC} Genomics},
	shortjournal = {{BMC} Genomics},
	author = {Panwar, Bharat and Arora, Amit and Raghava, Gajendra {PS}},
	urldate = {2019-07-25},
	date = {2014-02-13},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/XMXB92S2/Panwar et al. - 2014 - Prediction and classification of ncRNAs using stru.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/56J5DM8X/1471-2164-15-127.html:text/html}
}

@article{bao_searching_2012,
	title = {Searching for Non-coding {RNAs} in Genomic Sequences Using {ncRNAscout}},
	volume = {10},
	issn = {1672-0229},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054157/},
	doi = {10.1016/j.gpb.2012.05.004},
	abstract = {Recently non-coding {RNA} ({ncRNA}) genes have been found to serve many important functions in the cell such as regulation of gene expression at the transcriptional level. Potentially there are more {ncRNA} molecules yet to be found and their possible functions are to be revealed. The discovery of {ncRNAs} is a difficult task because they lack sequence indicators such as the start and stop codons displayed by protein-coding {RNAs}. Current methods utilize either sequence motifs or structural parameters to detect novel {ncRNAs} within genomes. Here, we present an ab initio {ncRNA} finder, named {ncRNAscout}, by utilizing both sequence motifs and structural parameters. Specifically, our method has three components: (i) a measure of the frequency of a sequence, (ii) a measure of the structural stability of a sequence contained in a t-score, and (iii) a measure of the frequency of certain patterns within a sequence that may indicate the presence of {ncRNA}. Experimental results show that, given a genome and a set of known {ncRNAs}, our method is able to accurately identify and locate a significant number of {ncRNA} sequences in the genome. The {ncRNAscout} tool is available for downloading at http://bioinformatics.njit.edu/{ncRNAscout}.},
	pages = {114--121},
	number = {2},
	journaltitle = {Genomics, Proteomics \& Bioinformatics},
	shortjournal = {Genomics Proteomics Bioinformatics},
	author = {Bao, Michael and Cervantes Cervantes, Miguel and Zhong, Ling and Wang, Jason T.L.},
	urldate = {2019-07-25},
	date = {2012-04},
	pmid = {22768985},
	pmcid = {PMC5054157},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/SE5DP28V/Bao et al. - 2012 - Searching for Non-coding RNAs in Genomic Sequences.pdf:application/pdf}
}

@article{eddy_noncoding_1999,
	title = {Noncoding {RNA} genes},
	volume = {9},
	issn = {0959-437X},
	abstract = {Some genes produce {RNAs} that are functional instead of encoding proteins. Noncoding {RNA} genes are surprisingly numerous. Recently, active research areas include small nucleolar {RNAs}, antisense riboregulator {RNAs}, and {RNAs} involved in X-dosage compensation. Genome sequences and new algorithms have begun to make systematic computational screens for noncoding {RNA} genes possible.},
	pages = {695--699},
	number = {6},
	journaltitle = {Current Opinion in Genetics \& Development},
	shortjournal = {Curr. Opin. Genet. Dev.},
	author = {Eddy, S. R.},
	date = {1999-12},
	pmid = {10607607},
	keywords = {Animals, Genome, Humans, {RNA}, Computational Biology, Genes, {RNA}, Transfer, {RNA}, Ribosomal, {RNA}, Antisense, {RNA}, Small Nuclear, {RNA}, Small Nucleolar}
}

@article{burge_prediction_1997,
	title = {Prediction of complete gene structures in human genomic {DNA}},
	volume = {268},
	issn = {0022-2836},
	doi = {10.1006/jmbi.1997.0951},
	abstract = {We introduce a general probabilistic model of the gene structure of human genomic sequences which incorporates descriptions of the basic transcriptional, translational and splicing signals, as well as length distributions and compositional features of exons, introns and intergenic regions. Distinct sets of model parameters are derived to account for the many substantial differences in gene density and structure observed in distinct C + G compositional regions of the human genome. In addition, new models of the donor and acceptor splice signals are described which capture potentially important dependencies between signal positions. The model is applied to the problem of gene identification in a computer program, {GENSCAN}, which identifies complete exon/intron structures of genes in genomic {DNA}. Novel features of the program include the capacity to predict multiple genes in a sequence, to deal with partial as well as complete genes, and to predict consistent sets of genes occurring on either or both {DNA} strands. {GENSCAN} is shown to have substantially higher accuracy than existing methods when tested on standardized sets of human and vertebrate genes, with 75 to 80\% of exons identified exactly. The program is also capable of indicating fairly accurately the reliability of each predicted exon. Consistently high levels of accuracy are observed for sequences of differing C + G content and for distinct groups of vertebrates.},
	pages = {78--94},
	number = {1},
	journaltitle = {Journal of Molecular Biology},
	shortjournal = {J. Mol. Biol.},
	author = {Burge, C. and Karlin, S.},
	date = {1997-04-25},
	pmid = {9149143},
	keywords = {Human, {DNA}, Sequence Analysis, Animals, Genetic, Genome, Humans, Promoter Regions, Proteins, Proteins: genetics, {RNA} Splicing, Exons, Introns, Software, Genes, Models, Molecular Sequence Data, Probability, Vertebrates, Markov Chains, Vertebrates: genetics, Sequence Analysis, {DNA}, Promoter Regions, Genetic, Models, Genetic, Genome, Human}
}

@article{korf_integrating_2001,
	title = {Integrating genomic homology into gene structure prediction},
	volume = {17 Suppl 1},
	issn = {1367-4803},
	doi = {10.1093/bioinformatics/17.suppl_1.s140},
	abstract = {{TWINSCAN} is a new gene-structure prediction system that directly extends the probability model of {GENSCAN}, allowing it to exploit homology between two related genomes. Separate probability models are used for conservation in exons, introns, splice sites, and {UTRs}, reflecting the differences among their patterns of evolutionary conservation. {TWINSCAN} is specifically designed for the analysis of high-throughput genomic sequences containing an unknown number of genes. In experiments on high-throughput mouse sequences, using homologous sequences from the human genome, {TWINSCAN} shows notable improvement over {GENSCAN} in exon sensitivity and specificity and dramatic improvement in exact gene sensitivity and specificity. This improvement can be attributed entirely to modeling the patterns of evolutionary conservation in genomic sequence.},
	pages = {S140--148},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Korf, I. and Flicek, P. and Duan, D. and Brent, M. R.},
	date = {2001},
	pmid = {11473003},
	keywords = {{DNA}, Animals, Base Sequence, Conserved Sequence, Genome, Humans, Mice, Computational Biology, Algorithms, Sensitivity and Specificity, Sequence Alignment, Evolution, Molecular, Genome, Human, Models, Statistical, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/JQ7CPL4H/Korf et al. - 2001 - Integrating genomic homology into gene structure p.pdf:application/pdf}
}

@article{flicek_using_2006,
	title = {Using several pair-wise informant sequences for de novo prediction of alternatively spliced transcripts},
	volume = {7 Suppl 1},
	issn = {1474-760X},
	doi = {10.1186/gb-2006-7-s1-s8},
	abstract = {{BACKGROUND}: As part of the {ENCODE} Genome Annotation Assessment Project ({EGASP}), we developed the {MARS} extension to the Twinscan algorithm. {MARS} is designed to find human alternatively spliced transcripts that are conserved in only one or a limited number of extant species. {MARS} is able to use an arbitrary number of informant sequences and predicts a number of alternative transcripts at each gene locus.
{RESULTS}: {MARS} uses the mouse, rat, dog, opossum, chicken, and frog genome sequences as pairwise informant sources for Twinscan and combines the resulting transcript predictions into genes based on coding ({CDS}) region overlap. Based on the {EGASP} assessment, {MARS} is one of the more accurate dual-genome prediction programs. Compared to the {GENCODE} annotation, we find that predictive sensitivity increases, while specificity decreases, as more informant species are used. {MARS} correctly predicts alternatively spliced transcripts for 11 of the 236 multi-exon {GENCODE} genes that are alternatively spliced in the coding region of their transcripts. For these genes a total of 24 correct transcripts are predicted.
{CONCLUSION}: The {MARS} algorithm is able to predict alternatively spliced transcripts without the use of expressed sequence information, although the number of loci in which multiple predicted transcripts match multiple alternatively spliced transcripts in the {GENCODE} annotation is relatively small.},
	pages = {S8.1--9},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol.},
	author = {Flicek, Paul and Brent, Michael R.},
	date = {2006},
	pmid = {16925842},
	pmcid = {PMC1810557},
	keywords = {Human, Genomics, Animals, Genome, Humans, Mice, {RNA}, Computational Biology, Messenger, Messenger: genetics, Algorithms, Computational Biology: methods, Software, Alternative Splicing, Chickens, Chickens: genetics, Dogs, Genes, Genomics: methods, Rats, Sequence Alignment, Opossums, Opossums: genetics, Ranidae, {RNA}, Messenger, Genome, Human},
	file = {Attachment:/home/jlagarde/Zotero/storage/UZNEC2T6/Flicek, Brent - 2006 - Using several pair-wise informant sequences for de novo prediction of alternatively spliced transcripts.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/RS9UKFAR/Flicek and Brent - 2006 - Using several pair-wise informant sequences for de.pdf:application/pdf}
}

@article{parra_comparative_2003,
	title = {Comparative Gene Prediction in Human and Mouse},
	volume = {13},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC430976/},
	doi = {10.1101/gr.871403},
	abstract = {The completion of the sequencing of the mouse genome promises to help predict human genes with greater accuracy. While current ab initio gene prediction programs are remarkably sensitive (i.e., they predict at least a fragment of most genes), their specificity is often low, predicting a large number of false-positive genes in the human genome. Sequence conservation at the protein level with the mouse genome can help eliminate some of those false positives. Here we describe {SGP}2, a gene prediction program that combines ab initio gene prediction with {TBLASTX} searches between two genome sequences to provide both sensitive and specific gene predictions. The accuracy of {SGP}2 when used to predict genes by comparing the human and mouse genomes is assessed on a number of data sets, including single-gene data sets, the highly curated human chromosome 22 predictions, and entire genome predictions from {ENSEMBL}. Results indicate that {SGP}2 outperforms purely ab initio gene prediction methods. Results also indicate that {SGP}2 works about as well with 3x shotgun data as it does with fully assembled genomes. {SGP}2 provides a high enough specificity that its predictions can be experimentally verified at a reasonable cost. {SGP}2 was used to generate a complete set of gene predictions on both the human and mouse by comparing the genomes of these two species. Our results suggest that another few thousand human and mouse genes currently not in {ENSEMBL} are worth verifying experimentally.},
	pages = {108--117},
	number = {1},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Parra, Genís and Agarwal, Pankaj and Abril, Josep F. and Wiehe, Thomas and Fickett, James W. and Guigó, Roderic},
	urldate = {2019-07-26},
	date = {2003-01-01},
	pmid = {12529313},
	pmcid = {PMC430976},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/CZTNCAS8/Parra et al. - 2003 - Comparative Gene Prediction in Human and Mouse.pdf:application/pdf}
}

@article{gross_contrast:_2007,
	title = {{CONTRAST}: a discriminative, phylogeny-free approach to multiple informant de novo gene prediction},
	volume = {8},
	issn = {1474-760X},
	doi = {10.1186/gb-2007-8-12-r269},
	shorttitle = {{CONTRAST}},
	abstract = {We describe {CONTRAST}, a gene predictor which directly incorporates information from multiple alignments rather than employing phylogenetic models. This is accomplished through the use of discriminative machine learning techniques, including a novel training algorithm. We use a two-stage approach, in which a set of binary classifiers designed to recognize coding region boundaries is combined with a global model of gene structure. {CONTRAST} predicts exact coding region structures for 65\% more human genes than the previous state-of-the-art method, misses 46\% fewer exons and displays comparable gains in specificity.},
	pages = {R269},
	number = {12},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol.},
	author = {Gross, Samuel S. and Do, Chuong B. and Sirota, Marina and Batzoglou, Serafim},
	date = {2007},
	pmid = {18096039},
	pmcid = {PMC2246271},
	keywords = {Genomics, Animals, Base Sequence, Humans, Proteins, Exons, Algorithms, Software, Artificial Intelligence, Expressed Sequence Tags, Sequence Alignment, Genome, Human},
	file = {Full Text:/home/jlagarde/Zotero/storage/F9AAMX2D/Gross et al. - 2007 - CONTRAST a discriminative, phylogeny-free approac.pdf:application/pdf}
}

@article{freyhult_exploring_2007,
	title = {Exploring genomic dark matter: A critical assessment of the performance of homology search methods on noncoding {RNA}},
	volume = {17},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/17/1/117},
	doi = {10.1101/gr.5890907},
	shorttitle = {Exploring genomic dark matter},
	abstract = {Homology search is one of the most ubiquitous bioinformatic tasks, yet it is unknown how effective the currently available tools are for identifying noncoding {RNAs} ({ncRNAs}). In this work, we use reliable {ncRNA} data sets to assess the effectiveness of methods such as {BLAST}, {FASTA}, {HMMer}, and Infernal. Surprisingly, the most popular homology search methods are often the least accurate. As a result, many studies have used inappropriate tools for their analyses. On the basis of our results, we suggest homology search strategies using the currently available tools and some directions for future development.},
	pages = {117--125},
	number = {1},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Freyhult, Eva K. and Bollback, Jonathan P. and Gardner, Paul P.},
	urldate = {2019-07-26},
	date = {2007-01-01},
	langid = {english},
	pmid = {17151342},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/LTQDZP87/Freyhult et al. - 2007 - Exploring genomic dark matter A critical assessme.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/3CLVK7IY/117.html:text/html}
}

@article{eddy_memory-efficient_2002,
	title = {A memory-efficient dynamic programming algorithm for optimal alignment of a sequence to an {RNA} secondary structure},
	volume = {3},
	issn = {1471-2105},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC119854/},
	doi = {10.1186/1471-2105-3-18},
	abstract = {Background
Covariance models ({CMs}) are probabilistic models of {RNA} secondary structure, analogous to profile hidden Markov models of linear sequence. The dynamic programming algorithm for aligning a {CM} to an {RNA} sequence of length N is O(N3) in memory. This is only practical for small {RNAs}.

Results
I describe a divide and conquer variant of the alignment algorithm that is analogous to memory-efficient Myers/Miller dynamic programming algorithms for linear sequence alignment. The new algorithm has an O(N2 log N) memory complexity, at the expense of a small constant factor in time.

Conclusions
Optimal ribosomal {RNA} structural alignments that previously required up to 150 {GB} of memory now require less than 270 {MB}.},
	pages = {18},
	journaltitle = {{BMC} Bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Eddy, Sean R},
	urldate = {2019-07-26},
	date = {2002-07-02},
	pmid = {12095421},
	pmcid = {PMC119854},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/5TVPGSFS/Eddy - 2002 - A memory-efficient dynamic programming algorithm f.pdf:application/pdf}
}

@article{washietl_mapping_2005,
	title = {Mapping of conserved {RNA} secondary structures predicts thousands of functional noncoding {RNAs} in the human genome},
	volume = {23},
	issn = {1087-0156},
	doi = {10.1038/nbt1144},
	abstract = {In contrast to the fairly reliable and complete annotation of the protein coding genes in the human genome, comparable information is lacking for noncoding {RNAs} ({ncRNAs}). We present a comparative screen of vertebrate genomes for structural noncoding {RNAs}, which evaluates conserved genomic {DNA} sequences for signatures of structural conservation of base-pairing patterns and exceptional thermodynamic stability. We predict more than 30,000 structured {RNA} elements in the human genome, almost 1,000 of which are conserved across all vertebrates. Roughly a third are found in introns of known genes, a sixth are potential regulatory elements in untranslated regions of protein-coding {mRNAs} and about half are located far away from any known gene. Only a small fraction of these sequences has been described previously. A comparison with recent tiling array data shows that more than 40\% of the predicted structured {RNAs} overlap with experimentally detected sites of transcription. The widespread conservation of secondary structure points to a large number of functional {ncRNAs} and cis-acting {mRNA} structures in the human genome.},
	pages = {1383--1390},
	number = {11},
	journaltitle = {Nature Biotechnology},
	shortjournal = {Nat. Biotechnol.},
	author = {Washietl, Stefan and Hofacker, Ivo L. and Lukasser, Melanie and Hüttenhofer, Alexander and Stadler, Peter F.},
	date = {2005-11},
	pmid = {16273071},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, {RNA}, Computational Biology, Introns, Base Pairing, Chromosome Mapping, Nucleic Acid Conformation, Phylogeny, Sensitivity and Specificity, Thermodynamics, {RNA}, Messenger, Transcription, Genetic, Sequence Analysis, {DNA}, {RNA}, Untranslated, Genome, Human, Models, Statistical, Regulatory Elements, Transcriptional},
	file = {Full Text:/home/jlagarde/Zotero/storage/66AGU5UW/Washietl et al. - 2005 - Mapping of conserved RNA secondary structures pred.pdf:application/pdf}
}

@article{zhang_review_2017,
	title = {A Review on Recent Computational Methods for Predicting Noncoding {RNAs}},
	volume = {2017},
	issn = {2314-6133},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434267/},
	doi = {10.1155/2017/9139504},
	abstract = {Noncoding {RNAs} ({ncRNAs}) play important roles in various cellular activities and diseases. In this paper, we presented a comprehensive review on computational methods for {ncRNA} prediction, which are generally grouped into four categories: (1) homology-based methods, that is, comparative methods involving evolutionarily conserved {RNA} sequences and structures, (2) de novo methods using {RNA} sequence and structure features, (3) transcriptional sequencing and assembling based methods, that is, methods designed for single and pair-ended reads generated from next-generation {RNA} sequencing, and (4) {RNA} family specific methods, for example, methods specific for {microRNAs} and long noncoding {RNAs}. In the end, we summarized the advantages and limitations of these methods and pointed out a few possible future directions for {ncRNA} prediction. In conclusion, many computational methods have been demonstrated to be effective in predicting {ncRNAs} for further experimental validation. They are critical in reducing the huge number of potential {ncRNAs} and pointing the community to high confidence candidates. In the future, high efficient mapping technology and more intrinsic sequence features (e.g., motif and k-mer frequencies) and structure features (e.g., minimum free energy, conserved stem-loop, or graph structures) are suggested to be combined with the next- and third-generation sequencing platforms to improve {ncRNA} prediction.},
	journaltitle = {{BioMed} Research International},
	shortjournal = {Biomed Res Int},
	author = {Zhang, Yi and Huang, Haiyun and Zhang, Dahan and Qiu, Jing and Yang, Jiasheng and Wang, Kejing and Zhu, Lijuan and Fan, Jingjing and Yang, Jialiang},
	urldate = {2019-07-26},
	date = {2017},
	pmid = {28553651},
	pmcid = {PMC5434267},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/GZK79LN4/Zhang et al. - 2017 - A Review on Recent Computational Methods for Predi.pdf:application/pdf}
}

@article{stark_rna_2019,
	title = {{RNA} sequencing: the teenage years},
	rights = {2019 Springer Nature Limited},
	issn = {1471-0064},
	url = {https://www.nature.com/articles/s41576-019-0150-2},
	doi = {10.1038/s41576-019-0150-2},
	shorttitle = {{RNA} sequencing},
	abstract = {This Review discusses advances in {RNA}-sequencing technologies and methods over the past decade and outlines adaptations that are enabling a fuller understanding of {RNA} biology, from when and where an {RNA} is expressed to the structures it adopts.},
	pages = {1},
	journaltitle = {Nature Reviews Genetics},
	author = {Stark, Rory and Grzelak, Marta and Hadfield, James},
	urldate = {2019-07-27},
	date = {2019-07-24},
	file = {Snapshot:/home/jlagarde/Zotero/storage/EMQM576K/s41576-019-0150-2.html:text/html;Stark et al. - 2019 - RNA sequencing the teenage years.pdf:/home/jlagarde/Zotero/storage/ZZXUM3G3/Stark et al. - 2019 - RNA sequencing the teenage years.pdf:application/pdf}
}

@article{stojic_high-content_2019,
	title = {A high-content {RNAi} screen reveals multiple roles for long noncoding {RNAs} in cell division},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NonCommercial}-{NoDerivs} 4.0 International), {CC} {BY}-{NC}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/709030v1},
	doi = {10.1101/709030},
	abstract = {{\textless}p{\textgreater}Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. The role of long noncoding {RNAs} ({lncRNAs}) in controlling these processes however remains largely unexplored. To identify {lncRNAs} with mitotic functions, we performed a high-content {RNAi} imaging screen targeting more than 2,000 human {lncRNAs}. By investigating major hallmarks of cell division such as chromosome segregation, mitotic duration and cytokinesis, we discovered numerous {lncRNAs} with functions in each of these processes. The chromatin-associated {lncRNA}, linc00899, was selected for in-depth studies due to the robust mitotic delay observed upon its depletion. Transcriptome analysis of linc00899-depleted cells together with gain-of-function and rescue experiments across multiple cell types identified the neuronal microtubule-binding protein, {TPPP}/p25, as a target of linc00899. Linc00899 binds the genomic locus of {TPPP}/p25 and suppresses its transcription through a cis-acting mechanism. In cells depleted of linc00899, the consequent upregulation of {TPPP}/p25 alters microtubule dynamics and is necessary and sufficient to delay mitosis. Overall, our comprehensive screen identified several {lncRNAs} with roles in genome stability and revealed a new {lncRNA} that controls microtubule behaviour with functional implications beyond cell division.{\textless}/p{\textgreater}},
	pages = {709030},
	journaltitle = {{bioRxiv}},
	author = {Stojic, Lovorka and Lun, Aaron T. L. and Mascalchi, Patrice and Ernst, Christina and Redmond, Aisling M. and Mangei, Jasmin and Barr, Alexis R. and Bousgouni, Vicky and Bakal, Chris and Marioni, John C. and Odom, Duncan T. and Gergely, Fanni},
	urldate = {2019-07-27},
	date = {2019-07-19},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/ZDGZDRRF/Stojic et al. - 2019 - A high-content RNAi screen reveals multiple roles .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/RXCQGG82/709030v1.html:text/html}
}

@article{wyman_technology-agnostic_2019,
	title = {A technology-agnostic long-read analysis pipeline for transcriptome discovery and quantification},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NoDerivs} 4.0 International), {CC} {BY}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/672931v1},
	doi = {10.1101/672931},
	abstract = {{\textless}p{\textgreater}Alternative splicing is widely acknowledged to be a crucial regulator of gene expression and is a key contributor to both normal developmental processes and disease states. While cost-effective and accurate for quantification, short-read {RNA}-seq lacks the ability to resolve full-length transcript isoforms despite increasingly sophisticated computational methods. Long-read sequencing platforms such as Pacific Biosciences ({PacBio}) and Oxford Nanopore ({ONT}) bypass the transcript reconstruction challenges of short-reads. Here we describe {TALON}, the {ENCODE}4 pipeline for analyzing {PacBio} {cDNA} and {ONT} direct-{RNA} transcriptomes. We apply {TALON} to three human {ENCODE} Tier 1 cell lines and show that while both technologies perform well at full-transcript discovery and quantification, each technology has its distinct artifacts. We further apply {TALON} to mouse cortical and hippocampal transcriptomes and find that a substantial proportion of neuronal genes have more reads associated with novel isoforms than annotated ones. The {TALON} pipeline for technology-agnostic, long-read transcriptome discovery and quantification tracks both known and novel transcript models as well as expression levels across datasets for both simple studies and larger projects such as {ENCODE} that seek to decode transcriptional regulation in the human and mouse genomes to predict more accurate expression levels of genes and transcripts than possible with short-reads alone.{\textless}/p{\textgreater}},
	pages = {672931},
	journaltitle = {{bioRxiv}},
	author = {Wyman, Dana and Balderrama-Gutierrez, Gabriela and Reese, Fairlie and Jiang, Shan and Rahmanian, Sorena and Zeng, Weihua and Williams, Brian and Trout, Diane and England, Whitney and Chu, Sophie and Spitale, Robert C. and Tenner, Andrea and Wold, Barbara and Mortazavi, Ali},
	urldate = {2019-07-27},
	date = {2019-06-18},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/RME3TRWJ/Wyman et al. - 2019 - A technology-agnostic long-read analysis pipeline .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/5W86NF4H/672931v1.html:text/html}
}

@article{wainberg_opportunities_2019,
	title = {Opportunities and challenges for transcriptome-wide association studies},
	volume = {51},
	rights = {2019 The Author(s), under exclusive licence to Springer Nature America, Inc.},
	issn = {1546-1718},
	url = {https://www.nature.com/articles/s41588-019-0385-z},
	doi = {10.1038/s41588-019-0385-z},
	abstract = {Transcriptome-wide association studies ({TWAS}) prioritize candidate causal genes at {GWAS} loci. This Perspective discusses the challenges to {TWAS} analysis, caveats to interpretation of results and opportunities for improvements to this class of methods.},
	pages = {592},
	number = {4},
	journaltitle = {Nature Genetics},
	author = {Wainberg, Michael and Sinnott-Armstrong, Nasa and Mancuso, Nicholas and Barbeira, Alvaro N. and Knowles, David A. and Golan, David and Ermel, Raili and Ruusalepp, Arno and Quertermous, Thomas and Hao, Ke and Björkegren, Johan L. M. and Im, Hae Kyung and Pasaniuc, Bogdan and Rivas, Manuel A. and Kundaje, Anshul},
	urldate = {2019-07-27},
	date = {2019-04},
	file = {Opportunities and challenges for transcriptome-wide association studies:/home/jlagarde/Zotero/storage/LNDD4UHA/10.1038@s41588-019-0385-z.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/E4NAGB7I/s41588-019-0385-z.html:text/html}
}

@article{wang_deep_2019,
	title = {A deep proteome and transcriptome abundance atlas of 29 healthy human tissues},
	volume = {15},
	issn = {1744-4292},
	url = {https://www.embopress.org/doi/abs/10.15252/msb.20188503},
	doi = {10.15252/msb.20188503},
	number = {2},
	journaltitle = {Molecular Systems Biology},
	author = {Wang, Dongxue and Eraslan, Basak and Wieland, Thomas and Hallström, Björn and Hopf, Thomas and Zolg, Daniel Paul and Zecha, Jana and Asplund, Anna and Li, Li-hua and Meng, Chen and Frejno, Martin and Schmidt, Tobias and Schnatbaum, Karsten and Wilhelm, Mathias and Ponten, Frederik and Uhlen, Mathias and Gagneur, Julien and Hahne, Hannes and Kuster, Bernhard},
	urldate = {2019-07-27},
	date = {2019-02-01},
	langid = {english},
	file = {A deep proteome and transcriptome abundance atlas of 29 healthy human tissues:/home/jlagarde/Zotero/storage/843P3I4C/10.15252@msb.20188503.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/GI9FV2CQ/Wang et al. - 2019 - A deep proteome and transcriptome abundance atlas .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/STEVLIEV/msb.html:text/html}
}

@article{xia_widespread_2019,
	title = {Widespread transcriptional scanning in the testis modulates gene evolution rates},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NonCommercial}-{NoDerivs} 4.0 International), {CC} {BY}-{NC}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/282129v2},
	doi = {10.1101/282129},
	abstract = {{\textless}p{\textgreater}The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Analyzing our single-cell transcriptomic maps of human and mouse spermatogenesis, we provide evidence that this widespread transcription serves to maintain {DNA} sequence integrity in the male germline by correcting {DNA} damage through 9transcriptional scanning9. Supporting this model, we find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population. Moreover, this effect is fine-tuned by the level of gene expression during spermatogenesis. The unexpressed genes, which in our model do not benefit from transcriptional scanning, diverge faster over evolutionary time-scales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning modulates germline mutation rates in a gene-specific manner, maintaining {DNA} sequence integrity for the bulk of genes but allowing for fast evolution in a specific subset.{\textless}/p{\textgreater}},
	pages = {282129},
	journaltitle = {{bioRxiv}},
	author = {Xia, Bo and Yan, Yun and Baron, Maayan and Wagner, Florian and Barkley, Dalia and Chiodin, Marta and Kim, Sang Y. and Keefe, David L. and Alukal, Joseph P. and Boeke, Jef D. and Yanai, Itai},
	urldate = {2019-07-27},
	date = {2019-01-22},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/D55ZLDMP/Xia et al. - 2019 - Widespread transcriptional scanning in the testis .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/NUYNQSNH/282129v2.html:text/html}
}

@article{temple_completion_2009,
	title = {The completion of the Mammalian Gene Collection ({MGC})},
	volume = {19},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792178/},
	doi = {10.1101/gr.095976.109},
	abstract = {Since its start, the Mammalian Gene Collection ({MGC}) has sought to provide at least one full-protein-coding sequence {cDNA} clone for every human and mouse gene with a {RefSeq} transcript, and at least 6200 rat genes. The {MGC} cloning effort initially relied on random expressed sequence tag screening of {cDNA} libraries. Here, we summarize our recent progress using directed {RT}-{PCR} cloning and {DNA} synthesis. The {MGC} now contains clones with the entire protein-coding sequence for 92\% of human and 89\% of mouse genes with curated {RefSeq} ({NM}-accession) transcripts, and for 97\% of human and 96\% of mouse genes with curated {RefSeq} transcripts that have one or more {PubMed} publications, in addition to clones for more than 6300 rat genes. These high-quality {MGC} clones and their sequences are accessible without restriction to researchers worldwide.},
	pages = {2324--2333},
	number = {12},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Temple, Gary and Gerhard, Daniela S. and Rasooly, Rebekah and Feingold, Elise A. and Good, Peter J. and Robinson, Cristen and Mandich, Allison and Derge, Jeffrey G. and Lewis, Jeanne and Shoaf, Debonny and Collins, Francis S. and Jang, Wonhee and Wagner, Lukas and Shenmen, Carolyn M. and Misquitta, Leonie and Schaefer, Carl F. and Buetow, Kenneth H. and Bonner, Tom I. and Yankie, Linda and Ward, Ming and Phan, Lon and Astashyn, Alex and Brown, Garth and Farrell, Catherine and Hart, Jennifer and Landrum, Melissa and Maidak, Bonnie L. and Murphy, Michael and Murphy, Terence and Rajput, Bhanu and Riddick, Lillian and Webb, David and Weber, Janet and Wu, Wendy and Pruitt, Kim D. and Maglott, Donna and Siepel, Adam and Brejova, Brona and Diekhans, Mark and Harte, Rachel and Baertsch, Robert and Kent, Jim and Haussler, David and Brent, Michael and Langton, Laura and Comstock, Charles L.G. and Stevens, Michael and Wei, Chaochun and van Baren, Marijke J. and Salehi-Ashtiani, Kourosh and Murray, Ryan R. and Ghamsari, Lila and Mello, Elizabeth and Lin, Chenwei and Pennacchio, Christa and Schreiber, Kirsten and Shapiro, Nicole and Marsh, Amber and Pardes, Elizabeth and Moore, Troy and Lebeau, Anita and Muratet, Mike and Simmons, Blake and Kloske, David and Sieja, Stephanie and Hudson, James and Sethupathy, Praveen and Brownstein, Michael and Bhat, Narayan and Lazar, Joseph and Jacob, Howard and Gruber, Chris E. and Smith, Mark R. and {McPherson}, John and Garcia, Angela M. and Gunaratne, Preethi H. and Wu, Jiaqian and Muzny, Donna and Gibbs, Richard A. and Young, Alice C. and Bouffard, Gerard G. and Blakesley, Robert W. and Mullikin, Jim and Green, Eric D. and Dickson, Mark C. and Rodriguez, Alex C. and Grimwood, Jane and Schmutz, Jeremy and Myers, Richard M. and Hirst, Martin and Zeng, Thomas and Tse, Kane and Moksa, Michelle and Deng, Merinda and Ma, Kevin and Mah, Diana and Pang, Johnson and Taylor, Greg and Chuah, Eric and Deng, Athena and Fichter, Keith and Go, Anne and Lee, Stephanie and Wang, Jing and Griffith, Malachi and Morin, Ryan and Moore, Richard A. and Mayo, Michael and Munro, Sarah and Wagner, Susan and Jones, Steven J.M. and Holt, Robert A. and Marra, Marco A. and Lu, Sun and Yang, Shuwei and Hartigan, James and Graf, Marcus and Wagner, Ralf and Letovksy, Stanley and Pulido, Jacqueline C. and Robison, Keith and Esposito, Dominic and Hartley, James and Wall, Vanessa E. and Hopkins, Ralph F. and Ohara, Osamu and Wiemann, Stefan},
	urldate = {2019-07-28},
	date = {2009-12},
	pmid = {19767417},
	pmcid = {PMC2792178},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/L3LCKMV9/Temple et al. - 2009 - The completion of the Mammalian Gene Collection (M.pdf:application/pdf}
}

@article{noauthor_generation_2002,
	title = {Generation and initial analysis of more than 15,000 full-length human and mouse {cDNA} sequences},
	volume = {99},
	issn = {0027-8424},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/},
	doi = {10.1073/pnas.242603899},
	abstract = {The National Institutes of Health Mammalian Gene Collection ({MGC}) Program is a multiinstitutional effort to identify and sequence a {cDNA} clone containing a complete {ORF} for each human and mouse gene. {ESTs} were generated from libraries enriched for full-length {cDNAs} and analyzed to identify candidate full-{ORF} clones, which then were sequenced to high accuracy. The {MGC} has currently sequenced and verified the full {ORF} for a nonredundant set of {\textgreater}9,000 human and {\textgreater}6,000 mouse genes. Candidate full-{ORF} clones for an additional 7,800 human and 3,500 mouse genes also have been identified. All {MGC} sequences and clones are available without restriction through public databases and clone distribution networks (see http://mgc.nci.nih.gov).},
	pages = {16899--16903},
	number = {26},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc Natl Acad Sci U S A},
	urldate = {2019-07-28},
	date = {2002-12-24},
	pmid = {12477932},
	pmcid = {PMC139241},
	file = {Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences:/home/jlagarde/Zotero/storage/HIWLXT6H/generation-and-initial-analysis-of-more-than-15000-fulllength-hu-2002.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/3P6TNWQ7/2002 - Generation and initial analysis of more than 15,00.pdf:application/pdf}
}

@article{adams_complementary_1991,
	title = {Complementary {DNA} sequencing: expressed sequence tags and human genome project},
	volume = {252},
	issn = {0036-8075},
	doi = {10.1126/science.2047873},
	shorttitle = {Complementary {DNA} sequencing},
	abstract = {Automated partial {DNA} sequencing was conducted on more than 600 randomly selected human brain complementary {DNA} ({cDNA}) clones to generate expressed sequence tags ({ESTs}). {ESTs} have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast {RNA} polymerase {II} subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six {ESTs} were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to {cDNA} characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields.},
	pages = {1651--1656},
	number = {5013},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Adams, M. D. and Kelley, J. M. and Gocayne, J. D. and Dubnick, M. and Polymeropoulos, M. H. and Xiao, H. and Merril, C. R. and Wu, A. and Olde, B. and Moreno, R. F.},
	date = {1991-06-21},
	pmid = {2047873},
	keywords = {{DNA}, Base Sequence, Humans, Amino Acid Sequence, Automation, Brain, Chromosome Mapping, Gene Expression, Gene Library, Human Genome Project, Molecular Sequence Data, Multigene Family, Polymerase Chain Reaction, Sequence Homology, Nucleic Acid},
	file = {Adams et al. - 1991 - Complementary DNA sequencing expressed sequence t.pdf:/home/jlagarde/Zotero/storage/T7HUZHTC/Adams et al. - 1991 - Complementary DNA sequencing expressed sequence t.pdf:application/pdf}
}

@article{nagaraj_hitchhikers_2007,
	title = {A hitchhiker's guide to expressed sequence tag ({EST}) analysis},
	volume = {8},
	issn = {1467-5463},
	url = {https://academic.oup.com/bib/article/8/1/6/264831},
	doi = {10.1093/bib/bbl015},
	abstract = {Abstract.  Expressed sequence tag ({EST}) sequencing projects are underway for numerous organisms, generating millions of short, single-pass nucleotide sequence r},
	pages = {6--21},
	number = {1},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief Bioinform},
	author = {Nagaraj, Shivashankar H. and Gasser, Robin B. and Ranganathan, Shoba},
	urldate = {2019-07-29},
	date = {2007-01-01},
	langid = {english},
	file = {A hitchhiker's guide to expressed sequence tag (EST) analysis:/home/jlagarde/Zotero/storage/4K99LPMT/nagaraj2006.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/MCKWBE3B/Nagaraj et al. - 2007 - A hitchhiker's guide to expressed sequence tag (ES.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/HX4CAXGY/264831.html:text/html}
}

@article{bonaldo_normalization_1996,
	title = {Normalization and subtraction: two approaches to facilitate gene discovery},
	volume = {6},
	issn = {1088-9051},
	doi = {10.1101/gr.6.9.791},
	shorttitle = {Normalization and subtraction},
	abstract = {Large-scale sequencing of {cDNAs} randomly picked from libraries has proven to be a very powerful approach to discover (putatively) expressed sequences that, in turn, once mapped, may greatly expedite the process involved in the identification and cloning of human disease genes. However, the integrity of the data and the pace at which novel sequences can be identified depends to a great extent on the {cDNA} libraries that are used. Because altogether, in a typical cell, the {mRNAs} of the prevalent and intermediate frequency classes comprise as much as 50-65\% of the total {mRNA} mass, but represent no more than 1000-2000 different {mRNAs}, redundant identification of {mRNAs} of these two frequency classes is destined to become overwhelming relatively early in any such random gene discovery programs, thus seriously compromising their cost-effectiveness. With the goal of facilitating such efforts, previously we developed a method to construct directionally cloned normalized {cDNA} libraries and applied it to generate infant brain ({INIB}) and fetal liver/spleen ({INFLS}) libraries, from which a total of 45,192 and 86,088 expressed sequence tags, respectively, have been derived. While improving the representation of the longest {cDNAs} in our libraries, we developed three additional methods to normalize {cDNA} libraries and generated over 35 libraries, most of which have been contributed to our integrated Molecular Analysis of Genomes and Their Expression ({IMAGE}) Consortium and thus distributed widely and used for sequencing and mapping. In an attempt to facilitate the process of gene discovery further, we have also developed a subtractive hybridization approach designed specifically to eliminate (or reduce significantly the representation of) large pools of arrayed and (mostly) sequenced clones from normalized libraries yet to be (or just partly) surveyed. Here we present a detailed description and a comparative analysis of four methods that we developed and used to generate normalize {cDNA} libraries from human (15), mouse (3), rat (2), as well as the parasite Schistosoma mansoni (1). In addition, we describe the construction and preliminary characterization of a subtracted liver/spleen library ({INFLS}-{SI}) that resulted from the elimination (or reduction of representation) of -5000 {INFLS}-{IMAGE} clones from the {INFLS} library.},
	pages = {791--806},
	number = {9},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Bonaldo, M. F. and Lennon, G. and Soares, M. B.},
	date = {1996-09},
	pmid = {8889548},
	keywords = {Animals, Base Sequence, Humans, Mice, Adult, {DNA} Primers, Female, Gene Library, Genetic Techniques, Molecular Sequence Data, Plasmids, Polymerase Chain Reaction, Rats, {RNA}, Messenger, Cloning, Molecular, {DNA}, Complementary, Multiple Sclerosis, Schistosoma mansoni},
	file = {Full Text:/home/jlagarde/Zotero/storage/WKUXQ48C/Bonaldo et al. - 1996 - Normalization and subtraction two approaches to f.pdf:application/pdf;Normalization and subtraction\: two approaches to facilitate gene discovery:/home/jlagarde/Zotero/storage/67P3PQZ2/bonaldo1996.pdf:application/pdf}
}

@article{wei_using_2006,
	title = {Using {ESTs} to improve the accuracy of de novo gene prediction},
	volume = {7},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-7-327},
	abstract = {{BACKGROUND}: {ESTs} are a tremendous resource for determining the exon-intron structures of genes, but even extensive {EST} sequencing tends to leave many exons and genes untouched. Gene prediction systems based exclusively on {EST} alignments miss these exons and genes, leading to poor sensitivity. De novo gene prediction systems, which ignore {ESTs} in favor of genomic sequence, can predict such "untouched" exons, but they are less accurate when predicting exons to which {ESTs} align. {TWINSCAN} is the most accurate de novo gene finder available for nematodes and N-{SCAN} is the most accurate for mammals, as measured by exact {CDS} gene prediction and exact exon prediction.
{RESULTS}: {TWINSCAN}\_EST is a new system that successfully combines {EST} alignments with {TWINSCAN}. On the whole C. elegans genome {TWINSCAN}\_EST shows 14\% improvement in sensitivity and 13\% in specificity in predicting exact gene structures compared to {TWINSCAN} without {EST} alignments. Not only are the structures revealed by {EST} alignments predicted correctly, but these also constrain the predictions without alignments, improving their accuracy. For the human genome, we used the same approach with N-{SCAN}, creating N-{SCAN}\_EST. On the whole genome, N-{SCAN}\_EST produced a 6\% improvement in sensitivity and 1\% in specificity of exact gene structure predictions compared to N-{SCAN}.
{CONCLUSION}: {TWINSCAN}\_EST and N-{SCAN}\_EST are more accurate than {TWINSCAN} and N-{SCAN}, while retaining their ability to discover novel genes to which no {ESTs} align. Thus, we recommend using the {EST} versions of these programs to annotate any genome for which {EST} information is available.{TWINSCAN}\_EST and N-{SCAN}\_EST are part of the {TWINSCAN} open source software package http://genes.cse.wustl.edu/distribution/download\_TS.html.},
	pages = {327},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Wei, Chaochun and Brent, Michael R.},
	date = {2006-07-03},
	pmid = {16817966},
	pmcid = {PMC1534067},
	keywords = {Genomics, Animals, Humans, Computational Biology, Exons, Reproducibility of Results, Algorithms, Caenorhabditis elegans, Software, Expressed Sequence Tags, Sensitivity and Specificity, Models, Genetic, Genome, Human, {DNA}, Complementary, Programming Languages},
	file = {Full Text:/home/jlagarde/Zotero/storage/6SSM22EK/Wei and Brent - 2006 - Using ESTs to improve the accuracy of de novo gene.pdf:application/pdf}
}

@article{guigo_comparison_2003,
	title = {Comparison of mouse and human genomes followed by experimental verification yields an estimated 1,019 additional genes},
	volume = {100},
	issn = {0027-8424},
	doi = {10.1073/pnas.0337561100},
	abstract = {A primary motivation for sequencing the mouse genome was to accelerate the discovery of mammalian genes by using sequence conservation between mouse and human to identify coding exons. Achieving this goal proved challenging because of the large proportion of the mouse and human genomes that is apparently conserved but apparently does not code for protein. We developed a two-stage procedure that exploits the mouse and human genome sequences to produce a set of genes with a much higher rate of experimental verification than previously reported prediction methods. {RT}-{PCR} amplification and direct sequencing applied to an initial sample of mouse predictions that do not overlap previously known genes verified the regions flanking one intron in 139 predictions, with verification rates reaching 76\%. On average, the confirmed predictions show more restricted expression patterns than the mouse orthologs of known human genes, and two-thirds lack homologs in fish genomes, demonstrating the sensitivity of this dual-genome approach to hard-to-find genes. We verified 112 previously unknown homologs of known proteins, including two homeobox proteins relevant to developmental biology, an aquaporin, and a homolog of dystrophin. We estimate that transcription and splicing can be verified for {\textgreater}1,000 gene predictions identified by this method that do not overlap known genes. This is likely to constitute a significant fraction of the previously unknown, multiexon mammalian genes.},
	pages = {1140--1145},
	number = {3},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Guigo, Roderic and Dermitzakis, Emmanouil T. and Agarwal, Pankaj and Ponting, Chris P. and Parra, Genis and Reymond, Alexandre and Abril, Josep F. and Keibler, Evan and Lyle, Robert and Ucla, Catherine and Antonarakis, Stylianos E. and Brent, Michael R.},
	date = {2003-02-04},
	pmid = {12552088},
	pmcid = {PMC298740},
	keywords = {Animals, Genome, Humans, Mice, Exons, Introns, Amino Acid Sequence, Genetic Techniques, Molecular Sequence Data, Reverse Transcriptase Polymerase Chain Reaction, Tissue Distribution, Sequence Analysis, {DNA}, Genome, Human, Sequence Homology, Amino Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/D5TJL5MP/Guigo et al. - 2003 - Comparison of mouse and human genomes followed by .pdf:application/pdf}
}

@article{gerhard_status_2004,
	title = {The status, quality, and expansion of the {NIH} full-length {cDNA} project: the Mammalian Gene Collection ({MGC})},
	volume = {14},
	issn = {1088-9051},
	doi = {10.1101/gr.2596504},
	shorttitle = {The status, quality, and expansion of the {NIH} full-length {cDNA} project},
	abstract = {The National Institutes of Health's Mammalian Gene Collection ({MGC}) project was designed to generate and sequence a publicly accessible {cDNA} resource containing a complete open reading frame ({ORF}) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of {cDNA} libraries from diverse tissues. Candidate clones were chosen based on 5'-{EST} sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in {MGC} by at least one clone with a full {ORF}. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the {MGC} clones to reference genome sequences reveals that most {cDNA} clones are of very high sequence quality, although it is likely that some {cDNAs} may carry missense variants as a consequence of experimental artifact, such as {PCR}, cloning, or reverse transcriptase errors. Recently, a rat {cDNA} component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) {cDNA} projects were expanded to take advantage of the high-throughput {MGC} pipeline.},
	pages = {2121--2127},
	number = {10},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Gerhard, Daniela S. and Wagner, Lukas and Feingold, Elise A. and Shenmen, Carolyn M. and Grouse, Lynette H. and Schuler, Greg and Klein, Steven L. and Old, Susan and Rasooly, Rebekah and Good, Peter and Guyer, Mark and Peck, Allison M. and Derge, Jeffery G. and Lipman, David and Collins, Francis S. and Jang, Wonhee and Sherry, Steven and Feolo, Mike and Misquitta, Leonie and Lee, Eduardo and Rotmistrovsky, Kirill and Greenhut, Susan F. and Schaefer, Carl F. and Buetow, Kenneth and Bonner, Tom I. and Haussler, David and Kent, Jim and Kiekhaus, Mark and Furey, Terry and Brent, Michael and Prange, Christa and Schreiber, Kirsten and Shapiro, Nicole and Bhat, Narayan K. and Hopkins, Ralph F. and Hsie, Florence and Driscoll, Tom and Soares, M. Bento and Casavant, Tom L. and Scheetz, Todd E. and Brown-stein, Michael J. and Usdin, Ted B. and Toshiyuki, Shiraki and Carninci, Piero and Piao, Yulan and Dudekula, Dawood B. and Ko, Minoru S. H. and Kawakami, Koichi and Suzuki, Yutaka and Sugano, Sumio and Gruber, C. E. and Smith, M. R. and Simmons, Blake and Moore, Troy and Waterman, Richard and Johnson, Stephen L. and Ruan, Yijun and Wei, Chia Lin and Mathavan, S. and Gunaratne, Preethi H. and Wu, Jiaqian and Garcia, Angela M. and Hulyk, Stephen W. and Fuh, Edwin and Yuan, Ye and Sneed, Anna and Kowis, Carla and Hodgson, Anne and Muzny, Donna M. and McPherson, John and Gibbs, Richard A. and Fahey, Jessica and Helton, Erin and Ketteman, Mark and Madan, Anuradha and Rodrigues, Stephanie and Sanchez, Amy and Whiting, Michelle and Madari, Anup and Young, Alice C. and Wetherby, Keith D. and Granite, Steven J. and Kwong, Peggy N. and Brinkley, Charles P. and Pearson, Russell L. and Bouffard, Gerard G. and Blakesly, Robert W. and Green, Eric D. and Dickson, Mark C. and Rodriguez, Alex C. and Grimwood, Jane and Schmutz, Jeremy and Myers, Richard M. and Butterfield, Yaron S. N. and Griffith, Malachi and Griffith, Obi L. and Krzywinski, Martin I. and Liao, Nancy and Morin, Ryan and Morrin, Ryan and Palmquist, Diana and Petrescu, Anca S. and Skalska, Ursula and Smailus, Duane E. and Stott, Jeff M. and Schnerch, Angelique and Schein, Jacqueline E. and Jones, Steven J. M. and Holt, Robert A. and Baross, Agnes and Marra, Marco A. and Clifton, Sandra and Makowski, Kathryn A. and Bosak, Stephanie and Malek, Joel and {MGC Project Team}},
	date = {2004-10},
	pmid = {15489334},
	pmcid = {PMC528928},
	keywords = {Animals, Humans, Mice, Computational Biology, Open Reading Frames, {DNA} Primers, Gene Library, Rats, Xenopus laevis, Zebrafish, United States, Cloning, Molecular, {DNA}, Complementary, National Institutes of Health (U.S.)},
	file = {Full Text:/home/jlagarde/Zotero/storage/X45UPNHT/Gerhard et al. - 2004 - The status, quality, and expansion of the NIH full.pdf:application/pdf}
}

@article{ota_complete_2004,
	title = {Complete sequencing and characterization of 21,243 full-length human {cDNAs}},
	volume = {36},
	issn = {1061-4036},
	doi = {10.1038/ng1285},
	abstract = {As a base for human transcriptome and functional genomics, we created the "full-length long Japan" ({FLJ}) collection of sequenced human {cDNAs}. We determined the entire sequence of 21,243 selected clones and found that 14,490 {cDNAs} (10,897 clusters) were unique to the {FLJ} collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of {GC} content of nonpredicted {cDNAs} had a peak at approximately 58\% compared with a peak at approximately 42\%for predicted {cDNAs}. Thus, there seems to be a slight bias against {GC}-rich transcripts in current gene prediction procedures. The rest of the {cDNAs} unique to the {FLJ} collection (5,481) contained no obvious open reading frames ({ORFs}) and thus are candidate noncoding {RNAs}. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of {GC} content of noncoding {cDNAs} was narrow and had a peak at approximately 42\%, relatively low compared with that of protein-coding {cDNAs}.},
	pages = {40--45},
	number = {1},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Ota, Toshio and Suzuki, Yutaka and Nishikawa, Tetsuo and Otsuki, Tetsuji and Sugiyama, Tomoyasu and Irie, Ryotaro and Wakamatsu, Ai and Hayashi, Koji and Sato, Hiroyuki and Nagai, Keiichi and Kimura, Kouichi and Makita, Hiroshi and Sekine, Mitsuo and Obayashi, Masaya and Nishi, Tatsunari and Shibahara, Toshikazu and Tanaka, Toshihiro and Ishii, Shizuko and Yamamoto, Jun-ichi and Saito, Kaoru and Kawai, Yuri and Isono, Yuko and Nakamura, Yoshitaka and Nagahari, Kenji and Murakami, Katsuhiko and Yasuda, Tomohiro and Iwayanagi, Takao and Wagatsuma, Masako and Shiratori, Akiko and Sudo, Hiroaki and Hosoiri, Takehiko and Kaku, Yoshiko and Kodaira, Hiroyo and Kondo, Hiroshi and Sugawara, Masanori and Takahashi, Makiko and Kanda, Katsuhiro and Yokoi, Takahide and Furuya, Takako and Kikkawa, Emiko and Omura, Yuhi and Abe, Kumi and Kamihara, Kumiko and Katsuta, Naoko and Sato, Kazuomi and Tanikawa, Machiko and Yamazaki, Makoto and Ninomiya, Ken and Ishibashi, Tadashi and Yamashita, Hiromichi and Murakawa, Katsuji and Fujimori, Kiyoshi and Tanai, Hiroyuki and Kimata, Manabu and Watanabe, Motoji and Hiraoka, Susumu and Chiba, Yoshiyuki and Ishida, Shinichi and Ono, Yukio and Takiguchi, Sumiyo and Watanabe, Susumu and Yosida, Makoto and Hotuta, Tomoko and Kusano, Junko and Kanehori, Keiichi and Takahashi-Fujii, Asako and Hara, Hiroto and Tanase, Tomo-o and Nomura, Yoshiko and Togiya, Sakae and Komai, Fukuyo and Hara, Reiko and Takeuchi, Kazuha and Arita, Miho and Imose, Nobuyuki and Musashino, Kaoru and Yuuki, Hisatsugu and Oshima, Atsushi and Sasaki, Naokazu and Aotsuka, Satoshi and Yoshikawa, Yoko and Matsunawa, Hiroshi and Ichihara, Tatsuo and Shiohata, Namiko and Sano, Sanae and Moriya, Shogo and Momiyama, Hiroko and Satoh, Noriko and Takami, Sachiko and Terashima, Yuko and Suzuki, Osamu and Nakagawa, Satoshi and Senoh, Akihiro and Mizoguchi, Hiroshi and Goto, Yoshihiro and Shimizu, Fumio and Wakebe, Hirokazu and Hishigaki, Haretsugu and Watanabe, Takeshi and Sugiyama, Akio and Takemoto, Makoto and Kawakami, Bunsei and Yamazaki, Masaaki and Watanabe, Koji and Kumagai, Ayako and Itakura, Shoko and Fukuzumi, Yasuhito and Fujimori, Yoshifumi and Komiyama, Megumi and Tashiro, Hiroyuki and Tanigami, Akira and Fujiwara, Tsutomu and Ono, Toshihide and Yamada, Katsue and Fujii, Yuka and Ozaki, Kouichi and Hirao, Maasa and Ohmori, Yoshihiro and Kawabata, Ayako and Hikiji, Takeshi and Kobatake, Naoko and Inagaki, Hiromi and Ikema, Yasuko and Okamoto, Sachiko and Okitani, Rie and Kawakami, Takuma and Noguchi, Saori and Itoh, Tomoko and Shigeta, Keiko and Senba, Tadashi and Matsumura, Kyoka and Nakajima, Yoshie and Mizuno, Takae and Morinaga, Misato and Sasaki, Masahide and Togashi, Takushi and Oyama, Masaaki and Hata, Hiroko and Watanabe, Manabu and Komatsu, Takami and Mizushima-Sugano, Junko and Satoh, Tadashi and Shirai, Yuko and Takahashi, Yukiko and Nakagawa, Kiyomi and Okumura, Koji and Nagase, Takahiro and Nomura, Nobuo and Kikuchi, Hisashi and Masuho, Yasuhiko and Yamashita, Riu and Nakai, Kenta and Yada, Tetsushi and Nakamura, Yusuke and Ohara, Osamu and Isogai, Takao and Sugano, Sumio},
	date = {2004-01},
	pmid = {14702039},
	keywords = {Humans, Computational Biology, Open Reading Frames, {RNA}, Messenger, Sequence Analysis, {DNA}, {DNA}, Complementary, Chromosomes, Human, 21-22 and Y, Chromosomes, Human, Pair 20},
	file = {Full Text:/home/jlagarde/Zotero/storage/8KFMZT39/Ota et al. - 2004 - Complete sequencing and characterization of 21,243.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/DEP66IIR/Ota et al. - 2004 - Complete sequencing and characterization of 21,243.pdf:application/pdf}
}

@article{oleary_reference_2016,
	title = {Reference sequence ({RefSeq}) database at {NCBI}: current status, taxonomic expansion, and functional annotation},
	volume = {44},
	issn = {1362-4962},
	doi = {10.1093/nar/gkv1189},
	shorttitle = {Reference sequence ({RefSeq}) database at {NCBI}},
	abstract = {The {RefSeq} project at the National Center for Biotechnology Information ({NCBI}) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The {RefSeq} project leverages the data submitted to the International Nucleotide Sequence Database Collaboration ({INSDC}) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The {RefSeq} project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55,000 organisms ({\textgreater}4800 viruses, {\textgreater}40,000 prokaryotes and {\textgreater}10,000 eukaryotes; {RefSeq} release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the {RefSeq} project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of {RefSeq} data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available {RNA}-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.},
	pages = {D733--745},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res.},
	author = {O'Leary, Nuala A. and Wright, Mathew W. and Brister, J. Rodney and Ciufo, Stacy and Haddad, Diana and {McVeigh}, Rich and Rajput, Bhanu and Robbertse, Barbara and Smith-White, Brian and Ako-Adjei, Danso and Astashyn, Alexander and Badretdin, Azat and Bao, Yiming and Blinkova, Olga and Brover, Vyacheslav and Chetvernin, Vyacheslav and Choi, Jinna and Cox, Eric and Ermolaeva, Olga and Farrell, Catherine M. and Goldfarb, Tamara and Gupta, Tripti and Haft, Daniel and Hatcher, Eneida and Hlavina, Wratko and Joardar, Vinita S. and Kodali, Vamsi K. and Li, Wenjun and Maglott, Donna and Masterson, Patrick and {McGarvey}, Kelly M. and Murphy, Michael R. and O'Neill, Kathleen and Pujar, Shashikant and Rangwala, Sanjida H. and Rausch, Daniel and Riddick, Lillian D. and Schoch, Conrad and Shkeda, Andrei and Storz, Susan S. and Sun, Hanzhen and Thibaud-Nissen, Francoise and Tolstoy, Igor and Tully, Raymond E. and Vatsan, Anjana R. and Wallin, Craig and Webb, David and Wu, Wendy and Landrum, Melissa J. and Kimchi, Avi and Tatusova, Tatiana and {DiCuccio}, Michael and Kitts, Paul and Murphy, Terence D. and Pruitt, Kim D.},
	date = {2016-01-04},
	pmid = {26553804},
	pmcid = {PMC4702849},
	keywords = {Genomics, Animals, Humans, Mice, Gene Expression Profiling, Cattle, Molecular Sequence Annotation, Phylogeny, Rats, Reference Standards, Vertebrates, Databases, Genetic, {RNA}, Long Noncoding, Sequence Analysis, {RNA}, Genome, Human, Genome, Fungal, Genome, Microbial, Genome, Plant, Genome, Viral, Invertebrates, Nematoda, Sequence Analysis, Protein},
	file = {Full Text:/home/jlagarde/Zotero/storage/SGZKGH85/O'Leary et al. - 2016 - Reference sequence (RefSeq) database at NCBI curr.pdf:application/pdf}
}

@article{kawai_functional_2001,
	title = {Functional annotation of a full-length mouse {cDNA} collection},
	volume = {409},
	issn = {0028-0836},
	doi = {10.1038/35055500},
	abstract = {The {RIKEN} Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary {DNAs} and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting ({FANTOM}) to annotate the first 21,076 {cDNAs} to be analysed in this project. Here we describe the first {RIKEN} clone collection, which is one of the largest described for any organism. Analysis of these {cDNAs} extends known gene families and identifies new ones.},
	pages = {685--690},
	number = {6821},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Kawai, J. and Shinagawa, A. and Shibata, K. and Yoshino, M. and Itoh, M. and Ishii, Y. and Arakawa, T. and Hara, A. and Fukunishi, Y. and Konno, H. and Adachi, J. and Fukuda, S. and Aizawa, K. and Izawa, M. and Nishi, K. and Kiyosawa, H. and Kondo, S. and Yamanaka, I. and Saito, T. and Okazaki, Y. and Gojobori, T. and Bono, H. and Kasukawa, T. and Saito, R. and Kadota, K. and Matsuda, H. and Ashburner, M. and Batalov, S. and Casavant, T. and Fleischmann, W. and Gaasterland, T. and Gissi, C. and King, B. and Kochiwa, H. and Kuehl, P. and Lewis, S. and Matsuo, Y. and Nikaido, I. and Pesole, G. and Quackenbush, J. and Schriml, L. M. and Staubli, F. and Suzuki, R. and Tomita, M. and Wagner, L. and Washio, T. and Sakai, K. and Okido, T. and Furuno, M. and Aono, H. and Baldarelli, R. and Barsh, G. and Blake, J. and Boffelli, D. and Bojunga, N. and Carninci, P. and de Bonaldo, M. F. and Brownstein, M. J. and Bult, C. and Fletcher, C. and Fujita, M. and Gariboldi, M. and Gustincich, S. and Hill, D. and Hofmann, M. and Hume, D. A. and Kamiya, M. and Lee, N. H. and Lyons, P. and Marchionni, L. and Mashima, J. and Mazzarelli, J. and Mombaerts, P. and Nordone, P. and Ring, B. and Ringwald, M. and Rodriguez, I. and Sakamoto, N. and Sasaki, H. and Sato, K. and Schönbach, C. and Seya, T. and Shibata, Y. and Storch, K. F. and Suzuki, H. and Toyo-oka, K. and Wang, K. H. and Weitz, C. and Whittaker, C. and Wilming, L. and Wynshaw-Boris, A. and Yoshida, K. and Hasegawa, Y. and Kawaji, H. and Kohtsuki, S. and Hayashizaki, Y. and {RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium}},
	date = {2001-02-08},
	pmid = {11217851},
	keywords = {Animals, Genome, Humans, Mice, Computational Biology, Chromosome Mapping, Gene Library, Protein Biosynthesis, {RNA}, Messenger, Sequence Analysis, {DNA}, Enzymes, {DNA}, Complementary, Mice, Inbred C57BL, Protein Structure, Tertiary}
}

@article{hillier_generation_1996,
	title = {Generation and analysis of 280,000 human expressed sequence tags.},
	volume = {6},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/6/9/807},
	doi = {10.1101/gr.6.9.807},
	abstract = {An international, peer-reviewed genome sciences journal featuring outstanding original research that offers novel insights into the biology of all organisms},
	pages = {807--828},
	number = {9},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Hillier, L. D. and Lennon, G. and Becker, M. and Bonaldo, M. F. and Chiapelli, B. and Chissoe, S. and Dietrich, N. and {DuBuque}, T. and Favello, A. and Gish, W. and Hawkins, M. and Hultman, M. and Kucaba, T. and Lacy, M. and Le, M. and Le, N. and Mardis, E. and Moore, B. and Morris, M. and Parsons, J. and Prange, C. and Rifkin, L. and Rohlfing, T. and Schellenberg, K. and Marra, M.},
	urldate = {2019-07-31},
	date = {1996-09-01},
	langid = {english},
	pmid = {8889549},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/662JP92J/Hillier et al. - 1996 - Generation and analysis of 280,000 human expressed.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/CLA8M6QR/807.full.html:text/html}
}

@article{altschul_gapped_1997,
	title = {Gapped {BLAST} and {PSI}-{BLAST}: a new generation of protein database search programs},
	volume = {25},
	issn = {0305-1048},
	doi = {10.1093/nar/25.17.3389},
	shorttitle = {Gapped {BLAST} and {PSI}-{BLAST}},
	abstract = {The {BLAST} programs are widely used tools for searching protein and {DNA} databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the {BLAST} programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped {BLAST} program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by {BLAST} into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated {BLAST} ({PSI}-{BLAST}) program runs at approximately the same speed per iteration as gapped {BLAST}, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. {PSI}-{BLAST} is used to uncover several new and interesting members of the {BRCT} superfamily.},
	pages = {3389--3402},
	number = {17},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res.},
	author = {Altschul, S. F. and Madden, T. L. and Schäffer, A. A. and Zhang, J. and Zhang, Z. and Miller, W. and Lipman, D. J.},
	date = {1997-09-01},
	pmid = {9254694},
	pmcid = {PMC146917},
	keywords = {{DNA}, Animals, Humans, Proteins, Algorithms, Software, Amino Acid Sequence, Molecular Sequence Data, Sequence Alignment, Databases, Factual},
	file = {Full Text:/home/jlagarde/Zotero/storage/A9A6HDN6/Altschul et al. - 1997 - Gapped BLAST and PSI-BLAST a new generation of pr.pdf:application/pdf}
}

@article{lu_hidden_nodate,
	title = {A hidden human proteome encoded by ‘non-coding’ genes},
	url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz646/5538014},
	doi = {10.1093/nar/gkz646},
	abstract = {Abstract.  It has been a long debate whether the 98\% ‘non-coding’ fraction of human genome can encode functional proteins besides short peptides. With full-leng},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Lu, Shaohua and Zhang, Jing and Lian, Xinlei and Sun, Li and Meng, Kun and Chen, Yang and Sun, Zhenghua and Yin, Xingfeng and Li, Yaxing and Zhao, Jing and Wang, Tong and Zhang, Gong and He, Qing-Yu},
	urldate = {2019-08-01},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/HBWH22ZZ/Lu et al. - A hidden human proteome encoded by ‘non-coding’ ge.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/96L388AJ/5538014.html:text/html}
}

@article{ozsolak_direct_2009,
	title = {Direct {RNA} sequencing},
	volume = {461},
	rights = {2009 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature08390},
	doi = {10.1038/nature08390},
	abstract = {Our understanding of human biology and disease is ultimately dependent on a complete understanding of the genome and its functions. The recent application of microarray and sequencing technologies to transcriptomics has changed the simplistic view of transcriptomes to a more complicated view of genome-wide transcription where a large fraction of transcripts emanates from unannotated parts of genomes1,2,3,4,5,6,7, and underlined our limited knowledge of the dynamic state of transcription. Most of this broad body of knowledge was obtained indirectly because current transcriptome analysis methods typically require {RNA} to be converted to complementary {DNA} ({cDNA}) before measurements, even though the {cDNA} synthesis step introduces multiple biases and artefacts that interfere with both the proper characterization and quantification of transcripts8,9,10,11,12,13,14,15,16,17,18. Furthermore, {cDNA} synthesis is not particularly suitable for the analysis of short, degraded and/or small quantity {RNA} samples. Here we report direct single molecule {RNA} sequencing without prior conversion of {RNA} to {cDNA}. We applied this technology to sequence femtomole quantities of poly(A)+ Saccharomyces cerevisiae {RNA} using a surface coated with poly({dT}) oligonucleotides to capture the {RNAs} at their natural poly(A) tails and initiate sequencing by synthesis. We observed transcript 3′ end heterogeneity and polyadenylated small nucleolar {RNAs}. This study provides a path to high-throughput and low-cost direct {RNA} sequencing and achieving the ultimate goal of a comprehensive and bias-free understanding of transcriptomes.},
	pages = {814--818},
	number = {7265},
	journaltitle = {Nature},
	author = {Ozsolak, Fatih and Platt, Adam R. and Jones, Dan R. and Reifenberger, Jeffrey G. and Sass, Lauryn E. and {McInerney}, Peter and Thompson, John F. and Bowers, Jayson and Jarosz, Mirna and Milos, Patrice M.},
	urldate = {2019-08-01},
	date = {2009-10},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/6HEHACYZ/nature08390.html:text/html}
}

@article{marioni_rna-seq:_2008,
	title = {{RNA}-seq: an assessment of technical reproducibility and comparison with gene expression arrays},
	volume = {18},
	issn = {1088-9051},
	doi = {10.1101/gr.079558.108},
	shorttitle = {{RNA}-seq},
	abstract = {Ultra-high-throughput sequencing is emerging as an attractive alternative to microarrays for genotyping, analysis of methylation patterns, and identification of transcription factor binding sites. Here, we describe an application of the Illumina sequencing (formerly Solexa sequencing) platform to study {mRNA} expression levels. Our goals were to estimate technical variance associated with Illumina sequencing in this context and to compare its ability to identify differentially expressed genes with existing array technologies. To do so, we estimated gene expression differences between liver and kidney {RNA} samples using multiple sequencing replicates, and compared the sequencing data to results obtained from Affymetrix arrays using the same {RNA} samples. We find that the Illumina sequencing data are highly replicable, with relatively little technical variation, and thus, for many purposes, it may suffice to sequence each {mRNA} sample only once (i.e., using one lane). The information in a single lane of Illumina sequencing data appears comparable to that in a single array in enabling identification of differentially expressed genes, while allowing for additional analyses such as detection of low-expressed genes, alternative splice variants, and novel transcripts. Based on our observations, we propose an empirical protocol and a statistical framework for the analysis of gene expression using ultra-high-throughput sequencing technology.},
	pages = {1509--1517},
	number = {9},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Marioni, John C. and Mason, Christopher E. and Mane, Shrikant M. and Stephens, Matthew and Gilad, Yoav},
	date = {2008-09},
	pmid = {18550803},
	pmcid = {PMC2527709},
	keywords = {Humans, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Reproducibility of Results, Likelihood Functions, Male, {RNA}, Messenger, Sequence Analysis, {RNA}, Models, Biological},
	file = {Full Text:/home/jlagarde/Zotero/storage/JS3BHR9Y/Marioni et al. - 2008 - RNA-seq an assessment of technical reproducibilit.pdf:application/pdf}
}

@article{morozova_applications_2009,
	title = {Applications of New Sequencing Technologies for Transcriptome Analysis},
	volume = {10},
	url = {https://doi.org/10.1146/annurev-genom-082908-145957},
	doi = {10.1146/annurev-genom-082908-145957},
	abstract = {Transcriptome analysis has been a key area of biological inquiry for decades. Over the years, research in the field has progressed from candidate gene-based detection of {RNAs} using Northern blotting to high-throughput expression profiling driven by the advent of microarrays. Next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution.},
	pages = {135--151},
	number = {1},
	journaltitle = {Annual Review of Genomics and Human Genetics},
	author = {Morozova, Olena and Hirst, Martin and Marra, Marco A.},
	urldate = {2019-08-02},
	date = {2009},
	pmid = {19715439},
	file = {Morozova et al. - 2009 - Applications of New Sequencing Technologies for Tr.pdf:/home/jlagarde/Zotero/storage/S9AE8HHB/Morozova et al. - 2009 - Applications of New Sequencing Technologies for Tr.pdf:application/pdf}
}

@article{margulies_genome_2005,
	title = {Genome sequencing in microfabricated high-density picolitre reactors},
	volume = {437},
	rights = {2005 The Author(s)},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature03959},
	doi = {10.1038/nature03959},
	abstract = {The race is on for a big prize: the job of providing the world's {DNA} sequencing laboratories with the successor to the ‘Sanger-based’ technology that gave us the first wave of genome sequences. One technology in the frame is that produced by 454 Life Sciences Corporation of Branford, Connecticut. Today's technology reads 67,000 base pairs per hour; this new approach is 100 times faster, reading 6 million base pairs per hour. The improved performance results from using picolitre-sized chemical reactors, enhanced light-emitting sequencing chemistries and complex informatics. Further miniaturization of the system is planned. Such leaps in technology may one day make it possible to analyse an individual's genome before designing therapy: the ultimate in personalized medicine.},
	pages = {376},
	number = {7057},
	journaltitle = {Nature},
	author = {Margulies, Marcel and Egholm, Michael and Altman, William E. and Attiya, Said and Bader, Joel S. and Bemben, Lisa A. and Berka, Jan and Braverman, Michael S. and Chen, Yi-Ju and Chen, Zhoutao and Dewell, Scott B. and Du, Lei and Fierro, Joseph M. and Gomes, Xavier V. and Godwin, Brian C. and He, Wen and Helgesen, Scott and Ho, Chun He and Irzyk, Gerard P. and Jando, Szilveszter C. and Alenquer, Maria L. I. and Jarvie, Thomas P. and Jirage, Kshama B. and Kim, Jong-Bum and Knight, James R. and Lanza, Janna R. and Leamon, John H. and Lefkowitz, Steven M. and Lei, Ming and Li, Jing and Lohman, Kenton L. and Lu, Hong and Makhijani, Vinod B. and {McDade}, Keith E. and {McKenna}, Michael P. and Myers, Eugene W. and Nickerson, Elizabeth and Nobile, John R. and Plant, Ramona and Puc, Bernard P. and Ronan, Michael T. and Roth, George T. and Sarkis, Gary J. and Simons, Jan Fredrik and Simpson, John W. and Srinivasan, Maithreyan and Tartaro, Karrie R. and Tomasz, Alexander and Vogt, Kari A. and Volkmer, Greg A. and Wang, Shally H. and Wang, Yong and Weiner, Michael P. and Yu, Pengguang and Begley, Richard F. and Rothberg, Jonathan M.},
	urldate = {2019-08-02},
	date = {2005-09},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/QB7TPY3Y/Margulies et al. - 2005 - Genome sequencing in microfabricated high-density .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/I36THCTH/nature03959.html:text/html}
}

@article{bennett_toward_2005,
	title = {Toward the \$1000 human genome},
	volume = {6},
	issn = {1462-2416},
	url = {https://www.futuremedicine.com/doi/abs/10.1517/14622416.6.4.373},
	doi = {10.1517/14622416.6.4.373},
	abstract = {Revolutionary new technologies, capable of transforming the economics of sequencing, are providing an unparalleled opportunity to analyze human genetic variation comprehensively at the whole-genome level within a realistic timeframe and at affordable costs. Current estimates suggest that it would cost somewhere in the region of {US}\$30 million to sequence an entire human genome using Sanger-based sequencing, and on one machine it would take about 60 years. Solexa is widely regarded as a company with the necessary disruptive technology to be the first to achieve the ultimate goal of the so-called \$1000 human genome – the conceptual cost-point needed for routine analysis of individual genomes. Solexa’s technology is based on completely novel sequencing chemistry capable of sequencing billions of individual {DNA} molecules simultaneously, a base at a time, to enable highly accurate, low cost analysis of an entire human genome in a single experiment. When applied over a large enough genomic region, these new approaches to resequencing will enable the simultaneous detection and typing of known, as well as unknown, polymorphisms, and will also offer information about patterns of linkage disequilibrium in the population being studied. Technological progress, leading to the advent of single-molecule-based approaches, is beginning to dramatically drive down costs and increase throughput to unprecedented levels, each being several orders of magnitude better than that which is currently available. A new sequencing paradigm based on single molecules will be faster, cheaper and more sensitive, and will permit routine analysis at the whole-genome level.},
	pages = {373--382},
	number = {4},
	journaltitle = {Pharmacogenomics},
	shortjournal = {Pharmacogenomics},
	author = {Bennett, Simon T and Barnes, Colin and Cox, Anthony and Davies, Lisa and Brown, Clive},
	urldate = {2019-08-02},
	date = {2005-07-01},
	file = {Snapshot:/home/jlagarde/Zotero/storage/GFMZ4ARU/14622416.6.4.html:text/html}
}

@article{garalde_highly_2018,
	title = {Highly parallel direct {RNA} sequencing on an array of nanopores},
	volume = {15},
	issn = {1548-7105},
	doi = {10.1038/nmeth.4577},
	abstract = {Sequencing the {RNA} in a biological sample can unlock a wealth of information, including the identity of bacteria and viruses, the nuances of alternative splicing or the transcriptional state of organisms. However, current methods have limitations due to short read lengths and reverse transcription or amplification biases. Here we demonstrate nanopore direct {RNA}-seq, a highly parallel, real-time, single-molecule method that circumvents reverse transcription or amplification steps. This method yields full-length, strand-specific {RNA} sequences and enables the direct detection of nucleotide analogs in {RNA}.},
	pages = {201--206},
	number = {3},
	journaltitle = {Nature Methods},
	shortjournal = {Nat. Methods},
	author = {Garalde, Daniel R. and Snell, Elizabeth A. and Jachimowicz, Daniel and Sipos, Botond and Lloyd, Joseph H. and Bruce, Mark and Pantic, Nadia and Admassu, Tigist and James, Phillip and Warland, Anthony and Jordan, Michael and Ciccone, Jonah and Serra, Sabrina and Keenan, Jemma and Martin, Samuel and {McNeill}, Luke and Wallace, E. Jayne and Jayasinghe, Lakmal and Wright, Chris and Blasco, Javier and Young, Stephen and Brocklebank, Denise and Juul, Sissel and Clarke, James and Heron, Andrew J. and Turner, Daniel J.},
	date = {2018},
	pmid = {29334379},
	keywords = {High-Throughput Nucleotide Sequencing, Saccharomyces cerevisiae, Sequence Analysis, {RNA}, {RNA}, Fungal, Nanopores, Saccharomyces cerevisiae Proteins}
}

@article{knierim_systematic_2011,
	title = {Systematic comparison of three methods for fragmentation of long-range {PCR} products for next generation sequencing},
	volume = {6},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0028240},
	abstract = {Next Generation Sequencing ({NGS}) technologies are gaining importance in the routine clinical diagnostic setting. It is thus desirable to simplify the workflow for high-throughput diagnostics. Fragmentation of {DNA} is a crucial step for preparation of template libraries and various methods are currently known. Here we evaluated the performance of nebulization, sonication and random enzymatic digestion of long-range {PCR} products on the results of {NGS}. All three methods produced high-quality sequencing libraries for the 454 platform. However, if long-range {PCR} products of different length were pooled equimolarly, sequence coverage drastically dropped for fragments below 3,000 bp. All three methods performed equally well with regard to overall sequence quality ({PHRED}) and read length. Enzymatic fragmentation showed highest consistency between three library preparations but performed slightly worse than sonication and nebulization with regard to insertions/deletions in the raw sequence reads. After filtering for homopolymer errors, enzymatic fragmentation performed best if compared to the results of classic Sanger sequencing. As the overall performance of all three methods was equal with only minor differences, a fragmentation method can be chosen solely according to lab facilities, feasibility and experimental design.},
	pages = {e28240},
	number = {11},
	journaltitle = {{PloS} One},
	shortjournal = {{PLoS} {ONE}},
	author = {Knierim, Ellen and Lucke, Barbara and Schwarz, Jana Marie and Schuelke, Markus and Seelow, Dominik},
	date = {2011},
	pmid = {22140562},
	pmcid = {PMC3227650},
	keywords = {Base Sequence, Humans, Polymerase Chain Reaction, Sequence Alignment, Sequence Deletion, Sequence Analysis, {DNA}, Mutagenesis, Insertional, Mutation, Missense},
	file = {Full Text:/home/jlagarde/Zotero/storage/Q3LL6SKC/Knierim et al. - 2011 - Systematic comparison of three methods for fragmen.pdf:application/pdf}
}

@article{ozsolak_rna_2011,
	title = {{RNA} sequencing: advances, challenges and opportunities},
	volume = {12},
	issn = {1471-0064},
	doi = {10.1038/nrg2934},
	shorttitle = {{RNA} sequencing},
	abstract = {In the few years since its initial application, massively parallel {cDNA} sequencing, or {RNA}-seq, has allowed many advances in the characterization and quantification of transcriptomes. Recently, several developments in {RNA}-seq methods have provided an even more complete characterization of {RNA} transcripts. These developments include improvements in transcription start site mapping, strand-specific measurements, gene fusion detection, small {RNA} characterization and detection of alternative splicing events. Ongoing developments promise further advances in the application of {RNA}-seq, particularly direct {RNA} sequencing and approaches that allow {RNA} quantification from very small amounts of cellular materials.},
	pages = {87--98},
	number = {2},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Ozsolak, Fatih and Milos, Patrice M.},
	date = {2011-02},
	pmid = {21191423},
	pmcid = {PMC3031867},
	keywords = {Animals, Humans, {RNA}, Alternative Splicing, Transcription, Genetic, Sequence Analysis, {RNA}},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/D94TFZYE/Ozsolak and Milos - 2011 - RNA sequencing advances, challenges and opportuni.pdf:application/pdf}
}

@article{roy_when_2008,
	title = {When good transcripts go bad: artifactual {RT}-{PCR} 'splicing' and genome analysis},
	volume = {30},
	issn = {1521-1878},
	doi = {10.1002/bies.20749},
	shorttitle = {When good transcripts go bad},
	abstract = {Gene and intron prediction are essential for accurate inferences about genome evolution. Recently, two genome-wide studies searched for recent intron gains in humans, reaching very different conclusions: either of a complete absence of intron gain since early mammalian evolution, or of creation of numerous introns by genomic duplication in repetitive regions. We discuss one possible explanation: the underappreciated phenomenon of "template switching", by which reverse transcriptase may create artifactual splicing-like events in the preparation of {cDNA}/{EST} libraries, may cause complications in searches for newly gained introns in repetitive regions. We report large numbers of apparent template switching in transcript sequences from the intron-poor protists Trichomonas vaginalis and Giardia lamblia. Supplementary material for this article can be found on the {BioEssays} website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html).},
	pages = {601--605},
	number = {6},
	journaltitle = {{BioEssays}: News and Reviews in Molecular, Cellular and Developmental Biology},
	shortjournal = {Bioessays},
	author = {Roy, Scott William and Irimia, Manuel},
	date = {2008-06},
	pmid = {18478540},
	keywords = {Genomics, Animals, Base Sequence, Humans, {RNA} Splicing, Introns, Alleles, Gene Duplication, Molecular Sequence Data, Reverse Transcriptase Polymerase Chain Reaction, {RNA}-Directed {DNA} Polymerase, Evolution, Molecular, Transcription, Genetic, Models, Genetic, Repetitive Sequences, Nucleic Acid, {DNA}, Protozoan, Giardia lamblia, Trichomonas vaginalis}
}

@article{nam_oligodt_2002,
	title = {Oligo({dT}) primer generates a high frequency of truncated {cDNAs} through internal poly(A) priming during reverse transcription},
	volume = {99},
	issn = {0027-8424},
	doi = {10.1073/pnas.092140899},
	abstract = {We have analyzed a systematic flaw in the current system of gene identification: the oligo({dT}) primer widely used for {cDNA} synthesis generates a high frequency of truncated {cDNAs} through internal poly(A) priming. Such truncated {cDNAs} may contribute to 12\% of the expressed sequence tags in the current {dbEST} database. By using a synthetic transcript and real {mRNA} templates as models, we characterized the patterns of internal poly(A) priming by oligo({dT}) primer. We further demonstrated that the internal poly(A) priming can be effectively diminished by replacing the oligo({dT}) primer with a set of anchored oligo({dT}) primers for reverse transcription. Our study indicates that {cDNAs} designed for genomewide gene identification should be synthesized by use of the anchored oligo({dT}) primers, rather than the oligo({dT}) primers, to diminish the generation of truncated {cDNAs} caused by internal poly(A) priming.},
	pages = {6152--6156},
	number = {9},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Nam, Douglas Kyung and Lee, Sanggyu and Zhou, Guolin and Cao, Xiaohong and Wang, Clarence and Clark, Terry and Chen, Jianjun and Rowley, Janet D. and Wang, San Ming},
	date = {2002-04-30},
	pmid = {11972056},
	pmcid = {PMC122918},
	keywords = {Animals, Humans, Expressed Sequence Tags, Oligodeoxyribonucleotides, Poly A, Polymerase Chain Reaction, {RNA}, Messenger, Transcription, Genetic, Sequence Analysis, {DNA}, Models, Genetic, Cloning, Molecular, {DNA}, Complementary, Databases as Topic, Dose-Response Relationship, Drug},
	file = {Full Text:/home/jlagarde/Zotero/storage/BLR7P7EQ/Nam et al. - 2002 - Oligo(dT) primer generates a high frequency of tru.pdf:application/pdf}
}

@article{alezz_unexpected_2019,
	title = {Unexpected features of {GC}-{AG} introns in long non-coding and protein-coding genes suggest a new role as regulatory elements},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/10.1101/683938v1},
	doi = {10.1101/683938},
	abstract = {{\textless}h3{\textgreater}{ABSTRACT}{\textless}/h3{\textgreater} {\textless}p{\textgreater}Long non-coding (lnc) {RNAs} are today recognized as a new class of regulatory molecules despite very little is known about their functions in the cell. Due to their overall low level of expression and tissue-specificity, their identification and annotation in many genomes remains challenging. In this study, we exploited recent annotations provided by the {GENCODE} project to characterize the genomic and splicing features of lnc-genes in comparison to protein-coding (pc) ones, both in human and mouse. Our analysis highlighted slight differences between the two classes of genes in terms of genome organization and gene architecture. Significant differences in the splice sites usage were observed between lnc- and pc-genes. While the frequency of non-canonical {GC}-{AG} splice junctions represents about 0.8\% of total splice sites in pc-genes, we identified a remarkable enrichment of the {GC}-{AG} splice sites in lnc-genes, both in human (3.0\%) and mouse (1.9\%). In addition, we found a positional bias of {GC}-{AG} splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker splice sites were found comparing {GC}-{AG} introns with the canonical {GT}-{AG} introns. The computational analysis of {GC}-{AG} splice sites strength revealed a strong reduction in both the donor and the acceptor splice sites scores especially in lnc first intron in both species. Genes containing at least one {GC}-{AG} intron were found conserved in many species and a functional enrichment analysis pointed toward their enrichment in specific biological processes. Furthermore, as previously suggested, {GC}-{AG}-containing genes were shown to be more prone to alternative splicing. Taken together, our study suggested that {GC}-{AG} introns could represent new regulatory elements mainly associated with lnc-genes.{\textless}/p{\textgreater}},
	pages = {683938},
	journaltitle = {{bioRxiv}},
	author = {Alezz, Monah Abou and Celli, Ludovica and Belotti, Giulia and Lisa, Antonella and Bione, Silvia},
	urldate = {2019-08-03},
	date = {2019-06-27},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/XLCP8NXG/Alezz et al. - 2019 - Unexpected features of GC-AG introns in long non-c.pdf:application/pdf}
}

@article{goodwin_coming_2016,
	title = {Coming of age: ten years of next-generation sequencing technologies},
	volume = {17},
	issn = {1471-0064},
	doi = {10.1038/nrg.2016.49},
	shorttitle = {Coming of age},
	abstract = {Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of {DNA}, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.},
	pages = {333--351},
	number = {6},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Goodwin, Sara and {McPherson}, John D. and {McCombie}, W. Richard},
	date = {2016},
	pmid = {27184599},
	keywords = {Genomics, Humans, Genetic Variation, High-Throughput Nucleotide Sequencing, Phenotype, Genome, Human},
	file = {Goodwin et al. - 2016 - Coming of age ten years of next-generation sequen.pdf:/home/jlagarde/Zotero/storage/6RXX9UYQ/Goodwin et al. - 2016 - Coming of age ten years of next-generation sequen.pdf:application/pdf}
}

@article{smith_reading_2019,
	title = {Reading canonical and modified nucleobases in 16S ribosomal {RNA} using nanopore native {RNA} sequencing},
	volume = {14},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0216709},
	abstract = {The ribosome small subunit is expressed in all living cells. It performs numerous essential functions during translation, including formation of the initiation complex and proofreading of base-pairs between {mRNA} codons and {tRNA} anticodons. The core constituent of the small ribosomal subunit is a {\textasciitilde}1.5 kb {RNA} strand in prokaryotes (16S {rRNA}) and a homologous {\textasciitilde}1.8 kb {RNA} strand in eukaryotes (18S {rRNA}). Traditional sequencing-by-synthesis ({SBS}) of {rRNA} genes or {rRNA} {cDNA} copies has achieved wide use as a 'molecular chronometer' for phylogenetic studies, and as a tool for identifying infectious organisms in the clinic. However, epigenetic modifications on {rRNA} are erased by {SBS} methods. Here we describe direct {MinION} nanopore sequencing of individual, full-length 16S {rRNA} absent reverse transcription or amplification. As little as 5 picograms ({\textasciitilde}10 attomole) of purified E. coli 16S {rRNA} was detected in 4.5 micrograms of total human {RNA}. Nanopore ionic current traces that deviated from canonical patterns revealed conserved E. coli 16S {rRNA} 7-methylguanosine and pseudouridine modifications, and a 7-methylguanosine modification that confers aminoglycoside resistance to some pathological E. coli strains.},
	pages = {e0216709},
	number = {5},
	journaltitle = {{PloS} One},
	shortjournal = {{PLoS} {ONE}},
	author = {Smith, Andrew M. and Jain, Miten and Mulroney, Logan and Garalde, Daniel R. and Akeson, Mark},
	date = {2019},
	pmid = {31095620},
	pmcid = {PMC6522004},
	file = {Full Text:/home/jlagarde/Zotero/storage/IEMLYS52/Smith et al. - 2019 - Reading canonical and modified nucleobases in 16S .pdf:application/pdf}
}

@article{liu_accurate_2019,
	title = {Accurate detection of m6A {RNA} modifications in native {RNA} sequences},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-{NonCommercial}-{NoDerivs} 4.0 International), {CC} {BY}-{NC}-{ND} 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/525741v1},
	doi = {10.1101/525741},
	abstract = {{\textless}h3{\textgreater}{ABSTRACT}{\textless}/h3{\textgreater} {\textless}p{\textgreater}The field of epitranscriptomics has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map {RNA} modifications transcriptome-wide. Here we show that using Oxford Nanopore Technologies, N6-methyladenosine (m6A) {RNA} modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Our results open new avenues to investigate the universe of {RNA} modifications with single nucleotide resolution, in individual {RNA} molecules.{\textless}/p{\textgreater}},
	pages = {525741},
	journaltitle = {{bioRxiv}},
	author = {Liu, Huanle and Begik, Oguzhan and Lucas, Morghan C. and Mason, Christopher E. and Schwartz, Schraga and Mattick, John S. and Smith, Martin A. and Novoa, Eva Maria},
	urldate = {2019-08-03},
	date = {2019-01-21},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/Q786PQL8/Liu et al. - 2019 - Accurate detection of m6A RNA modifications in nat.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/K2SPD8DK/525741v1.html:text/html}
}

@article{tilgner_microfluidic_2018,
	title = {Microfluidic isoform sequencing shows widespread splicing coordination in the human transcriptome},
	volume = {28},
	issn = {1549-5469},
	doi = {10.1101/gr.230516.117},
	abstract = {Understanding transcriptome complexity is crucial for understanding human biology and disease. Technologies such as Synthetic long-read {RNA} sequencing ({SLR}-{RNA}-seq) delivered 5 million isoforms and allowed assessing splicing coordination. Pacific Biosciences and Oxford Nanopore increase throughput also but require high input amounts or amplification. Our new droplet-based method, sparse isoform sequencing ({spISO}-seq), sequences 100k-200k partitions of 10-200 molecules at a time, enabling analysis of 10-100 million {RNA} molecules. {SpISO}-seq requires less than 1 ng of input {cDNA}, limiting or removing the need for prior amplification with its associated biases. Adjusting the number of reads devoted to each molecule reduces sequencing lanes and cost, with little loss in detection power. The increased number of molecules expands our understanding of isoform complexity. In addition to confirming our previously published cases of splicing coordination (e.g., {BIN}1), the greater depth reveals many new cases, such as {MAPT} Coordination of internal exons is found to be extensive among protein coding genes: 23.5\%-59.3\% (95\% confidence interval) of highly expressed genes with distant alternative exons exhibit coordination, showcasing the need for long-read transcriptomics. However, coordination is less frequent for noncoding sequences, suggesting a larger role of splicing coordination in shaping proteins. Groups of genes with coordination are involved in protein-protein interactions with each other, raising the possibility that coordination facilitates complex formation and/or function. We also find new splicing coordination types, involving initial and terminal exons. Our results provide a more comprehensive understanding of the human transcriptome and a general, cost-effective method to analyze it.},
	pages = {231--242},
	number = {2},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Tilgner, Hagen and Jahanbani, Fereshteh and Gupta, Ishaan and Collier, Paul and Wei, Eric and Rasmussen, Morten and Snyder, Michael},
	date = {2018},
	pmid = {29196558},
	pmcid = {PMC5793787},
	keywords = {Transcriptome, Humans, {RNA} Splicing, Gene Expression Regulation, Computational Biology, Alternative Splicing, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Protein Isoforms, Sequence Analysis, {RNA}, Microfluidics},
	file = {Full Text:/home/jlagarde/Zotero/storage/IICHN9WQ/Tilgner et al. - 2018 - Microfluidic isoform sequencing shows widespread s.pdf:application/pdf}
}

@article{dijk_third_2018,
	title = {The Third Revolution in Sequencing Technology},
	volume = {34},
	issn = {0168-9525},
	url = {https://www.cell.com/trends/genetics/abstract/S0168-9525(18)30096-9},
	doi = {10.1016/j.tig.2018.05.008},
	pages = {666--681},
	number = {9},
	journaltitle = {Trends in Genetics},
	shortjournal = {Trends in Genetics},
	author = {Dijk, Erwin L. van and Jaszczyszyn, Yan and Naquin, Delphine and Thermes, Claude},
	urldate = {2019-08-04},
	date = {2018-09-01},
	pmid = {29941292},
	keywords = {long-read sequencing, nanopore sequencing, next-generation sequencing, single-molecule real-time sequencing, synthetic long-read sequencing, third-generation sequencing},
	file = {Snapshot:/home/jlagarde/Zotero/storage/C9CUYXUU/S0168-9525(18)30096-9.html:text/html}
}

@article{sharon_single-molecule_2013,
	title = {A single-molecule long-read survey of the human transcriptome},
	volume = {31},
	issn = {1087-0156},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075632/},
	doi = {10.1038/nbt.2705},
	abstract = {Global {RNA} studies have become central to understanding biological
processes, but methods such as microarrays and short-read sequencing are unable
to describe an entire {RNA} molecule from 5′ to 3′ end. Here we
use single-molecule long-read sequencing technology from Pacific Biosciences to
sequence the polyadenylated {RNA} complement of a pooled set of 20 human organs
and tissues without the need for fragmentation or amplification. We show that
full-length {RNA} molecules of up to 1.5 kb can readily be monitored with little
sequence loss at the 5′ ends. For longer {RNA} molecules more 5′
nucleotides are missing, but complete intron structures are often preserved. In
total, we identify {\textasciitilde}14,000 spliced {GENCODE} genes. High-confidence
mappings are consistent with {GENCODE} annotations, but {\textgreater}10\% of
the alignments represent intron structures that were not previously annotated.
As a group, transcripts mapping to unannotated regions have features of long,
noncoding {RNAs}. Our results show the feasibility of deep sequencing full-length
{RNA} from complex eukaryotic transcriptomes on a single-molecule level.},
	pages = {1009--1014},
	number = {11},
	journaltitle = {Nature biotechnology},
	shortjournal = {Nat Biotechnol},
	author = {Sharon, Donald and Tilgner, Hagen and Grubert, Fabian and Snyder, Michael},
	urldate = {2019-08-05},
	date = {2013-11},
	pmid = {24108091},
	pmcid = {PMC4075632},
	file = {A single-molecule long-read survey of the human transcriptome:/home/jlagarde/Zotero/storage/9P9TYPVE/sharon2013.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/Z7RIGD7L/Sharon et al. - 2013 - A single-molecule long-read survey of the human tr.pdf:application/pdf}
}

@article{clarke_continuous_2009,
	title = {Continuous base identification for single-molecule nanopore {DNA} sequencing},
	volume = {4},
	issn = {1748-3395},
	doi = {10.1038/nnano.2009.12},
	abstract = {A single-molecule method for sequencing {DNA} that does not require fluorescent labelling could reduce costs and increase sequencing speeds. An exonuclease enzyme might be used to cleave individual nucleotide molecules from the {DNA}, and when coupled to an appropriate detection system, these nucleotides could be identified in the correct order. Here, we show that a protein nanopore with a covalently attached adapter molecule can continuously identify unlabelled nucleoside 5'-monophosphate molecules with accuracies averaging 99.8\%. Methylated cytosine can also be distinguished from the four standard {DNA} bases: guanine, adenine, thymine and cytosine. The operating conditions are compatible with the exonuclease, and the kinetic data show that the nucleotides have a high probability of translocation through the nanopore and, therefore, of not being registered twice. This highly accurate tool is suitable for integration into a system for sequencing nucleic acids and for analysing epigenetic modifications.},
	pages = {265--270},
	number = {4},
	journaltitle = {Nature Nanotechnology},
	shortjournal = {Nat Nanotechnol},
	author = {Clarke, James and Wu, Hai-Chen and Jayasinghe, Lakmal and Patel, Alpesh and Reid, Stuart and Bayley, Hagan},
	date = {2009-04},
	pmid = {19350039},
	keywords = {{DNA}, Base Sequence, Macromolecular Substances, Molecular Conformation, Molecular Sequence Data, Particle Size, Porosity, Sequence Analysis, {DNA}, Crystallization, Materials Testing, Nanostructures, Nanotechnology, Surface Properties}
}

@article{payne_whale_2018,
	title = {Whale watching with {BulkVis}: A graphical viewer for Oxford Nanopore bulk fast5 files},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/312256v1},
	doi = {10.1101/312256},
	shorttitle = {Whale watching with {BulkVis}},
	abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}h3{\textgreater}Motivation{\textless}/h3{\textgreater} {\textless}p{\textgreater}The Oxford Nanopore Technologies ({ONT}) {MinION} is used for sequencing a wide variety of sample types with diverse methods of sample extraction. Nanopore sequencers output fast5 files containing signal data subsequently base called to fastq format. Optionally, {ONT} devices can collect data from all sequencing channels simultaneously in a bulk fast5 file enabling inspection of signal in any channel at any point. We sought to visualise this signal to inspect challenging or difficult to sequence samples, or where flow cell performance is modified by an external agent, such as ‘Read Until’.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Results{\textless}/h3{\textgreater} {\textless}p{\textgreater}The {BulkVis} tool can load a bulk fast5 file and overlays {MinKNOW} classifications on the signal trace. Users can navigate to a channel and time or, given a fastq header from a read, jump to its specific position. {BulkVis} can export regions as Nanopore base caller compatible reads. Using {BulkVis}, we find long reads can be incorrectly divided by {MinKNOW} resulting in single {DNA} molecules being split into two or more reads. The longest seen to date is 2,272,580 bases in length and reported in eleven consecutive reads. We provide helper scripts that identify and reconstruct split reads given a sequencing summary file and alignment to a reference. We note that incorrect read splitting appears to vary according to input sample type and is more common in ‘ultra long’ read preparations.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Availability{\textless}/h3{\textgreater} {\textless}p{\textgreater}The software is available freely under an {MIT} license at https://github.com/{LooseLab}/{bulkVis}. The software requires python3 to run.{\textless}/p{\textgreater}},
	pages = {312256},
	journaltitle = {{bioRxiv}},
	author = {Payne, Alexander and Holmes, Nadine and Rakyan, Vardhman and Loose, Matthew},
	urldate = {2019-08-05},
	date = {2018-05-03},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/4ELAG6QG/Payne et al. - 2018 - Whale watching with BulkVis A graphical viewer fo.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/NVNUN47J/312256v1.html:text/html}
}

@article{malone_microarrays_2011,
	title = {Microarrays, deep sequencing and the true measure of the transcriptome},
	volume = {9},
	issn = {1741-7007},
	doi = {10.1186/1741-7007-9-34},
	abstract = {Microarrays first made the analysis of the transcriptome possible, and have produced much important information. Today, however, researchers are increasingly turning to direct high-throughput sequencing -- {RNA}-Seq -- which has considerable advantages for examining transcriptome fine structure -- for example in the detection of allele-specific expression and splice junctions. In this article, we discuss the relative merits of the two techniques, the inherent biases in each, and whether all of the vast body of array work needs to be revisited using the newer technology. We conclude that microarrays remain useful and accurate tools for measuring expression levels, and {RNA}-Seq complements and extends microarray measurements.},
	pages = {34},
	journaltitle = {{BMC} biology},
	shortjournal = {{BMC} Biol.},
	author = {Malone, John H. and Oliver, Brian},
	date = {2011-05-31},
	pmid = {21627854},
	pmcid = {PMC3104486},
	keywords = {Animals, Humans, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Drosophila, High-Throughput Nucleotide Sequencing, Sequence Analysis, {RNA}},
	file = {Full Text:/home/jlagarde/Zotero/storage/P8B4NFZU/Malone and Oliver - 2011 - Microarrays, deep sequencing and the true measure .pdf:application/pdf}
}

@article{sims_sequencing_2014,
	title = {Sequencing depth and coverage: key considerations in genomic analyses},
	volume = {15},
	issn = {1471-0064},
	doi = {10.1038/nrg3642},
	shorttitle = {Sequencing depth and coverage},
	abstract = {Sequencing technologies have placed a wide range of genomic analyses within the capabilities of many laboratories. However, sequencing costs often set limits to the amount of sequences that can be generated and, consequently, the biological outcomes that can be achieved from an experimental design. In this Review, we discuss the issue of sequencing depth in the design of next-generation sequencing experiments. We review current guidelines and precedents on the issue of coverage, as well as their underlying considerations, for four major study designs, which include de novo genome sequencing, genome resequencing, transcriptome sequencing and genomic location analyses (for example, chromatin immunoprecipitation followed by sequencing ({ChIP}-seq) and chromosome conformation capture (3C)).},
	pages = {121--132},
	number = {2},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Sims, David and Sudbery, Ian and Ilott, Nicholas E. and Heger, Andreas and Ponting, Chris P.},
	date = {2014-02},
	pmid = {24434847},
	keywords = {Genomics, Animals, Humans, Gene Expression Profiling, Chromatin Immunoprecipitation, High-Throughput Nucleotide Sequencing, Guidelines as Topic},
	file = {Sims et al. - 2014 - Sequencing depth and coverage key considerations .pdf:/home/jlagarde/Zotero/storage/HGCL7464/Sims et al. - 2014 - Sequencing depth and coverage key considerations .pdf:application/pdf}
}

@article{velculescu_analysis_1999,
	title = {Analysis of human transcriptomes},
	volume = {23},
	issn = {1061-4036},
	doi = {10.1038/70487},
	pages = {387--388},
	number = {4},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Velculescu, V. E. and Madden, S. L. and Zhang, L. and Lash, A. E. and Yu, J. and Rago, C. and Lal, A. and Wang, C. J. and Beaudry, G. A. and Ciriello, K. M. and Cook, B. P. and Dufault, M. R. and Ferguson, A. T. and Gao, Y. and He, T. C. and Hermeking, H. and Hiraldo, S. K. and Hwang, P. M. and Lopez, M. A. and Luderer, H. F. and Mathews, B. and Petroziello, J. M. and Polyak, K. and Zawel, L. and Kinzler, K. W.},
	date = {1999-12},
	pmid = {10581018},
	keywords = {Humans, Colorectal Neoplasms, Female, Gene Expression, Male, Neoplasms, Tissue Distribution, Genome, Human, Tumor Cells, Cultured}
}

@article{daley_predicting_2013,
	title = {Predicting the molecular complexity of sequencing libraries},
	volume = {10},
	issn = {1548-7091},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612374/},
	doi = {10.1038/nmeth.2375},
	abstract = {Predicting the molecular complexity of a genomic sequencing library has emerged as a critical but difficult problem in modern applications of genome sequencing. Available methods to determine either how deeply to sequence, or predict the benefits of additional sequencing, are almost completely lacking. We introduce an empirical Bayesian method to implicitly model any source of bias and accurately characterize the molecular complexity of a {DNA} sample or library in almost any sequencing application.},
	pages = {325--327},
	number = {4},
	journaltitle = {Nature methods},
	shortjournal = {Nat Methods},
	author = {Daley, Timothy and Smith, Andrew D},
	urldate = {2019-08-06},
	date = {2013-04},
	pmid = {23435259},
	pmcid = {PMC3612374},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/JGWY23FS/Daley and Smith - 2013 - Predicting the molecular complexity of sequencing .pdf:application/pdf}
}

@article{legnini_flam-seq:_2019,
	title = {{FLAM}-seq: full-length {mRNA} sequencing reveals principles of poly(A) tail length control},
	rights = {2019 The Author(s), under exclusive licence to Springer Nature America, Inc.},
	issn = {1548-7105},
	url = {https://www.nature.com/articles/s41592-019-0503-y},
	doi = {10.1038/s41592-019-0503-y},
	shorttitle = {{FLAM}-seq},
	abstract = {{FLAM}-seq implements a {cDNA} library preparation followed by single-molecule sequencing, for determining full-length {mRNA} molecules, including poly(A) tails.},
	pages = {1--8},
	journaltitle = {Nature Methods},
	shortjournal = {Nat Methods},
	author = {Legnini, Ivano and Alles, Jonathan and Karaiskos, Nikos and Ayoub, Salah and Rajewsky, Nikolaus},
	urldate = {2019-08-06},
	date = {2019-08-05},
	langid = {english},
	file = {FLAM-seq\: full-length mRNA sequencing reveals principles of poly(A) tail length control:/home/jlagarde/Zotero/storage/9LBP5HX7/10.1038@s41592-019-0503-y.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/PS54ZHMN/s41592-019-0503-y.html:text/html}
}

@article{tarazona_differential_2011,
	title = {Differential expression in {RNA}-seq: A matter of depth},
	volume = {21},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227109/},
	doi = {10.1101/gr.124321.111},
	shorttitle = {Differential expression in {RNA}-seq},
	abstract = {Next-generation sequencing ({NGS}) technologies are revolutionizing genome research, and in particular, their application to transcriptomics ({RNA}-seq) is increasingly being used for gene expression profiling as a replacement for microarrays. However, the properties of {RNA}-seq data have not been yet fully established, and additional research is needed for understanding how these data respond to differential expression analysis. In this work, we set out to gain insights into the characteristics of {RNA}-seq data analysis by studying an important parameter of this technology: the sequencing depth. We have analyzed how sequencing depth affects the detection of transcripts and their identification as differentially expressed, looking at aspects such as transcript biotype, length, expression level, and fold-change. We have evaluated different algorithms available for the analysis of {RNA}-seq and proposed a novel approach—{NOISeq}—that differs from existing methods in that it is data-adaptive and nonparametric. Our results reveal that most existing methodologies suffer from a strong dependency on sequencing depth for their differential expression calls and that this results in a considerable number of false positives that increases as the number of reads grows. In contrast, our proposed method models the noise distribution from the actual data, can therefore better adapt to the size of the data set, and is more effective in controlling the rate of false discoveries. This work discusses the true potential of {RNA}-seq for studying regulation at low expression ranges, the noise within {RNA}-seq data, and the issue of replication.},
	pages = {2213--2223},
	number = {12},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Tarazona, Sonia and García-Alcalde, Fernando and Dopazo, Joaquín and Ferrer, Alberto and Conesa, Ana},
	urldate = {2019-08-06},
	date = {2011-12},
	pmid = {21903743},
	pmcid = {PMC3227109},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/5L8XVPF4/Tarazona et al. - 2011 - Differential expression in RNA-seq A matter of de.pdf:application/pdf}
}

@article{blencowe_current-generation_2009,
	title = {Current-generation high-throughput sequencing: deepening insights into mammalian transcriptomes},
	volume = {23},
	issn = {1549-5477},
	doi = {10.1101/gad.1788009},
	shorttitle = {Current-generation high-throughput sequencing},
	abstract = {Recent papers have described the first application of high-throughput sequencing ({HTS}) technologies to the characterization of transcriptomes. These studies emphasize the tremendous power of this new technology, in terms of both profiling coverage and quantitative accuracy. Initial discoveries include the detection of substantial new transcript complexity, the elucidation of binding maps and regulatory properties of {RNA}-binding proteins, and new insights into the links between different steps in pre-{mRNA} processing. We review these findings, focusing on results from profiling mammalian transcriptomes. The strengths and limitations of {HTS} relative to microarray profiling are discussed. We also consider how future advances in {HTS} technology are likely to transform our understanding of integrated cellular networks operating at the {RNA} level.},
	pages = {1379--1386},
	number = {12},
	journaltitle = {Genes \& Development},
	shortjournal = {Genes Dev.},
	author = {Blencowe, Benjamin J. and Ahmad, Sidrah and Lee, Leo J.},
	date = {2009-06-15},
	pmid = {19528315},
	keywords = {Animals, Gene Expression Regulation, Gene Expression Profiling, Mammals, Trans-Activators, {RNA} Processing, Post-Transcriptional, Sequence Analysis, {RNA}},
	file = {Full Text:/home/jlagarde/Zotero/storage/S8RT5HLC/Blencowe et al. - 2009 - Current-generation high-throughput sequencing dee.pdf:application/pdf}
}

@article{field_structurally_2019,
	title = {Structurally Conserved Primate {LncRNAs} Are Transiently Expressed during Human Cortical Differentiation and Influence Cell-Type-Specific Genes},
	volume = {12},
	issn = {2213-6711},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372947/},
	doi = {10.1016/j.stemcr.2018.12.006},
	abstract = {The cerebral cortex has expanded in size and complexity in primates, yet the molecular innovations that enabled primate-specific brain attributes remain obscure. We generated cerebral cortex organoids from human, chimpanzee, orangutan, and rhesus pluripotent stem cells and sequenced their transcriptomes at weekly time points for comparative analysis. We used transcript structure and expression conservation to discover gene regulatory long non-coding {RNAs} ({lncRNAs}). Of 2,975 human, multi-exonic {lncRNAs}, 2,472 were structurally conserved in at least one other species and 920 were conserved in all. Three hundred eighty-six human {lncRNAs} were transiently expressed ({TrEx}) and many were also {TrEx} in great apes (46\%) and rhesus (31\%). Many {TrEx} {lncRNAs} are expressed in specific cell types by single-cell {RNA} sequencing. Four {TrEx} {lncRNAs} selected based on cell-type specificity, gene structure, and expression pattern conservation were ectopically expressed in {HEK}293 cells by {CRISPRa}. All induced trans gene expression changes were consistent with neural gene regulatory activity., 
          
            
              •
              New orangutan and chimpanzee {iPSC} lines enable pan-primate gene expression analysis
            
            
              •
              Transiently expressed ({TrEx}) {lncRNAs} identified in primate cerebral cortex organoids
            
            
              •
              Conserved {TrEx} pattern correlates with cell-type specificity by single-cell {RNA}-seq
            
            
              •
              Four primate-conserved {TrEx} {lncRNAs} influence neural genes when ectopically expressed
            
          
        , In this article, Salama and colleagues identified transiently expressed ({TrEx}) {lncRNAs} from human, chimpanzee, orangutan, and rhesus pluripotent stem cell-derived cerebral cortex organoids and assessed their structural and expression conservation. Transient expression correlated with cell-type specificity as measured by single-cell {RNA}-seq. Ectopic expression of {TrEx} {lncRNAs} by {CRISPRa} modulated expression of neural genes in trans, suggesting regulatory function.},
	pages = {245--257},
	number = {2},
	journaltitle = {Stem Cell Reports},
	shortjournal = {Stem Cell Reports},
	author = {Field, Andrew R. and Jacobs, Frank M.J. and Fiddes, Ian T. and Phillips, Alex P.R. and Reyes-Ortiz, Andrea M. and {LaMontagne}, Erin and Whitehead, Lila and Meng, Vincent and Rosenkrantz, Jimi L. and Olsen, Mari and Hauessler, Max and Katzman, Sol and Salama, Sofie R. and Haussler, David},
	urldate = {2019-08-07},
	date = {2019-01-10},
	pmid = {30639214},
	pmcid = {PMC6372947},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/U9SPPMVF/Field et al. - 2019 - Structurally Conserved Primate LncRNAs Are Transie.pdf:application/pdf;Structurally Conserved Primate LncRNAs Are Transiently Expressed during Human Cortical Differentiation and Influence Cell-Type-Specific Genes:/home/jlagarde/Zotero/storage/6EPDKBXV/10.1016@j.stemcr.2018.12.006.pdf:application/pdf}
}

@article{svensson_exponential_2018,
	title = {Exponential scaling of single-cell {RNA}-seq in the past decade},
	volume = {13},
	issn = {1750-2799},
	doi = {10.1038/nprot.2017.149},
	abstract = {Measurement of the transcriptomes of single cells has been feasible for only a few years, but it has become an extremely popular assay. While many types of analysis can be carried out and various questions can be answered by single-cell {RNA}-seq, a central focus is the ability to survey the diversity of cell types in a sample. Unbiased and reproducible cataloging of gene expression patterns in distinct cell types requires large numbers of cells. Technological developments and protocol improvements have fueled consistent and exponential increases in the number of cells that can be studied in single-cell {RNA}-seq analyses. In this Perspective, we highlight the key technological developments that have enabled this growth in the data obtained from single-cell {RNA}-seq experiments.},
	pages = {599--604},
	number = {4},
	journaltitle = {Nature Protocols},
	shortjournal = {Nat Protoc},
	author = {Svensson, Valentine and Vento-Tormo, Roser and Teichmann, Sarah A.},
	date = {2018},
	pmid = {29494575},
	keywords = {Gene Expression Profiling, Single-Cell Analysis, Sequence Analysis, {RNA}, History, 21st Century}
}

@article{kolodziejczyk_technology_2015,
	title = {The technology and biology of single-cell {RNA} sequencing},
	volume = {58},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2015.04.005},
	abstract = {The differences between individual cells can have profound functional consequences, in both unicellular and multicellular organisms. Recently developed single-cell {mRNA}-sequencing methods enable unbiased, high-throughput, and high-resolution transcriptomic analysis of individual cells. This provides an additional dimension to transcriptomic information relative to traditional methods that profile bulk populations of cells. Already, single-cell {RNA}-sequencing methods have revealed new biology in terms of the composition of tissues, the dynamics of transcription, and the regulatory relationships between genes. Rapid technological developments at the level of cell capture, phenotyping, molecular biology, and bioinformatics promise an exciting future with numerous biological and medical applications.},
	pages = {610--620},
	number = {4},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Kolodziejczyk, Aleksandra A. and Kim, Jong Kyoung and Svensson, Valentine and Marioni, John C. and Teichmann, Sarah A.},
	date = {2015-05-21},
	pmid = {26000846},
	keywords = {Animals, Humans, Gene Expression Profiling, Alternative Splicing, Cell Lineage, Gene Regulatory Networks, Genetic Variation, Single-Cell Analysis, Models, Genetic, Sequence Analysis, {RNA}}
}

@article{sandberg_entering_2014,
	title = {Entering the era of single-cell transcriptomics in biology and medicine},
	volume = {11},
	issn = {1548-7105},
	pages = {22--24},
	number = {1},
	journaltitle = {Nature Methods},
	shortjournal = {Nat. Methods},
	author = {Sandberg, Rickard},
	date = {2014-01},
	pmid = {24524133},
	keywords = {Transcriptome, Animals, Humans, Gene Expression Regulation, Gene Expression Profiling, Single-Cell Analysis, Sequence Analysis, {DNA}, Sequence Analysis, {RNA}}
}

@article{tang_mrna-seq_2009,
	title = {{mRNA}-Seq whole-transcriptome analysis of a single cell},
	volume = {6},
	issn = {1548-7105},
	doi = {10.1038/nmeth.1315},
	abstract = {Next-generation sequencing technology is a powerful tool for transcriptome analysis. However, under certain conditions, only a small amount of material is available, which requires more sensitive techniques that can preferably be used at the single-cell level. Here we describe a single-cell digital gene expression profiling assay. Using our {mRNA}-Seq assay with only a single mouse blastomere, we detected the expression of 75\% (5,270) more genes than microarray techniques and identified 1,753 previously unknown splice junctions called by at least 5 reads. Moreover, 8-19\% of the genes with multiple known transcript isoforms expressed at least two isoforms in the same blastomere or oocyte, which unambiguously demonstrated the complexity of the transcript variants at whole-genome scale in individual cells. Finally, for Dicer1(-/-) and Ago2(-/-) (Eif2c2(-/-)) oocytes, we found that 1,696 and 1,553 genes, respectively, were abnormally upregulated compared to wild-type controls, with 619 genes in common.},
	pages = {377--382},
	number = {5},
	journaltitle = {Nature Methods},
	shortjournal = {Nat. Methods},
	author = {Tang, Fuchou and Barbacioru, Catalin and Wang, Yangzhou and Nordman, Ellen and Lee, Clarence and Xu, Nanlan and Wang, Xiaohui and Bodeau, John and Tuch, Brian B. and Siddiqui, Asim and Lao, Kaiqin and Surani, M. Azim},
	date = {2009-05},
	pmid = {19349980},
	keywords = {Animals, Mice, Proteins, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Algorithms, Argonaute Proteins, {DEAD}-box {RNA} Helicases, Female, Kruppel-Like Transcription Factors, Oocytes, Polymerase Chain Reaction, Protein Isoforms, Ribonuclease {III}, Sequence Alignment, Up-Regulation, {RNA}, Messenger, Sequence Analysis, {DNA}, Mice, Knockout, Mice, Transgenic, Databases, Nucleic Acid, {DNA}, Complementary, Blastomeres, Cyclin E, Endoribonucleases, Eukaryotic Initiation Factor-2, Mice, Inbred Strains}
}

@article{ulitsky_evolution_2016,
	title = {Evolution to the rescue: using comparative genomics to understand long non-coding {RNAs}},
	volume = {17},
	rights = {2016 Nature Publishing Group},
	issn = {1471-0064},
	url = {https://www.nature.com/articles/nrg.2016.85},
	doi = {10.1038/nrg.2016.85},
	shorttitle = {Evolution to the rescue},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) have emerged in recent years as major players in a multitude of pathways across species, but it remains challenging to understand which of them are important and how their functions are performed. Comparative sequence analysis has been instrumental for studying proteins and small {RNAs}, but the rapid evolution of {lncRNAs} poses new challenges that demand new approaches. Here, I review the lessons learned so far from genome-wide mapping and comparisons of {lncRNAs} across different species. I also discuss how comparative analyses can help us to understand {lncRNA} function and provide practical considerations for examining functional conservation of {lncRNA} genes.},
	pages = {601--614},
	number = {10},
	journaltitle = {Nature Reviews Genetics},
	author = {Ulitsky, Igor},
	urldate = {2019-08-07},
	date = {2016-10},
	langid = {english},
	file = {Evolution to the rescue\: using comparative genomics to understand long non-coding RNAs:/home/jlagarde/Zotero/storage/SJEBNDUA/ulitsky2016.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/GJ9JEB5V/nrg.2016.html:text/html;ulitsky2016.pdf:/home/jlagarde/Zotero/storage/GLFTPNML/ulitsky2016.pdf:application/pdf}
}

@article{bahar_halpern_bursty_2015,
	title = {Bursty gene expression in the intact mammalian liver},
	volume = {58},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2015.01.027},
	abstract = {Bursts of nascent {mRNA} have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript counting with dual-color labeling and quantification of nascent {mRNA} to characterize promoter states, transcription rates, and transcript lifetimes in the intact mouse liver. We find that liver gene expression is highly bursty, with promoters stochastically switching between transcriptionally active and inactive states. Promoters of genes with short {mRNA} lifetimes are active longer, facilitating rapid response while reducing burst-associated noise. Moreover, polyploid hepatocytes exhibit less noise than diploid hepatocytes, suggesting a possible benefit to liver polyploidy. Thus, temporal averaging and liver polyploidy dampen the intrinsic variability associated with transcriptional bursts. Our approach can be used to study transcriptional bursting in diverse mammalian tissues.},
	pages = {147--156},
	number = {1},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Bahar Halpern, Keren and Tanami, Sivan and Landen, Shanie and Chapal, Michal and Szlak, Liran and Hutzler, Anat and Nizhberg, Anna and Itzkovitz, Shalev},
	date = {2015-04-02},
	pmid = {25728770},
	pmcid = {PMC4500162},
	keywords = {Animals, Mice, Gene Expression Regulation, Half-Life, Homeostasis, Liver, Male, Ploidies, {RNA} Stability, Single-Cell Analysis, {RNA}, Messenger, Transcription, Genetic, Promoter Regions, Genetic, Models, Genetic, Mice, Inbred C57BL, Hepatocytes},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/MBLVYFPI/Bahar Halpern et al. - 2015 - Bursty gene expression in the intact mammalian liv.pdf:application/pdf;Bursty gene expression in the intact mammalian liver:/home/jlagarde/Zotero/storage/8LJVZ9M8/baharhalpern2015.pdf:application/pdf}
}

@article{dar_transcriptional_2012,
	title = {Transcriptional burst frequency and burst size are equally modulated across the human genome},
	volume = {109},
	issn = {1091-6490},
	doi = {10.1073/pnas.1213530109},
	abstract = {Gene expression occurs either as an episodic process, characterized by pulsatile bursts, or as a constitutive process, characterized by a Poisson-like accumulation of gene products. It is not clear which mode of gene expression (constitutive versus bursty) predominates across a genome or how transcriptional dynamics are influenced by genomic position and promoter sequence. Here, we use time-lapse fluorescence microscopy to analyze 8,000 individual human genomic loci and find that at virtually all loci, episodic bursting--as opposed to constitutive expression--is the predominant mode of expression. Quantitative analysis of the expression dynamics at these 8,000 loci indicates that both the frequency and size of the transcriptional bursts varies equally across the human genome, independent of promoter sequence. Strikingly, weaker expression loci modulate burst frequency to increase activity, whereas stronger expression loci modulate burst size to increase activity. Transcriptional activators such as trichostatin A ({TSA}) and tumor necrosis factor α ({TNF}) only modulate burst size and frequency along a constrained trend line governed by the promoter. In summary, transcriptional bursting dominates across the human genome, both burst frequency and burst size vary by chromosomal location, and transcriptional activators alter burst frequency and burst size, depending on the expression level of the locus.},
	pages = {17454--17459},
	number = {43},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Dar, Roy D. and Razooky, Brandon S. and Singh, Abhyudai and Trimeloni, Thomas V. and {McCollum}, James M. and Cox, Chris D. and Simpson, Michael L. and Weinberger, Leor S.},
	date = {2012-10-23},
	pmid = {23064634},
	pmcid = {PMC3491463},
	keywords = {Humans, Gene Expression, Genetic Vectors, Lentivirus, Transcription, Genetic, Promoter Regions, Genetic, Genome, Human, Hydroxamic Acids, Microscopy, Fluorescence, Tumor Necrosis Factor-alpha},
	file = {Full Text:/home/jlagarde/Zotero/storage/2YUTXGQY/Dar et al. - 2012 - Transcriptional burst frequency and burst size are.pdf:application/pdf;Transcriptional burst frequency and burst size are equally modulated across the human genome:/home/jlagarde/Zotero/storage/KEL497CT/dar2012.pdf:application/pdf}
}

@article{pedraza_effects_2008,
	title = {Effects of molecular memory and bursting on fluctuations in gene expression},
	volume = {319},
	issn = {1095-9203},
	doi = {10.1126/science.1144331},
	abstract = {Many cellular components are present in such low numbers per cell that random births and deaths of individual molecules can cause substantial "noise" in concentrations. But biochemical events do not necessarily occur in single steps of individual molecules. Some processes are greatly randomized when synthesis or degradation occurs in large bursts of many molecules during a short time interval. Conversely, each birth or death of a macromolecule could involve several small steps, creating a memory between individual events. We present a generalized theory for stochastic gene expression, formulating the variance in protein abundance in terms of the randomness of the individual gene expression events. We show that common types of molecular mechanisms can produce gestation and senescence periods that reduce noise without requiring higher abundances, shorter lifetimes, or any concentration-dependent control loops. We also show that most single-cell experimental methods cannot distinguish between qualitatively different stochastic principles, although this in turn makes such methods better suited for identifying which components introduce fluctuations. Characterizing the random events that give rise to noise in concentrations instead requires dynamic measurements with single-molecule resolution.},
	pages = {339--343},
	number = {5861},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Pedraza, Juan M. and Paulsson, Johan},
	date = {2008-01-18},
	pmid = {18202292},
	keywords = {Proteins, Gene Expression, Gene Regulatory Networks, Mathematics, Protein Biosynthesis, {RNA}, Messenger, Transcription, Genetic, Models, Genetic, Stochastic Processes}
}

@article{rabani_metabolic_2011,
	title = {Metabolic labeling of {RNA} uncovers principles of {RNA} production and degradation dynamics in mammalian cells},
	volume = {29},
	issn = {1546-1696},
	doi = {10.1038/nbt.1861},
	abstract = {Cellular {RNA} levels are determined by the interplay of {RNA} production, processing and degradation. However, because most studies of {RNA} regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of {RNA} at high temporal resolution with advanced {RNA} quantification and computational modeling to estimate {RNA} transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in {RNA} levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed {RNA} population to estimate temporally constant {RNA} processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of {RNA} regulation.},
	pages = {436--442},
	number = {5},
	journaltitle = {Nature Biotechnology},
	shortjournal = {Nat. Biotechnol.},
	author = {Rabani, Michal and Levin, Joshua Z. and Fan, Lin and Adiconis, Xian and Raychowdhury, Raktima and Garber, Manuel and Gnirke, Andreas and Nusbaum, Chad and Hacohen, Nir and Friedman, Nir and Amit, Ido and Regev, Aviv},
	date = {2011-05},
	pmid = {21516085},
	pmcid = {PMC3114636},
	keywords = {Animals, Mice, {RNA}, Computational Biology, Biotinylation, Down-Regulation, Female, Genetic Association Studies, Transcription Factors, Up-Regulation, {RNA} Polymerase {II}, {RNA}, Messenger, Transcription, Genetic, Cells, Cultured, Sequence Analysis, {RNA}, Mice, Inbred C57BL, Dendritic Cells, Lipopolysaccharides, Models, Molecular},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/H5P6YGWS/Rabani et al. - 2011 - Metabolic labeling of RNA uncovers principles of R.pdf:application/pdf}
}

@article{bogdanov_normalizing_2010,
	title = {Normalizing {cDNA} libraries},
	volume = {Chapter 5},
	issn = {1934-3647},
	doi = {10.1002/0471142727.mb0512s90},
	abstract = {The characterization of rare messages in {cDNA} libraries is complicated by the substantial variations that exist in the abundance levels of different transcripts in cells and tissues. The equalization (normalization) of {cDNA} is a helpful approach for decreasing the prevalence of abundant transcripts, thereby facilitating the assessment of rare transcripts. This unit provides a method for duplex-specific nuclease ({DSN})-based normalization, which allows for the fast and reliable equalization of {cDNA}, thereby facilitating the generation of normalized, full-length-enriched {cDNA} libraries, and enabling efficient {RNA} analyses.},
	pages = {Unit 5.12.1--27},
	journaltitle = {Current Protocols in Molecular Biology},
	shortjournal = {Curr Protoc Mol Biol},
	author = {Bogdanov, Ekaterina A. and Shagina, Irina and Barsova, Ekaterina V. and Kelmanson, Ilya and Shagin, Dmitry A. and Lukyanov, Sergey A.},
	date = {2010-04},
	pmid = {20373503},
	keywords = {Base Sequence, Deoxyribonucleases, Gene Library, Molecular Sequence Data, Oligonucleotides, Polymerase Chain Reaction, Cloning, Molecular, {DNA}, Complementary}
}

@article{wilhelm_dynamic_2008,
	title = {Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution},
	volume = {453},
	issn = {1476-4687},
	doi = {10.1038/nature07002},
	abstract = {Recent data from several organisms indicate that the transcribed portions of genomes are larger and more complex than expected, and that many functional properties of transcripts are based not on coding sequences but on regulatory sequences in untranslated regions or non-coding {RNAs}. Alternative start and polyadenylation sites and regulation of intron splicing add additional dimensions to the rich transcriptional output. This transcriptional complexity has been sampled mainly using hybridization-based methods under one or few experimental conditions. Here we applied direct high-throughput sequencing of complementary {DNAs} ({RNA}-Seq), supplemented with data from high-density tiling arrays, to globally sample transcripts of the fission yeast Schizosaccharomyces pombe, independently from available gene annotations. We interrogated transcriptomes under multiple conditions, including rapid proliferation, meiotic differentiation and environmental stress, as well as in {RNA} processing mutants to reveal the dynamic plasticity of the transcriptional landscape as a function of environmental, developmental and genetic factors. High-throughput sequencing proved to be a powerful and quantitative method to sample transcriptomes deeply at maximal resolution. In contrast to hybridization, sequencing showed little, if any, background noise and was sensitive enough to detect widespread transcription in {\textgreater}90\% of the genome, including traces of {RNAs} that were not robustly transcribed or rapidly degraded. The combined sequencing and strand-specific array data provide rich condition-specific information on novel, mostly non-coding transcripts, untranslated regions and gene structures, thus improving the existing genome annotation. Sequence reads spanning exon-exon or exon-intron junctions give unique insight into a surprising variability in splicing efficiency across introns, genes and conditions. Splicing efficiency was largely coordinated with transcript levels, and increased transcription led to increased splicing in test genes. Hundreds of introns showed such regulated splicing during cellular proliferation or differentiation.},
	pages = {1239--1243},
	number = {7199},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Wilhelm, Brian T. and Marguerat, Samuel and Watt, Stephen and Schubert, Falk and Wood, Valerie and Goodhead, Ian and Penkett, Christopher J. and Rogers, Jane and Bähler, Jürg},
	date = {2008-06-26},
	pmid = {18488015},
	keywords = {Exons, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Introns, Alternative Splicing, Chromatin Immunoprecipitation, Eukaryotic Cells, Sensitivity and Specificity, {RNA} Polymerase {II}, {RNA}, Messenger, Transcription, Genetic, Genes, Fungal, {RNA}, Fungal, Gene Expression Regulation, Fungal, Schizosaccharomyces, Schizosaccharomyces pombe Proteins}
}

@article{kingston_preparation_2001,
	title = {Preparation of poly(A)+ {RNA}},
	volume = {Chapter 4},
	issn = {1934-3647},
	doi = {10.1002/0471142727.mb0405s21},
	abstract = {Most messenger {RNAs} contain a poly(A) tail, while structural {RNAs} do not. Poly(A) selection therefore enriches for messenger {RNA}. The technique has proved essential for construction of {cDNA} libraries. It is also useful when analyzing the structure of low-abundance {mRNAs}. Removing the ribosomal and {tRNAs} from a preparation increases the amount of {RNA} that can be clearly analyzed by S1 analysis, for example, thus allowing detection of a low level message. This protocol separates poly(A)+ {RNA} from the remainder of total {RNA}, which is largely {rRNA} and {tRNA}. Total {RNA} is denatured to expose the poly(A) (polyadenylated) tails. Poly(A)-containing {RNA} is then bound to oligo({dT}) cellulose, with the remainder of the {RNA} washing through. The poly(A)+ {RNA} is eluted by removing salt from the solution, thus destabilizing the {dT}:{rA} hybrid. The column can then be repeated to remove contaminating poly(A)- {RNA}.},
	pages = {Unit4.5},
	journaltitle = {Current Protocols in Molecular Biology},
	shortjournal = {Curr Protoc Mol Biol},
	author = {Kingston, R. E.},
	date = {2001-05},
	pmid = {18265239},
	keywords = {Indicators and Reagents, Oligodeoxyribonucleotides, Sensitivity and Specificity, {RNA}, Messenger, Solutions}
}

@article{bogdanova_normalization_2011,
	title = {Normalization of full-length-enriched {cDNA}},
	volume = {729},
	issn = {1940-6029},
	doi = {10.1007/978-1-61779-065-2_6},
	abstract = {A well-recognized obstacle to efficient high-throughput analysis of {cDNA} libraries is the differential abundance of various transcripts in any particular cell type. Decreasing the prevalence of clones representing abundant transcripts before sequencing, using {cDNA} normalization, may significantly increase the efficacy of random sequencing and is essential for rare gene discovery. Duplex-specific nuclease ({DSN}) normalization allows the generation of normalized full-length-enriched {cDNA} libraries to permit a high gene discovery rate. The method is based on the unique properties of {DSN} from the Kamchatka crab and involves denaturation-reassociation of {cDNA}, degradation of the ds-fraction formed by abundant transcripts by {DSN}, and {PCR} amplification of the remaining ss-{DNA} fraction. The method has been evaluated in various plant and animal models.},
	pages = {85--98},
	journaltitle = {Methods in Molecular Biology (Clifton, N.J.)},
	shortjournal = {Methods Mol. Biol.},
	author = {Bogdanova, Ekaterina A. and Barsova, Ekaterina V. and Shagina, Irina A. and Scheglov, Alexander and Anisimova, Veronika and Vagner, Laura L. and Lukyanov, Sergey A. and Shagin, Dmitry A.},
	date = {2011},
	pmid = {21365485},
	keywords = {Sequence Analysis, Animals, Gene Library, Nucleic Acid Denaturation, Nucleic Acid Hybridization, Polymerase Chain Reaction, Deoxyribonucleotides, {DNA}, Complementary, Anomura, {DNA}, Single-Stranded, Electrophoresis, Agar Gel, Endonucleases}
}

@article{shapiro_single-cell_2013,
	title = {Single-cell sequencing-based technologies will revolutionize whole-organism science},
	volume = {14},
	issn = {1471-0064},
	doi = {10.1038/nrg3542},
	abstract = {The unabated progress in next-generation sequencing technologies is fostering a wave of new genomics, epigenomics, transcriptomics and proteomics technologies. These sequencing-based technologies are increasingly being targeted to individual cells, which will allow many new and longstanding questions to be addressed. For example, single-cell genomics will help to uncover cell lineage relationships; single-cell transcriptomics will supplant the coarse notion of marker-based cell types; and single-cell epigenomics and proteomics will allow the functional states of individual cells to be analysed. These technologies will become integrated within a decade or so, enabling high-throughput, multi-dimensional analyses of individual cells that will produce detailed knowledge of the cell lineage trees of higher organisms, including humans. Such studies will have important implications for both basic biological research and medicine.},
	pages = {618--630},
	number = {9},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Shapiro, Ehud and Biezuner, Tamir and Linnarsson, Sten},
	date = {2013-09},
	pmid = {23897237},
	keywords = {Epigenomics, Genomics, Animals, Humans, Gene Expression Profiling, Cell Separation, High-Throughput Nucleotide Sequencing, Proteomics, Single-Cell Analysis}
}

@article{carninci_normalization_2000,
	title = {Normalization and Subtraction of Cap-Trapper-Selected {cDNAs} to Prepare Full-Length {cDNA} Libraries for Rapid Discovery of New Genes},
	volume = {10},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC310980/},
	abstract = {In the effort to prepare the mouse full-length {cDNA} encyclopedia, we previously developed several techniques to prepare and select full-length {cDNAs}. To increase the number of different {cDNAs}, we introduce here a strategy to prepare normalized and subtracted {cDNA} libraries in a single step. The method is based on hybridization of the first-strand, full-length {cDNA} with several {RNA} drivers, including starting {mRNA} as the normalizing driver and run-off transcripts from minilibraries containing highly expressed genes, rearrayed clones, and previously sequenced {cDNAs} as subtracting drivers. Our method keeps the proportion of full-length {cDNAs} in the subtracted/normalized library high. Moreover, our method dramatically enhances the discovery of new genes as compared to results obtained by using standard, full-length {cDNA} libraries. This procedure can be extended to the preparation of full-length {cDNA} encyclopedias from other organisms.},
	pages = {1617--1630},
	number = {10},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Carninci, Piero and Shibata, Yuko and Hayatsu, Norihito and Sugahara, Yuichi and Shibata, Kazuhiro and Itoh, Masayoshi and Konno, Hideaki and Okazaki, Yasushi and Muramatsu, Masami and Hayashizaki, Yoshihide},
	urldate = {2019-08-08},
	date = {2000-10},
	pmid = {11042159},
	pmcid = {PMC310980},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/YK6WX8SA/Carninci et al. - 2000 - Normalization and Subtraction of Cap-Trapper-Selec.pdf:application/pdf}
}

@article{zhulidov_simple_2004,
	title = {Simple {cDNA} normalization using kamchatka crab duplex-specific nuclease},
	volume = {32},
	issn = {0305-1048},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC373426/},
	doi = {10.1093/nar/gnh031},
	abstract = {We developed a novel simple {cDNA} normalization method [termed duplex-specific nuclease ({DSN}) normalization] that may be effectively used for samples enriched with full-length {cDNA} sequences. {DSN} normalization involves the denaturation–reassociation of {cDNA}, degradation of the double-stranded (ds) fraction formed by abundant transcripts and {PCR} amplification of the equalized single-stranded (ss) {DNA} fraction. The key element of this method is the degradation of the ds fraction formed during reassociation of {cDNA} using the kamchatka crab {DSN}, as described recently. This thermostable enzyme displays a strong preference for cleaving ds {DNA} and {DNA} in {DNA}–{RNA} hybrid duplexes compared with ss {DNA} and {RNA}, irrespective of sequence length. We developed normalization protocols for both first-strand {cDNA} [when poly(A)+ {RNA} is available] and amplified {cDNA} (when only total {RNA} can be obtained). Both protocols were evaluated in model experiments using human skeletal muscle {cDNA}. We also employed {DSN} normalization to normalize {cDNA} from nervous tissues of the marine mollusc Aplysia californica (a popular model organism in neuroscience) to illustrate further the efficiency of the normalization technique.},
	pages = {e37},
	number = {3},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Zhulidov, Pavel A. and Bogdanova, Ekaterina A. and Shcheglov, Alex S. and Vagner, Laura L. and Khaspekov, George L. and Kozhemyako, Valery B. and Matz, Mikhail V. and Meleshkevitch, Ella and Moroz, Leonid L. and Lukyanov, Sergey A. and Shagin, Dmitry A.},
	urldate = {2019-08-08},
	date = {2004},
	pmid = {14973331},
	pmcid = {PMC373426},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/3K7YDZ2K/Zhulidov et al. - 2004 - Simple cDNA normalization using kamchatka crab dup.pdf:application/pdf}
}

@article{levin_targeted_2009,
	title = {Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts},
	volume = {10},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/gb-2009-10-10-r115},
	doi = {10.1186/gb-2009-10-10-r115},
	abstract = {Targeted {RNA}-Seq combines next-generation sequencing with capture of sequences from a relevant subset of a transcriptome. When testing by capturing sequences from a tumor {cDNA} library by hybridization to oligonucleotide probes specific for 467 cancer-related genes, this method showed high selectivity, improved mutation detection enabling discovery of novel chimeric transcripts, and provided {RNA} expression data. Thus, targeted {RNA}-Seq produces an enhanced view of the molecular state of a set of "high interest" genes.},
	pages = {R115},
	number = {10},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Levin, Joshua Z. and Berger, Michael F. and Adiconis, Xian and Rogov, Peter and Melnikov, Alexandre and Fennell, Timothy and Nusbaum, Chad and Garraway, Levi A. and Gnirke, Andreas},
	urldate = {2019-08-09},
	date = {2009-10-16},
	file = {Full Text:/home/jlagarde/Zotero/storage/YVFIF69R/Levin et al. - 2009 - Targeted next-generation sequencing of a cancer tr.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/LEKVD7Q5/gb-2009-10-10-r115.html:text/html}
}

@article{teer_systematic_2010,
	title = {Systematic comparison of three genomic enrichment methods for massively parallel {DNA} sequencing},
	volume = {20},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/20/10/1420},
	doi = {10.1101/gr.106716.110},
	abstract = {Massively parallel {DNA} sequencing technologies have greatly increased our ability to generate large amounts of sequencing data at a rapid pace. Several methods have been developed to enrich for genomic regions of interest for targeted sequencing. We have compared three of these methods: Molecular Inversion Probes ({MIP}), Solution Hybrid Selection ({SHS}), and Microarray-based Genomic Selection ({MGS}). Using {HapMap} {DNA} samples, we compared each of these methods with respect to their ability to capture an identical set of exons and evolutionarily conserved regions associated with 528 genes (2.61 Mb). For sequence analysis, we developed and used a novel Bayesian genotype-assigning algorithm, Most Probable Genotype ({MPG}). All three capture methods were effective, but sensitivities (percentage of targeted bases associated with high-quality genotypes) varied for an equivalent amount of pass-filtered sequence: for example, 70\% ({MIP}), 84\% ({SHS}), and 91\% ({MGS}) for 400 Mb. In contrast, all methods yielded similar accuracies of {\textgreater}99.84\% when compared to Infinium 1M {SNP} {BeadChip}-derived genotypes and {\textgreater}99.998\% when compared to 30-fold coverage whole-genome shotgun sequencing data. We also observed a low false-positive rate with all three methods; of the heterozygous positions identified by each of the capture methods, {\textgreater}99.57\% agreed with 1M {SNP} {BeadChip}, and {\textgreater}98.840\% agreed with the whole-genome shotgun data. In addition, we successfully piloted the genomic enrichment of a set of 12 pooled samples via the {MGS} method using molecular bar codes. We find that these three genomic enrichment methods are highly accurate and practical, with sensitivities comparable to that of 30-fold coverage whole-genome shotgun data.},
	pages = {1420--1431},
	number = {10},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Teer, Jamie K. and Bonnycastle, Lori L. and Chines, Peter S. and Hansen, Nancy F. and Aoyama, Natsuyo and Swift, Amy J. and Abaan, Hatice Ozel and Albert, Thomas J. and Program, {NISC} Comparative Sequencing and Margulies, Elliott H. and Green, Eric D. and Collins, Francis S. and Mullikin, James C. and Biesecker, Leslie G.},
	urldate = {2019-08-09},
	date = {2010-10-01},
	langid = {english},
	pmid = {20810667},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/A5EVIW5U/Teer et al. - 2010 - Systematic comparison of three genomic enrichment .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/ZQYF6VEY/1420.html:text/html}
}

@article{yehle_solution_1987,
	title = {A solution hybridization assay for ribosomal {RNA} from bacteria using biotinylated {DNA} probes and enzyme-labeled antibody to {DNA}:{RNA}},
	volume = {1},
	issn = {0890-8508},
	shorttitle = {A solution hybridization assay for ribosomal {RNA} from bacteria using biotinylated {DNA} probes and enzyme-labeled antibody to {DNA}},
	abstract = {Rapid, convenient and non-isotopic nucleic-acid hybridization methods are needed for this technology to have practical use in clinical diagnostic tests. A method for hybridization of {RNA} with a {DNA} probe in solution followed by capture and measurement of the hybrid is described. {DNA} probes complementary to 23S {rRNAs} from Escherichia coli and Bacillus subtilis were labeled with a photoactivable biotin reagent. Hybridization of the biotinylated probes with {rRNA} was complete in less than 5 min. The resultant hybrids were allowed to bind simultaneously to succinylated avidin immobilized on latex and to beta-galactosidase-labeled Fab' fragments of a monoclonal antibody-specific for {DNA}:{RNA}. Finally, beta-galactosidase associated with the captured hybrids was measured colorimetrically. The hybridization method can detect less than 1000 bacteria per assay and has broad specificity to permit detection of the various genera of bacteria that infect the urinary tract.},
	pages = {177--193},
	number = {2},
	journaltitle = {Molecular and Cellular Probes},
	shortjournal = {Mol. Cell. Probes},
	author = {Yehle, C. O. and Patterson, W. L. and Boguslawski, S. J. and Albarella, J. P. and Yip, K. F. and Carrico, R. J.},
	date = {1987-06},
	pmid = {2456459},
	keywords = {{DNA}, Animals, Biotin, Immunoenzyme Techniques, Leukocytes, Nucleic Acid Hybridization, Escherichia coli, {RNA}, Bacterial, {RNA}, Ribosomal, Avidin, Bacteriological Techniques, {RNA}, Ribosomal, 23S}
}

@article{hoang_impact_2019,
	title = {The Impact of {cDNA} Normalization on Long-Read Sequencing of a Complex Transcriptome},
	volume = {10},
	issn = {1664-8021},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664245/},
	abstract = {Normalization of {cDNA} is widely used to improve the coverage of rare transcripts in analysis of transcriptomes employing next-generation sequencing. Recently, long-read technology has been emerging as a powerful tool for sequencing and construction of transcriptomes, especially for complex genomes containing highly similar transcripts and transcript-spliced isoforms. Here, we analyzed the transcriptome of sugarcane, a highly polyploidy plant genome, by {PacBio} isoform sequencing (Iso-Seq) of two different {cDNA} library preparations, with and without a normalization step. The results demonstrated that, while the two libraries included many of the same transcripts, many longer transcripts were removed, and many new generally shorter transcripts were detected by normalization. For the same input {cDNA} and data yield, the normalized library recovered more total transcript isoforms and number of predicted gene families and orthologous groups, resulting in a higher representation for the sugarcane transcriptome, compared to the non-normalized library. The non-normalized library, on the other hand, included a wider transcript length range with more longer transcripts above ∼1.25 kb and more transcript isoforms per gene family and gene ontology terms per transcript. A large proportion of the unique transcripts comprising ∼52\% of the normalized library were expressed at a lower level than the unique transcripts from the non-normalized library, across three tissue types tested including leaf, stalk, and root. About 83\% of the total 5,348 predicted long noncoding transcripts was derived from the normalized library, of which ∼80\% was derived from the lowly expressed fraction. Functional annotation of the unique transcripts suggested that each library enriched different functional transcript fractions. This demonstrated the complementation of the two approaches in obtaining a complete transcriptome of a complex genome at the sequencing depth used in this study.},
	journaltitle = {Frontiers in Genetics},
	shortjournal = {Front Genet},
	author = {Hoang, Nam V. and Furtado, Agnelo and Perlo, Virginie and Botha, Frederik C. and Henry, Robert J.},
	urldate = {2019-08-09},
	date = {2019-07-23},
	pmid = {null},
	pmcid = {PMC6664245},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/USU2Q4MS/Hoang et al. - 2019 - The Impact of cDNA Normalization on Long-Read Sequ.pdf:application/pdf;The Impact of cDNA Normalization on Long-Read Sequencing of a Complex Transcriptome:/home/jlagarde/Zotero/storage/ZWPZCR7G/10.3389@fgene.2019.00654.pdf:application/pdf}
}

@article{horn_target_2012,
	title = {Target enrichment via {DNA} hybridization capture},
	volume = {840},
	issn = {1940-6029},
	doi = {10.1007/978-1-61779-516-9_21},
	abstract = {Recent advances in high-throughput {DNA} sequencing technologies have allowed entire nuclear genomes to be shotgun sequenced from ancient {DNA} ({aDNA}) extracts. Nonetheless, targeted analyses of specific genomic loci will remain an important tool for future {aDNA} studies. {DNA} capture via hybridization allows the efficient exploitation of current high-throughput sequencing for population genetic analyses using {aDNA} samples. Specifically, hybridization capture allows larger data sets to be generated for multiple target loci as well as for multiple samples in parallel. "Bait" molecules are used to select target regions from {DNA} libraries for sequencing. Here we present a brief overview of the currently available hybridization capture protocols using either an in-solution or a solid-phase (immobilized) approach. While it is possible to purchase ready-made kits for this purpose, I present a protocol that allows users to generate their own custom bait to be used for hybridization capture.},
	pages = {177--188},
	journaltitle = {Methods in Molecular Biology (Clifton, N.J.)},
	shortjournal = {Methods Mol. Biol.},
	author = {Horn, Susanne},
	date = {2012},
	pmid = {22237535},
	keywords = {{DNA}, Animals, Fossils, Gene Library, High-Throughput Nucleotide Sequencing, Nucleic Acid Hybridization},
	file = {Target enrichment via DNA hybridization capture:/home/jlagarde/Zotero/storage/ILTPU3QL/horn2011.pdf:application/pdf}
}

@article{gerstein_what_2007,
	title = {What is a gene, post-{ENCODE}? History and updated definition},
	volume = {17},
	issn = {1088-9051},
	doi = {10.1101/gr.6339607},
	shorttitle = {What is a gene, post-{ENCODE}?},
	abstract = {While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the {ENCODE} project, together with non-genic conservation and the abundance of noncoding {RNA} genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day {ORFs} enumerated in the sequence databanks. We then summarize the current {ENCODE} findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.},
	pages = {669--681},
	number = {6},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Gerstein, Mark B. and Bruce, Can and Rozowsky, Joel S. and Zheng, Deyou and Du, Jiang and Korbel, Jan O. and Emanuelsson, Olof and Zhang, Zhengdong D. and Weissman, Sherman and Snyder, Michael},
	date = {2007-06},
	pmid = {17567988},
	keywords = {Humans, Open Reading Frames, Chromosome Mapping, Human Genome Project, {RNA}, Untranslated, Genome, Human, History, 21st Century, History, 19th Century, History, 20th Century},
	file = {Full Text:/home/jlagarde/Zotero/storage/VNUCFFGC/Gerstein et al. - 2007 - What is a gene, post-ENCODE History and updated d.pdf:application/pdf;What is a gene, post-ENCODE? History and updated definition:/home/jlagarde/Zotero/storage/EYHF3DTF/gerstein2007.pdf:application/pdf}
}

@article{li_fast_2009,
	title = {Fast and accurate short read alignment with Burrows-Wheeler transform},
	volume = {25},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/btp324},
	abstract = {{MOTIVATION}: The enormous amount of short reads generated by the new {DNA} sequencing technologies call for the development of fast and accurate read alignment programs. A first generation of hash table-based methods has been developed, including {MAQ}, which is accurate, feature rich and fast enough to align short reads from a single individual. However, {MAQ} does not support gapped alignment for single-end reads, which makes it unsuitable for alignment of longer reads where indels may occur frequently. The speed of {MAQ} is also a concern when the alignment is scaled up to the resequencing of hundreds of individuals.
{RESULTS}: We implemented Burrows-Wheeler Alignment tool ({BWA}), a new read alignment package that is based on backward search with Burrows-Wheeler Transform ({BWT}), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps. {BWA} supports both base space reads, e.g. from Illumina sequencing machines, and color space reads from {AB} {SOLiD} machines. Evaluations on both simulated and real data suggest that {BWA} is approximately 10-20x faster than {MAQ}, while achieving similar accuracy. In addition, {BWA} outputs alignment in the new standard {SAM} (Sequence Alignment/Map) format. Variant calling and other downstream analyses after the alignment can be achieved with the open source {SAMtools} software package.
{AVAILABILITY}: http://maq.sourceforge.net.},
	pages = {1754--1760},
	number = {14},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Li, Heng and Durbin, Richard},
	date = {2009-07-15},
	pmid = {19451168},
	pmcid = {PMC2705234},
	keywords = {Genomics, Algorithms, Software, Sequence Alignment, Sequence Analysis, {DNA}},
	file = {Fast and accurate short read alignment with Burrows-Wheeler transform:/home/jlagarde/Zotero/storage/Z9PRUBYM/li2009.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/RHTX6QX8/Li and Durbin - 2009 - Fast and accurate short read alignment with Burrow.pdf:application/pdf}
}

@article{abascal_loose_2018,
	title = {Loose ends: almost one in five human genes still have unresolved coding status},
	volume = {46},
	issn = {0305-1048},
	url = {https://academic.oup.com/nar/article/46/14/7070/5047265},
	doi = {10.1093/nar/gky587},
	shorttitle = {Loose ends},
	abstract = {Abstract.  Seventeen years after the sequencing of the human genome, the human proteome is still under revision. One in eight of the 22 210 coding genes listed},
	pages = {7070--7084},
	number = {14},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Abascal, Federico and Juan, David and Jungreis, Irwin and Martinez, Laura and Rigau, Maria and Rodriguez, Jose Manuel and Vazquez, Jesus and Tress, Michael L.},
	urldate = {2019-08-11},
	date = {2018-08-21},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/ZBK3Y5XR/Abascal et al. - 2018 - Loose ends almost one in five human genes still h.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TW53VAQC/5047265.html:text/html}
}

@article{mott_est_genome:_1997,
	title = {{EST}\_GENOME: a program to align spliced {DNA} sequences to unspliced genomic {DNA}},
	volume = {13},
	issn = {0266-7061},
	shorttitle = {{EST}\_GENOME},
	pages = {477--478},
	number = {4},
	journaltitle = {Computer applications in the biosciences: {CABIOS}},
	shortjournal = {Comput. Appl. Biosci.},
	author = {Mott, R.},
	date = {1997-08},
	pmid = {9283765},
	keywords = {Base Sequence, Genome, Humans, Algorithms, Software, Gene Expression, Molecular Sequence Data, Sequence Alignment, {DNA}, Recombinant, Sequence Homology, Nucleic Acid, {DNA}, Complementary, Chromosomes, Human, Pair 16, Evaluation Studies as Topic}
}

@article{wu_assessing_2013,
	title = {Assessing the impact of human genome annotation choice on {RNA}-seq expression estimates},
	volume = {14},
	issn = {1471-2105},
	url = {https://doi.org/10.1186/1471-2105-14-S11-S8},
	doi = {10.1186/1471-2105-14-S11-S8},
	abstract = {Genome annotation is a crucial component of {RNA}-seq data analysis. Much effort has been devoted to producing an accurate and rational annotation of the human genome. An annotated genome provides a comprehensive catalogue of genomic functional elements. Currently, at least six human genome annotations are publicly available, including {AceView} Genes, Ensembl Genes, H-{InvDB} Genes, {RefSeq} Genes, {UCSC} Known Genes, and Vega Genes. Characteristics of these annotations differ because of variations in annotation strategies and information sources. When performing {RNA}-seq data analysis, researchers need to choose a genome annotation. However, the effect of genome annotation choice on downstream {RNA}-seq expression estimates is still unclear. This study (1) investigates the effect of different genome annotations on {RNA}-seq quantification and (2) provides guidelines for choosing a genome annotation based on research focus.},
	pages = {S8},
	number = {11},
	journaltitle = {{BMC} Bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Wu, Po-Yen and Phan, John H. and Wang, May D.},
	urldate = {2019-08-12},
	date = {2013-11-04},
	file = {Assessing the impact of human genome annotation choice on RNA-seq expression estimates:/home/jlagarde/Zotero/storage/Z2JI7N6L/wu2013.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/LL8HBCVJ/Wu et al. - 2013 - Assessing the impact of human genome annotation ch.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/RTKR3RKX/Wu et al. - 2013 - Assessing the impact of human genome annotation ch.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/FVHSEMYS/1471-2105-14-S11-S8.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/ALWZF6WJ/1471-2105-14-S11-S8.html:text/html}
}

@article{zhao_comprehensive_2015,
	title = {A comprehensive evaluation of ensembl, {RefSeq}, and {UCSC} annotations in the context of {RNA}-seq read mapping and gene quantification},
	volume = {16},
	issn = {1471-2164},
	url = {https://doi.org/10.1186/s12864-015-1308-8},
	doi = {10.1186/s12864-015-1308-8},
	abstract = {{RNA}-Seq has become increasingly popular in transcriptome profiling. One aspect of transcriptome research is to quantify the expression levels of genomic elements, such as genes, their transcripts and exons. Acquiring a transcriptome expression profile requires genomic elements to be defined in the context of the genome. Multiple human genome annotation databases exist, including {RefGene} ({RefSeq} Gene), Ensembl, and the {UCSC} annotation database. The impact of the choice of an annotation on estimating gene expression remains insufficiently investigated.},
	pages = {97},
	number = {1},
	journaltitle = {{BMC} Genomics},
	shortjournal = {{BMC} Genomics},
	author = {Zhao, Shanrong and Zhang, Baohong},
	urldate = {2019-08-12},
	date = {2015-02-18},
	file = {A comprehensive evaluation of ensembl, RefSeq, and UCSC annotations in the context of RNA-seq read mapping and gene quantification:/home/jlagarde/Zotero/storage/J4QJUWVN/zhao2015.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/NBG2QKIJ/Zhao and Zhang - 2015 - A comprehensive evaluation of ensembl, RefSeq, and.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/ZDTEK5X4/Zhao and Zhang - 2015 - A comprehensive evaluation of ensembl, RefSeq, and.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/939X5EWS/s12864-015-1308-8.html:text/html;Snapshot:/home/jlagarde/Zotero/storage/RN5EF6XA/s12864-015-1308-8.html:text/html}
}

@article{shendure_next-generation_2008,
	title = {Next-generation {DNA} sequencing},
	volume = {26},
	issn = {1546-1696},
	doi = {10.1038/nbt1486},
	abstract = {{DNA} sequence represents a single format onto which a broad range of biological phenomena can be projected for high-throughput data collection. Over the past three years, massively parallel {DNA} sequencing platforms have become widely available, reducing the cost of {DNA} sequencing by over two orders of magnitude, and democratizing the field by putting the sequencing capacity of a major genome center in the hands of individual investigators. These new technologies are rapidly evolving, and near-term challenges include the development of robust protocols for generating sequencing libraries, building effective new approaches to data-analysis, and often a rethinking of experimental design. Next-generation {DNA} sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.},
	pages = {1135--1145},
	number = {10},
	journaltitle = {Nature Biotechnology},
	shortjournal = {Nat. Biotechnol.},
	author = {Shendure, Jay and Ji, Hanlee},
	date = {2008-10},
	pmid = {18846087},
	keywords = {Genomics, Chromosome Mapping, Forecasting, Sequence Alignment, Sequence Analysis, {DNA}}
}

@article{bernstein_nih_2010,
	title = {The {NIH} Roadmap Epigenomics Mapping Consortium},
	volume = {28},
	issn = {1087-0156},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607281/},
	doi = {10.1038/nbt1010-1045},
	pages = {1045--1048},
	number = {10},
	journaltitle = {Nature biotechnology},
	shortjournal = {Nat Biotechnol},
	author = {Bernstein, Bradley E and Stamatoyannopoulos, John A and Costello, Joseph F and Ren, Bing and Milosavljevic, Aleksandar and Meissner, Alexander and Kellis, Manolis and Marra, Marco A and Beaudet, Arthur L and Ecker, Joseph R and Farnham, Peggy J and Hirst, Martin and Lander, Eric S and Mikkelsen, Tarjei S and Thomson, James A},
	urldate = {2019-08-12},
	date = {2010-10},
	pmid = {20944595},
	pmcid = {PMC3607281},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/75RNJ8BJ/Bernstein et al. - 2010 - The NIH Roadmap Epigenomics Mapping Consortium.pdf:application/pdf}
}

@article{thurman_accessible_2012,
	title = {The accessible chromatin landscape of the human genome},
	volume = {489},
	issn = {1476-4687},
	doi = {10.1038/nature11232},
	abstract = {{DNase} I hypersensitive sites ({DHSs}) are markers of regulatory {DNA} and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human {DHSs} identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million {DHSs} that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using {ENCODE} data reveals novel relationships between chromatin accessibility, transcription, {DNA} methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal {DHSs} with their target promoters, revealing systematic pairing of different classes of distal {DHSs} and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular {DNase} I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The {DHS} landscape shows signatures of recent functional evolutionary constraint. However, the {DHS} compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation.},
	pages = {75--82},
	number = {7414},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Thurman, Robert E. and Rynes, Eric and Humbert, Richard and Vierstra, Jeff and Maurano, Matthew T. and Haugen, Eric and Sheffield, Nathan C. and Stergachis, Andrew B. and Wang, Hao and Vernot, Benjamin and Garg, Kavita and John, Sam and Sandstrom, Richard and Bates, Daniel and Boatman, Lisa and Canfield, Theresa K. and Diegel, Morgan and Dunn, Douglas and Ebersol, Abigail K. and Frum, Tristan and Giste, Erika and Johnson, Audra K. and Johnson, Ericka M. and Kutyavin, Tanya and Lajoie, Bryan and Lee, Bum-Kyu and Lee, Kristen and London, Darin and Lotakis, Dimitra and Neph, Shane and Neri, Fidencio and Nguyen, Eric D. and Qu, Hongzhu and Reynolds, Alex P. and Roach, Vaughn and Safi, Alexias and Sanchez, Minerva E. and Sanyal, Amartya and Shafer, Anthony and Simon, Jeremy M. and Song, Lingyun and Vong, Shinny and Weaver, Molly and Yan, Yongqi and Zhang, Zhancheng and Zhang, Zhuzhu and Lenhard, Boris and Tewari, Muneesh and Dorschner, Michael O. and Hansen, R. Scott and Navas, Patrick A. and Stamatoyannopoulos, George and Iyer, Vishwanath R. and Lieb, Jason D. and Sunyaev, Shamil R. and Akey, Joshua M. and Sabo, Peter J. and Kaul, Rajinder and Furey, Terrence S. and Dekker, Job and Crawford, Gregory E. and Stamatoyannopoulos, John A.},
	date = {2012-09-06},
	pmid = {22955617},
	pmcid = {PMC3721348},
	keywords = {Genomics, {DNA}, Humans, Transcription Initiation Site, Chromatin, Deoxyribonuclease I, {DNA} Footprinting, {DNA} Methylation, {DNA}-Binding Proteins, Encyclopedias as Topic, Molecular Sequence Annotation, Mutation Rate, Transcription Factors, Evolution, Molecular, Transcription, Genetic, Promoter Regions, Genetic, Genome, Human, Regulatory Sequences, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/XUPXJQQP/Thurman et al. - 2012 - The accessible chromatin landscape of the human ge.pdf:application/pdf;The accessible chromatin landscape of the human genome:/home/jlagarde/Zotero/storage/2B2A4MC5/thurman2012.pdf:application/pdf}
}

@article{neph_expansive_2012,
	title = {An expansive human regulatory lexicon encoded in transcription factor footprints},
	volume = {489},
	rights = {2012 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature11212},
	doi = {10.1038/nature11212},
	abstract = {Regulatory factor binding to genomic {DNA} protects the underlying sequence from cleavage by {DNase} I, leaving nucleotide-resolution footprints. Using genomic {DNase} I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for {DNA}-binding proteins that nearly doubles the size of the human cis–regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from {DNA} methylation. High-resolution {DNase} I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein–{DNA} interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.},
	pages = {83--90},
	number = {7414},
	journaltitle = {Nature},
	author = {Neph, Shane and Vierstra, Jeff and Stergachis, Andrew B. and Reynolds, Alex P. and Haugen, Eric and Vernot, Benjamin and Thurman, Robert E. and John, Sam and Sandstrom, Richard and Johnson, Audra K. and Maurano, Matthew T. and Humbert, Richard and Rynes, Eric and Wang, Hao and Vong, Shinny and Lee, Kristen and Bates, Daniel and Diegel, Morgan and Roach, Vaughn and Dunn, Douglas and Neri, Jun and Schafer, Anthony and Hansen, R. Scott and Kutyavin, Tanya and Giste, Erika and Weaver, Molly and Canfield, Theresa and Sabo, Peter and Zhang, Miaohua and Balasundaram, Gayathri and Byron, Rachel and {MacCoss}, Michael J. and Akey, Joshua M. and Bender, M. A. and Groudine, Mark and Kaul, Rajinder and Stamatoyannopoulos, John A.},
	urldate = {2019-08-12},
	date = {2012-09},
	langid = {english},
	file = {An expansive human regulatory lexicon encoded in transcription factor footprints:/home/jlagarde/Zotero/storage/3D74W7RM/neph2012.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/GSAUNATV/Neph et al. - 2012 - An expansive human regulatory lexicon encoded in t.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/MI79RT9J/nature11212.html:text/html}
}

@article{ernst_systematic_2011,
	title = {Systematic analysis of chromatin state dynamics in nine human cell types},
	volume = {473},
	issn = {0028-0836},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088773/},
	doi = {10.1038/nature09906},
	abstract = {Chromatin profiling has emerged as a powerful means for genome annotation and detection of regulatory activity. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell type-specificities, and their functional interactions. Focusing on cell type-specific patterns of promoters and enhancers, we define multi-cell activity profiles for chromatin state, gene expression, regulatory motif enrichment, and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for interpreting genome-wide association studies. Top-scoring disease {SNPs} are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus proposing a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.},
	pages = {43--49},
	number = {7345},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Ernst, Jason and Kheradpour, Pouya and Mikkelsen, Tarjei S. and Shoresh, Noam and Ward, Lucas D. and Epstein, Charles B. and Zhang, Xiaolan and Wang, Li and Issner, Robbyn and Coyne, Michael and Ku, Manching and Durham, Timothy and Kellis, Manolis and Bernstein, Bradley E.},
	urldate = {2019-08-12},
	date = {2011-05-05},
	pmid = {21441907},
	pmcid = {PMC3088773},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/XJTFZM7D/Ernst et al. - 2011 - Systematic analysis of chromatin state dynamics in.pdf:application/pdf;Systematic analysis of chromatin state dynamics in nine human cell types:/home/jlagarde/Zotero/storage/TCH9NNUJ/ernst2011.pdf:application/pdf}
}

@article{carlevaro-fita_global_2019,
	title = {Global Positioning System: Understanding Long Noncoding {RNAs} through Subcellular Localization},
	volume = {73},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2019.02.008},
	shorttitle = {Global Positioning System},
	abstract = {The localization of long noncoding {RNAs} ({lncRNAs}) within the cell is the primary determinant of their molecular functions. {LncRNAs} are often thought of as chromatin-restricted regulators of gene transcription and chromatin structure. However, a rich population of cytoplasmic {lncRNAs} has come to light, with diverse roles including translational regulation, signaling, and respiration. {RNA} maps of increasing resolution and scope are revealing a subcellular world of highly specific localization patterns and hint at sequence-based address codes specifying {lncRNA} fates. We propose a new framework for analyzing sequencing-based data, which suggests that numbers of cytoplasmic {lncRNA} molecules rival those in the nucleus. New techniques promise to create high-resolution, transcriptome-wide maps associated with all organelles of the mammalian cell. Given its intimate link to molecular roles, subcellular localization provides a means of unlocking the mystery of {lncRNA} functions.},
	pages = {869--883},
	number = {5},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Carlevaro-Fita, Joana and Johnson, Rory},
	date = {2019},
	pmid = {30849394},
	keywords = {Animals, Humans, Gene Expression Regulation, Cell Nucleus, Chromatin Assembly and Disassembly, Cytoplasm, Genetic Techniques, Signal Transduction, {RNA}, Long Noncoding, Active Transport, Cell Nucleus},
	file = {Global Positioning System\: Understanding Long Noncoding RNAs through Subcellular Localization:/home/jlagarde/Zotero/storage/LXB866K9/10.1016@j.molcel.2019.02.008.pdf:application/pdf}
}

@article{carlevaro-fita_ancient_2019,
	title = {Ancient exapted transposable elements promote nuclear enrichment of human long noncoding {RNAs}},
	volume = {29},
	issn = {1549-5469},
	doi = {10.1101/gr.229922.117},
	abstract = {The sequence domains underlying long noncoding {RNA} ({lncRNA}) activities, including their characteristic nuclear enrichment, remain largely unknown. It has been proposed that these domains can originate from neofunctionalized fragments of transposable elements ({TEs}), otherwise known as {RIDLs} (repeat insertion domains of {lncRNA}), although just a handful have been identified. It is challenging to distinguish functional {RIDL} instances against a numerous genomic background of neutrally evolving {TEs}. We here show evidence that a subset of {TE} types experience evolutionary selection in the context of {lncRNA} exons. Together these comprise an enrichment group of 5374 {TE} fragments in 3566 loci. Their host {lncRNAs} tend to be functionally validated and associated with disease. This {RIDL} group was used to explore the relationship between {TEs} and {lncRNA} subcellular localization. By using global localization data from 10 human cell lines, we uncover a dose-dependent relationship between nuclear/cytoplasmic distribution and evolutionarily conserved L2b, {MIRb}, and {MIRc} elements. This is observed in multiple cell types and is unaffected by confounders of transcript length or expression. Experimental validation with engineered transgenes shows that these {TEs} drive nuclear enrichment in a natural sequence context. Together these data reveal a role for {TEs} in regulating the subcellular localization of {lncRNAs}.},
	pages = {208--222},
	number = {2},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Carlevaro-Fita, Joana and Polidori, Taisia and Das, Monalisa and Navarro, Carmen and Zoller, Tatjana I. and Johnson, Rory},
	date = {2019},
	pmid = {30587508},
	pmcid = {PMC6360812},
	keywords = {Humans, Exons, Cell Nucleus, Disease, {DNA} Transposable Elements, Molecular Sequence Annotation, {RNA}, Long Noncoding},
	file = {Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs:/home/jlagarde/Zotero/storage/D5AWWWB9/carlevaro-fita2018.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/TK9R8GVV/Carlevaro-Fita et al. - 2019 - Ancient exapted transposable elements promote nucl.pdf:application/pdf}
}

@article{volden_improving_2018,
	title = {Improving nanopore read accuracy with the R2C2 method enables the sequencing of highly multiplexed full-length single-cell {cDNA}},
	volume = {115},
	rights = {Copyright © 2018 the Author(s). Published by {PNAS}.. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-{NonCommercial}-{NoDerivatives} License 4.0 ({CC} {BY}-{NC}-{ND}).},
	issn = {0027-8424, 1091-6490},
	url = {https://www.pnas.org/content/115/39/9726},
	doi = {10.1073/pnas.1806447115},
	abstract = {High-throughput short-read sequencing has revolutionized how transcriptomes are quantified and annotated. However, while Illumina short-read sequencers can be used to analyze entire transcriptomes down to the level of individual splicing events with great accuracy, they fall short of analyzing how these individual events are combined into complete {RNA} transcript isoforms. Because of this shortfall, long-distance information is required to complement short-read sequencing to analyze transcriptomes on the level of full-length {RNA} transcript isoforms. While long-read sequencing technology can provide this long-distance information, there are issues with both Pacific Biosciences ({PacBio}) and Oxford Nanopore Technologies ({ONT}) long-read sequencing technologies that prevent their widespread adoption. Briefly, {PacBio} sequencers produce low numbers of reads with high accuracy, while {ONT} sequencers produce higher numbers of reads with lower accuracy. Here, we introduce and validate a long-read {ONT}-based sequencing method. At the same cost, our Rolling Circle Amplification to Concatemeric Consensus (R2C2) method generates more accurate reads of full-length {RNA} transcript isoforms than any other available long-read sequencing method. These reads can then be used to generate isoform-level transcriptomes for both genome annotation and differential expression analysis in bulk or single-cell samples.},
	pages = {9726--9731},
	number = {39},
	journaltitle = {Proceedings of the National Academy of Sciences},
	shortjournal = {{PNAS}},
	author = {Volden, Roger and Palmer, Theron and Byrne, Ashley and Cole, Charles and Schmitz, Robert J. and Green, Richard E. and Vollmers, Christopher},
	urldate = {2019-08-13},
	date = {2018-09-25},
	langid = {english},
	pmid = {30201725},
	keywords = {nanopore sequencing, B cells, full-length {cDNA} sequencing, isoforms, single-cell transcriptomics},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/2MJCEGYA/Volden et al. - 2018 - Improving nanopore read accuracy with the R2C2 met.pdf:application/pdf}
}

@article{borgstrom_large_2011,
	title = {Large scale library generation for high throughput sequencing},
	volume = {6},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0019119},
	abstract = {{BACKGROUND}: Large efforts have recently been made to automate the sample preparation protocols for massively parallel sequencing in order to match the increasing instrument throughput. Still, the size selection through agarose gel electrophoresis separation is a labor-intensive bottleneck of these protocols.
{METHODOLOGY}/{PRINCIPAL} {FINDINGS}: In this study a method for automatic library preparation and size selection on a liquid handling robot is presented. The method utilizes selective precipitation of certain sizes of {DNA} molecules on to paramagnetic beads for cleanup and selection after standard enzymatic reactions.
{CONCLUSIONS}/{SIGNIFICANCE}: The method is used to generate libraries for de novo and re-sequencing on the Illumina {HiSeq} 2000 instrument with a throughput of 12 samples per instrument in approximately 4 hours. The resulting output data show quality scores and pass filter rates comparable to manually prepared samples. The sample size distribution can be adjusted for each application, and are suitable for all high throughput {DNA} processing protocols seeking to control size intervals.},
	pages = {e19119},
	number = {4},
	journaltitle = {{PloS} One},
	shortjournal = {{PLoS} {ONE}},
	author = {Borgström, Erik and Lundin, Sverker and Lundeberg, Joakim},
	date = {2011-04-27},
	pmid = {21589638},
	pmcid = {PMC3083417},
	keywords = {Automation, Gene Library, High-Throughput Nucleotide Sequencing, Sequence Analysis, {DNA}},
	file = {Full Text:/home/jlagarde/Zotero/storage/BFPAS7VY/Borgström et al. - 2011 - Large scale library generation for high throughput.pdf:application/pdf;Large scale library generation for high throughput sequencing:/home/jlagarde/Zotero/storage/SKP3KK8B/10.1371@journal.pone.0019119.pdf:application/pdf}
}

@article{frankish_comparison_2015,
	title = {Comparison of {GENCODE} and {RefSeq} gene annotation and the impact of reference geneset on variant effect prediction},
	volume = {16},
	issn = {1471-2164},
	url = {https://doi.org/10.1186/1471-2164-16-S8-S2},
	doi = {10.1186/1471-2164-16-S8-S2},
	abstract = {A vast amount of {DNA} variation is being identified by increasingly large-scale exome and genome sequencing projects. To be useful, variants require accurate functional annotation and a wide range of tools are available to this end. {McCarthy} et al recently demonstrated the large differences in prediction of loss-of-function ({LoF}) variation when {RefSeq} and Ensembl transcripts are used for annotation, highlighting the importance of the reference transcripts on which variant functional annotation is based.},
	pages = {S2},
	number = {8},
	journaltitle = {{BMC} Genomics},
	shortjournal = {{BMC} Genomics},
	author = {Frankish, Adam and Uszczynska, Barbara and Ritchie, Graham {RS} and Gonzalez, Jose M. and Pervouchine, Dmitri and Petryszak, Robert and Mudge, Jonathan M. and Fonseca, Nuno and Brazma, Alvis and Guigo, Roderic and Harrow, Jennifer},
	urldate = {2019-08-14},
	date = {2015-06-18},
	file = {Comparison of GENCODE and RefSeq gene annotation and the impact of reference geneset on variant effect prediction:/home/jlagarde/Zotero/storage/4GJGVRFN/frankish2015.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/CYBMJPGV/Frankish et al. - 2015 - Comparison of GENCODE and RefSeq gene annotation a.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/D5PBSZQN/1471-2164-16-S8-S2.html:text/html}
}

@article{li_impact_2017,
	title = {The impact of rare variation on gene expression across tissues},
	volume = {550},
	rights = {2017 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature24267},
	doi = {10.1038/nature24267},
	abstract = {Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk1,2,3,4. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants1,5. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles1,6,7, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues8,9,10,11, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue {RNA}-sequencing data from the Genotype-Tissue Expression ({GTEx}) project v6p release12. We find that 58\% of underexpression and 28\% of overexpression outliers have nearby conserved rare variants compared to 8\% of non-outliers. Additionally, we developed {RIVER} ({RNA}-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.},
	pages = {239--243},
	number = {7675},
	journaltitle = {Nature},
	author = {Li, Xin and Kim, Yungil and Tsang, Emily K. and Davis, Joe R. and Damani, Farhan N. and Chiang, Colby and Hess, Gaelen T. and Zappala, Zachary and Strober, Benjamin J. and Scott, Alexandra J. and Li, Amy and Ganna, Andrea and Bassik, Michael C. and Merker, Jason D. and {GTEx Consortium} and Hall, Ira M. and Battle, Alexis and Montgomery, Stephen B.},
	urldate = {2019-08-14},
	date = {2017-10},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/WNZQDNER/Li et al. - 2017 - The impact of rare variation on gene expression ac.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/V4IYWMP9/nature24267.html:text/html}
}

@article{gtex_consortium_genetic_2017,
	title = {Genetic effects on gene expression across human tissues},
	volume = {550},
	issn = {1476-4687},
	doi = {10.1038/nature24277},
	abstract = {Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression ({GTEx}) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.},
	pages = {204--213},
	number = {7675},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {{GTEx Consortium} and {Laboratory, Data Analysis \&Coordinating Center (LDACC)—Analysis Working Group} and {Statistical Methods groups—Analysis Working Group} and {Enhancing GTEx (eGTEx) groups} and {NIH Common Fund} and {NIH/NCI} and {NIH/NHGRI} and {NIH/NIMH} and {NIH/NIDA} and {Biospecimen Collection Source Site—NDRI} and {Biospecimen Collection Source Site—RPCI} and {Biospecimen Core Resource—VARI} and {Brain Bank Repository—University of Miami Brain Endowment Bank} and {Leidos Biomedical—Project Management} and {ELSI Study} and {Genome Browser Data Integration \&Visualization—EBI} and {Genome Browser Data Integration \&Visualization—UCSC Genomics Institute, University of California Santa Cruz} and {Lead analysts:} and {Laboratory, Data Analysis \&Coordinating Center (LDACC):} and {NIH program management:} and {Biospecimen collection:} and {Pathology:} and {eQTL manuscript working group:} and Battle, Alexis and Brown, Christopher D. and Engelhardt, Barbara E. and Montgomery, Stephen B.},
	date = {2017},
	pmid = {29022597},
	pmcid = {PMC5776756},
	keywords = {Humans, Gene Expression Regulation, Gene Expression Profiling, Organ Specificity, Disease, Alleles, Female, Genetic Variation, Genotype, Male, Quantitative Trait Loci, Genome, Human, Chromosomes, Human},
	file = {Full Text:/home/jlagarde/Zotero/storage/PH78U2HM/GTEx Consortium et al. - 2017 - Genetic effects on gene expression across human ti.pdf:application/pdf}
}

@article{gamazon_using_2018,
	title = {Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation},
	volume = {50},
	rights = {2018 The Author(s)},
	issn = {1546-1718},
	url = {https://www.nature.com/articles/s41588-018-0154-4},
	doi = {10.1038/s41588-018-0154-4},
	abstract = {Integration of expression quantitative trait locus ({eQTL}) data from the Genotype-Tissue Expression project with genome-wide association study data shows that {eQTLs} are enriched for trait associations in disease-relevant tissues.},
	pages = {956--967},
	number = {7},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat Genet},
	author = {Gamazon, Eric R. and Segrè, Ayellet V. and Bunt, Martijn van de and Wen, Xiaoquan and Xi, Hualin S. and Hormozdiari, Farhad and Ongen, Halit and Konkashbaev, Anuar and Derks, Eske M. and Aguet, François and Quan, Jie and Nicolae, Dan L. and Eskin, Eleazar and Kellis, Manolis and Getz, Gad and {McCarthy}, Mark I. and Dermitzakis, Emmanouil T. and Cox, Nancy J. and Ardlie, Kristin G.},
	urldate = {2019-08-14},
	date = {2018-07},
	langid = {english},
	file = {Full Text:/home/jlagarde/Zotero/storage/FSBJ4WHV/Gamazon et al. - 2018 - Using an atlas of gene regulation across 44 human .pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TU6XIZCE/s41588-018-0154-4.html:text/html}
}

@article{doolittle_we_2018,
	title = {We simply cannot go on being so vague about ‘function’},
	volume = {19},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-018-1600-4},
	doi = {10.1186/s13059-018-1600-4},
	abstract = {Function is an onerous concept, as the recent study by Steven Salzberg and colleagues demonstrates. We should be careful and always specific in using the ‘F-word’.},
	pages = {223},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Doolittle, W. Ford},
	urldate = {2019-08-14},
	date = {2018-12-18},
	file = {Full Text:/home/jlagarde/Zotero/storage/LFL6PLZX/Doolittle - 2018 - We simply cannot go on being so vague about ‘funct.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/JWUBFUQZ/s13059-018-1600-4.html:text/html;We simply cannot go on being so vague about ‘function’:/home/jlagarde/Zotero/storage/CPTXBB3Q/doolittle2018.pdf:application/pdf}
}

@article{vogel_preliminary_1964,
	title = {A Preliminary Estimate of the Number of Human Genes},
	volume = {201},
	rights = {1964 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/201847a0},
	doi = {10.1038/201847a0},
	abstract = {{RECENT} results of molecular genetics enable us to estimate the number of human genes, if certain assumptions are made. The following data are available: (1) The α-chain of human hæmoglobin contains 141, the β-chain contains 146 amino-acids, corresponding to a molecular weight of about 17,000 each1. Assuming a triplet code2,3 this means that the α- and β-chains are determined by 423 and 438 nucleotide pairs, respectively. According to ‘Svedberg's law’4, many proteins consist of sub-units of the same order of magnitude (molecular weight of about 17,500). Hence, the assumption seems to be warranted that one average structural geno might have a length of about 450 nucleotide pairs. (2) The weight of one haploid human chromosome set in human spermatozoa is about 2.72 × 10−12 g. Granulocytes contain about 6.23 × 10−12 g; lymphocytes contain about 5.84 × −12 g (ref. 5). Extensive examinations have shown that the {DKA}. content is constant in all resting cells of one species, which have the same number of chromosome sets, and depends on the degree of polyploidy5,6. The assumption seems to be justified that most of the {DNA} works as genetic material, even if in some cells minor fractions with other functions might possibly be present7. In the following calculations the total amount of {DNA} in a haploid human chromosome set is estimated to be about 3 × 10−12 g. (3) Usually the genetic variants of human haemoglobins differ in one amino-acid substitution only1,8. One structural gene can only produce one single type of genetically determined polypeptide chain. As much as we know, this applies for other genetically determined proteins as well. This means that the genetic information for these structural genes can only be present once. Any degree of polyteny for these loci in the germ cells is highly unlikely. As has been mentioned, however, the {DNA} content of diploid cells is about twice the content of (haploid) spermatozoa. We assume that the total genetic information is only present once.},
	pages = {847--847},
	number = {4921},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Vogel, F.},
	urldate = {2019-08-14},
	date = {1964-02},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/AZYAFWJN/201847a0.html:text/html}
}

@article{antequera_predicting_1994,
	title = {Predicting the total number of human genes},
	volume = {8},
	rights = {1994 Nature Publishing Group},
	issn = {1546-1718},
	url = {https://www.nature.com/articles/ng1094-114a},
	doi = {10.1038/ng1094-114a},
	abstract = {Correspondence,},
	pages = {114--114},
	number = {2},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat Genet},
	author = {Antequera, Francisco and Bird, Adrian},
	urldate = {2019-08-14},
	date = {1994-10},
	langid = {english}
}

@article{fields_how_1994,
	title = {How many genes in the human genome?},
	volume = {7},
	rights = {1994 Nature Publishing Group},
	issn = {1546-1718},
	url = {https://www.nature.com/articles/ng0794-345},
	doi = {10.1038/ng0794-345},
	abstract = {News \& Views,},
	pages = {345--346},
	number = {3},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat Genet},
	author = {Fields, Chris and Adams, Mark D. and White, Owen and Venter, J. Craig},
	urldate = {2019-08-14},
	date = {1994-07},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/BKXTIQS2/ng0794-345.html:text/html}
}

@article{willyard_new_2018,
	title = {New human gene tally reignites debate},
	volume = {558},
	rights = {2018 Nature},
	url = {http://www.nature.com/articles/d41586-018-05462-w},
	doi = {10.1038/d41586-018-05462-w},
	abstract = {Some fifteen years after the human genome was sequenced, researchers still can’t agree on how many genes it contains.},
	pages = {354--355},
	journaltitle = {Nature},
	author = {Willyard, Cassandra},
	urldate = {2019-08-14},
	date = {2018-06-19},
	file = {Full Text:/home/jlagarde/Zotero/storage/DGT7YACU/Willyard - 2018 - New human gene tally reignites debate.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/I7R6LK47/d41586-018-05462-w.html:text/html}
}

@article{pertea_chess:_2018,
	title = {{CHESS}: a new human gene catalog curated from thousands of large-scale {RNA} sequencing experiments reveals extensive transcriptional noise},
	volume = {19},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-018-1590-2},
	doi = {10.1186/s13059-018-1590-2},
	shorttitle = {{CHESS}},
	abstract = {We assembled the sequences from deep {RNA} sequencing experiments by the Genotype-Tissue Expression ({GTEx}) project, to create a new catalog of human genes and transcripts, called {CHESS}. The new database contains 42,611 genes, of which 20,352 are potentially protein-coding and 22,259 are noncoding, and a total of 323,258 transcripts. These include 224 novel protein-coding genes and 116,156 novel transcripts. We detected over 30 million additional transcripts at more than 650,000 genomic loci, nearly all of which are likely nonfunctional, revealing a heretofore unappreciated amount of transcriptional noise in human cells. The {CHESS} database is available at http://ccb.jhu.edu/chess.},
	pages = {208},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Pertea, Mihaela and Shumate, Alaina and Pertea, Geo and Varabyou, Ales and Breitwieser, Florian P. and Chang, Yu-Chi and Madugundu, Anil K. and Pandey, Akhilesh and Salzberg, Steven L.},
	urldate = {2019-08-14},
	date = {2018-11-28},
	file = {Full Text:/home/jlagarde/Zotero/storage/EBERSV8A/Pertea et al. - 2018 - CHESS a new human gene catalog curated from thous.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/JW5TLQ2D/s13059-018-1590-2.html:text/html}
}

@article{jungreis_nearly_2018,
	title = {Nearly all new protein-coding predictions in the {CHESS} database are not protein-coding},
	rights = {© 2018, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), {CC} {BY} 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/360602v1},
	doi = {10.1101/360602},
	abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}p{\textgreater}In a 2018 paper posted to {bioRxiv}, Pertea et al. presented the {CHESS} database, a new catalog of human gene annotations that includes 1,178 new protein-coding predictions. These are based on evidence of transcription in human tissues and homology to earlier annotations in human and other mammals. Here, we reanalyze the evidence used by {CHESS}, and find that nearly all protein-coding predictions are false positives. We find that 86\% overlap transposons marked by {RepeatMasker} that are known to frequently result in false positive protein-coding predictions. More than half are homologous to only nine \textit{Alu}-derived primate sequences corresponding to an erroneous and previously withdrawn Pfam protein domain. The entire set shows poor evolutionary conservation and {PhyloCSF} protein-coding evolutionary signatures indistinguishable from noncoding {RNAs}, indicating lack of protein-coding constraint. Only four predictions are supported by mass spectrometry evidence, and even those matches are inconclusive. Overall, the new protein-coding predictions are unsupported by any credible experimental or evolutionary evidence of function, result primarily from homology to genes incorrectly classified as protein-coding, and are unlikely to encode functional proteins.{\textless}/p{\textgreater}},
	pages = {360602},
	journaltitle = {{bioRxiv}},
	author = {Jungreis, Irwin and Tress, Michael L. and Mudge, Jonathan and Sisu, Cristina and Hunt, Toby and Johnson, Rory and Uszczynska-Ratajczak, Barbara and Lagarde, Julien and Wright, James and Muir, Paul and Gerstein, Mark and Guigo, Roderic and Kellis, Manolis and Frankish, Adam and Flicek, Paul and Consortium, The {GENCODE}},
	urldate = {2019-08-14},
	date = {2018-07-02},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/ZH6DWMUC/Jungreis et al. - 2018 - Nearly all new protein-coding predictions in the C.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/G545HCMG/360602v1.html:text/html}
}

@article{gregory_modulation_1999,
	title = {The Modulation of {DNA} Content: Proximate Causes and Ultimate Consequences},
	volume = {9},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/9/4/317},
	doi = {10.1101/gr.9.4.317},
	shorttitle = {The Modulation of {DNA} Content},
	abstract = {The forces responsible for modulating the large-scale features of the genome remain one of the most difficult issues confronting evolutionary biology. Although diversity in chromosomal architecture, nucleotide composition, and genome size has been well documented, there is little understanding of either the evolutionary origins or impact of much of this variation. The 80,000-fold divergence in genome sizes among eukaryotes represents perhaps the greatest challenge for genomic holists. Although some researchers continue to characterize much variation in genome size as a mere by-product of an intragenomic selfish {DNA} “free-for-all” there is increasing evidence for the primacy of selection in molding genome sizes via impacts on cell size and division rates. Moreover, processes inducing quantum or doubling series variation in gametic or somatic genome sizes are common. These abrupt shifts have broad effects on phenotypic attributes at both cellular and organismal levels and may play an important role in explaining episodes of rapid—or even saltational—character state evolution.},
	pages = {317--324},
	number = {4},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Gregory, T. Ryan and Hebert, Paul D. N.},
	urldate = {2019-08-15},
	date = {1999-04-01},
	langid = {english},
	pmid = {10207154},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/H87ZSP5D/Gregory and Hebert - 1999 - The Modulation of DNA Content Proximate Causes an.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/4DQ62MUD/317.html:text/html;The Modulation of DNA Content\: Proximate Causes and Ultimate Consequences:/home/jlagarde/Zotero/storage/FVTI54PK/10.1101@gr.9.4.317.pdf:application/pdf}
}

@article{elgar_tuning_2008,
	title = {Tuning in to the signals: noncoding sequence conservation in vertebrate genomes},
	volume = {24},
	issn = {0168-9525},
	doi = {10.1016/j.tig.2008.04.005},
	shorttitle = {Tuning in to the signals},
	abstract = {Aligning and comparing genomic sequences enables the identification of conserved sequence signatures and can enrich for coding and noncoding functional regions. In vertebrates, the comparison of human and rodent genomes and the comparison of evolutionarily distant genomes, such as human and pufferfish, have identified specific sets of 'ultraconserved' sequence elements associated with the control of early development. However, is this just the tip of a 'conservation iceberg' or do these sequences represent a specific class of regulatory element? Studies on the zebrafish phox2b gene region and the {ENCODE} project suggest that many regulatory elements are not highly conserved, posing intriguing questions about the relationship between noncoding sequence conservation and function and the evolution of regulatory sequences.},
	pages = {344--352},
	number = {7},
	journaltitle = {Trends in genetics: {TIG}},
	shortjournal = {Trends Genet.},
	author = {Elgar, Greg and Vavouri, Tanya},
	date = {2008-07},
	pmid = {18514361},
	keywords = {Animals, Conserved Sequence, Genome, Humans, Computational Biology, Vertebrates, {DNA}, Intergenic, Invertebrates}
}

@article{elliott_whats_2015,
	title = {What's in a genome? The C-value enigma and the evolution of eukaryotic genome content},
	volume = {370},
	issn = {0962-8436},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571570/},
	doi = {10.1098/rstb.2014.0331},
	shorttitle = {What's in a genome?},
	abstract = {Some notable exceptions aside, eukaryotic genomes are distinguished from those of Bacteria and Archaea in a number of ways, including chromosome structure and number, repetitive {DNA} content, and the presence of introns in protein-coding regions. One of the most notable differences between eukaryotic and prokaryotic genomes is in size. Unlike their prokaryotic counterparts, eukaryotes exhibit enormous (more than 60 000-fold) variability in genome size which is not explained by differences in gene number. Genome size is known to correlate with cell size and division rate, and by extension with numerous organism-level traits such as metabolism, developmental rate or body size. Less well described are the relationships between genome size and other properties of the genome, such as gene content, transposable element content, base pair composition and related features. The rapid expansion of ‘complete’ genome sequencing projects has, for the first time, made it possible to examine these relationships across a wide range of eukaryotes in order to shed new light on the causes and correlates of genome size diversity. This study presents the results of phylogenetically informed comparisons of genome data for more than 500 species of eukaryotes. Several relationships are described between genome size and other genomic parameters, and some recommendations are presented for how these insights can be extended even more broadly in the future.},
	number = {1678},
	journaltitle = {Philosophical Transactions of the Royal Society B: Biological Sciences},
	shortjournal = {Philos Trans R Soc Lond B Biol Sci},
	author = {Elliott, Tyler A. and Gregory, T. Ryan},
	urldate = {2019-08-15},
	date = {2015-09-26},
	pmid = {26323762},
	pmcid = {PMC4571570},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/GQND4EHB/Elliott and Gregory - 2015 - What's in a genome The C-value enigma and the evo.pdf:application/pdf}
}

@article{ponting_evolution_2009,
	title = {Evolution and Functions of Long Noncoding {RNAs}},
	volume = {136},
	issn = {0092-8674},
	url = {http://www.sciencedirect.com/science/article/pii/S0092867409001421},
	doi = {10.1016/j.cell.2009.02.006},
	abstract = {{RNA} is not only a messenger operating between {DNA} and protein. Transcription of essentially the entire eukaryotic genome generates a myriad of non-protein-coding {RNA} species that show complex overlapping patterns of expression and regulation. Although long noncoding {RNAs} ({lncRNAs}) are among the least well-understood of these transcript species, they cannot all be dismissed as merely transcriptional “noise.” Here, we review the evolution of {lncRNAs} and their roles in transcriptional regulation, epigenetic gene regulation, and disease.},
	pages = {629--641},
	number = {4},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Ponting, Chris P. and Oliver, Peter L. and Reik, Wolf},
	urldate = {2019-08-19},
	date = {2009-02-20},
	file = {ScienceDirect Snapshot:/home/jlagarde/Zotero/storage/NE636UZZ/S0092867409001421.html:text/html}
}

@article{taft_relationship_2007,
	title = {The relationship between non-protein-coding {DNA} and eukaryotic complexity},
	volume = {29},
	issn = {0265-9247},
	doi = {10.1002/bies.20544},
	abstract = {There are two intriguing paradoxes in molecular biology--the inconsistent relationship between organismal complexity and (1) cellular {DNA} content and (2) the number of protein-coding genes--referred to as the C-value and G-value paradoxes, respectively. The C-value paradox may be largely explained by varying ploidy. The G-value paradox is more problematic, as the extent of protein coding sequence remains relatively static over a wide range of developmental complexity. We show by analysis of sequenced genomes that the relative amount of non-protein-coding sequence increases consistently with complexity. We also show that the distribution of introns in complex organisms is non-random. Genes composed of large amounts of intronic sequence are significantly overrepresented amongst genes that are highly expressed in the nervous system, and amongst genes downregulated in embryonic stem cells and cancers. We suggest that the informational paradox in complex organisms may be explained by the expansion of cis-acting regulatory elements and genes specifying trans-acting non-protein-coding {RNAs}.},
	pages = {288--299},
	number = {3},
	journaltitle = {{BioEssays}: News and Reviews in Molecular, Cellular and Developmental Biology},
	shortjournal = {Bioessays},
	author = {Taft, Ryan J. and Pheasant, Michael and Mattick, John S.},
	date = {2007-03},
	pmid = {17295292},
	keywords = {Animals, Genome, Humans, Proteins, {RNA}, Introns, Eukaryotic Cells, Genes, Evolution, Molecular, Regulatory Sequences, Nucleic Acid, {DNA}, Intergenic}
}

@article{graur_upper_2017,
	title = {An Upper Limit on the Functional Fraction of the Human Genome},
	volume = {9},
	url = {https://academic.oup.com/gbe/article/9/7/1880/3952726},
	doi = {10.1093/gbe/evx121},
	abstract = {Abstract.  For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the},
	pages = {1880--1885},
	number = {7},
	journaltitle = {Genome Biology and Evolution},
	shortjournal = {Genome Biol Evol},
	author = {Graur, Dan},
	urldate = {2019-08-19},
	date = {2017-07-01},
	langid = {english},
	file = {An Upper Limit on the Functional Fraction of the Human Genome:/home/jlagarde/Zotero/storage/R2L26FU6/graur2017.pdf:application/pdf;Full Text PDF:/home/jlagarde/Zotero/storage/6U6T8ESH/Graur - 2017 - An Upper Limit on the Functional Fraction of the H.pdf:application/pdf}
}

@article{doolittle_distinguishing_2014,
	title = {Distinguishing between “Function” and “Effect” in Genome Biology},
	volume = {6},
	issn = {1759-6653},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041003/},
	doi = {10.1093/gbe/evu098},
	abstract = {Much confusion in genome biology results from conflation of possible meanings of the word “function.” We suggest that, in this connection, attention should be paid to evolutionary biologists and philosophers who have previously dealt with this problem. We need only decide that although all genomic structures have effects, only some of them should be said to have functions. Although it will very often be difficult or impossible to establish function (strictly defined), it should not automatically be assumed. We enjoin genomicists in particular to pay greater attention to parsing biological effects.},
	pages = {1234--1237},
	number = {5},
	journaltitle = {Genome Biology and Evolution},
	shortjournal = {Genome Biol Evol},
	author = {Doolittle, W. Ford and Brunet, Tyler D.P. and Linquist, Stefan and Gregory, T. Ryan},
	urldate = {2019-08-20},
	date = {2014-05-09},
	pmid = {24814287},
	pmcid = {PMC4041003},
	file = {Distinguishing between “Function” and “Effect” in Genome Biology:/home/jlagarde/Zotero/storage/3DVQEJWU/doolittle2014.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/QDNZ9TAD/Doolittle et al. - 2014 - Distinguishing between “Function” and “Effect” in .pdf:application/pdf}
}

@article{konstantinidis_trends_2004,
	title = {Trends between gene content and genome size in prokaryotic species with larger genomes},
	volume = {101},
	rights = {Copyright © 2004, The National Academy of Sciences},
	issn = {0027-8424, 1091-6490},
	url = {https://www.pnas.org/content/101/9/3160},
	doi = {10.1073/pnas.0308653100},
	abstract = {{\textless}p{\textgreater}Although the evolution process and ecological benefits of symbiotic species with small genomes are well understood, these issues remain poorly elucidated for free-living species with large genomes. We have compared 115 completed prokaryotic genomes by using the Clusters of Orthologous Groups database to determine whether there are changes with genome size in the proportion of the genome attributable to particular cellular processes, because this may reflect both cellular and ecological strategies associated with genome expansion. We found that large genomes are disproportionately enriched in regulation and secondary metabolism genes and depleted in protein translation, {DNA} replication, cell division, and nucleotide metabolism genes compared to medium- and small-sized genomes. Furthermore, large genomes do not accumulate noncoding {DNA} or hypothetical {ORFs}, because the portion of the genome devoted to these functions remained constant with genome size. Traits other than genome size or strain-specific processes are reflected by the dispersion around the mean for cell functions that showed no correlation with genome size. For example, Archaea had significantly more genes in energy production, coenzyme metabolism, and the poorly characterized category, and fewer in cell membrane biogenesis and carbohydrate metabolism than Bacteria. The trends we noted with genome size by using Clusters of Orthologous Groups were confirmed by our independent analysis with The Institute for Genomic Research9s Comprehensive Microbial Resource and Kyoto Encyclopedia of Genes and Genomes9 Orthology annotation databases. These trends suggest that larger genome-sized species may dominate in environments where resources are scarce but diverse and where there is little penalty for slow growth, such as soil.{\textless}/p{\textgreater}},
	pages = {3160--3165},
	number = {9},
	journaltitle = {Proceedings of the National Academy of Sciences},
	shortjournal = {{PNAS}},
	author = {Konstantinidis, Konstantinos T. and Tiedje, James M.},
	urldate = {2019-08-20},
	date = {2004-03-02},
	langid = {english},
	pmid = {14973198},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/46F95BRF/Konstantinidis and Tiedje - 2004 - Trends between gene content and genome size in pro.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/GJ3CMIE9/tab-figures-data.html:text/html;Trends between gene content and genome size in prokaryotic species with larger genomes:/home/jlagarde/Zotero/storage/56KUDQTD/konstantinidis2004.pdf:application/pdf}
}

@article{international_wheat_genome_sequencing_consortium_iwgsc_shifting_2018,
	title = {Shifting the limits in wheat research and breeding using a fully annotated reference genome},
	volume = {361},
	issn = {1095-9203},
	doi = {10.1126/science.aar7191},
	abstract = {An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94\% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.},
	number = {6403},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {{International Wheat Genome Sequencing Consortium (IWGSC)} and {IWGSC RefSeq principal investigators:} and Appels, Rudi and Eversole, Kellye and Feuillet, Catherine and Keller, Beat and Rogers, Jane and Stein, Nils and {IWGSC whole-genome assembly principal investigators:} and Pozniak, Curtis J. and Stein, Nils and Choulet, Frédéric and Distelfeld, Assaf and Eversole, Kellye and Poland, Jesse and Rogers, Jane and Ronen, Gil and Sharpe, Andrew G. and {Whole-genome sequencing and assembly:} and Pozniak, Curtis and Ronen, Gil and Stein, Nils and Barad, Omer and Baruch, Kobi and Choulet, Frédéric and Keeble-Gagnère, Gabriel and Mascher, Martin and Sharpe, Andrew G. and Ben-Zvi, Gil and Josselin, Ambre-Aurore and {Hi-C data-based scaffolding:} and Stein, Nils and Mascher, Martin and Himmelbach, Axel and {Whole-genome assembly quality control and analyses:} and Choulet, Frédéric and Keeble-Gagnère, Gabriel and Mascher, Martin and Rogers, Jane and Balfourier, François and Gutierrez-Gonzalez, Juan and Hayden, Matthew and Josselin, Ambre-Aurore and Koh, ChuShin and Muehlbauer, Gary and Pasam, Raj K. and Paux, Etienne and Pozniak, Curtis J. and Rigault, Philippe and Sharpe, Andrew G. and Tibbits, Josquin and Tiwari, Vijay and {Pseudomolecule assembly:} and Choulet, Frédéric and Keeble-Gagnère, Gabriel and Mascher, Martin and Josselin, Ambre-Aurore and Rogers, Jane and {RefSeq genome structure and gene analyses:} and Spannagl, Manuel and Choulet, Frédéric and Lang, Daniel and Gundlach, Heidrun and Haberer, Georg and Keeble-Gagnère, Gabriel and Mayer, Klaus F. X. and Ormanbekova, Danara and Paux, Etienne and Prade, Verena and Šimková, Hana and Wicker, Thomas and {Automated annotation:} and Choulet, Frédéric and Spannagl, Manuel and Swarbreck, David and Rimbert, Hélène and Felder, Marius and Guilhot, Nicolas and Gundlach, Heidrun and Haberer, Georg and Kaithakottil, Gemy and Keilwagen, Jens and Lang, Daniel and Leroy, Philippe and Lux, Thomas and Mayer, Klaus F. X. and Twardziok, Sven and Venturini, Luca and {Manual gene curation:} and Appels, Rudi and Rimbert, Hélène and Choulet, Frédéric and Juhász, Angéla and Keeble-Gagnère, Gabriel and {Subgenome comparative analyses:} and Choulet, Frédéric and Spannagl, Manuel and Lang, Daniel and Abrouk, Michael and Haberer, Georg and Keeble-Gagnère, Gabriel and Mayer, Klaus F. X. and Wicker, Thomas and {Transposable elements:} and Choulet, Frédéric and Wicker, Thomas and Gundlach, Heidrun and Lang, Daniel and Spannagl, Manuel and {Phylogenomic analyses:} and Lang, Daniel and Spannagl, Manuel and Appels, Rudi and Fischer, Iris and {Transcriptome analyses and RNA-seq data:} and Uauy, Cristobal and Borrill, Philippa and Ramirez-Gonzalez, Ricardo H. and Appels, Rudi and Arnaud, Dominique and Chalabi, Smahane and Chalhoub, Boulos and Choulet, Frédéric and Cory, Aron and Datla, Raju and Davey, Mark W. and Hayden, Matthew and Jacobs, John and Lang, Daniel and Robinson, Stephen J. and Spannagl, Manuel and Steuernagel, Burkhard and Tibbits, Josquin and Tiwari, Vijay and van Ex, Fred and Wulff, Brande B. H. and {Whole-genome methylome:} and Pozniak, Curtis J. and Robinson, Stephen J. and Sharpe, Andrew G. and Cory, Aron and {Histone mark analyses:} and Benhamed, Moussa and Paux, Etienne and Bendahmane, Abdelhafid and Concia, Lorenzo and Latrasse, David and {BAC chromosome MTP IWGSC–Bayer Whole-Genome Profiling (WGP) tags:} and Rogers, Jane and Jacobs, John and Alaux, Michael and Appels, Rudi and Bartoš, Jan and Bellec, Arnaud and Berges, Hélène and Doležel, Jaroslav and Feuillet, Catherine and Frenkel, Zeev and Gill, Bikram and Korol, Abraham and Letellier, Thomas and Olsen, Odd-Arne and Šimková, Hana and Singh, Kuldeep and Valárik, Miroslav and van der Vossen, Edwin and Vautrin, Sonia and Weining, Song and {Chromosome LTC mapping and physical mapping quality control:} and Korol, Abraham and Frenkel, Zeev and Fahima, Tzion and Glikson, Vladimir and Raats, Dina and Rogers, Jane and {RH mapping:} and Tiwari, Vijay and Gill, Bikram and Paux, Etienne and Poland, Jesse and {Optical mapping:} and Doležel, Jaroslav and Číhalíková, Jarmila and Šimková, Hana and Toegelová, Helena and Vrána, Jan and {Recombination analyses:} and Sourdille, Pierre and Darrier, Benoit and {Gene family analyses:} and Appels, Rudi and Spannagl, Manuel and Lang, Daniel and Fischer, Iris and Ormanbekova, Danara and Prade, Verena and {CBF gene family:} and Barabaschi, Delfina and Cattivelli, Luigi and {Dehydrin gene family:} and Hernandez, Pilar and Galvez, Sergio and Budak, Hikmet and {NLR gene family:} and Steuernagel, Burkhard and Jones, Jonathan D. G. and Witek, Kamil and Wulff, Brande B. H. and Yu, Guotai and {PPR gene family:} and Small, Ian and Melonek, Joanna and Zhou, Ruonan and {Prolamin gene family:} and Juhász, Angéla and Belova, Tatiana and Appels, Rudi and Olsen, Odd-Arne and {WAK gene family:} and Kanyuka, Kostya and King, Robert and {Stem solidness (SSt1) QTL team:} and Nilsen, Kirby and Walkowiak, Sean and Pozniak, Curtis J. and Cuthbert, Richard and Datla, Raju and Knox, Ron and Wiebe, Krysta and Xiang, Daoquan and {Flowering locus C (FLC) gene team:} and Rohde, Antje and Golds, Timothy and {Genome size analysis:} and Doležel, Jaroslav and Čížková, Jana and Tibbits, Josquin and {MicroRNA and tRNA annotation:} and Budak, Hikmet and Akpinar, Bala Ani and Biyiklioglu, Sezgi and {Genetic maps and mapping:} and Muehlbauer, Gary and Poland, Jesse and Gao, Liangliang and Gutierrez-Gonzalez, Juan and N'Daiye, Amidou and {BAC libraries and chromosome sorting:} and Doležel, Jaroslav and Šimková, Hana and Číhalíková, Jarmila and Kubaláková, Marie and Šafář, Jan and Vrána, Jan and {BAC pooling, BAC library repository, and access:} and Berges, Hélène and Bellec, Arnaud and Vautrin, Sonia and {IWGSC sequence and data repository and access:} and Alaux, Michael and Alfama, Françoise and Adam-Blondon, Anne-Françoise and Flores, Raphael and Guerche, Claire and Letellier, Thomas and Loaec, Mikaël and Quesneville, Hadi and {Physical maps and BAC-based sequences:} and {1A BAC sequencing and assembly:} and Pozniak, Curtis J. and Sharpe, Andrew G. and Walkowiak, Sean and Budak, Hikmet and Condie, Janet and Ens, Jennifer and Koh, ChuShin and Maclachlan, Ron and Tan, Yifang and Wicker, Thomas and {1B BAC sequencing and assembly:} and Choulet, Frédéric and Paux, Etienne and Alberti, Adriana and Aury, Jean-Marc and Balfourier, François and Barbe, Valérie and Couloux, Arnaud and Cruaud, Corinne and Labadie, Karine and Mangenot, Sophie and Wincker, Patrick and {1D, 4D, and 6D physical mapping:} and Gill, Bikram and Kaur, Gaganpreet and Luo, Mingcheng and Sehgal, Sunish and {2AL physical mapping:} and Singh, Kuldeep and Chhuneja, Parveen and Gupta, Om Prakash and Jindal, Suruchi and Kaur, Parampreet and Malik, Palvi and Sharma, Priti and Yadav, Bharat and {2AS physical mapping:} and Singh, Nagendra K. and Khurana, JitendraP and Chaudhary, Chanderkant and Khurana, Paramjit and Kumar, Vinod and Mahato, Ajay and Mathur, Saloni and Sevanthi, Amitha and Sharma, Naveen and Tomar, Ram Sewak and {2B, 2D, 4B, 5BL, and 5DL IWGSC–Bayer Whole-Genome Profiling (WGP) physical maps:} and Rogers, Jane and Jacobs, John and Alaux, Michael and Bellec, Arnaud and Berges, Hélène and Doležel, Jaroslav and Feuillet, Catherine and Frenkel, Zeev and Gill, Bikram and Korol, Abraham and van der Vossen, Edwin and Vautrin, Sonia and {3AL physical mapping:} and Gill, Bikram and Kaur, Gaganpreet and Luo, Mingcheng and Sehgal, Sunish and {3DS physical mapping and BAC sequencing and assembly:} and Bartoš, Jan and Holušová, Kateřina and Plíhal, Ondřej and {3DL BAC sequencing and assembly:} and Clark, Matthew D. and Heavens, Darren and Kettleborough, George and Wright, Jon and {4A physical mapping, BAC sequencing, assembly, and annotation:} and Valárik, Miroslav and Abrouk, Michael and Balcárková, Barbora and Holušová, Kateřina and Hu, Yuqin and Luo, Mingcheng and {5BS BAC sequencing and assembly:} and Salina, Elena and Ravin, Nikolai and Skryabin, Konstantin and Beletsky, Alexey and Kadnikov, Vitaly and Mardanov, Andrey and Nesterov, Michail and Rakitin, Andrey and Sergeeva, Ekaterina and {6B BAC sequencing and assembly:} and Handa, Hirokazu and Kanamori, Hiroyuki and Katagiri, Satoshi and Kobayashi, Fuminori and Nasuda, Shuhei and Tanaka, Tsuyoshi and Wu, Jianzhong and {7A physical mapping and BAC sequencing:} and Appels, Rudi and Hayden, Matthew and Keeble-Gagnère, Gabriel and Rigault, Philippe and Tibbits, Josquin and {7B physical mapping, BAC sequencing, and assembly:} and Olsen, Odd-Arne and Belova, Tatiana and Cattonaro, Federica and Jiumeng, Min and Kugler, Karl and Mayer, Klaus F. X. and Pfeifer, Matthias and Sandve, Simen and Xun, Xu and Zhan, Bujie and {7DS BAC sequencing and assembly:} and Šimková, Hana and Abrouk, Michael and Batley, Jacqueline and Bayer, Philipp E. and Edwards, David and Hayashi, Satomi and Toegelová, Helena and Tulpová, Zuzana and Visendi, Paul and {7DL physical mapping and BAC sequencing:} and Weining, Song and Cui, Licao and Du, Xianghong and Feng, Kewei and Nie, Xiaojun and Tong, Wei and Wang, Le and {Figures:} and Borrill, Philippa and Gundlach, Heidrun and Galvez, Sergio and Kaithakottil, Gemy and Lang, Daniel and Lux, Thomas and Mascher, Martin and Ormanbekova, Danara and Prade, Verena and Ramirez-Gonzalez, Ricardo H. and Spannagl, Manuel and Stein, Nils and Uauy, Cristobal and Venturini, Luca and {Manuscript writing team:} and Stein, Nils and Appels, Rudi and Eversole, Kellye and Rogers, Jane and Borrill, Philippa and Cattivelli, Luigi and Choulet, Frédéric and Hernandez, Pilar and Kanyuka, Kostya and Lang, Daniel and Mascher, Martin and Nilsen, Kirby and Paux, Etienne and Pozniak, Curtis J. and Ramirez-Gonzalez, Ricardo H. and Šimková, Hana and Small, Ian and Spannagl, Manuel and Swarbreck, David and Uauy, Cristobal},
	date = {2018},
	pmid = {30115783},
	keywords = {Transcriptome, Atlases as Topic, Molecular Sequence Annotation, Multigene Family, Phylogeny, Quantitative Trait Loci, Reference Standards, Genome, Plant, Bread, Breeding, Gene Expression Regulation, Developmental, Gene Expression Regulation, Plant, Triticum},
	file = {Full Text:/home/jlagarde/Zotero/storage/8NFSNQ2F/International Wheat Genome Sequencing Consortium (IWGSC) et al. - 2018 - Shifting the limits in wheat research and breeding.pdf:application/pdf}
}

@article{pertea_between_2010,
	title = {Between a chicken and a grape: estimating the number of human genes},
	volume = {11},
	issn = {1474-760X},
	doi = {10.1186/gb-2010-11-5-206},
	shorttitle = {Between a chicken and a grape},
	abstract = {Many people expected the question 'How many genes in the human genome?' to be resolved with the publication of the genome sequence in 2001, but estimates continue to fluctuate.},
	pages = {206},
	number = {5},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol.},
	author = {Pertea, Mihaela and Salzberg, Steven L.},
	date = {2010},
	pmid = {20441615},
	pmcid = {PMC2898077},
	keywords = {Animals, Humans, Chickens, Genes, Transcription, Genetic, Genome, Human, Vitis},
	file = {Full Text:/home/jlagarde/Zotero/storage/W4R349A9/Pertea and Salzberg - 2010 - Between a chicken and a grape estimating the numb.pdf:application/pdf}
}

@article{montalbano_high-throughput_2017,
	title = {High-Throughput Approaches to Pinpoint Function within the Noncoding Genome},
	volume = {68},
	issn = {1097-2765},
	url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(17)30668-8},
	doi = {10.1016/j.molcel.2017.09.017},
	pages = {44--59},
	number = {1},
	journaltitle = {Molecular Cell},
	shortjournal = {Molecular Cell},
	author = {Montalbano, Antonino and Canver, Matthew C. and Sanjana, Neville E.},
	urldate = {2019-08-20},
	date = {2017-10-05},
	pmid = {28985510},
	keywords = {Cas9, conservation, {CRISPR}, enhancers, functional genomics, gene editing, gene expression, mutagenesis, noncoding genome, pooled screens},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/9XDW7HPP/Montalbano et al. - 2017 - High-Throughput Approaches to Pinpoint Function wi.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/L4XL37Y7/S1097-2765(17)30668-8.html:text/html}
}

@article{schneiker_complete_2007,
	title = {Complete genome sequence of the myxobacterium \textit{Sorangium cellulosum}},
	volume = {25},
	rights = {2007 Nature Publishing Group},
	issn = {1546-1696},
	url = {https://www.nature.com/articles/nbt1354},
	doi = {10.1038/nbt1354},
	abstract = {The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome sequenced to date. No global synteny with the genome of Myxococcus xanthus is apparent, revealing an unanticipated level of divergence between these myxobacteria. A large percentage of the genome is devoted to regulation, particularly post-translational phosphorylation, which probably supports the strain's complex, social lifestyle. This regulatory network includes the highest number of eukaryotic protein kinase–like kinases discovered in any organism. Seventeen secondary metabolite loci are encoded in the genome, as well as many enzymes with potential utility in industry.},
	pages = {1281--1289},
	number = {11},
	journaltitle = {Nature Biotechnology},
	author = {Schneiker, Susanne and Perlova, Olena and Kaiser, Olaf and Gerth, Klaus and Alici, Aysel and Altmeyer, Matthias O. and Bartels, Daniela and Bekel, Thomas and Beyer, Stefan and Bode, Edna and Bode, Helge B. and Bolten, Christoph J. and Choudhuri, Jomuna V. and Doss, Sabrina and Elnakady, Yasser A. and Frank, Bettina and Gaigalat, Lars and Goesmann, Alexander and Groeger, Carolin and Gross, Frank and Jelsbak, Lars and Jelsbak, Lotte and Kalinowski, Jörn and Kegler, Carsten and Knauber, Tina and Konietzny, Sebastian and Kopp, Maren and Krause, Lutz and Krug, Daniel and Linke, Bukhard and Mahmud, Taifo and Martinez-Arias, Rosa and {McHardy}, Alice C. and Merai, Michelle and Meyer, Folker and Mormann, Sascha and Muñoz-Dorado, Jose and Perez, Juana and Pradella, Silke and Rachid, Shwan and Raddatz, Günter and Rosenau, Frank and Rückert, Christian and Sasse, Florenz and Scharfe, Maren and Schuster, Stephan C. and Suen, Garret and Treuner-Lange, Anke and Velicer, Gregory J. and Vorhölter, Frank-Jörg and Weissman, Kira J. and Welch, Roy D. and Wenzel, Silke C. and Whitworth, David E. and Wilhelm, Susanne and Wittmann, Christoph and Blöcker, Helmut and Pühler, Alfred and Müller, Rolf},
	urldate = {2019-08-20},
	date = {2007-11},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/5D5MH46D/Schneiker et al. - 2007 - Complete genome sequence of the myxobacterium iS.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/Y56TL5Q2/nbt1354.html:text/html}
}

@article{mirsky_desoxyribonucleic_1951,
	title = {The desoxyribonucleic acid content of animal cells and its evolutionary significance},
	volume = {34},
	issn = {0022-1295},
	doi = {10.1085/jgp.34.4.451},
	abstract = {1. Evidence is summarized for the constancy of {DNA} content for each set of chromosomes in the various cells of an organism. 2. The {DNA} contents of the egg and sperm nuclei are the same. 3. A brief survey is given of {DNA} contents per cell in invertebrates and vertebrates. (a) In invertebrates there is some slight evidence that when primitive and higher forms are compared the amount of {DNA} per cell is increased in the latter. (b) In fishes there is a tendency for the amount of {DNA} per cell to remain constant within the different species of a family. (c) The values of {DNA} per cell in lung fishes, amphibians, reptiles, and birds suggest that in the evolution of these vertebrates there has been a decline in {DNA} content per cell. 4. Concerning the significance of quantity of {DNA} per cell in vertebrates: (a) It appears not to be in proportion to the number of different genes in a cell. (b) It may be related to the number of strands in the chromosomes. (c) In homologous cells of different animals it is directly related to the mass of the cell.},
	pages = {451--462},
	number = {4},
	journaltitle = {The Journal of General Physiology},
	shortjournal = {J. Gen. Physiol.},
	author = {Mirsky, A. E. and Ris, H.},
	date = {1951-03-20},
	pmid = {14824511},
	pmcid = {PMC2147229},
	keywords = {{DNA}, Animals, Cells, Amphibians, Biological Evolution, Vertebrates, Birds, {CELLS}, Fishes, Nucleic Acids, {NUCLEIC} {ACIDS}},
	file = {Full Text:/home/jlagarde/Zotero/storage/NQGJJ2W9/Mirsky and Ris - 1951 - The desoxyribonucleic acid content of animal cells.pdf:application/pdf}
}

@article{thomas_genetic_1971,
	title = {The genetic organization of chromosomes},
	volume = {5},
	issn = {0066-4197},
	doi = {10.1146/annurev.ge.05.120171.001321},
	pages = {237--256},
	journaltitle = {Annual Review of Genetics},
	shortjournal = {Annu. Rev. Genet.},
	author = {Thomas, C. A.},
	date = {1971},
	pmid = {16097657},
	keywords = {{DNA}, Chromosomes, {DNA} Replication, Models, Genetic, Chromatids, Prokaryotic Cells}
}

@article{price_genome_2005,
	title = {Genome evolution in the genus Sorghum (Poaceae)},
	volume = {95},
	issn = {0305-7364},
	doi = {10.1093/aob/mci015},
	abstract = {{BACKGROUND} {AND} {AIMS}: The roles of variation in {DNA} content in plant evolution and adaptation remain a major biological enigma. Chromosome number and 2C {DNA} content were determined for 21 of the 25 species of the genus Sorghum and analysed from a phylogenetic perspective.
{METHODS}: {DNA} content was determined by flow cytometry. A Sorghum phylogeny was constructed based on combined nuclear {ITS} and chloroplast {ndhF} {DNA} sequences.
{KEY} {RESULTS}: Chromosome counts (2n = 10, 20, 30, 40) were, with few exceptions, concordant with published numbers. New chromosome numbers were obtained for S. amplum (2n = 30) and S. leiocladum (2n = 10). 2C {DNA} content varies 8.1-fold (1.27-10.30 pg) among the 21 Sorghum species. 2C {DNA} content varies 3.6-fold from 1.27 pg to 4.60 pg among the 2n = 10 species and 5.8-fold (1.52-8.79 pg) among the 2n = 20 species. The x = 5 genome size varies over an 8.8-fold range from 0.26 pg to 2.30 pg. The mean 2C {DNA} content of perennial species (6.20 pg) is significantly greater than the mean (2.92 pg) of the annuals. Among the 21 species studied, the mean x = 5 genome size of annuals (1.15 pg) and of perennials (1.29 pg) is not significantly different. Statistical analysis of Australian species showed: (a) mean 2C {DNA} content of annual (2.89 pg) and perennial (7.73 pg) species is significantly different; (b) mean x = 5 genome size of perennials (1.66 pg) is significantly greater than that of the annuals (1.09 pg); (c) the mean maximum latitude at which perennial species grow (-25.4 degrees) is significantly greater than the mean maximum latitude (-17.6) at which annual species grow.
{CONCLUSIONS}: The {DNA} sequence phylogeny splits Sorghum into two lineages, one comprising the 2n = 10 species with large genomes and their polyploid relatives, and the other with the 2n = 20, 40 species with relatively small genomes. An apparent phylogenetic reduction in genome size has occurred in the 2n = 10 lineage. Genome size evolution in the genus Sorghum apparently did not involve a 'one way ticket to genomic obesity' as has been proposed for the grasses.},
	pages = {219--227},
	number = {1},
	journaltitle = {Annals of Botany},
	shortjournal = {Ann. Bot.},
	author = {Price, H. James and Dillon, Sally L. and Hodnett, George and Rooney, William L. and Ross, Larry and Johnston, J. Spencer},
	date = {2005-01},
	pmid = {15596469},
	pmcid = {PMC4246720},
	keywords = {Cell Nucleus, Karyotyping, Phylogeny, Evolution, Molecular, Genome, Plant, Chromosomes, Plant, {DNA}, Plant, Sorghum},
	file = {Full Text:/home/jlagarde/Zotero/storage/VLW3SHNP/Price et al. - 2005 - Genome evolution in the genus Sorghum (Poaceae).pdf:application/pdf}
}

@article{ohno_so_1972,
	title = {So much "junk" {DNA} in our genome},
	volume = {23},
	issn = {0068-2799},
	pages = {366--370},
	journaltitle = {Brookhaven Symposia in Biology},
	shortjournal = {Brookhaven Symp. Biol.},
	author = {Ohno, S.},
	date = {1972},
	pmid = {5065367},
	keywords = {{DNA}, Animals, Base Sequence, Genes, Mammals, Mutation, Genes, Regulator}
}

@article{doolittle_selfish_1980,
	title = {Selfish genes, the phenotype paradigm and genome evolution},
	volume = {284},
	issn = {0028-0836},
	doi = {10.1038/284601a0},
	abstract = {Natural selection operating within genomes will inevitably result in the appearance of {DNAs} with no phenotypic expression whose only 'function' is survival within genomes. Prokaryotic transposable elements and eukaryotic middle-repetitive sequences can be seen as such {DNA}'s and thus no phenotypic or evolutionary function need be assigned to them.},
	pages = {601--603},
	number = {5757},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Doolittle, W. F. and Sapienza, C.},
	date = {1980-04-17},
	pmid = {6245369},
	keywords = {{DNA}, Base Sequence, Biological Evolution, {DNA} Transposable Elements, Eukaryotic Cells, Phenotype, Selection, Genetic, {DNA}, Fungal, {DNA}, Bacterial, Cell Physiological Phenomena},
	file = {Selfish genes, the phenotype paradigm and genome evolution:/home/jlagarde/Zotero/storage/29PDVJFK/doolittle1980.pdf:application/pdf}
}

@article{orgel_selfish_1980,
	title = {Selfish {DNA}: the ultimate parasite},
	volume = {284},
	issn = {0028-0836},
	doi = {10.1038/284604a0},
	shorttitle = {Selfish {DNA}},
	abstract = {The {DNA} of higher organisms usually falls into two classes, one specific and the other comparatively nonspecific. It seems plausible that most of the latter originates by the spreading of sequences which had little or no effect on the phenotype. We examine this idea from the point of view of the natural selection of preferred replicators within the genome.},
	pages = {604--607},
	number = {5757},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Orgel, L. E. and Crick, F. H.},
	date = {1980-04-17},
	pmid = {7366731},
	keywords = {{DNA}, Animals, Base Sequence, Humans, Biological Evolution, {DNA} Replication, Energy Metabolism, Genes, Phenotype, Time Factors, {RNA}, Messenger, Selection, Genetic, Genes, Regulator, {RNA}, Heterogeneous Nuclear},
	file = {Selfish DNA\: the ultimate parasite:/home/jlagarde/Zotero/storage/E5H9HLJC/orgel1980.pdf:application/pdf}
}

@article{pace_evolutionary_2007,
	title = {The evolutionary history of human {DNA} transposons: Evidence for intense activity in the primate lineage},
	volume = {17},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832089/},
	doi = {10.1101/gr.5826307},
	shorttitle = {The evolutionary history of human {DNA} transposons},
	abstract = {Class 2, or {DNA} transposons, make up ∼3\% of the human genome, yet the evolutionary history of these elements has been largely overlooked and remains poorly understood. Here we carried out the first comprehensive analysis of the activity of human {DNA} transposons over the course of primate evolution using three independent computational methods. First, we conducted an exhaustive search for human {DNA} transposons nested within L1 and Alu elements known to be primate specific. Second, we assessed the presence/absence of 794 human {DNA} transposons at orthologous positions in 10 mammalian species using sequence data generated by The {ENCODE} Project. These two approaches, which do not rely upon sequence divergence, allowed us to classify {DNA} transposons into three different categories: anthropoid specific (40–63 My), primate specific (64–80 My), and eutherian wide (81–150 My). Finally, we used this data to calculate the substitution rates of {DNA} transposons for each category and refine the age of each family based on the average percent divergence of individual copies to their consensus. Based on these combined methods, we can confidently estimate that at least 40 human {DNA} transposon families, representing ∼98,000 elements (∼33 Mb) in the human genome, have been active in the primate lineage. There was a cessation in the transpositional activity of {DNA} transposons during the later phase of the primate radiation, with no evidence of elements younger than ∼37 My. This data points to intense activity of {DNA} transposons during the mammalian radiation and early primate evolution, followed, apparently, by their mass extinction in an anthropoid primate ancestor.},
	pages = {422--432},
	number = {4},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Pace, John K. and Feschotte, Cédric},
	urldate = {2019-08-20},
	date = {2007-04},
	pmid = {17339369},
	pmcid = {PMC1832089},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/UAH55TEH/Pace and Feschotte - 2007 - The evolutionary history of human DNA transposons.pdf:application/pdf;The evolutionary history of human DNA transposons\: Evidence for intense activity in the primate lineage:/home/jlagarde/Zotero/storage/86P4IMCR/pace2007.pdf:application/pdf}
}

@article{lee_transposable_2014,
	title = {Transposable Elements and Genome Size Variations in Plants},
	volume = {12},
	issn = {1598-866X},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196380/},
	doi = {10.5808/GI.2014.12.3.87},
	abstract = {Although the number of protein-coding genes is not highly variable between plant taxa, the {DNA} content in their genomes is highly variable, by as much as 2,056-fold from a 1C amount of 0.0648 pg to 132.5 pg. The mean 1C-value in plants is 2.4 pg, and genome size expansion/contraction is lineage-specific in plant taxonomy. Transposable element fractions in plant genomes are also variable, as low as {\textasciitilde}3\% in small genomes and as high as {\textasciitilde}85\% in large genomes, indicating that genome size is a linear function of transposable element content. Of the 2 classes of transposable elements, the dynamics of class 1 long terminal repeat ({LTR}) retrotransposons is a major contributor to the 1C value differences among plants. The activity of {LTR} retrotransposons is under the control of epigenetic suppressing mechanisms. Also, genome-purging mechanisms have been adopted to counter-balance the genome size amplification. With a wealth of information on whole-genome sequences in plant genomes, it was revealed that several genome-purging mechanisms have been employed, depending on plant taxa. Two genera, Lilium and Fritillaria, are known to have large genomes in angiosperms. There were twice times of concerted genome size evolutions in the family Liliaceae during the divergence of the current genera in Liliaceae. In addition to the {LTR} retrotransposons, non-{LTR} retrotransposons and satellite {DNAs} contributed to the huge genomes in the two genera by possible failure of genome counter-balancing mechanisms.},
	pages = {87--97},
	number = {3},
	journaltitle = {Genomics \& Informatics},
	shortjournal = {Genomics Inform},
	author = {Lee, Sung-Il and Kim, Nam-Soo},
	urldate = {2019-08-20},
	date = {2014-09},
	pmid = {25317107},
	pmcid = {PMC4196380},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/2SID86H6/Lee and Kim - 2014 - Transposable Elements and Genome Size Variations i.pdf:application/pdf}
}

@article{graur_evolutionary_2015,
	title = {An Evolutionary Classification of Genomic Function},
	volume = {7},
	issn = {1759-6653},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322545/},
	doi = {10.1093/gbe/evv021},
	abstract = {The pronouncements of the {ENCODE} Project Consortium regarding “junk {DNA}” exposed the need for an evolutionary classification of genomic elements according to their selected-effect function. In the classification scheme presented here, we divide the genome into “functional {DNA},” that is, {DNA} sequences that have a selected-effect function, and “rubbish {DNA},” that is, sequences that do not. Functional {DNA} is further subdivided into “literal {DNA}” and “indifferent {DNA}.” In literal {DNA}, the order of nucleotides is under selection; in indifferent {DNA}, only the presence or absence of the sequence is under selection. Rubbish {DNA} is further subdivided into “junk {DNA}” and “garbage {DNA}.” Junk {DNA} neither contributes to nor detracts from the fitness of the organism and, hence, evolves under selective neutrality. Garbage {DNA}, on the other hand, decreases the fitness of its carriers. Garbage {DNA} exists in the genome only because natural selection is neither omnipotent nor instantaneous. Each of these four functional categories can be 1) transcribed and translated, 2) transcribed but not translated, or 3) not transcribed. The affiliation of a {DNA} segment to a particular functional category may change during evolution: Functional {DNA} may become junk {DNA}, junk {DNA} may become garbage {DNA}, rubbish {DNA} may become functional {DNA}, and so on; however, determining the functionality or nonfunctionality of a genomic sequence must be based on its present status rather than on its potential to change (or not to change) in the future. Changes in functional affiliation are divided into pseudogenes, Lazarus {DNA}, zombie {DNA}, and Jekyll-to-Hyde {DNA}.},
	pages = {642--645},
	number = {3},
	journaltitle = {Genome Biology and Evolution},
	shortjournal = {Genome Biol Evol},
	author = {Graur, Dan and Zheng, Yichen and Azevedo, Ricardo B.R.},
	urldate = {2019-08-21},
	date = {2015-01-28},
	pmid = {25635041},
	pmcid = {PMC5322545},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/X3W33XY3/Graur et al. - 2015 - An Evolutionary Classification of Genomic Function.pdf:application/pdf}
}

@article{hahn_g-value_2002,
	title = {The g-value paradox},
	volume = {4},
	rights = {2002 {BLACKWELL} {SCIENCE}, {INC}.},
	issn = {1525-142X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-142X.2002.01069.x},
	doi = {10.1046/j.1525-142X.2002.01069.x},
	pages = {73--75},
	number = {2},
	journaltitle = {Evolution \& Development},
	author = {Hahn, Matthew W. and Wray, Gregory A.},
	urldate = {2019-08-21},
	date = {2002},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/FDK3ENG2/j.1525-142X.2002.01069.html:text/html}
}

@article{claverie_what_2001,
	title = {What if there are only 30,000 human genes?},
	volume = {291},
	issn = {0036-8075},
	doi = {10.1126/science.1058969},
	pages = {1255--1257},
	number = {5507},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Claverie, J. M.},
	date = {2001-02-16},
	pmid = {11233450},
	keywords = {Genomics, Animals, Humans, Proteins, Gene Expression Regulation, Computational Biology, Drug Industry, Expressed Sequence Tags, Gene Expression, Genes, Genetic Techniques, Human Genome Project, {RNA}, Messenger, Models, Genetic, Genome, Human, Polymorphism, Single Nucleotide}
}

@article{su_evolution_2006,
	title = {Evolution of alternative splicing after gene duplication},
	volume = {16},
	issn = {1088-9051},
	doi = {10.1101/gr.4197006},
	abstract = {Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice ({AS}) forms than single-copy genes, and that a negative correlation exists between the mean number of {AS} forms and the gene family size. Interestingly, we found that the loss of alternative splicing in duplicate genes may occur shortly after the gene duplication. These results support the subfunctionization model of alternative splicing in the early stage after gene duplication. Further analysis of the alternative splicing distribution in human duplicate pairs showed the asymmetric evolution of alternative splicing after gene duplications; i.e., the {AS} forms between duplicates may differ dramatically. We therefore conclude that alternative splicing and gene duplication may not evolve independently. In the early stage after gene duplication, young duplicates may take over a certain amount of protein function diversity that previously was carried out by the alternative splicing mechanism. In the late stage, the gain and loss of alternative splicing seem to be independent between duplicates.},
	pages = {182--189},
	number = {2},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Su, Zhixi and Wang, Jianmin and Yu, Jun and Huang, Xiaoqiu and Gu, Xun},
	date = {2006-02},
	pmid = {16365379},
	pmcid = {PMC1361713},
	keywords = {Humans, Alternative Splicing, Gene Duplication, Evolution, Molecular, Models, Genetic},
	file = {Full Text:/home/jlagarde/Zotero/storage/LCVYSWHS/Su et al. - 2006 - Evolution of alternative splicing after gene dupli.pdf:application/pdf}
}

@article{nilsen_expansion_2010,
	title = {Expansion of the eukaryotic proteome by alternative splicing},
	volume = {463},
	issn = {1476-4687},
	doi = {10.1038/nature08909},
	abstract = {The collection of components required to carry out the intricate processes involved in generating and maintaining a living, breathing and, sometimes, thinking organism is staggeringly complex. Where do all of the parts come from? Early estimates stated that about 100,000 genes would be required to make up a mammal; however, the actual number is less than one-quarter of that, barely four times the number of genes in budding yeast. It is now clear that the 'missing' information is in large part provided by alternative splicing, the process by which multiple different functional messenger {RNAs}, and therefore proteins, can be synthesized from a single gene.},
	pages = {457--463},
	number = {7280},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Nilsen, Timothy W. and Graveley, Brenton R.},
	date = {2010-01-28},
	pmid = {20110989},
	pmcid = {PMC3443858},
	keywords = {Animals, Humans, Computational Biology, Alternative Splicing, Proteome, Eukaryota, Evolution, Molecular, {RNA}, Messenger},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/UEWSF9JF/Nilsen and Graveley - 2010 - Expansion of the eukaryotic proteome by alternativ.pdf:application/pdf}
}

@article{xing_relating_2007,
	title = {Relating alternative splicing to proteome complexity and genome evolution},
	volume = {623},
	issn = {0065-2598},
	doi = {10.1007/978-0-387-77374-2_3},
	abstract = {Prior to genomics, studies of alternative splicing primarily focused on the function and mechanism of alternative splicing in individual genes and exons. This has changed dramatically since the late 1990s. High-throughput genomics technologies, such as {EST} sequencing and microarrays designed to detect changes in splicing, led to genome-wide discoveries and quantification of alternative splicing in a wide range of species from human to Arabidopsis. Consensus estimates of {AS} frequency in the human genome grew from less than 5\% in mid-1990s to as high as 60-74\% now. The rapid growth in sequence and microarray data for alternative splicing has made it possible to look into the global impact of alternative splicing on protein function and evolution of genomes. In this chapter, we review recent research on alternative splicing's impact on proteomic complexity and its role in genome evolution.},
	pages = {36--49},
	journaltitle = {Advances in Experimental Medicine and Biology},
	shortjournal = {Adv. Exp. Med. Biol.},
	author = {Xing, Yi and Lee, Christopher},
	date = {2007},
	pmid = {18380339},
	keywords = {Animals, Genome, Humans, Alternative Splicing, Proteome, Evolution, Molecular}
}

@article{lynch_evolutionary_2000,
	title = {The evolutionary fate and consequences of duplicate genes},
	volume = {290},
	issn = {0036-8075},
	doi = {10.1126/science.290.5494.1151},
	abstract = {Gene duplication has generally been viewed as a necessary source of material for the origin of evolutionary novelties, but it is unclear how often gene duplicates arise and how frequently they evolve new functions. Observations from the genomic databases for several eukaryotic species suggest that duplicate genes arise at a very high rate, on average 0.01 per gene per million years. Most duplicated genes experience a brief period of relaxed selection early in their history, with a moderate fraction of them evolving in an effectively neutral manner during this period. However, the vast majority of gene duplicates are silenced within a few million years, with the few survivors subsequently experiencing strong purifying selection. Although duplicate genes may only rarely evolve new functions, the stochastic silencing of such genes may play a significant role in the passive origin of new species.},
	pages = {1151--1155},
	number = {5494},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Lynch, M. and Conery, J. S.},
	date = {2000-11-10},
	pmid = {11073452},
	keywords = {Animals, Base Sequence, Genome, Humans, Mice, Proteins, Caenorhabditis elegans, Drosophila melanogaster, Amino Acid Substitution, Arabidopsis, Chickens, Gene Duplication, Gene Silencing, Mutation, Probability, Saccharomyces cerevisiae, Time Factors, Evolution, Molecular, Selection, Genetic, Models, Genetic, Databases, Factual, Stochastic Processes, Genes, Duplicate, Oryza}
}

@article{holland_new_2017,
	title = {New genes from old: asymmetric divergence of gene duplicates and the evolution of development},
	volume = {372},
	issn = {1471-2970},
	doi = {10.1098/rstb.2015.0480},
	shorttitle = {New genes from old},
	abstract = {Gene duplications and gene losses have been frequent events in the evolution of animal genomes, with the balance between these two dynamic processes contributing to major differences in gene number between species. After gene duplication, it is common for both daughter genes to accumulate sequence change at approximately equal rates. In some cases, however, the accumulation of sequence change is highly uneven with one copy radically diverging from its paralogue. Such 'asymmetric evolution' seems commoner after tandem gene duplication than after whole-genome duplication, and can generate substantially novel genes. We describe examples of asymmetric evolution in duplicated homeobox genes of moths, molluscs and mammals, in each case generating new homeobox genes that were recruited to novel developmental roles. The prevalence of asymmetric divergence of gene duplicates has been underappreciated, in part, because the origin of highly divergent genes can be difficult to resolve using standard phylogenetic methods.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.},
	number = {1713},
	journaltitle = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences},
	shortjournal = {Philos. Trans. R. Soc. Lond., B, Biol. Sci.},
	author = {Holland, Peter W. H. and Marlétaz, Ferdinand and Maeso, Ignacio and Dunwell, Thomas L. and Paps, Jordi},
	date = {2017},
	pmid = {27994121},
	pmcid = {PMC5182412},
	keywords = {Animals, Biological Evolution, Mollusca, Evolution, Molecular, Genes, Duplicate, Genes, Homeobox, genome duplication, Growth and Development, homeobox, Lepidoptera, Mammalia, tandem duplication},
	file = {Full Text:/home/jlagarde/Zotero/storage/PMU9VPRC/Holland et al. - 2017 - New genes from old asymmetric divergence of gene .pdf:application/pdf}
}

@article{talavera_dependence_2007,
	title = {The (in)dependence of alternative splicing and gene duplication},
	volume = {3},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.0030033},
	abstract = {Alternative splicing ({AS}) and gene duplication ({GD}) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by {AS} may be comparable to those introduced by {GD}. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of {AS} and {GD} per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in {mRNA} expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of {AS} and {GD} at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of {AS} and {GD} in a gene family, and to the selection pressure imposed by the environment.},
	pages = {e33},
	number = {3},
	journaltitle = {{PLoS} computational biology},
	shortjournal = {{PLoS} Comput. Biol.},
	author = {Talavera, David and Vogel, Christine and Orozco, Modesto and Teichmann, Sarah A. and de la Cruz, Xavier},
	date = {2007-03-02},
	pmid = {17335345},
	pmcid = {PMC1808492},
	keywords = {Base Sequence, Alternative Splicing, Computer Simulation, {DNA} Mutational Analysis, Gene Duplication, Genetic Variation, Molecular Sequence Data, Proteome, Evolution, Molecular, Sequence Analysis, {DNA}, Models, Genetic},
	file = {Full Text:/home/jlagarde/Zotero/storage/2FPYF7LX/Talavera et al. - 2007 - The (in)dependence of alternative splicing and gen.pdf:application/pdf}
}

@article{kopelman_alternative_2005,
	title = {Alternative splicing and gene duplication are inversely correlated evolutionary mechanisms},
	volume = {37},
	issn = {1061-4036},
	doi = {10.1038/ng1575},
	abstract = {Gene duplication and alternative splicing are distinct evolutionary mechanisms that provide the raw material for new biological functions. We explored their relationships in human and mouse and found an inverse correlation between the size of a gene's family and its use of alternatively spliced isoforms. A cross-organism analysis suggests that selection for genome-wide genic proliferation might be interchangeably met by either evolutionary mechanism.},
	pages = {588--589},
	number = {6},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Kopelman, Naama M. and Lancet, Doron and Yanai, Itai},
	date = {2005-06},
	pmid = {15895079},
	keywords = {Animals, Humans, Mice, Alternative Splicing, Gene Duplication, Evolution, Molecular, Selection, Genetic}
}

@article{copley_animal_2008,
	title = {The animal in the genome: comparative genomics and evolution},
	volume = {363},
	issn = {0962-8436},
	doi = {10.1098/rstb.2007.2235},
	shorttitle = {The animal in the genome},
	abstract = {Comparisons between completely sequenced metazoan genomes have generally emphasized how similar their encoded protein content is, even when the comparison is between phyla. Given the manifest differences between phyla and, in particular, intuitive notions that some animals are more complex than others, this creates something of a paradox. Simplistic explanations have included arguments such as increased numbers of genes; greater numbers of protein products produced through alternative splicing; increased numbers of regulatory non-coding {RNAs} and increased complexity of the cis-regulatory code. An obvious value of complete genome sequences lies in their ability to provide us with inventories of such components. I examine progress being made in linking genome content to the pattern of animal evolution, and argue that the gap between genomic and phenotypic complexity can only be understood through the totality of interacting components.},
	pages = {1453--1461},
	number = {1496},
	journaltitle = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences},
	shortjournal = {Philos. Trans. R. Soc. Lond., B, Biol. Sci.},
	author = {Copley, Richard R.},
	date = {2008-04-27},
	pmid = {18192189},
	pmcid = {PMC2614226},
	keywords = {Genomics, {DNA}, Animals, Base Sequence, Conserved Sequence, Genome, Humans, Proteins, Alternative Splicing, Amino Acid Sequence, Biological Evolution, Drosophila, Molecular Sequence Data, Phenotype, Sequence Alignment, Transcription Factors, Repressor Proteins, Evolution, Molecular, Enhancer Elements, Genetic, Models, Molecular, Drosophila Proteins},
	file = {Full Text:/home/jlagarde/Zotero/storage/GU858BYS/Copley - 2008 - The animal in the genome comparative genomics and.pdf:application/pdf}
}

@article{ouma_topological_2018,
	title = {Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties},
	volume = {14},
	issn = {1553-7358},
	url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006098},
	doi = {10.1371/journal.pcbi.1006098},
	abstract = {Understanding complexity in physical, biological, social and information systems is predicated on describing interactions amongst different components. Advances in genomics are facilitating the high-throughput identification of molecular interactions, and graphs are emerging as indispensable tools in explaining how the connections in the network drive organismal phenotypic plasticity. Here, we describe the architectural organization and associated emergent topological properties of gene regulatory networks ({GRNs}) that describe protein-{DNA} interactions ({PDIs}) in several model eukaryotes. By analyzing {GRN} connectivity, our results show that the anticipated scale-free network architectures are characterized by organism-specific power law scaling exponents. These exponents are independent of the fraction of the {GRN} experimentally sampled, enabling prediction of properties of the complete {GRN} for an organism. We further demonstrate that the exponents describe inequalities in transcription factor ({TF})-target gene recognition across {GRNs}. These observations have the important biological implication that they predict the existence of an intrinsic organism-specific trans and/or cis regulatory landscape that constrains {GRN} topologies. Consequently, architectural {GRN} organization drives not only phenotypic plasticity within a species, but is also likely implicated in species-specific phenotype.},
	pages = {e1006098},
	number = {4},
	journaltitle = {{PLOS} Computational Biology},
	shortjournal = {{PLOS} Computational Biology},
	author = {Ouma, Wilberforce Zachary and Pogacar, Katja and Grotewold, Erich},
	urldate = {2019-08-21},
	date = {2018-04-30},
	langid = {english},
	keywords = {Gene regulation, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis thaliana, Invertebrate genomics, Protein interaction networks, Scale-free networks},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/N3Y57LL5/Ouma et al. - 2018 - Topological and statistical analyses of gene regul.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/GW9TCL3K/article.html:text/html;Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties:/home/jlagarde/Zotero/storage/STFK38S8/ouma2018.pdf:application/pdf}
}

@article{barabasi_network_2004,
	title = {Network biology: understanding the cell's functional organization},
	volume = {5},
	issn = {1471-0056},
	doi = {10.1038/nrg1272},
	shorttitle = {Network biology},
	pages = {101--113},
	number = {2},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Barabási, Albert-László and Oltvai, Zoltán N.},
	date = {2004-02},
	pmid = {14735121},
	keywords = {Animals, Humans, Cell Compartmentation, Models, Biological, Cell Physiological Phenomena, Cell Communication, Metabolism},
	file = {Network biology\: understanding the cell's functional organization:/home/jlagarde/Zotero/storage/2PW2X8AI/10.1038@nrg1272.pdf:application/pdf}
}

@article{rands_8.2_2014,
	title = {8.2\% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage},
	volume = {10},
	issn = {1553-7390},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109858/},
	doi = {10.1371/journal.pgen.1004525},
	shorttitle = {8.2\% of the Human Genome Is Constrained},
	abstract = {Ten years on from the finishing of the human reference genome sequence, it remains unclear what fraction of the human genome confers function, where this sequence resides, and how much is shared with other mammalian species. When addressing these questions, functional sequence has often been equated with pan-mammalian conserved sequence. However, functional elements that are short-lived, including those contributing to species-specific biology, will not leave a footprint of long-lasting negative selection. Here, we address these issues by identifying and characterising sequence that has been constrained with respect to insertions and deletions for pairs of eutherian genomes over a range of divergences. Within noncoding sequence, we find increasing amounts of mutually constrained sequence as species pairs become more closely related, indicating that noncoding constrained sequence turns over rapidly. We estimate that half of present-day noncoding constrained sequence has been gained or lost in approximately the last 130 million years (half-life in units of divergence time, d1/2 = 0.25–0.31). While enriched with {ENCODE} biochemical annotations, much of the short-lived constrained sequences we identify are not detected by models optimized for wider pan-mammalian conservation. Constrained {DNase} 1 hypersensitivity sites, promoters and untranslated regions have been more evolutionarily stable than long noncoding {RNA} loci which have turned over especially rapidly. By contrast, protein coding sequence has been highly stable, with an estimated half-life of over a billion years (d1/2 = 2.1–5.0). From extrapolations we estimate that 8.2\% (7.1–9.2\%) of the human genome is presently subject to negative selection and thus is likely to be functional, while only 2.2\% has maintained constraint in both human and mouse since these species diverged. These results reveal that the evolutionary history of the human genome has been highly dynamic, particularly for its noncoding yet biologically functional fraction., Nearly 99\% of the human genome does not encode proteins, and while there recently has been extensive biochemical annotation of the remaining noncoding fraction, it remains unclear whether or not the bulk of these {DNA} sequences have important functional roles. By comparing the genome sequences of different species we identify genomic regions that have evolved unexpectedly slowly, a signature of natural selection upon functional sequence. Using a high resolution evolutionary approach to find sequence showing evolutionary signatures of functionality we estimate that a total of 8.2\% (7.1–9.2\%) of the human genome is presently functional, more than three times as much than is functional and shared between human and mouse. This implies that there is an abundance of sequences with short lived lineage-specific functionality. As expected, most of the sequence involved in this functional “turnover” is noncoding, while protein coding sequence is stably preserved over longer evolutionary timescales. More generally, we find that the rate of functional turnover varies significantly across categories of functional noncoding elements. Our results provide a pan-mammalian and whole genome perspective on how rapidly different classes of sequence have gained and lost functionality down the human lineage.},
	number = {7},
	journaltitle = {{PLoS} Genetics},
	shortjournal = {{PLoS} Genet},
	author = {Rands, Chris M. and Meader, Stephen and Ponting, Chris P. and Lunter, Gerton},
	urldate = {2019-08-22},
	date = {2014-07-24},
	pmid = {25057982},
	pmcid = {PMC4109858},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/C7LDSTBS/Rands et al. - 2014 - 8.2% of the Human Genome Is Constrained Variation.pdf:application/pdf}
}

@article{palazzo_case_2014,
	title = {The Case for Junk {DNA}},
	volume = {10},
	issn = {1553-7404},
	url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351},
	doi = {10.1371/journal.pgen.1004351},
	pages = {e1004351},
	number = {5},
	journaltitle = {{PLOS} Genetics},
	shortjournal = {{PLOS} Genetics},
	author = {Palazzo, Alexander F. and Gregory, T. Ryan},
	urldate = {2019-08-22},
	date = {2014-05-08},
	langid = {english},
	keywords = {Introns, Pseudogenes, Eukaryota, {DNA} transcription, Human genomics, Amphibian genomics, Non-coding {DNA}, Sequence motif analysis},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/8H4RAKVP/Palazzo and Gregory - 2014 - The Case for Junk DNA.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/TDAR9ZVB/article.html:text/html}
}

@article{elliott_conceptual_2014,
	title = {Conceptual and empirical challenges of ascribing functions to transposable elements},
	volume = {184},
	issn = {1537-5323},
	doi = {10.1086/676588},
	abstract = {Media attention and the subsequent scientific backlash engendered by the claim by spokespeople for the Encyclopedia of {DNA} Elements ({ENCODE}) project that 80\% of the human genome has a biochemical function highlight the need for a clearer understanding of function concepts in biology. This article provides an overview of two major function concepts that have been developed in the philosophy of science--the causal role concept and the selected effects concept--and their relevance to {ENCODE}. Unlike in some previous critiques, the {ENCODE} project is not considered problematic here because it employed a causal role definition of function (which is relatively common in genetics) but because of how this concept was misused. In addition, several unique challenges that arise when dealing with transposable elements ({TEs}) but that were ignored by {ENCODE} are highlighted. These include issues surrounding {TE}-level versus organism-level selection, the origins versus the persistence of elements, and accidental versus functional organism-level benefits. Finally, some key questions are presented that should be addressed in any study aiming to ascribe functions to major portions of large eukaryotic genomes, the majorities of which are made up of transposable elements.},
	pages = {14--24},
	number = {1},
	journaltitle = {The American Naturalist},
	shortjournal = {Am. Nat.},
	author = {Elliott, Tyler A. and Linquist, Stefan and Gregory, T. Ryan},
	date = {2014-07},
	pmid = {24921597},
	keywords = {{DNA}, Humans, {DNA} Transposable Elements, Eukaryota, Evolution, Molecular, Selection, Genetic, Genome, Human}
}

@article{sinzelle_molecular_2009,
	title = {Molecular domestication of transposable elements: from detrimental parasites to useful host genes},
	volume = {66},
	issn = {1420-9071},
	doi = {10.1007/s00018-009-8376-3},
	shorttitle = {Molecular domestication of transposable elements},
	abstract = {Transposable elements ({TEs}) are commonly viewed as molecular parasites producing mainly neutral or deleterious effects in host genomes through their ability to move. However, during the past two decades, major interest has been focusing on the positive contribution of these elements in the evolution of gene regulation and in the creation of diverse structural host genes. Indeed, {DNA} transposons carry an attractive and elaborate enzymatic machinery as well as {DNA} components that have been co-opted in several cases by the host genome via an evolutionary process referred to as molecular domestication. A large number of transposon-derived genes known to date have been recruited by the host to function as transcriptional regulators; however, the biological role of the majority of them remains undetermined. Our knowledge on the structure, distribution, evolution and mechanism of transposons will continue to provide important contributions to our understanding of host genome functions.},
	pages = {1073--1093},
	number = {6},
	journaltitle = {Cellular and molecular life sciences: {CMLS}},
	shortjournal = {Cell. Mol. Life Sci.},
	author = {Sinzelle, L. and Izsvák, Z. and Ivics, Z.},
	date = {2009-03},
	pmid = {19132291},
	keywords = {Animals, Genome, Humans, Apoptosis, Cell Cycle, {DNA} Transposable Elements, {DNA}-Binding Proteins, Transcription Factors, Evolution, Molecular}
}

@article{comings_structure_1972,
	title = {The structure and function of chromatin},
	volume = {3},
	issn = {0065-275X},
	pages = {237--431},
	journaltitle = {Advances in Human Genetics},
	shortjournal = {Adv. Hum. Genet.},
	author = {Comings, D. E.},
	date = {1972},
	pmid = {4578264},
	keywords = {{DNA}, Animals, Humans, Amino Acid Sequence, Chromatin, {DNA} Replication, Histones, Nucleic Acid Conformation, X-Ray Diffraction, Molecular Biology, {RNA}, Messenger, Transcription, Genetic, Genes, Regulator, Heterochromatin, {DNA}-Directed {RNA} Polymerases, Models, Theoretical}
}

@article{ludwig_functional_2002,
	title = {Functional evolution of noncoding {DNA}},
	volume = {12},
	issn = {0959-437X},
	abstract = {Noncoding {DNA} in eukaryotes encodes functionally important signals for the regulation of chromosome assembly, {DNA} replication, and gene expression. The increasing availability of whole-genome sequences of related taxa has led to interest in the evolution of these signals, and the phylogenetic footprints they produce. Cis-regulatory sequences controlling gene expression are often conserved among related species, but are rarely conserved between distantly related taxa. Several experimentally characterized regulatory elements have failed to show sequence similarity even between closely related species.},
	pages = {634--639},
	number = {6},
	journaltitle = {Current Opinion in Genetics \& Development},
	shortjournal = {Curr. Opin. Genet. Dev.},
	author = {Ludwig, Michael Z.},
	date = {2002-12},
	pmid = {12433575},
	keywords = {Animals, Drosophila, Evolution, Molecular, Selection, Genetic, Enhancer Elements, Genetic, {DNA}, Intergenic, Caenorhabditis}
}

@article{cobb_searching_2008,
	title = {Searching for functional genetic variants in non-coding {DNA}},
	volume = {35},
	issn = {1440-1681},
	doi = {10.1111/j.1440-1681.2008.04880.x},
	abstract = {1. The search for {DNA} sequence variants for complex human polygenic conditions has been a strong focus of recent genetic research. While gene loci have been identified, few variants in the coding sequences of these genes have been found, suggesting that non-coding sequence variation may underlie many complex conditions. 2. Non-coding {DNA} harbours regulatory elements capable of making changes to gene expression. However, regulatory {DNA} sequences are currently difficult to recognize and their function is poorly understood, complicating the task of assigning potential functional significance to non-coding variation. 3. Comparative genomics, the study of evolutionary {DNA} conservation, has enabled the emergent field of non-coding {DNA} identification in human disease analysis. 4. This brief review will focus on the potential of a relatively high throughput technique based on comparative genomics, that may aid in the identification of functionally important non-coding sequence variation in complex diseases.},
	pages = {372--375},
	number = {4},
	journaltitle = {Clinical and Experimental Pharmacology \& Physiology},
	shortjournal = {Clin. Exp. Pharmacol. Physiol.},
	author = {Cobb, Joanna and Büsst, Cara and Petrou, Steven and Harrap, Stephen and Ellis, Justine},
	date = {2008-04},
	pmid = {18307723},
	keywords = {Genomics, {DNA}, Animals, Humans, Genetic Variation, Evolution, Molecular}
}

@article{khurana_integrative_2013,
	title = {Integrative annotation of variants from 1092 humans: application to cancer genomics},
	volume = {342},
	issn = {1095-9203},
	doi = {10.1126/science.1235587},
	shorttitle = {Integrative annotation of variants from 1092 humans},
	abstract = {Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool ({FunSeq}), whose application to {\textasciitilde}90 cancer genomes reveals nearly a hundred candidate noncoding drivers.},
	pages = {1235587},
	number = {6154},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Khurana, Ekta and Fu, Yao and Colonna, Vincenza and Mu, Xinmeng Jasmine and Kang, Hyun Min and Lappalainen, Tuuli and Sboner, Andrea and Lochovsky, Lucas and Chen, Jieming and Harmanci, Arif and Das, Jishnu and Abyzov, Alexej and Balasubramanian, Suganthi and Beal, Kathryn and Chakravarty, Dimple and Challis, Daniel and Chen, Yuan and Clarke, Declan and Clarke, Laura and Cunningham, Fiona and Evani, Uday S. and Flicek, Paul and Fragoza, Robert and Garrison, Erik and Gibbs, Richard and Gümüş, Zeynep H. and Herrero, Javier and Kitabayashi, Naoki and Kong, Yong and Lage, Kasper and Liluashvili, Vaja and Lipkin, Steven M. and MacArthur, Daniel G. and Marth, Gabor and Muzny, Donna and Pers, Tune H. and Ritchie, Graham R. S. and Rosenfeld, Jeffrey A. and Sisu, Cristina and Wei, Xiaomu and Wilson, Michael and Xue, Yali and Yu, Fuli and {1000 Genomes Project Consortium} and Dermitzakis, Emmanouil T. and Yu, Haiyuan and Rubin, Mark A. and Tyler-Smith, Chris and Gerstein, Mark},
	date = {2013-10-04},
	pmid = {24092746},
	pmcid = {PMC3947637},
	keywords = {Genomics, Humans, Binding Sites, Genetic Variation, Kruppel-Like Transcription Factors, Molecular Sequence Annotation, Mutation, Neoplasms, Population, Selection, Genetic, {RNA}, Untranslated, Genome, Human, Polymorphism, Single Nucleotide},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/SDD3I2WG/Khurana et al. - 2013 - Integrative annotation of variants from 1092 human.pdf:application/pdf}
}

@article{maeso_deep_2013,
	title = {Deep conservation of cis-regulatory elements in metazoans},
	volume = {368},
	issn = {0962-8436},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826494/},
	doi = {10.1098/rstb.2013.0020},
	abstract = {Despite the vast morphological variation observed across phyla, animals share multiple basic developmental processes orchestrated by a common ancestral gene toolkit. These genes interact with each other building complex gene regulatory networks ({GRNs}), which are encoded in the genome by cis-regulatory elements ({CREs}) that serve as computational units of the network. Although {GRN} subcircuits involved in ancient developmental processes are expected to be at least partially conserved, identification of {CREs} that are conserved across phyla has remained elusive. Here, we review recent studies that revealed such deeply conserved {CREs} do exist, discuss the difficulties associated with their identification and describe new approaches that will facilitate this search.},
	number = {1632},
	journaltitle = {Philosophical Transactions of the Royal Society B: Biological Sciences},
	shortjournal = {Philos Trans R Soc Lond B Biol Sci},
	author = {Maeso, Ignacio and Irimia, Manuel and Tena, Juan J. and Casares, Fernando and Gómez-Skarmeta, José Luis},
	urldate = {2019-08-23},
	date = {2013-12-19},
	pmid = {24218633},
	pmcid = {PMC3826494},
	keywords = {Epigenomics, Animals, Conserved Sequence, Gene Regulatory Networks, Species Specificity, evolution, Evolution, Molecular, Regulatory Elements, Transcriptional, Gene Expression Regulation, Developmental, cis-regulatory element, development, gene regulatory networks},
	file = {Full Text:/home/jlagarde/Zotero/storage/BG979GQC/Maeso et al. - 2013 - Deep conservation of cis-regulatory elements in me.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/GSHKIMDY/Maeso et al. - 2013 - Deep conservation of cis-regulatory elements in me.pdf:application/pdf}
}

@article{vavouri_conserved_2009,
	title = {Conserved noncoding elements and the evolution of animal body plans},
	volume = {31},
	issn = {1521-1878},
	doi = {10.1002/bies.200900014},
	abstract = {The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements ({CNEs}). {CNEs} cluster around genes that regulate development, and where tested, they can act as transcriptional enhancers. Within an animal group {CNEs} are the most conserved sequences but between groups they are normally diverged beyond recognition. Alternative {CNEs} are, however, associated with an overlapping set of genes that control development in all animals. Here, we discuss the evidence that {CNEs} are part of the core gene regulatory networks ({GRNs}) that specify alternative animal body plans. The major animal groups arose {\textgreater}550 million years ago. We propose that the cis-regulatory inputs identified by {CNEs} arose during the "re-wiring" of regulatory interactions that occurred during early animal evolution. Consequently, different animal groups, with different core {GRNs}, contain alternative sets of {CNEs}. Due to the subsequent stability of animal body plans, these core regulatory sequences have been evolving in parallel under strong purifying selection in different animal groups.},
	pages = {727--735},
	number = {7},
	journaltitle = {{BioEssays}: News and Reviews in Molecular, Cellular and Developmental Biology},
	shortjournal = {Bioessays},
	author = {Vavouri, Tanya and Lehner, Ben},
	date = {2009-07},
	pmid = {19492354},
	keywords = {Animals, Conserved Sequence, Biological Evolution, Models, Genetic, {DNA}, Intergenic, Gene Expression Regulation, Developmental, Body Patterning},
	file = {Full Text:/home/jlagarde/Zotero/storage/S5N6AKYY/Vavouri and Lehner - 2009 - Conserved noncoding elements and the evolution of .pdf:application/pdf}
}

@article{thomas_comparative_2003,
	title = {Comparative analyses of multi-species sequences from targeted genomic regions},
	volume = {424},
	issn = {1476-4687},
	doi = {10.1038/nature01858},
	abstract = {The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.},
	pages = {788--793},
	number = {6950},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Thomas, J. W. and Touchman, J. W. and Blakesley, R. W. and Bouffard, G. G. and Beckstrom-Sternberg, S. M. and Margulies, E. H. and Blanchette, M. and Siepel, A. C. and Thomas, P. J. and {McDowell}, J. C. and Maskeri, B. and Hansen, N. F. and Schwartz, M. S. and Weber, R. J. and Kent, W. J. and Karolchik, D. and Bruen, T. C. and Bevan, R. and Cutler, D. J. and Schwartz, S. and Elnitski, L. and Idol, J. R. and Prasad, A. B. and Lee-Lin, S.-Q. and Maduro, V. V. B. and Summers, T. J. and Portnoy, M. E. and Dietrich, N. L. and Akhter, N. and Ayele, K. and Benjamin, B. and Cariaga, K. and Brinkley, C. P. and Brooks, S. Y. and Granite, S. and Guan, X. and Gupta, J. and Haghighi, P. and Ho, S.-L. and Huang, M. C. and Karlins, E. and Laric, P. L. and Legaspi, R. and Lim, M. J. and Maduro, Q. L. and Masiello, C. A. and Mastrian, S. D. and {McCloskey}, J. C. and Pearson, R. and Stantripop, S. and Tiongson, E. E. and Tran, J. T. and Tsurgeon, C. and Vogt, J. L. and Walker, M. A. and Wetherby, K. D. and Wiggins, L. S. and Young, A. C. and Zhang, L.-H. and Osoegawa, K. and Zhu, B. and Zhao, B. and Shu, C. L. and De Jong, P. J. and Lawrence, C. E. and Smit, A. F. and Chakravarti, A. and Haussler, D. and Green, P. and Miller, W. and Green, E. D.},
	date = {2003-08-14},
	pmid = {12917688},
	keywords = {Genomics, Animals, Conserved Sequence, Genome, Humans, {DNA} Transposable Elements, Mammals, Mutagenesis, Phylogeny, Sequence Alignment, Species Specificity, Vertebrates, Evolution, Molecular, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 7, Cystic Fibrosis Transmembrane Conductance Regulator}
}

@article{blow_chip-seq_2010,
	title = {{ChIP}-Seq identification of weakly conserved heart enhancers},
	volume = {42},
	issn = {1546-1718},
	doi = {10.1038/ng.650},
	abstract = {Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used {ChIP}-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.},
	pages = {806--810},
	number = {9},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Blow, Matthew J. and {McCulley}, David J. and Li, Zirong and Zhang, Tao and Akiyama, Jennifer A. and Holt, Amy and Plajzer-Frick, Ingrid and Shoukry, Malak and Wright, Crystal and Chen, Feng and Afzal, Veena and Bristow, James and Ren, Bing and Black, Brian L. and Rubin, Edward M. and Visel, Axel and Pennacchio, Len A.},
	date = {2010-09},
	pmid = {20729851},
	pmcid = {PMC3138496},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, Mice, Organ Specificity, Chromatin Immunoprecipitation, Myocardium, Phylogeny, Vertebrates, Evolution, Molecular, Sequence Analysis, {DNA}, Enhancer Elements, Genetic, Mice, Transgenic, Models, Biological, Gene Expression Regulation, Developmental, Embryo, Mammalian, Heart},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/PJ9H8A4W/Blow et al. - 2010 - ChIP-Seq identification of weakly conserved heart .pdf:application/pdf}
}

@article{kunarso_transposable_2010,
	title = {Transposable elements have rewired the core regulatory network of human embryonic stem cells},
	volume = {42},
	issn = {1546-1718},
	doi = {10.1038/ng.600},
	abstract = {Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins ({POU}5F1, also known as {OCT}4; {NANOG}; and {CTCF}) in human and mouse embryonic stem cells. In contrast to {CTCF}, we found that the binding profiles of {OCT}4 and {NANOG} are markedly different, with only approximately 5\% of the regions being homologously occupied. We show that transposable elements contributed up to 25\% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.},
	pages = {631--634},
	number = {7},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Kunarso, Galih and Chia, Na-Yu and Jeyakani, Justin and Hwang, Catalina and Lu, Xinyi and Chan, Yun-Shen and Ng, Huck-Hui and Bourque, Guillaume},
	date = {2010-07},
	pmid = {20526341},
	keywords = {Animals, Humans, Mice, Binding Sites, Protein Binding, Gene Expression Profiling, {DNA} Transposable Elements, Embryonic Stem Cells, Gene Regulatory Networks, Genome-Wide Association Study, Homeodomain Proteins, {RNA} Interference, Species Specificity, Repressor Proteins, Models, Genetic, {CCCTC}-Binding Factor, Regulatory Sequences, Nucleic Acid, Nanog Homeobox Protein, Octamer Transcription Factor-3}
}

@article{schmidt_five-vertebrate_2010,
	title = {Five-vertebrate {ChIP}-seq reveals the evolutionary dynamics of transcription factor binding},
	volume = {328},
	issn = {1095-9203},
	doi = {10.1126/science.1186176},
	abstract = {Transcription factors ({TFs}) direct gene expression by binding to {DNA} regulatory regions. To explore the evolution of gene regulation, we used chromatin immunoprecipitation with high-throughput sequencing ({ChIP}-seq) to determine experimentally the genome-wide occupancy of two {TFs}, {CCAAT}/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in the livers of five vertebrates. Although each {TF} displays highly conserved {DNA} binding preferences, most binding is species-specific, and aligned binding events present in all five species are rare. Regions near genes with expression levels that are dependent on a {TF} are often bound by the {TF} in multiple species yet show no enhanced {DNA} sequence constraint. Binding divergence between species can be largely explained by sequence changes to the bound motifs. Among the binding events lost in one lineage, only half are recovered by another binding event within 10 kilobases. Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution.},
	pages = {1036--1040},
	number = {5981},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Schmidt, Dominic and Wilson, Michael D. and Ballester, Benoit and Schwalie, Petra C. and Brown, Gordon D. and Marshall, Aileen and Kutter, Claudia and Watt, Stephen and Martinez-Jimenez, Celia P. and Mackay, Sarah and Talianidis, Iannis and Flicek, Paul and Odom, Duncan T.},
	date = {2010-05-21},
	pmid = {20378774},
	pmcid = {PMC3008766},
	keywords = {{DNA}, Animals, Base Sequence, Genome, Humans, Mice, Binding Sites, Gene Expression Regulation, Protein Binding, Algorithms, Biological Evolution, Chickens, Chromatin Immunoprecipitation, Dogs, Liver, Species Specificity, Vertebrates, Opossums, Evolution, Molecular, Sequence Analysis, {DNA}, Genome, Human, Regulatory Sequences, Nucleic Acid, {CCAAT}-Enhancer-Binding Protein-alpha, Hepatocyte Nuclear Factor 4},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/E6WAZL3Z/Schmidt et al. - 2010 - Five-vertebrate ChIP-seq reveals the evolutionary .pdf:application/pdf}
}

@article{xie_rewirable_2010,
	title = {Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species},
	volume = {20},
	issn = {1549-5469},
	doi = {10.1101/gr.100594.109},
	abstract = {Mammalian preimplantation embryonic development ({PED}) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could "rewire" the gene regulatory networks ({GRN}) that control {PED}. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of {PED}, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2\% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the {ChIP}-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules ({CRMs}) by transposons. About 10\% of transposons are estimated to carry {CRMs}, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of {MTF}2, which links {POU}5F1/{NANOG} to {NOTCH} signaling. We reconstructed the transition of the {GRN} structures as a function of time during {PED}. A comparison of the {GRN} transition processes among the three species suggested that in the bovine system, {POU}5F1's interacting partner {SOX}2 may be replaced by {HMGB}1 (a {TF} sharing the same {DNA} binding domain with {SOX}2), resulting in rewiring of {GRN} by a trans change.},
	pages = {804--815},
	number = {6},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Xie, Dan and Chen, Chieh-Chun and Ptaszek, Leon M. and Xiao, Shu and Cao, Xiaoyi and Fang, Fang and Ng, Huck H. and Lewin, Harris A. and Cowan, Chad and Zhong, Sheng},
	date = {2010-06},
	pmid = {20219939},
	pmcid = {PMC2877577},
	keywords = {{DNA}, Animals, Base Sequence, Humans, Mice, Blastocyst, Cattle, {DNA} Transposable Elements, Embryonic Development, Gene Regulatory Networks, Molecular Sequence Data, Point Mutation, Species Specificity, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/33RZ7FGP/Xie et al. - 2010 - Rewirable gene regulatory networks in the preimpla.pdf:application/pdf}
}

@article{gerstberger_evolutionary_2014,
	title = {Evolutionary Conservation and Expression of Human {RNA}-Binding Proteins and Their Role in Human Genetic Disease},
	volume = {825},
	issn = {0065-2598},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180674/},
	doi = {10.1007/978-1-4939-1221-6_1},
	abstract = {{RNA}-binding proteins ({RBPs}) are effectors and regulators of posttranscriptional gene regulation ({PTGR}). {RBPs} regulate stability, maturation, and turnover of all {RNAs}, often binding thousands of targets at many sites. The importance of {RBPs} is underscored by their dysregulation or mutations causing a variety of developmental and neurological diseases. This chapter globally discusses human {RBPs} and provides a brief introduction to their identification and {RNA} targets. We review {RBPs} based on common structural {RNA}-binding domains, study their evolutionary conservation and expression, and summarize disease associations of different {RBP} classes.},
	pages = {1--55},
	journaltitle = {Advances in experimental medicine and biology},
	shortjournal = {Adv Exp Med Biol},
	author = {Gerstberger, Stefanie and Hafner, Markus and Ascano, Manuel and Tuschl, Thomas},
	urldate = {2019-08-23},
	date = {2014},
	pmid = {25201102},
	pmcid = {PMC4180674},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/Q3ZGFPT6/Gerstberger et al. - 2014 - Evolutionary Conservation and Expression of Human .pdf:application/pdf}
}

@article{yao_cmfinder--covariance_2006,
	title = {{CMfinder}--a covariance model based {RNA} motif finding algorithm},
	volume = {22},
	issn = {1367-4803},
	doi = {10.1093/bioinformatics/btk008},
	abstract = {{MOTIVATION}: The recent discoveries of large numbers of non-coding {RNAs} and computational advances in genome-scale {RNA} search create a need for tools for automatic, high quality identification and characterization of conserved {RNA} motifs that can be readily used for database search. Previous tools fall short of this goal.
{RESULTS}: {CMfinder} is a new tool to predict {RNA} motifs in unaligned sequences. It is an expectation maximization algorithm using covariance models for motif description, featuring novel integration of multiple techniques for effective search of motif space, and a Bayesian framework that blends mutual information-based and folding energy-based approaches to predict structure in a principled way. Extensive tests show that our method works well on datasets with either low or high sequence similarity, is robust to inclusion of lengthy extraneous flanking sequence and/or completely unrelated sequences, and is reasonably fast and scalable. In testing on 19 known {ncRNA} families, including some difficult cases with poor sequence conservation and large indels, our method demonstrates excellent average per-base-pair accuracy--79\% compared with at most 60\% for alternative methods. More importantly, the resulting probabilistic model can be directly used for homology search, allowing iterative refinement of structural models based on additional homologs. We have used this approach to obtain highly accurate covariance models of known {RNA} motifs based on small numbers of related sequences, which identified homologs in deeply-diverged species.},
	pages = {445--452},
	number = {4},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Yao, Zizhen and Weinberg, Zasha and Ruzzo, Walter L.},
	date = {2006-02-15},
	pmid = {16357030},
	keywords = {Base Sequence, Conserved Sequence, Algorithms, Software, Computer Simulation, Molecular Sequence Data, Sequence Alignment, Statistics as Topic, Models, Genetic, Sequence Analysis, {RNA}, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/DUVEXU5Z/Yao et al. - 2006 - CMfinder--a covariance model based RNA motif findi.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/A7DVM4FR/Yao et al. - 2006 - CMfinder--a covariance model based RNA motif findi.pdf:application/pdf}
}

@article{reneker_long_2012,
	title = {Long identical multispecies elements in plant and animal genomes},
	volume = {109},
	issn = {1091-6490},
	doi = {10.1073/pnas.1121356109},
	abstract = {Ultraconserved elements ({UCEs}) are {DNA} sequences that are 100\% identical (no base substitutions, insertions, or deletions) and located in syntenic positions in at least two genomes. Although hundreds of {UCEs} have been found in animal genomes, little is known about the incidence of ultraconservation in plant genomes. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements ({LIMEs}), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Among six animal genomes, we found the previously known syntenic {UCEs} as well as previously undescribed nonsyntenic elements. In contrast, among six plant genomes, we only found nonsyntenic {LIMEs}. {LIMEs} can also be classified as either simple (repetitive) or complex (nonrepetitive), they may occur in multiple copies in a genome, and they are often spread across multiple chromosomes. Although complex {LIMEs} were found in both animal and plant genomes, they differed significantly in their composition and copy number. Further analyses of plant {LIMEs} revealed their functional diversity, encompassing elements found near {rRNA} and enzyme-coding genes, as well as those found in transposons and noncoding {DNA}. We conclude that despite the common presence of {LIMEs} in both animal and plant lineages, the evolutionary processes involved in the creation and maintenance of these elements differ in the two groups and are likely attributable to several mechanisms, including transfer of genetic material from organellar to nuclear genomes, de novo sequence manufacturing, and purifying selection.},
	pages = {E1183--1191},
	number = {19},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Reneker, Jeff and Lyons, Eric and Conant, Gavin C. and Pires, J. Chris and Freeling, Michael and Shyu, Chi-Ren and Korkin, Dmitry},
	date = {2012-05-08},
	pmid = {22496592},
	pmcid = {PMC3358895},
	keywords = {Animals, Base Sequence, Conserved Sequence, Genome, Humans, Mice, Cell Nucleus, Amino Acid Sequence, Arabidopsis, Chromosome Mapping, Gene Regulatory Networks, Molecular Sequence Data, Rats, Species Specificity, Synteny, Evolution, Molecular, Models, Genetic, Chromosomes, Mammalian, Genome, Plant, Chromosomes, Plant, Genome, Mitochondrial},
	file = {Full Text:/home/jlagarde/Zotero/storage/85VMP9SH/Reneker et al. - 2012 - Long identical multispecies elements in plant and .pdf:application/pdf}
}

@article{dickel_ultraconserved_2018,
	title = {Ultraconserved Enhancers Are Required for Normal Development},
	volume = {172},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2017.12.017},
	abstract = {Non-coding "ultraconserved" regions containing hundreds of consecutive bases of perfect sequence conservation across mammalian genomes can function as distant-acting enhancers. However, initial deletion studies in mice revealed that loss of such extraordinarily constrained sequences had no immediate impact on viability. Here, we show that ultraconserved enhancers are required for normal development. Focusing on some of the longest ultraconserved sites genome wide, located near the essential neuronal transcription factor Arx, we used genome editing to create an expanded series of knockout mice lacking individual or combinations of ultraconserved enhancers. Mice with single or pairwise deletions of ultraconserved enhancers were viable and fertile but in nearly all cases showed neurological or growth abnormalities, including substantial alterations of neuron populations and structural brain defects. Our results demonstrate the functional importance of ultraconserved enhancers and indicate that remarkably strong sequence conservation likely results from fitness deficits that appear subtle in a laboratory setting.},
	pages = {491--499.e15},
	number = {3},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Dickel, Diane E. and Ypsilanti, Athena R. and Pla, Ramón and Zhu, Yiwen and Barozzi, Iros and Mannion, Brandon J. and Khin, Yupar S. and Fukuda-Yuzawa, Yoko and Plajzer-Frick, Ingrid and Pickle, Catherine S. and Lee, Elizabeth A. and Harrington, Anne N. and Pham, Quan T. and Garvin, Tyler H. and Kato, Momoe and Osterwalder, Marco and Akiyama, Jennifer A. and Afzal, Veena and Rubenstein, John L. R. and Pennacchio, Len A. and Visel, Axel},
	date = {2018},
	pmid = {29358049},
	pmcid = {PMC5786478},
	keywords = {Animals, Conserved Sequence, Mice, Brain, Embryonic Development, Female, Gene Deletion, Homeodomain Proteins, Male, Transcription Factors, Enhancer Elements, Genetic, Arx, brain development, enhancer, gene regulation, hippocampus, in vivo, knockout, neurons, noncoding, ultraconserved},
	file = {Full Text:/home/jlagarde/Zotero/storage/3CPF432H/Dickel et al. - 2018 - Ultraconserved Enhancers Are Required for Normal D.pdf:application/pdf}
}

@article{schaub_linking_2012,
	title = {Linking disease associations with regulatory information in the human genome},
	volume = {22},
	issn = {1549-5469},
	doi = {10.1101/gr.136127.111},
	abstract = {Genome-wide association studies have been successful in identifying single nucleotide polymorphisms ({SNPs}) associated with a large number of phenotypes. However, an associated {SNP} is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the {SNPs} that have a biological link with the phenotype. We have systematically investigated the association of multiple types of {ENCODE} data with disease-associated {SNPs} and show that there is significant enrichment for functional {SNPs} among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated {SNPs} are used. We propose an approach that integrates multiple types of functional data generated by the {ENCODE} Consortium to help identify "functional {SNPs}" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80\% of all previously reported associations. We show that for most associations, the functional {SNP} most strongly supported by experimental evidence is a {SNP} in linkage disequilibrium with the reported association rather than the reported {SNP} itself. Our results show that the experimental data sets generated by the {ENCODE} Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.},
	pages = {1748--1759},
	number = {9},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Schaub, Marc A. and Boyle, Alan P. and Kundaje, Anshul and Batzoglou, Serafim and Snyder, Michael},
	date = {2012-09},
	pmid = {22955986},
	pmcid = {PMC3431491},
	keywords = {Base Sequence, Humans, Binding Sites, Gene Expression Regulation, Chromatin Immunoprecipitation, Chromosome Mapping, Genetic Linkage, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Linkage Disequilibrium, Molecular Sequence Annotation, Molecular Sequence Data, Nucleotide Motifs, Phenotype, Genome, Human, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Coronary Artery Disease, {STAT}1 Transcription Factor},
	file = {Full Text:/home/jlagarde/Zotero/storage/4YW5584W/Schaub et al. - 2012 - Linking disease associations with regulatory infor.pdf:application/pdf}
}

@article{teer_exome_2010,
	title = {Exome sequencing: the sweet spot before whole genomes},
	volume = {19},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddq333},
	shorttitle = {Exome sequencing},
	abstract = {The development of massively parallel sequencing technologies, coupled with new massively parallel {DNA} enrichment technologies (genomic capture), has allowed the sequencing of targeted regions of the human genome in rapidly increasing numbers of samples. Genomic capture can target specific areas in the genome, including genes of interest and linkage regions, but this limits the study to what is already known. Exome capture allows an unbiased investigation of the complete protein-coding regions in the genome. Researchers can use exome capture to focus on a critical part of the human genome, allowing larger numbers of samples than are currently practical with whole-genome sequencing. In this review, we briefly describe some of the methodologies currently used for genomic and exome capture and highlight recent applications of this technology.},
	pages = {R145--151},
	issue = {R2},
	journaltitle = {Human Molecular Genetics},
	shortjournal = {Hum. Mol. Genet.},
	author = {Teer, Jamie K. and Mullikin, James C.},
	date = {2010-10-15},
	pmid = {20705737},
	pmcid = {PMC2953745},
	keywords = {Humans, Chromosome Mapping, Sequence Analysis, {DNA}, Genome, Human},
	file = {Exome sequencing\: the sweet spot before whole genomes:/home/jlagarde/Zotero/storage/GD3UJH2N/teer2010.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/IEA3BWW8/Teer and Mullikin - 2010 - Exome sequencing the sweet spot before whole geno.pdf:application/pdf}
}

@article{bashiardes_direct_2005,
	title = {Direct genomic selection},
	volume = {2},
	issn = {1548-7091},
	doi = {10.1038/nmeth0105-63},
	pages = {63--69},
	number = {1},
	journaltitle = {Nature Methods},
	shortjournal = {Nat. Methods},
	author = {Bashiardes, Stavros and Veile, Rose and Helms, Cynthia and Mardis, Elaine R. and Bowcock, Anne M. and Lovett, Michael},
	date = {2005-01},
	pmid = {16152676},
	keywords = {Humans, Biotinylation, Mutation, Nucleic Acid Hybridization, Polymerase Chain Reaction, Genome, Human, Cloning, Molecular, {DNA}, Complementary, Chromosomes, Artificial, Bacterial, Polymorphism, Genetic},
	file = {Direct genomic selection:/home/jlagarde/Zotero/storage/TBUJMT5R/bashiardes2005.pdf:application/pdf}
}

@article{ward_evidence_2012,
	title = {Evidence of abundant purifying selection in humans for recently acquired regulatory functions},
	volume = {337},
	issn = {1095-9203},
	doi = {10.1126/science.1225057},
	abstract = {Although only 5\% of the human genome is conserved across mammals, a substantially larger portion is biochemically active, raising the question of whether the additional elements evolve neutrally or confer a lineage-specific fitness advantage. To address this question, we integrate human variation information from the 1000 Genomes Project and activity data from the {ENCODE} Project. A broad range of transcribed and regulatory nonconserved elements show decreased human diversity, suggesting lineage-specific purifying selection. Conversely, conserved elements lacking activity show increased human diversity, suggesting that some recently became nonfunctional. Regulatory elements under human constraint in nonconserved regions were found near color vision and nerve-growth genes, consistent with purifying selection for recently evolved functions. Our results suggest continued turnover in regulatory regions, with at least an additional 4\% of the human genome subject to lineage-specific constraint.},
	pages = {1675--1678},
	number = {6102},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Ward, Lucas D. and Kellis, Manolis},
	date = {2012-09-28},
	pmid = {22956687},
	pmcid = {PMC4104271},
	keywords = {Conserved Sequence, Humans, Gene Expression Regulation, Disease, Genetic Variation, Selection, Genetic, Transcription, Genetic, Genome, Human, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/QGJRGVA7/Ward and Kellis - 2012 - Evidence of abundant purifying selection in humans.pdf:application/pdf}
}

@article{dermitzakis_conserved_2005,
	title = {Conserved non-genic sequences — an unexpected feature of mammalian genomes},
	volume = {6},
	rights = {2005 Nature Publishing Group},
	issn = {1471-0064},
	url = {https://www.nature.com/articles/nrg1527},
	doi = {10.1038/nrg1527},
	abstract = {Mammalian genomes contain highly conserved sequences that are not functionally transcribed. These sequences are single copy and comprise approximately 1–2\% of the human genome. Evolutionary analysis strongly supports their functional conservation, although their potentially diverse, functional attributes remain unknown. It is likely that genomic variation in conserved non-genic sequences is associated with phenotypic variability and human disorders. So how might their function and contribution to human disorders be examined?},
	pages = {151--157},
	number = {2},
	journaltitle = {Nature Reviews Genetics},
	shortjournal = {Nat Rev Genet},
	author = {Dermitzakis, Emmanouil T. and Reymond, Alexandre and Antonarakis, Stylianos E.},
	urldate = {2019-08-24},
	date = {2005-02},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/ZIYI4ERS/nrg1527.html:text/html}
}

@article{woolfe_highly_2004,
	title = {Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development},
	volume = {3},
	issn = {1545-7885},
	url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0030007},
	doi = {10.1371/journal.pbio.0030007},
	abstract = {In addition to protein coding sequence, the human genome contains a significant amount of regulatory {DNA}, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90\% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators ({SOX}21, {PAX}6, {HLXB}9, and {SHH}), in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development, including many transcription factors. These highly conserved non-coding sequences are likely to form part of the genomic circuitry that uniquely defines vertebrate development.},
	pages = {e7},
	number = {1},
	journaltitle = {{PLOS} Biology},
	shortjournal = {{PLOS} Biology},
	author = {Woolfe, Adam and Goodson, Martin and Goode, Debbie K. and Snell, Phil and {McEwen}, Gayle K. and Vavouri, Tanya and Smith, Sarah F. and North, Phil and Callaway, Heather and Kelly, Krys and Walter, Klaudia and Abnizova, Irina and Gilks, Walter and Edwards, Yvonne J. K. and Cooke, Julie E. and Elgar, Greg},
	urldate = {2019-08-24},
	date = {2004-11-11},
	langid = {english},
	keywords = {Comparative genomics, Vertebrates, Human genomics, Mammalian genomics, Sequence alignment, Invertebrate genomics, Embryos, Genome analysis},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/264PWI48/Woolfe et al. - 2004 - Highly Conserved Non-Coding Sequences Are Associat.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/SZBP9TSE/article.html:text/html}
}

@article{pennacchio_vivo_2006,
	title = {In vivo enhancer analysis of human conserved non-coding sequences},
	volume = {444},
	rights = {2006 Nature Publishing Group},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/nature05295},
	doi = {10.1038/nature05295},
	abstract = {Identifying the non-coding {DNA} sequences that act at a distance to regulate patterns of gene expression is not a simple matter; one useful pointer is evolutionary sequence conservation. An in vivo analysis of 167 non-coding elements in the human genome that are extremely conserved based on comparisons with pufferfish, rat and mouse genomes, has identified 75 previously unknown tissue-specific enhancers. These are active in embryos on day 11, most of them directing expression in the developing nervous system. The success of this method suggests that the further 5,500 non-coding sequences conserved between humans and pufferfish may yield another new batch of gene enhancers.},
	pages = {499--502},
	number = {7118},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Pennacchio, Len A. and Ahituv, Nadav and Moses, Alan M. and Prabhakar, Shyam and Nobrega, Marcelo A. and Shoukry, Malak and Minovitsky, Simon and Dubchak, Inna and Holt, Amy and Lewis, Keith D. and Plajzer-Frick, Ingrid and Akiyama, Jennifer and Val, Sarah De and Afzal, Veena and Black, Brian L. and Couronne, Olivier and Eisen, Michael B. and Visel, Axel and Rubin, Edward M.},
	urldate = {2019-08-24},
	date = {2006-11},
	langid = {english},
	file = {Snapshot:/home/jlagarde/Zotero/storage/QLN3QS62/nature05295.html:text/html;Submitted Version:/home/jlagarde/Zotero/storage/IVCX8N98/Pennacchio et al. - 2006 - In vivo enhancer analysis of human conserved non-c.pdf:application/pdf}
}

@article{bejerano_ultraconserved_2004,
	title = {Ultraconserved Elements in the Human Genome},
	volume = {304},
	rights = {American Association for the Advancement of Science},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/304/5675/1321},
	doi = {10.1126/science.1098119},
	abstract = {There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100\% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99\% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in {RNA} processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.
Nearly 500 200-base pair sequences that may be involved in vertebrate development are identical in the human, mouse, and rat genomes and are similar in other vertebrates.
Nearly 500 200-base pair sequences that may be involved in vertebrate development are identical in the human, mouse, and rat genomes and are similar in other vertebrates.},
	pages = {1321--1325},
	number = {5675},
	journaltitle = {Science},
	author = {Bejerano, Gill and Pheasant, Michael and Makunin, Igor and Stephen, Stuart and Kent, W. James and Mattick, John S. and Haussler, David},
	urldate = {2019-08-24},
	date = {2004-05-28},
	langid = {english},
	pmid = {15131266},
	file = {Snapshot:/home/jlagarde/Zotero/storage/AJUUIE8D/1321.html:text/html;Submitted Version:/home/jlagarde/Zotero/storage/DN7YSDQN/Bejerano et al. - 2004 - Ultraconserved Elements in the Human Genome.pdf:application/pdf}
}

@article{ahituv_deletion_2007,
	title = {Deletion of Ultraconserved Elements Yields Viable Mice},
	volume = {5},
	issn = {1545-7885},
	url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0050234},
	doi = {10.1371/journal.pbio.0050234},
	abstract = {Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.},
	pages = {e234},
	number = {9},
	journaltitle = {{PLOS} Biology},
	shortjournal = {{PLOS} Biology},
	author = {Ahituv, Nadav and Zhu, Yiwen and Visel, Axel and Holt, Amy and Afzal, Veena and Pennacchio, Len A. and Rubin, Edward M.},
	urldate = {2019-08-24},
	date = {2007-09-04},
	langid = {english},
	keywords = {Human genomics, Mammalian genomics, Embryos, Chemical elements, Enhancer elements, Genetic screens, Genome evolution, Mouse models},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/MFKD4IIT/Ahituv et al. - 2007 - Deletion of Ultraconserved Elements Yields Viable .pdf:application/pdf}
}

@article{braconi_expression_2011,
	title = {Expression and functional role of a transcribed noncoding {RNA} with an ultraconserved element in hepatocellular carcinoma},
	volume = {108},
	issn = {1091-6490},
	doi = {10.1073/pnas.1011098108},
	abstract = {Although expression of non-protein-coding {RNA} ({ncRNA}) can be altered in human cancers, their functional relevance is unknown. Ultraconserved regions are noncoding genomic segments that are 100\% conserved across humans, mice, and rats. Conservation of gene sequences across species may indicate an essential functional role, and therefore we evaluated the expression of ultraconserved {RNAs} ({ucRNA}) in hepatocellular cancer ({HCC}). The global expression of {ucRNAs} was analyzed with a custom microarray. Expression was verified in cell lines by real-time {PCR} or in tissues by in situ hybridization using tissue microarrays. Cellular {ucRNA} expression was modulated with {siRNAs}, and the effects on global gene expression and growth of human and murine {HCC} cells were evaluated. Fifty-six {ucRNAs} were aberrantly expressed in {HepG}2 cells compared with nonmalignant hepatocytes. Among these {ucRNAs}, the greatest change was noted for ultraconserved element 338 (uc.338), which was dramatically increased in human {HCC} compared with noncancerous adjacent tissues. Although uc.338 is partially located within the poly({rC}) binding protein 2 ({PCBP}2) gene, the transcribed {ncRNA} encoding uc.338 is expressed independently of {PCBP}2 and was cloned as a 590-bp {RNA} gene, termed {TUC}338. Functional gene annotation analysis indicated predominant effects on genes involved in cell growth. These effects were experimentally demonstrated in both human and murine cells. {siRNA} to {TUC}338 decreased both anchorage-dependent and anchorage-independent growth of {HCC} cells. These studies identify a critical role for {TUC}338 in regulation of transformed cell growth and of transcribed ultraconserved {ncRNA} as a unique class of genes involved in the pathobiology of {HCC}.},
	pages = {786--791},
	number = {2},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Braconi, Chiara and Valeri, Nicola and Kogure, Takayuki and Gasparini, Pierluigi and Huang, Nianyuan and Nuovo, Gerard J. and Terracciano, Luigi and Croce, Carlo M. and Patel, Tushar},
	date = {2011-01-11},
	pmid = {21187392},
	pmcid = {PMC3021052},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, Mice, {DNA} Transposable Elements, In Situ Hybridization, Liver Neoplasms, Molecular Sequence Data, Models, Genetic, {RNA}, Untranslated, Hepatocytes, Gene Expression Regulation, Neoplastic, Carcinoma, Hepatocellular, Cell Line, Tumor},
	file = {Full Text:/home/jlagarde/Zotero/storage/BZ9JL99U/Braconi et al. - 2011 - Expression and functional role of a transcribed no.pdf:application/pdf}
}

@article{mccole_abnormal_2014,
	title = {Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells},
	volume = {10},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1004646},
	abstract = {Ultraconserved elements ({UCEs}) are strongly depleted from segmental duplications and copy number variations ({CNVs}) in the human genome, suggesting that deletion or duplication of a {UCE} can be deleterious to the mammalian cell. Here we address the process by which {CNVs} become depleted of {UCEs}. We begin by showing that depletion for {UCEs} characterizes the most recent large-scale human {CNV} datasets and then find that even newly formed de novo {CNVs}, which have passed through meiosis at most once, are significantly depleted for {UCEs}. In striking contrast, {CNVs} arising specifically in cancer cells are, as a rule, not depleted for {UCEs} and can even become significantly enriched. This observation raises the possibility that {CNVs} that arise somatically and are relatively newly formed are less likely to have established a {CNV} profile that is depleted for {UCEs}. Alternatively, lack of depletion for {UCEs} from cancer {CNVs} may reflect the diseased state. In support of this latter explanation, somatic {CNVs} that are not associated with disease are depleted for {UCEs}. Finally, we show that it is possible to observe the {CNVs} of induced pluripotent stem ({iPS}) cells become depleted of {UCEs} over time, suggesting that depletion may be established through selection against {UCE}-disrupting {CNVs} without the requirement for meiotic divisions.},
	pages = {e1004646},
	number = {10},
	journaltitle = {{PLoS} genetics},
	shortjournal = {{PLoS} Genet.},
	author = {{McCole}, Ruth B. and Fonseka, Chamith Y. and Koren, Amnon and Wu, C.-Ting},
	date = {2014-10},
	pmid = {25340765},
	pmcid = {PMC4207606},
	keywords = {Animals, Conserved Sequence, Humans, {DNA} Copy Number Variations, Gene Dosage, Mammals, Neoplasms, Sequence Deletion, Evolution, Molecular, Genome, Human, Chromosome Walking, Induced Pluripotent Stem Cells, Pluripotent Stem Cells},
	file = {Full Text:/home/jlagarde/Zotero/storage/LUL2SYKP/McCole et al. - 2014 - Abnormal dosage of ultraconserved elements is high.pdf:application/pdf}
}

@article{de_lara_enhancer_2019,
	title = {Enhancer {RNAs}: Insights Into Their Biological Role},
	volume = {12},
	issn = {2516-8657},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505235/},
	doi = {10.1177/2516865719846093},
	shorttitle = {Enhancer {RNAs}},
	abstract = {Enhancers play a central role in the transcriptional regulation of metazoans.
Almost a decade ago, the discovery of their pervasive transcription into
noncoding {RNAs}, termed enhancer {RNAs} ({eRNAs}), opened a whole new field of study.
The presence of {eRNAs} correlates with enhancer activity; however, whether they
act as functional molecules remains controversial. Here we review direct
experimental evidence supporting a functional role of {eRNAs} in transcription and
provide a general pipeline that could help in the design of experimental
approaches to investigate the function of {eRNAs}. We propose that induction of
transcriptional activity at enhancers promotes an increase in its activity by an
{RNA}-mediated titration of regulatory proteins that can impact different
processes like chromatin accessibility or chromatin looping. In a few cases,
transcripts originating from enhancers have acquired specific molecular
functions to regulate gene expression. We speculate that these transcripts are
either nonannotated long noncoding {RNAs} ({lncRNAs}) or are evolving toward
functional {lncRNAs}. Further work will be needed to comprehend better the
biological activity of these transcripts.},
	journaltitle = {Epigenetics Insights},
	shortjournal = {Epigenet Insights},
	author = {de Lara, Josué Cortés-Fernández and Arzate-Mejía, Rodrigo G and Recillas-Targa, Félix},
	urldate = {2019-08-24},
	date = {2019-05-07},
	pmid = {31106290},
	pmcid = {PMC6505235},
	keywords = {{lncRNAs}, chromatin, gene expression, enhancer, chromatin loop, {eRNAs}},
	file = {Full Text:/home/jlagarde/Zotero/storage/P6JDSX89/de Lara et al. - 2019 - Enhancer RNAs Insights Into Their Biological Role.pdf:application/pdf;PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/MIWNZD5H/de Lara et al. - 2019 - Enhancer RNAs Insights Into Their Biological Role.pdf:application/pdf}
}

@article{de_santa_large_2010,
	title = {A large fraction of extragenic {RNA} pol {II} transcription sites overlap enhancers},
	volume = {8},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.1000384},
	abstract = {Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding {RNAs} ({lncRNAs}), some of which result from Pol\_II transcription of bona-fide {RNA} genes. Whether all {lncRNAs} described insofar are products of {RNA} genes, however, is still unclear. Here we have characterized transcription sites located outside protein-coding genes in a highly regulated response, macrophage activation by endotoxin. Using chromatin signatures, we could unambiguously classify extragenic Pol\_II binding sites as belonging to either canonical {RNA} genes or transcribed enhancers. Unexpectedly, 70\% of extragenic Pol\_II peaks were associated with genomic regions with a canonical chromatin signature of enhancers. Enhancer-associated extragenic transcription was frequently adjacent to inducible inflammatory genes, was regulated in response to endotoxin stimulation, and generated very low abundance transcripts. Moreover, transcribed enhancers were under purifying selection and contained binding sites for inflammatory transcription factors, thus suggesting their functionality. These data demonstrate that a large fraction of extragenic Pol\_II transcription sites can be ascribed to cis-regulatory genomic regions. Discrimination between {lncRNAs} generated by canonical {RNA} genes and products of transcribed enhancers will provide a framework for experimental approaches to {lncRNAs} and help complete the annotation of mammalian genomes.},
	pages = {e1000384},
	number = {5},
	journaltitle = {{PLoS} biology},
	shortjournal = {{PLoS} Biol.},
	author = {De Santa, Francesca and Barozzi, Iros and Mietton, Flore and Ghisletti, Serena and Polletti, Sara and Tusi, Betsabeh Khoramian and Muller, Heiko and Ragoussis, Jiannis and Wei, Chia-Lin and Natoli, Gioacchino},
	date = {2010-05-11},
	pmid = {20485488},
	pmcid = {PMC2867938},
	keywords = {Animals, Humans, Mice, Binding Sites, Gene Expression Regulation, Female, Macrophage Activation, {RNA} Polymerase {II}, Transcription, Genetic, Promoter Regions, Genetic, {RNA}, Untranslated, Regulatory Sequences, Nucleic Acid, Lipopolysaccharides},
	file = {Full Text:/home/jlagarde/Zotero/storage/KJ2H7HDW/De Santa et al. - 2010 - A large fraction of extragenic RNA pol II transcri.pdf:application/pdf}
}

@article{bose_rna_2017,
	title = {{RNA} Binding to {CBP} Stimulates Histone Acetylation and Transcription},
	volume = {168},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2016.12.020},
	abstract = {{CBP}/p300 are transcription co-activators whose binding is a signature of enhancers, cis-regulatory elements that control patterns of gene expression in multicellular organisms. Active enhancers produce bi-directional enhancer {RNAs} ({eRNAs}) and display {CBP}/p300-dependent histone acetylation. Here, we demonstrate that {CBP} binds directly to {RNAs} in vivo and in vitro. {RNAs} bound to {CBP} in vivo include a large number of {eRNAs}. Using steady-state histone acetyltransferase ({HAT}) assays, we show that an {RNA} binding region in the {HAT} domain of {CBP}-a regulatory motif unique to {CBP}/p300-allows {RNA} to stimulate {CBP}'s {HAT} activity. At enhancers where {CBP} interacts with {eRNAs}, stimulation manifests in {RNA}-dependent changes in the histone acetylation mediated by {CBP}, such as H3K27ac, and by corresponding changes in gene expression. By interacting directly with {CBP}, {eRNAs} contribute to the unique chromatin structure at active enhancers, which, in turn, is required for regulation of target genes.},
	pages = {135--149.e22},
	number = {1},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Bose, Daniel A. and Donahue, Greg and Reinberg, Danny and Shiekhattar, Ramin and Bonasio, Roberto and Berger, Shelley L.},
	date = {2017-01-12},
	pmid = {28086087},
	pmcid = {PMC5325706},
	keywords = {Animals, Mice, Acetylation, Cell Line, Fibroblasts, Histone Acetyltransferases, Histones, Enhancer Elements, Genetic, {RNA}, Untranslated, enhancers, gene regulation, acetyltransferase, {CBP}/p300, chromatin modification, epigenetic enzymes, {eRNA}, histone acetylation, non-coding {RNA}, p300-{CBP} Transcription Factors, {RNA}-binding},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/7U528KVC/Bose et al. - 2017 - RNA Binding to CBP Stimulates Histone Acetylation .pdf:application/pdf}
}

@article{eddy_computational_2014,
	title = {Computational analysis of conserved {RNA} secondary structure in transcriptomes and genomes},
	volume = {43},
	issn = {1936-1238},
	doi = {10.1146/annurev-biophys-051013-022950},
	abstract = {Transcriptomics experiments and computational predictions both enable systematic discovery of new functional {RNAs}. However, many putative noncoding transcripts arise instead from artifacts and biological noise, and current computational prediction methods have high false positive rates. I discuss prospects for improving computational methods for analyzing and identifying functional {RNAs}, with a focus on detecting signatures of conserved {RNA} secondary structure. An interesting new front is the application of chemical and enzymatic experiments that probe {RNA} structure on a transcriptome-wide scale. I review several proposed approaches for incorporating structure probing data into the computational prediction of {RNA} secondary structure. Using probabilistic inference formalisms, I show how all these approaches can be unified in a well-principled framework, which in turn allows {RNA} probing data to be easily integrated into a wide range of analyses that depend on {RNA} secondary structure inference. Such analyses include homology search and genome-wide detection of new structural {RNAs}.},
	pages = {433--456},
	journaltitle = {Annual Review of Biophysics},
	shortjournal = {Annu Rev Biophys},
	author = {Eddy, Sean R.},
	date = {2014},
	pmid = {24895857},
	pmcid = {PMC5541781},
	keywords = {{lncRNA}, noncoding {RNA}, Animals, Humans, {RNA}, Computational Biology, Algorithms, Nucleic Acid Conformation, Bacteria, probing, {SHAPE}, statistical inference},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/2ZAJGBXQ/Eddy - 2014 - Computational analysis of conserved RNA secondary .pdf:application/pdf}
}

@article{babak_considerations_2007,
	title = {Considerations in the identification of functional {RNA} structural elements in genomic alignments},
	volume = {8},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-8-33},
	abstract = {{BACKGROUND}: Accurate identification of novel, functional noncoding (nc) {RNA} features in genome sequence has proven more difficult than for exons. Current algorithms identify and score potential {RNA} secondary structures on the basis of thermodynamic stability, conservation, and/or covariance in sequence alignments. Neither the algorithms nor the information gained from the individual inputs have been independently assessed. Furthermore, due to issues in modelling background signal, it has been difficult to gauge the precision of these algorithms on a genomic scale, in which even a seemingly small false-positive rate can result in a vast excess of false discoveries.
{RESULTS}: We developed a shuffling algorithm, shuffle-pair.pl, that simultaneously preserves dinucleotide frequency, gaps, and local conservation in pairwise sequence alignments. We used shuffle-pair.pl to assess precision and recall of six {ncRNA} search tools ({MSARI}, {QRNA}, {ddbRNA}, {RNAz}, Evofold, and several variants of simple thermodynamic stability on a test set of 3046 alignments of known {ncRNAs}. Relative to mononucleotide shuffling, preservation of dinucleotide content in shuffling the alignments resulted in a drastic increase in estimated false-positive detection rates for {ncRNA} elements, precluding evaluation of higher order alignments, which cannot not be adequately shuffled maintaining both dinucleotides and alignment structure. On pairwise alignments, none of the covariance-based tools performed markedly better than thermodynamic scoring alone. Although the high false-positive rates call into question the veracity of any individual predicted secondary structural element in our analysis, we nevertheless identified intriguing global trends in human genome alignments. The distribution of {ncRNA} prediction scores in 75-base windows overlapping {UTRs}, introns, and intergenic regions analyzed using both thermodynamic stability and {EvoFold} (which has no thermodynamic component) was significantly higher for real than shuffled sequence, while the distribution for coding sequences was lower than that of corresponding shuffles.
{CONCLUSION}: Accurate prediction of novel {RNA} structural elements in genome sequence remains a difficult problem, and development of an appropriate negative-control strategy for multiple alignments is an important practical challenge. Nonetheless, the general trends we observed for the distributions of predicted {ncRNAs} across genomic features are biologically meaningful, supporting the presence of secondary structural elements in many 3' {UTRs}, and providing evidence for evolutionary selection against secondary structures in coding regions.},
	pages = {33},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Babak, Tomas and Blencowe, Benjamin J. and Hughes, Timothy R.},
	date = {2007-01-30},
	pmid = {17263882},
	pmcid = {PMC1803800},
	keywords = {Base Sequence, Conserved Sequence, {RNA}, Algorithms, Chromosome Mapping, Molecular Sequence Data, Sequence Alignment, Sequence Analysis, {RNA}},
	file = {Full Text:/home/jlagarde/Zotero/storage/LUGA6LB6/Babak et al. - 2007 - Considerations in the identification of functional.pdf:application/pdf}
}

@article{nordstrom_critical_2009,
	title = {Critical evaluation of the {FANTOM}3 non-coding {RNA} transcripts},
	volume = {94},
	issn = {1089-8646},
	doi = {10.1016/j.ygeno.2009.05.012},
	abstract = {We studied the genomic positions of 38,129 putative {ncRNAs} from the {RIKEN} dataset in relation to protein-coding genes. We found that the dataset has 41\% sense, 6\% antisense, 24\% intronic and 29\% intergenic transcripts. Interestingly, 17,678 (47\%) of the {FANTOM}3 transcripts were found to potentially be internally primed from longer transcripts. The highest fraction of these transcripts was found among the intronic transcripts and as many as 77\% or 6929 intronic transcripts were both internally primed and unspliced. We defined a filtered subset of 8535 transcripts that did not overlap with protein-coding genes, did not contain {ORFs} longer than 100 residues and were not internally primed. This dataset contains 53\% of the {FANTOM}3 transcripts associated to known {ncRNA} in {RNAdb} and expands previous similar efforts with 6523 novel transcripts. This bioinformatic filtering of the {FANTOM}3 non-coding dataset has generated a lead dataset of transcripts without signs of being artefacts, providing a suitable dataset for investigation with hybridization-based techniques.},
	pages = {169--176},
	number = {3},
	journaltitle = {Genomics},
	shortjournal = {Genomics},
	author = {Nordström, Karl J. V. and Mirza, Majd A. I. and Almén, Markus Sällman and Gloriam, David E. and Fredriksson, Robert and Schiöth, Helgi B.},
	date = {2009-09},
	pmid = {19505569},
	keywords = {Humans, Proteins, Computational Biology, Introns, Expressed Sequence Tags, Databases, Genetic, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated, Sequence Analysis, {RNA}, Genome, Human}
}

@article{rivas_noncoding_2001,
	title = {Noncoding {RNA} gene detection using comparative sequence analysis},
	volume = {2},
	issn = {1471-2105},
	abstract = {{BACKGROUND}: Noncoding {RNA} genes produce transcripts that exert their function without ever producing proteins. Noncoding {RNA} gene sequences do not have strong statistical signals, unlike protein coding genes. A reliable general purpose computational genefinder for noncoding {RNA} genes has been elusive.
{RESULTS}: We describe a comparative sequence analysis algorithm for detecting novel structural {RNA} genes. The key idea is to test the pattern of substitutions observed in a pairwise alignment of two homologous sequences. A conserved coding region tends to show a pattern of synonymous substitutions, whereas a conserved structural {RNA} tends to show a pattern of compensatory mutations consistent with some base-paired secondary structure. We formalize this intuition using three probabilistic "pair-grammars": a pair stochastic context free grammar modeling alignments constrained by structural {RNA} evolution, a pair hidden Markov model modeling alignments constrained by coding sequence evolution, and a pair hidden Markov model modeling a null hypothesis of position-independent evolution. Given an input pairwise sequence alignment (e.g. from a {BLASTN} comparison of two related genomes) we classify the alignment into the coding, {RNA}, or null class according to the posterior probability of each class.
{CONCLUSIONS}: We have implemented this approach as a program, {QRNA}, which we consider to be a prototype structural noncoding {RNA} genefinder. Tests suggest that this approach detects noncoding {RNA} genes with a fair degree of reliability.},
	pages = {8},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Rivas, E. and Eddy, S. R.},
	date = {2001},
	pmid = {11801179},
	pmcid = {PMC64605},
	keywords = {Animals, Base Sequence, Genome, Computational Biology, Algorithms, Caenorhabditis elegans, Bayes Theorem, Computer Simulation, Molecular Sequence Data, Sensitivity and Specificity, Escherichia coli, Models, Genetic, {RNA}, Untranslated, Sequence Analysis, {RNA}, {RNA}, Helminth, Genome, Bacterial, {RNA}, Bacterial, Caenorhabditis, Salmonella typhi}
}

@article{coventry_msari:_2004,
	title = {{MSARI}: multiple sequence alignments for statistical detection of {RNA} secondary structure},
	volume = {101},
	issn = {0027-8424},
	doi = {10.1073/pnas.0404193101},
	shorttitle = {{MSARI}},
	abstract = {We present a highly accurate method for identifying genes with conserved {RNA} secondary structure by searching multiple sequence alignments of a large set of candidate orthologs for correlated arrangements of reverse-complementary regions. This approach is growing increasingly feasible as the genomes of ever more organisms are sequenced. A program called msari implements this method and is significantly more accurate than existing methods in the context of automatically generated alignments, making it particularly applicable to high-throughput scans. In our tests, it discerned clustalw-generated multiple sequence alignments of signal recognition particle or {RNaseP} orthologs from controls with 89.1\% sensitivity at 97.5\% specificity and with 74.4\% sensitivity with no false positives in 494 controls. We used msari to conduct a comprehensive scan for secondary structure in {mRNAs} of coding genes, and we found many genes with known {mRNA} secondary structure and compelling evidence for secondary structure in other genes. msari uses a method for coping with sequence redundancy that is likely to have applications in a large set of other comparison-based search methods. The program is available for download from http://theory.csail.mit.edu/{MSARi}.},
	pages = {12102--12107},
	number = {33},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Coventry, Alex and Kleitman, Daniel J. and Berger, Bonnie},
	date = {2004-08-17},
	pmid = {15304649},
	pmcid = {PMC514400},
	keywords = {Base Sequence, Conserved Sequence, {RNA}, Algorithms, Software, Nucleic Acid Conformation, Sensitivity and Specificity, Sequence Alignment, Databases, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/5PHL3Q3N/Coventry et al. - 2004 - MSARI multiple sequence alignments for statistica.pdf:application/pdf}
}

@article{gruber_strategies_2008,
	title = {Strategies for measuring evolutionary conservation of {RNA} secondary structures},
	volume = {9},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-9-122},
	abstract = {{BACKGROUND}: Evolutionary conservation of {RNA} secondary structure is a typical feature of many functional non-coding {RNAs}. Since almost all of the available methods used for prediction and annotation of non-coding {RNA} genes rely on this evolutionary signature, accurate measures for structural conservation are essential.
{RESULTS}: We systematically assessed the ability of various measures to detect conserved {RNA} structures in multiple sequence alignments. We tested three existing and eight novel strategies that are based on metrics of folding energies, metrics of single optimal structure predictions, and metrics of structure ensembles. We find that the folding energy based {SCI} score used in the {RNAz} program and a simple base-pair distance metric are by far the most accurate. The use of more complex metrics like for example tree editing does not improve performance. A variant of the {SCI} performed particularly well on highly conserved alignments and is thus a viable alternative when only little evolutionary information is available. Surprisingly, ensemble based methods that, in principle, could benefit from the additional information contained in sub-optimal structures, perform particularly poorly. As a general trend, we observed that methods that include a consensus structure prediction outperformed equivalent methods that only consider pairwise comparisons.
{CONCLUSION}: Structural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future {RNA} gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences.},
	pages = {122},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Gruber, Andreas R. and Bernhart, Stephan H. and Hofacker, Ivo L. and Washietl, Stefan},
	date = {2008-02-26},
	pmid = {18302738},
	pmcid = {PMC2335298},
	keywords = {Base Sequence, Conserved Sequence, {RNA}, Algorithms, Base Pair Mismatch, Molecular Sequence Data, Sequence Alignment, Evolution, Molecular, Sequence Analysis, {RNA}, Sequence Homology, Nucleic Acid},
	file = {Full Text:/home/jlagarde/Zotero/storage/NDNMEH5W/Gruber et al. - 2008 - Strategies for measuring evolutionary conservation.pdf:application/pdf}
}

@article{washietl_consensus_2004,
	title = {Consensus folding of aligned sequences as a new measure for the detection of functional {RNAs} by comparative genomics},
	volume = {342},
	issn = {0022-2836},
	doi = {10.1016/j.jmb.2004.07.018},
	abstract = {Facing the ever-growing list of newly discovered classes of functional {RNAs}, it can be expected that further types of functional {RNAs} are still hidden in recently completed genomes. The computational identification of such {RNA} genes is, therefore, of major importance. While most known functional {RNAs} have characteristic secondary structures, their free energies are generally not statistically significant enough to distinguish {RNA} genes from the genomic background. Additional information is required. Considering the wide availability of new genomic data of closely related species, comparative studies seem to be the most promising approach. Here, we show that prediction of consensus structures of aligned sequences can be a significant measure to detect functional {RNAs}. We report a new method to test multiple sequence alignments for the existence of an unusually structured and conserved fold. We show for alignments of six types of well-known functional {RNA} that an energy score consisting of free energy and a covariation term significantly improves sensitivity compared to single sequence predictions. We further test our method on a number of non-coding {RNAs} from Caenorhabditis elegans/Caenorhabditis briggsae and seven Saccharomyces species. Most {RNAs} can be detected with high significance. We provide a Perl implementation that can be used readily to score single alignments and discuss how the methods described here can be extended to allow for efficient genome-wide screens.},
	pages = {19--30},
	number = {1},
	journaltitle = {Journal of Molecular Biology},
	shortjournal = {J. Mol. Biol.},
	author = {Washietl, Stefan and Hofacker, Ivo L.},
	date = {2004-09-03},
	pmid = {15313604},
	keywords = {Genomics, Animals, Base Sequence, Genome, Algorithms, Molecular Sequence Data, Nucleic Acid Conformation, Sequence Alignment, {RNA}, Untranslated, Caenorhabditis, Random Allocation, Saccharomyces},
	file = {Submitted Version:/home/jlagarde/Zotero/storage/I26JVPB9/Washietl and Hofacker - 2004 - Consensus folding of aligned sequences as a new me.pdf:application/pdf}
}

@article{le_program_1988,
	title = {A program for predicting significant {RNA} secondary structures},
	volume = {4},
	issn = {0266-7061},
	abstract = {We describe a program for the analysis of {RNA} secondary structure. There are two new features in this program. (i) To get vector speeds on a vector pipeline machine (such as Cray X-{MP}/24) we have vectorized the secondary structure dynamic algorithm. (ii) The statistical significance of a locally 'optimal' secondary structure is assessed by a Monte Carlo method. The results can be depicted graphically including profiles of the stability of local secondary structures and the distribution of the potentially significant secondary structures in the {RNA} molecules. Interesting regions where both the potentially significant secondary structures and 'open' structures (single-stranded coils) occur can be identified by the plots mentioned above. Furthermore, the speed of the vectorized code allows repeated Monte Carlo simulations with different overlapping window sizes. Thus, the optimal size of the significant secondary structure occurring in the interesting region can be assessed by repeating the Monte Carlo simulation. The power of the program is demonstrated in the analysis of local secondary structures of human T-cell lymphotrophic virus type {III} ({HIV}).},
	pages = {153--159},
	number = {1},
	journaltitle = {Computer applications in the biosciences: {CABIOS}},
	shortjournal = {Comput. Appl. Biosci.},
	author = {Le, S. V. and Chen, J. H. and Currey, K. M. and Maizel, J. V.},
	date = {1988-03},
	pmid = {2454711},
	keywords = {{RNA}, Algorithms, Software, Nucleic Acid Conformation, Thermodynamics, {RNA}, Viral, {HIV}, Monte Carlo Method}
}

@article{rivas_secondary_2000,
	title = {Secondary structure alone is generally not statistically significant for the detection of noncoding {RNAs}},
	volume = {16},
	issn = {1367-4803},
	doi = {10.1093/bioinformatics/16.7.583},
	abstract = {{MOTIVATION}: Several results in the literature suggest that biologically interesting {RNAs} have secondary structures that are more stable than expected by chance. Based on these observations, we developed a scanning algorithm for detecting noncoding {RNA} genes in genome sequences, using a fully probabilistic version of the Zuker minimum-energy folding algorithm.
{RESULTS}: Preliminary results were encouraging, but certain anomalies led us to do a carefully controlled investigation of this class of methods. Ultimately, our results argue that for the probabilistic model there is indeed a statistical effect, but it comes mostly from local base-composition bias and not from {RNA} secondary structure. For the thermodynamic implementation (which evaluates statistical significance by doing Monte Carlo shuffling in fixed-length sequence windows, thus eliminating the base-composition effect) the signals for noncoding {RNAs} are still usually indistinguishable from noise, especially when certain statistical artifacts resulting from local base-composition inhomogeneity are taken into account. We conclude that although a distinct, stable secondary structure is undoubtedly important in most noncoding {RNAs}, the stability of most noncoding {RNA} secondary structures is not sufficiently different from the predicted stability of a random sequence to be useful as a general genefinding approach.},
	pages = {583--605},
	number = {7},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Rivas, E. and Eddy, S. R.},
	date = {2000-07},
	pmid = {11038329},
	keywords = {Animals, {RNA}, Algorithms, Caenorhabditis elegans, Base Composition, Nucleic Acid Conformation, {RNA}, Helminth, Models, Statistical, Data Interpretation, Statistical, Methanococcus},
	file = {Full Text:/home/jlagarde/Zotero/storage/PS6Q76FS/Rivas and Eddy - 2000 - Secondary structure alone is generally not statist.pdf:application/pdf;Full Text:/home/jlagarde/Zotero/storage/M9KRHSS3/Rivas and Eddy - 2000 - Secondary structure alone is generally not statist.pdf:application/pdf}
}

@article{kapusta_volatile_2014,
	title = {Volatile evolution of long noncoding {RNA} repertoires: mechanisms and biological implications},
	volume = {30},
	issn = {0168-9525},
	doi = {10.1016/j.tig.2014.08.004},
	shorttitle = {Volatile evolution of long noncoding {RNA} repertoires},
	abstract = {Thousands of genes encoding long noncoding {RNAs} ({lncRNAs}) have been identified in all vertebrate genomes thus far examined. The list of {lncRNAs} partaking in arguably important biochemical, cellular, and developmental activities is steadily growing. However, it is increasingly clear that {lncRNA} repertoires are subject to weak functional constraint and rapid turnover during vertebrate evolution. We discuss here some of the factors that may explain this apparent paradox, including relaxed constraint on sequence to maintain {lncRNA} structure/function, extensive redundancy in the regulatory circuits in which {lncRNAs} act, as well as adaptive and non-adaptive forces such as genetic drift. We explore the molecular mechanisms promoting the birth and rapid evolution of {lncRNA} genes, with an emphasis on the influence of bidirectional transcription and transposable elements, two pervasive features of vertebrate genomes. Together these properties reveal a remarkably dynamic and malleable noncoding transcriptome which may represent an important source of robustness and evolvability.},
	pages = {439--452},
	number = {10},
	journaltitle = {Trends in genetics: {TIG}},
	shortjournal = {Trends Genet.},
	author = {Kapusta, Aurélie and Feschotte, Cédric},
	date = {2014-10},
	pmid = {25218058},
	pmcid = {PMC4464757},
	keywords = {Animals, Humans, Exons, {DNA} Transposable Elements, Nucleic Acid Conformation, Evolution, Molecular, {RNA}, Long Noncoding, Transcription, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/TIUP767K/Kapusta and Feschotte - 2014 - Volatile evolution of long noncoding RNA repertoir.pdf:application/pdf}
}

@article{tavares_phylogenetic_2019,
	title = {Phylogenetic Analysis with Improved Parameters Reveals Conservation in {lncRNA} Structures},
	volume = {431},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2019.03.012},
	abstract = {The existence of evolutionary conservation in base pairing is strong evidence for functional elements of {RNA} structure, although available tools for rigorous identification of structural conservation are limited. R-scape is a recently developed program for statistical prediction of pairwise covariation from sequence alignments, but it initially showed limited utility on long {RNAs}, especially those of eukaryotic origin. Here we show that R-scape can be adapted for a more powerful analysis of structure conservation in long {RNA} molecules, including mammalian {lncRNAs}.},
	pages = {1592--1603},
	number = {8},
	journaltitle = {Journal of Molecular Biology},
	shortjournal = {J. Mol. Biol.},
	author = {Tavares, Rafael C. A. and Pyle, Anna Marie and Somarowthu, Srinivas},
	date = {2019-04-05},
	pmid = {30890332},
	pmcid = {PMC6515926},
	keywords = {conserved structure, covariation analysis, {lncRNA} structure, long non-coding {RNAs}, {RNAalifold}}
}

@article{thompson_long_2016,
	title = {Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire},
	volume = {62},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2016.03.029},
	shorttitle = {Long Terminal Repeats},
	abstract = {The life cycle of endogenous retroviruses ({ERVs}), also called long terminal repeat ({LTR}) retrotransposons, begins with transcription by {RNA} polymerase {II} followed by reverse transcription and re-integration into the host genome. While most {ERVs} are relics of ancient integration events, "young" proviruses competent for retrotransposition-found in many mammals, but not humans-represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post-transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that {LTR} sequences derived from distantly related {ERVs} have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of {ERV} {LTRs} acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for {LTR} exaptation in developmental and tissue-specific gene regulation.},
	pages = {766--776},
	number = {5},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Thompson, Peter J. and Macfarlan, Todd S. and Lorincz, Matthew C.},
	date = {2016},
	pmid = {27259207},
	pmcid = {PMC4910160},
	keywords = {Animals, Humans, Chromatin Assembly and Disassembly, {DNA} Replication, Host-Pathogen Interactions, Terminal Repeat Sequences, Virus Replication, {RNA}-Directed {DNA} Polymerase, {RNA} Polymerase {II}, {RNA}, Long Noncoding, Transcription, Genetic, Promoter Regions, Genetic, {DNA}, Viral, Endogenous Retroviruses, Gene Expression Regulation, Viral},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/NA44U94Q/Thompson et al. - 2016 - Long Terminal Repeats From Parasitic Elements to .pdf:application/pdf}
}

@article{sundaram_widespread_2014,
	title = {Widespread contribution of transposable elements to the innovation of gene regulatory networks},
	volume = {24},
	issn = {1549-5469},
	doi = {10.1101/gr.168872.113},
	abstract = {Transposable elements ({TEs}) have been shown to contain functional binding sites for certain transcription factors ({TFs}). However, the extent to which {TEs} contribute to the evolution of {TF} binding sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous {TFs} in two pairs of human and mouse cell lines (representing two cell lineages), along with epigenomic profiles, including {DNA} methylation and six histone modifications. Overall, we found that 20\% of binding sites were embedded within {TEs}. This number varied across different {TFs}, ranging from 2\% to 40\%. We further identified 710 {TF}-{TE} relationships in which genomic copies of a {TE} subfamily contributed a significant number of binding peaks for a {TF}, and we found that {LTR} elements dominated these relationships in human. Importantly, {TE}-derived binding peaks were strongly associated with open and active chromatin signatures, including reduced {DNA} methylation and increased enhancer-associated histone marks. On average, 66\% of {TE}-derived binding events were cell type-specific with a cell type-specific epigenetic landscape. Most of the binding sites contributed by {TEs} were species-specific, but we also identified binding sites conserved between human and mouse, the functional relevance of which was supported by a signature of purifying selection on {DNA} sequences of these {TEs}. Interestingly, several {TFs} had significantly expanded binding site landscapes only in one species, which were linked to species-specific gene functions, suggesting that {TEs} are an important driving force for regulatory innovation. Taken together, our data suggest that {TEs} have significantly and continuously shaped gene regulatory networks during mammalian evolution.},
	pages = {1963--1976},
	number = {12},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Sundaram, Vasavi and Cheng, Yong and Ma, Zhihai and Li, Daofeng and Xing, Xiaoyun and Edge, Peter and Snyder, Michael P. and Wang, Ting},
	date = {2014-12},
	pmid = {25319995},
	pmcid = {PMC4248313},
	keywords = {Epigenomics, Animals, Humans, Mice, Binding Sites, Protein Binding, Organ Specificity, Cell Line, Chromatin, Chromatin Immunoprecipitation, {DNA} Transposable Elements, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Multigene Family, Nucleotide Motifs, Position-Specific Scoring Matrices, Transcription Factors, Evolution, Molecular},
	file = {Full Text:/home/jlagarde/Zotero/storage/VLUQ58ZV/Sundaram et al. - 2014 - Widespread contribution of transposable elements t.pdf:application/pdf}
}

@article{feschotte_transposable_2008,
	title = {Transposable elements and the evolution of regulatory networks},
	volume = {9},
	issn = {1471-0064},
	doi = {10.1038/nrg2337},
	abstract = {The control and coordination of eukaryotic gene expression rely on transcriptional and post-transcriptional regulatory networks. Although progress has been made in mapping the components and deciphering the function of these networks, the mechanisms by which such intricate circuits originate and evolve remain poorly understood. Here I revisit and expand earlier models and propose that genomic repeats, and in particular transposable elements, have been a rich source of material for the assembly and tinkering of eukaryotic gene regulatory systems.},
	pages = {397--405},
	number = {5},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Feschotte, Cédric},
	date = {2008-05},
	pmid = {18368054},
	pmcid = {PMC2596197},
	keywords = {Animals, Genome, Humans, Gene Expression Regulation, Chromosome Mapping, {DNA} Transposable Elements, Eukaryotic Cells},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/HTFXC9EW/Feschotte - 2008 - Transposable elements and the evolution of regulat.pdf:application/pdf}
}

@article{mcclintock_controlling_1956,
	title = {Controlling elements and the gene},
	volume = {21},
	issn = {0091-7451},
	pages = {197--216},
	journaltitle = {Cold Spring Harbor Symposia on Quantitative Biology},
	shortjournal = {Cold Spring Harb. Symp. Quant. Biol.},
	author = {Mcclintock, B.},
	date = {1956},
	pmid = {13433592},
	keywords = {Humans, Chromosomes, {CHROMOSOMES}}
}

@article{roberts_burgeoning_2014,
	title = {Burgeoning evidence indicates that {microRNAs} were initially formed from transposable element sequences},
	volume = {4},
	issn = {2159-2543},
	doi = {10.4161/mge.29255},
	abstract = {{MicroRNAs} ({miRNAs}) constitute a recently discovered class of noncoding {RNAs} that play key roles in the regulation of gene expression. Despite being only {\textasciitilde}20 nucleotides in length, these highly versatile molecules have been shown to play pivotal roles in development, basic cellular metabolism, apoptosis, and disease. While over 24,000 {miRNAs} have been characterized since they were first isolated in mammals in 2001, the functions of the majority of these {miRNAs} remain largely undescribed. That said, many now suggest that characterization of the relationships between {miRNAs} and transposable elements ({TEs}) can help elucidate {miRNA} functionality. Strikingly, over 20 publications have now reported the initial formation of thousands of {miRNA} loci from {TE} sequences. In this review we chronicle the findings of these reports, discuss the evolution of the field along with future directions, and examine how this information can be used to ascertain insights into {miRNA} transcriptional regulation and how it can be exploited to facilitate {miRNA} target prediction.},
	pages = {e29255},
	journaltitle = {Mobile Genetic Elements},
	shortjournal = {Mob Genet Elements},
	author = {Roberts, Justin T. and Cardin, Sara E. and Borchert, Glen M.},
	date = {2014},
	pmid = {25054081},
	pmcid = {PMC4091103},
	keywords = {{microRNA}, {miR}, {miRNA}, repetitive, retrotransposon, transposable, transposon},
	file = {Full Text:/home/jlagarde/Zotero/storage/A55S5AGY/Roberts et al. - 2014 - Burgeoning evidence indicates that microRNAs were .pdf:application/pdf}
}

@article{lev-maor_birth_2003,
	title = {The birth of an alternatively spliced exon: 3' splice-site selection in Alu exons},
	volume = {300},
	issn = {1095-9203},
	doi = {10.1126/science.1082588},
	shorttitle = {The birth of an alternatively spliced exon},
	abstract = {Alu repetitive elements can be inserted into mature messenger {RNAs} via a splicing-mediated process termed exonization. To understand the molecular basis and the regulation of the process of turning intronic Alus into new exons, we compiled and analyzed a data set of human exonized Alus. We revealed a mechanism that governs 3' splice-site selection in these exons during alternative splicing. On the basis of these findings, we identified mutations that activated the exonization of a silent intronic Alu.},
	pages = {1288--1291},
	number = {5623},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Lev-Maor, Galit and Sorek, Rotem and Shomron, Noam and Ast, Gil},
	date = {2003-05-23},
	pmid = {12764196},
	keywords = {Humans, Exons, Introns, Alternative Splicing, Cell Line, Dinucleoside Phosphates, Point Mutation, Polymerase Chain Reaction, {RNA}-Binding Proteins, Transfection, Alu Elements, Genome, Human, Cloning, Molecular, {RNA} Splicing Factors, Tumor Cells, Cultured, Adenosine Deaminase, {DNA}, Antisense, Glucosyltransferases, Mutagenesis, Site-Directed, Ribonucleoproteins, Small Nuclear, Spliceosomes}
}

@article{ling_solitary_2002,
	title = {The solitary long terminal repeats of {ERV}-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells},
	volume = {76},
	issn = {0022-538X},
	doi = {10.1128/jvi.76.5.2410-2423.2002},
	abstract = {The solitary long terminal repeats ({LTRs}) of {ERV}-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive {DNAs} present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5" boundary area of the erythroid beta-globin locus control region (beta-{LCR}) and the intron of the embryonic axin gene show that a solitary {ERV}-9 {LTR} has been stably integrated in the respective loci for at least 15 million years in the higher primates from orangutan to human. Functional studies utilizing the green fluorescent protein ({GFP}) gene as the reporter in transfection experiments show that the U3 region of the {LTRs} possesses strong enhancer activity in embryonic cells of widely different tissue origins and in adult cells of blood lineages. In both the genomic {LTRs} of embryonic placental cells and erythroid K562 cells and transfected {LTRs} of recombinant {GFP} plasmids in K562 cells, the U3 enhancer activates synthesis of {RNAs} that are initiated from a specific site 25 bases downstream of the {AATAAA} ({TATA}) motif in the U3 promoter. A second {AATAAA} motif in the R region does not serve as the {TATA} box or as the polyadenylation signal. The {LTR}-initiated {RNAs} extend through the R and U5 regions into the downstream genomic {DNA}. The results suggest that the {ERV}-9 {LTR}-initiated transcription process may modulate transcription of the associated gene loci in embryonic and hematopoietic cells.},
	pages = {2410--2423},
	number = {5},
	journaltitle = {Journal of Virology},
	shortjournal = {J. Virol.},
	author = {Ling, Jianhua and Pi, Wenhu and Bollag, Roni and Zeng, Shan and Keskintepe, Meral and Saliman, Hatem and Krantz, Sanford and Whitney, Barry and Tuan, Dorothy},
	date = {2002-03},
	pmid = {11836419},
	pmcid = {PMC153808},
	keywords = {Animals, Base Sequence, Conserved Sequence, Humans, Introns, Biological Evolution, Cell Line, Flow Cytometry, Molecular Sequence Data, Primates, Terminal Repeat Sequences, Transfection, Promoter Regions, Genetic, Enhancer Elements, Genetic, Genes, Reporter, Embryo, Mammalian, Endogenous Retroviruses, Retroelements, Globins, Hematopoietic Stem Cells},
	file = {Full Text:/home/jlagarde/Zotero/storage/V37FTXCV/Ling et al. - 2002 - The solitary long terminal repeats of ERV-9 endoge.pdf:application/pdf}
}

@article{pi_ltr_2004,
	title = {The {LTR} enhancer of {ERV}-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans},
	volume = {101},
	issn = {0027-8424},
	doi = {10.1073/pnas.0307698100},
	abstract = {The solitary {LTRs} of {ERV}-9 human endogenous retrovirus are middle repetitive {DNAs} associated with 3,000-4,000 human gene loci including the beta-globin gene locus where the {ERV}-9 {LTR} is juxtaposed to the locus control region (beta-{LCR}) far upstream of the globin genes. The {ERV}-9 {LTRs} are conserved during primate evolution, but their function in the primate genomes is unknown. Here, we show that in transgenic zebrafish harboring the beta-globin {ERV}-9 {LTR} coupled to the {GFP} gene, the {LTR} enhancer was active and initiated synthesis of {GFP} {mRNA} in oocytes but not in spermatozoa, and {GFP} expression in the embryos was maternally inherited. The {LTR} enhancer was active also in stem/progenitor cell regions of adult tissues of transgenic zebrafish. In human tissues, {ERV}-9 {LTR} enhancer was active also in oocytes and stem/progenitor cells but not in spermatozoa and a number of differentiated, adult somatic cells. Transcriptional analyses of the human beta-globin gene locus showed that the beta-globin {ERV}-9 {LTR} enhancer initiated {RNA} synthesis from the {LTR} in the direction of the downstream beta locus control region and globin genes in ovary and erythroid progenitor cells. The findings suggest that, during oogenesis, {ERV}-9 {LTR} enhancers in the human genome could activate the cis-linked gene loci to synthesize maternal {mRNAs} required for early embryogenesis. Alternatively, the {ERV}-9 {LTR} enhancers, in initiating {RNA} syntheses into the downstream genomic {DNAs}, could transcriptionally potentiate and preset chromatin structure of the cis-linked gene loci in oocytes and adult stem/progenitor cells.},
	pages = {805--810},
	number = {3},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Pi, Wenhu and Yang, Zhongan and Wang, Jian and Ruan, Ling and Yu, Xiuping and Ling, Jianhua and Krantz, Sanford and Isales, Carlos and Conway, Simon J. and Lin, Shuo and Tuan, Dorothy},
	date = {2004-01-20},
	pmid = {14718667},
	pmcid = {PMC321762},
	keywords = {Animals, Humans, Cell Differentiation, Female, Green Fluorescent Proteins, Male, Oocytes, Stem Cells, Terminal Repeat Sequences, Zebrafish, Enhancer Elements, Genetic, Locus Control Region, Endogenous Retroviruses, Globins, Animals, Genetically Modified, Luminescent Proteins, {NASA} Discipline Musculoskeletal, Non-{NASA} Center, Oogenesis, Recombinant Proteins, Spermatozoa},
	file = {Full Text:/home/jlagarde/Zotero/storage/M48Y2H7G/Pi et al. - 2004 - The LTR enhancer of ERV-9 human endogenous retrovi.pdf:application/pdf}
}

@article{lowe_29_2012,
	title = {29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome},
	volume = {7},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0043128},
	abstract = {Recent research supports the view that changes in gene regulation, as opposed to changes in the genes themselves, play a significant role in morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers are now able to use the available 29 mammalian genomes to measure selective constraint at the level of binding sites. This detailed map of constraint suggests that mammalian genomes co-opt fragments of mobile elements to act as gene regulatory sequence on a large scale. In the human genome we detect over 280,000 putative regulatory elements, totaling approximately 7 Mb of sequence, that originated as mobile element insertions. These putative regulatory regions are conserved non-exonic elements ({CNEEs}), which show considerable cross-species constraint and signatures of continued negative selection in humans, yet do not appear in a known mature transcript. These putative regulatory elements were co-opted from {SINE}, {LINE}, {LTR} and {DNA} transposon insertions. We demonstrate that at least 11\%, and an estimated 20\%, of gene regulatory sequence in the human genome showing cross-species conservation was co-opted from mobile elements. The location in the genome of {CNEEs} co-opted from mobile elements closely resembles that of {CNEEs} in general, except in the centers of the largest gene deserts where recognizable co-option events are relatively rare. We find that regions of certain mobile element insertions are more likely to be held under purifying selection than others. In particular, we show 6 examples where paralogous instances of an often co-opted mobile element region define a sequence motif that closely matches a transcription factor's binding profile.},
	pages = {e43128},
	number = {8},
	journaltitle = {{PloS} One},
	shortjournal = {{PLoS} {ONE}},
	author = {Lowe, Craig B. and Haussler, David},
	date = {2012},
	pmid = {22952639},
	pmcid = {PMC3428314},
	keywords = {Animals, Genome, Humans, Binding Sites, Protein Binding, 5' Untranslated Regions, Gene Frequency, Mammals, Phylogeny, Sequence Alignment, Transcription Factors, Models, Genetic, Genome, Human, Models, Statistical, Regulatory Elements, Transcriptional},
	file = {Full Text:/home/jlagarde/Zotero/storage/WRWFLE3V/Lowe and Haussler - 2012 - 29 mammalian genomes reveal novel exaptations of m.pdf:application/pdf}
}

@article{pennacchio_enhancers:_2013,
	title = {Enhancers: five essential questions},
	volume = {14},
	issn = {1471-0064},
	doi = {10.1038/nrg3458},
	shorttitle = {Enhancers},
	abstract = {It is estimated that the human genome contains hundreds of thousands of enhancers, so understanding these gene-regulatory elements is a crucial goal. Several fundamental questions need to be addressed about enhancers, such as how do we identify them all, how do they work, and how do they contribute to disease and evolution? Five prominent researchers in this field look at how much we know already and what needs to be done to answer these questions.},
	pages = {288--295},
	number = {4},
	journaltitle = {Nature Reviews. Genetics},
	shortjournal = {Nat. Rev. Genet.},
	author = {Pennacchio, Len A. and Bickmore, Wendy and Dean, Ann and Nobrega, Marcelo A. and Bejerano, Gill},
	date = {2013},
	pmid = {23503198},
	pmcid = {PMC4445073},
	keywords = {Humans, Gene Expression Regulation, Genetic Predisposition to Disease, Mutation, Evolution, Molecular, Promoter Regions, Genetic, Enhancer Elements, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/LRC4DDC6/Pennacchio et al. - 2013 - Enhancers five essential questions.pdf:application/pdf}
}

@article{smemo_obesity-associated_2014,
	title = {Obesity-associated variants within {FTO} form long-range functional connections with {IRX}3},
	volume = {507},
	issn = {1476-4687},
	doi = {10.1038/nature13138},
	abstract = {Genome-wide association studies ({GWAS}) have reproducibly associated variants within introns of {FTO} with increased risk for obesity and type 2 diabetes (T2D). Although the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that {FTO} expression levels influence body mass and composition phenotypes. However, no direct connection between the obesity-associated variants and {FTO} expression or function has been made. Here we show that the obesity-associated noncoding sequences within {FTO} are functionally connected, at megabase distances, with the homeobox gene {IRX}3. The obesity-associated {FTO} region directly interacts with the promoters of {IRX}3 as well as {FTO} in the human, mouse and zebrafish genomes. Furthermore, long-range enhancers within this region recapitulate aspects of {IRX}3 expression, suggesting that the obesity-associated interval belongs to the regulatory landscape of {IRX}3. Consistent with this, obesity-associated single nucleotide polymorphisms are associated with expression of {IRX}3, but not {FTO}, in human brains. A direct link between {IRX}3 expression and regulation of body mass and composition is demonstrated by a reduction in body weight of 25 to 30\% in Irx3-deficient mice, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue. Finally, hypothalamic expression of a dominant-negative form of Irx3 reproduces the metabolic phenotypes of Irx3-deficient mice. Our data suggest that {IRX}3 is a functional long-range target of obesity-associated variants within {FTO} and represents a novel determinant of body mass and composition.},
	pages = {371--375},
	number = {7492},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Smemo, Scott and Tena, Juan J. and Kim, Kyoung-Han and Gamazon, Eric R. and Sakabe, Noboru J. and Gómez-Marín, Carlos and Aneas, Ivy and Credidio, Flavia L. and Sobreira, Débora R. and Wasserman, Nora F. and Lee, Ju Hee and Puviindran, Vijitha and Tam, Davis and Shen, Michael and Son, Joe Eun and Vakili, Niki Alizadeh and Sung, Hoon-Ki and Naranjo, Silvia and Acemel, Rafael D. and Manzanares, Miguel and Nagy, Andras and Cox, Nancy J. and Hui, Chi-Chung and Gomez-Skarmeta, Jose Luis and Nóbrega, Marcelo A.},
	date = {2014-03-20},
	pmid = {24646999},
	pmcid = {PMC4113484},
	keywords = {Animals, Humans, Mice, Proteins, Introns, Brain, Homeodomain Proteins, Male, Phenotype, Transcription Factors, Zebrafish, Promoter Regions, Genetic, Polymorphism, Single Nucleotide, Adipose Tissue, Alpha-Ketoglutarate-Dependent Dioxygenase {FTO}, Basal Metabolism, Body Mass Index, Body Weight, Diabetes Mellitus, Type 2, Diet, Genes, Dominant, Hypothalamus, Mixed Function Oxygenases, Obesity, Oxo-Acid-Lyases, Thinness},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/ZZ7KHEBF/Smemo et al. - 2014 - Obesity-associated variants within FTO form long-r.pdf:application/pdf}
}

@article{ashe_intergenic_1997,
	title = {Intergenic transcription and transinduction of the human beta-globin locus},
	volume = {11},
	issn = {0890-9369},
	doi = {10.1101/gad.11.19.2494},
	abstract = {We have identified novel nuclear transcripts in the human beta-globin locus using nuclear run-on analysis in erythroid cell lines and in situ hybridization analysis of erythroid tissue. These transcripts extend across the {LCR} and intergenic regions but are undetectable in nonerythroid cells. Surprisingly, transient transfection of a beta-globin gene (epsilon, gamma, or beta) induces transcription of the {LCR} and intergenic regions from the chromosomal beta-globin locus in nonerythroid cell lines. The beta-globin genes themselves, however, remain transcriptionally silent. Induction is dependent on transcription of the globin gene in the transfected plasmid but does not require protein expression. Using in situ hybridization analysis, we show that the plasmid colocalizes with the endogenous beta-globin locus providing insight into the mechanism of transinduction.},
	pages = {2494--2509},
	number = {19},
	journaltitle = {Genes \& Development},
	shortjournal = {Genes Dev.},
	author = {Ashe, H. L. and Monks, J. and Wijgerde, M. and Fraser, P. and Proudfoot, N. J.},
	date = {1997-10-01},
	pmid = {9334315},
	pmcid = {PMC316561},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, Cell Line, {DNA} Probes, Liver, Plasmids, Transfection, Transcription, Genetic, Locus Control Region, Mice, Transgenic, Tumor Cells, Cultured, {DNA}, Single-Stranded, Globins, Erythrocytes, In Situ Hybridization, Fluorescence},
	file = {Full Text:/home/jlagarde/Zotero/storage/QUBRBZTD/Ashe et al. - 1997 - Intergenic transcription and transinduction of the.pdf:application/pdf}
}

@article{kapranov_rna_2007,
	title = {{RNA} maps reveal new {RNA} classes and a possible function for pervasive transcription},
	volume = {316},
	issn = {1095-9203},
	doi = {10.1126/science.1138341},
	abstract = {Significant fractions of eukaryotic genomes give rise to {RNA}, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated {RNAs} longer than 200 nucleotides (nt) and whole-cell {RNAs} less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected {RNAs} were assigned, and their potential processing into short {RNAs} was investigated. Taken together, these observations suggest a novel role for some unannotated {RNAs} as primary transcripts for the production of short {RNAs}. Three potentially functional classes of {RNAs} have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.},
	pages = {1484--1488},
	number = {5830},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Kapranov, Philipp and Cheng, Jill and Dike, Sujit and Nix, David A. and Duttagupta, Radharani and Willingham, Aarron T. and Stadler, Peter F. and Hertel, Jana and Hackermüller, Jörg and Hofacker, Ivo L. and Bell, Ian and Cheung, Evelyn and Drenkow, Jorg and Dumais, Erica and Patel, Sandeep and Helt, Gregg and Ganesh, Madhavan and Ghosh, Srinka and Piccolboni, Antonio and Sementchenko, Victor and Tammana, Hari and Gingeras, Thomas R.},
	date = {2007-06-08},
	pmid = {17510325},
	keywords = {Animals, Genome, Humans, Mice, {RNA}, Exons, Cell Nucleus, Gene Expression, {HeLa} Cells, {RNA} Precursors, Synteny, {RNA}, Messenger, Transcription, Genetic, Promoter Regions, Genetic, Genome, Human, Cell Line, Tumor, Terminator Regions, Genetic, Cytosol}
}

@article{cheng_transcriptional_2005,
	title = {Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution},
	volume = {308},
	issn = {1095-9203},
	doi = {10.1126/science.1108625},
	abstract = {Sites of transcription of polyadenylated and nonpolyadenylated {RNAs} for 10 human chromosomes were mapped at 5-base pair resolution in eight cell lines. Unannotated, nonpolyadenylated transcripts comprise the major proportion of the transcriptional output of the human genome. Of all transcribed sequences, 19.4, 43.7, and 36.9\% were observed to be polyadenylated, nonpolyadenylated, and bimorphic, respectively. Half of all transcribed sequences are found only in the nucleus and for the most part are unannotated. Overall, the transcribed portions of the human genome are predominantly composed of interlaced networks of both poly A+ and poly A- annotated transcripts and unannotated transcripts of unknown function. This organization has important implications for interpreting genotype-phenotype associations, regulation of gene expression, and the definition of a gene.},
	pages = {1149--1154},
	number = {5725},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Cheng, Jill and Kapranov, Philipp and Drenkow, Jorg and Dike, Sujit and Brubaker, Shane and Patel, Sandeep and Long, Jeffrey and Stern, David and Tammana, Hari and Helt, Gregg and Sementchenko, Victor and Piccolboni, Antonio and Bekiranov, Stefan and Bailey, Dione K. and Ganesh, Madhavan and Ghosh, Srinka and Bell, Ian and Gerhard, Daniela S. and Gingeras, Thomas R.},
	date = {2005-05-20},
	pmid = {15790807},
	keywords = {Humans, {RNA} Splicing, Computational Biology, Exons, Oligonucleotide Array Sequence Analysis, Cell Nucleus, Introns, Cell Line, Female, Male, Molecular Sequence Data, Nucleic Acid Amplification Techniques, {RNA}, Messenger, Transcription, Genetic, Chromosomes, Human, X, Chromosomes, Human, Y, Genome, Human, Physical Chromosome Mapping, {DNA}, Intergenic, {DNA}, Complementary, Chromosomes, Human, Pair 20, Chromosomes, Human, Chromosomes, Human, Pair 7, Cell Line, Tumor, Cytosol, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 6}
}

@article{international_wheat_genome_sequencing_consortium_iwgsc_chromosome-based_2014,
	title = {A chromosome-based draft sequence of the hexaploid bread wheat (Triticum aestivum) genome},
	volume = {345},
	issn = {1095-9203},
	doi = {10.1126/science.1251788},
	abstract = {An ordered draft sequence of the 17-gigabase hexaploid bread wheat (Triticum aestivum) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.},
	pages = {1251788},
	number = {6194},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {{International Wheat Genome Sequencing Consortium (IWGSC)}},
	date = {2014-07-18},
	pmid = {25035500},
	keywords = {Transcriptome, Gene Order, Genetic Variation, Molecular Sequence Annotation, Phylogeny, Evolution, Molecular, Sequence Analysis, {DNA}, Genome, Plant, Bread, Triticum, Chromosomes, Plant, Plant Proteins, Polyploidy}
}

@article{kim_high-resolution_2005,
	title = {A high-resolution map of active promoters in the human genome},
	volume = {436},
	issn = {1476-4687},
	doi = {10.1038/nature03877},
	abstract = {In eukaryotic cells, transcription of every protein-coding gene begins with the assembly of an {RNA} polymerase {II} preinitiation complex ({PIC}) on the promoter. The promoters, in conjunction with enhancers, silencers and insulators, define the combinatorial codes that specify gene expression patterns. Our ability to analyse the control logic encoded in the human genome is currently limited by a lack of accurate information regarding the promoters for most genes. Here we describe a genome-wide map of active promoters in human fibroblast cells, determined by experimentally locating the sites of {PIC} binding throughout the human genome. This map defines 10,567 active promoters corresponding to 6,763 known genes and at least 1,196 un-annotated transcriptional units. Features of the map suggest extensive use of multiple promoters by the human genes and widespread clustering of active promoters in the genome. In addition, examination of the genome-wide expression profile reveals four general classes of promoters that define the transcriptome of the cell. These results provide a global view of the functional relationships among transcriptional machinery, chromatin structure and gene expression in human cells.},
	pages = {876--880},
	number = {7052},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Kim, Tae Hoon and Barrera, Leah O. and Zheng, Ming and Qu, Chunxu and Singer, Michael A. and Richmond, Todd A. and Wu, Yingnian and Green, Roland D. and Ren, Bing},
	date = {2005-08-11},
	pmid = {15988478},
	pmcid = {PMC1895599},
	keywords = {Genomics, Humans, Gene Expression Regulation, Chromatin, Fibroblasts, Sensitivity and Specificity, Transcription, Genetic, Promoter Regions, Genetic, Genome, Human, Physical Chromosome Mapping},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/J87NJF6C/Kim et al. - 2005 - A high-resolution map of active promoters in the h.pdf:application/pdf}
}

@article{he_antisense_2008,
	title = {The antisense transcriptomes of human cells},
	volume = {322},
	issn = {1095-9203},
	doi = {10.1126/science.1163853},
	abstract = {Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the plus or minus strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here, we describe a technique that can be used to (i) identify the {DNA} strand of origin for any particular {RNA} transcript, and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was nonrandom across the genome, and differed among cell types. Antisense transcripts thus appear to be a pervasive feature of human cells, which suggests that they are a fundamental component of gene regulation.},
	pages = {1855--1857},
	number = {5909},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {He, Yiping and Vogelstein, Bert and Velculescu, Victor E. and Papadopoulos, Nickolas and Kinzler, Kenneth W.},
	date = {2008-12-19},
	pmid = {19056939},
	pmcid = {PMC2824178},
	keywords = {Humans, Exons, Gene Expression Profiling, Introns, Cell Line, Gene Expression, {RNA}, Messenger, Transcription, Genetic, Promoter Regions, Genetic, Genome, Human, {RNA}, Antisense, Cell Line, Tumor, Leukocytes, Mononuclear},
	file = {Full Text:/home/jlagarde/Zotero/storage/CZY5GKHN/He et al. - 2008 - The antisense transcriptomes of human cells.pdf:application/pdf}
}

@article{buratowski_transcription._2008,
	title = {Transcription. Gene expression--where to start?},
	volume = {322},
	issn = {1095-9203},
	doi = {10.1126/science.1168805},
	pages = {1804--1805},
	number = {5909},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Buratowski, Stephen},
	date = {2008-12-19},
	pmid = {19095933},
	pmcid = {PMC3516868},
	keywords = {{RNA}, Transcription Initiation Site, Gene Expression Profiling, Protein Biosynthesis, Nucleosomes, {RNA} Polymerase {II}, {RNA}, Messenger, Transcription, Genetic, Promoter Regions, Genetic, Enhancer Elements, Genetic, {RNA}, Antisense},
	file = {Full Text:/home/jlagarde/Zotero/storage/55NQ6JGG/Buratowski - 2008 - Transcription. Gene expression--where to start.pdf:application/pdf}
}

@article{brenner_refuge_1998,
	title = {Refuge of spandrels},
	volume = {8},
	issn = {1879-0445},
	doi = {10.1016/s0960-9822(98)70427-0},
	pages = {R669},
	number = {19},
	journaltitle = {Current biology: {CB}},
	shortjournal = {Curr. Biol.},
	author = {Brenner, null},
	date = {1998-09-24},
	pmid = {9776723}
}

@article{white_massively_2013,
	title = {Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of {ChIP}-seq peaks},
	volume = {110},
	issn = {1091-6490},
	doi = {10.1073/pnas.1307449110},
	abstract = {Transcription factors ({TFs}) recognize short sequence motifs that are present in millions of copies in large eukaryotic genomes. {TFsmust} distinguish their target binding sites from a vast genomic excess of spurious motif occurrences; however, it is unclear whether functional sites are distinguished from nonfunctional motifs by local primary sequence features or by the larger genomic context in which motifs reside. We used a massively parallel enhancer assay in living mouse retinas to compare 1,300 sequences bound in the genome by the photoreceptor transcription factor Cone-rod homeobox (Crx), to 3,000 control sequences. We found that very short sequences bound in the genome by Crx activated transcription at high levels, whereas unbound genomic regions with equal numbers of Crx motifs did not activate above background levels, even when liberated from their larger genomic context. High local {GC} content strongly distinguishes bound motifs from unbound motifs across the entire genome. Our results show that the cis-regulatory potential of {TF}-bound {DNA} is determined largely by highly local sequence features and not by genomic context.},
	pages = {11952--11957},
	number = {29},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {White, Michael A. and Myers, Connie A. and Corbo, Joseph C. and Cohen, Barak A.},
	date = {2013-07-16},
	pmid = {23818646},
	pmcid = {PMC3718143},
	keywords = {{DNA}, Animals, Base Sequence, Mice, Gene Expression Regulation, Base Composition, Chromatin Immunoprecipitation, {DNA} Primers, Gene Library, High-Throughput Nucleotide Sequencing, Homeodomain Proteins, Molecular Sequence Data, Trans-Activators, Models, Genetic, gene regulation, Retina, Statistics, Nonparametric, systems biology, transcription factor binding},
	file = {Full Text:/home/jlagarde/Zotero/storage/99NPGQ5D/White et al. - 2013 - Massively parallel in vivo enhancer assay reveals .pdf:application/pdf}
}

@article{cheung_chromatin-_2008,
	title = {Chromatin- and transcription-related factors repress transcription from within coding regions throughout the Saccharomyces cerevisiae genome},
	volume = {6},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.0060277},
	abstract = {Previous studies in Saccharomyces cerevisiae have demonstrated that cryptic promoters within coding regions activate transcription in particular mutants. We have performed a comprehensive analysis of cryptic transcription in order to identify factors that normally repress cryptic promoters, to determine the amount of cryptic transcription genome-wide, and to study the potential for expression of genetic information by cryptic transcription. Our results show that a large number of factors that control chromatin structure and transcription are required to repress cryptic transcription from at least 1,000 locations across the S. cerevisiae genome. Two results suggest that some cryptic transcripts are translated. First, as expected, many cryptic transcripts contain an {ATG} and an open reading frame of at least 100 codons. Second, several cryptic transcripts are translated into proteins. Furthermore, a subset of cryptic transcripts tested is transiently induced in wild-type cells following a nutritional shift, suggesting a possible physiological role in response to a change in growth conditions. Taken together, our results demonstrate that, during normal growth, the global integrity of gene expression is maintained by a wide range of factors and suggest that, under altered genetic or physiological conditions, the expression of alternative genetic information may occur.},
	pages = {e277},
	number = {11},
	journaltitle = {{PLoS} biology},
	shortjournal = {{PLoS} Biol.},
	author = {Cheung, Vanessa and Chua, Gordon and Batada, Nizar N. and Landry, Christian R. and Michnick, Stephen W. and Hughes, Timothy R. and Winston, Fred},
	date = {2008-11-11},
	pmid = {18998772},
	pmcid = {PMC2581627},
	keywords = {Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Open Reading Frames, Chromatin, Molecular Sequence Data, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Genome, Fungal, Saccharomyces cerevisiae Proteins, Gene Expression Regulation, Fungal},
	file = {Full Text:/home/jlagarde/Zotero/storage/UF7T3RA6/Cheung et al. - 2008 - Chromatin- and transcription-related factors repre.pdf:application/pdf}
}

@article{babak_systematic_2005,
	title = {A systematic search for new mammalian noncoding {RNAs} indicates little conserved intergenic transcription},
	volume = {6},
	issn = {1471-2164},
	doi = {10.1186/1471-2164-6-104},
	abstract = {{BACKGROUND}: Systematic identification and functional characterization of novel types of noncoding (nc){RNA} in genomes is more difficult than it is for protein coding {mRNAs}, since {ncRNAs} typically do not possess sequence features such as splicing or translation signals, or long open reading frames. Recent "tiling" microarray studies have reported that a surprisingly larger proportion of mammalian genomes is transcribed than was previously anticipated. However, these non-genic transcripts often appear to be low in abundance, and their functional significance is not known.
{RESULTS}: To systematically search for functional {ncRNAs}, we designed microarrays to detect 3,478 intergenic and intronic sequences that are conserved between the human, mouse, and rat genomes, and that score highly by other criteria that characterize {ncRNAs}. We probed these arrays with total {RNA} isolated from 16 wild-type mouse tissues. Among 55 candidates for highly-expressed novel {ncRNAs} tested by northern blotting, eight were confirmed as small, highly-and ubiquitously-expressed {RNAs} in mouse. Of the eight, five were also detected in rat tissues, but none were detected at appreciable levels in human tissues or cultured cells.
{CONCLUSION}: Since the sequence and expression of most known coding transcripts and functional {ncRNAs} is conserved between human and mouse, the lack of northern-detectable expression in human cells and tissues of the novel mouse and rat {ncRNAs} that we identified suggests that they are not functional or possibly have rodent-specific functions. Our results confirm that relatively little of the intergenic sequence conserved between human, mouse and rat is transcribed at high levels in mammalian tissues, possibly suggesting a limited role for transcribed intergenic and intronic sequences as independent functional elements.},
	pages = {104},
	journaltitle = {{BMC} genomics},
	shortjournal = {{BMC} Genomics},
	author = {Babak, Tomas and Blencowe, Benjamin J. and Hughes, Timothy R.},
	date = {2005-08-05},
	pmid = {16083503},
	pmcid = {PMC1199595},
	keywords = {Animals, Genome, Humans, Mice, {RNA}, Computational Biology, Oligonucleotide Array Sequence Analysis, Open Reading Frames, Introns, Software, {DNA} Primers, Genetic Techniques, {HeLa} Cells, Nucleic Acid Hybridization, Rats, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated, {DNA}, Intergenic, Blotting, Northern},
	file = {Full Text:/home/jlagarde/Zotero/storage/YW4PVXNK/Babak et al. - 2005 - A systematic search for new mammalian noncoding RN.pdf:application/pdf}
}

@article{ecker_genomics:_2012,
	title = {Genomics: {ENCODE} explained},
	volume = {489},
	issn = {1476-4687},
	doi = {10.1038/489052a},
	shorttitle = {Genomics},
	pages = {52--55},
	number = {7414},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Ecker, Joseph R. and Bickmore, Wendy A. and Barroso, Inês and Pritchard, Jonathan K. and Gilad, Yoav and Segal, Eran},
	date = {2012-09-06},
	pmid = {22955614},
	keywords = {Genomics, {DNA}, Sequence Analysis, Humans, Gene Expression Regulation, Chromatin, Deoxyribonuclease I, {DNA} Methylation, Encyclopedias as Topic, Gene Regulatory Networks, Molecular Sequence Annotation, Transcription Factors, Evolution, Molecular, {RNA}, Untranslated, Genome, Human, Regulatory Sequences, Nucleic Acid, Interdisciplinary Communication}
}

@article{jain_incidental_1980,
	title = {Incidental {DNA}},
	volume = {288},
	issn = {0028-0836},
	doi = {10.1038/288647a0},
	pages = {647--648},
	number = {5792},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Jain, H. K.},
	date = {1980-12-25},
	pmid = {7453799},
	keywords = {{DNA}, Animals, Humans, Biological Evolution, {DNA} Replication, Mutation, Gene Amplification}
}

@article{palazzo_non-coding_2015,
	title = {Non-coding {RNA}: what is functional and what is junk?},
	volume = {6},
	issn = {1664-8021},
	doi = {10.3389/fgene.2015.00002},
	shorttitle = {Non-coding {RNA}},
	abstract = {The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding {DNA}. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into {RNA} at some low level. Unfortunately these {RNAs} have been arbitrarily assigned various names, such as "intergenic {RNA}," "long non-coding {RNAs}" etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding {RNAs} ({ncRNAs}), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional {ncRNAs} yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given {ncRNA} has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the {RNA} in question is junk.},
	pages = {2},
	journaltitle = {Frontiers in Genetics},
	shortjournal = {Front Genet},
	author = {Palazzo, Alexander F. and Lee, Eliza S.},
	date = {2015},
	pmid = {25674102},
	pmcid = {PMC4306305},
	keywords = {evolution, non-coding {RNA}, genome biology, Junk {DNA}, Junk {RNA}},
	file = {Full Text:/home/jlagarde/Zotero/storage/847V66I3/Palazzo and Lee - 2015 - Non-coding RNA what is functional and what is jun.pdf:application/pdf}
}

@article{jarroux_history_2017,
	title = {History, Discovery, and Classification of {lncRNAs}},
	volume = {1008},
	issn = {0065-2598},
	doi = {10.1007/978-981-10-5203-3_1},
	abstract = {The {RNA} World Hypothesis suggests that prebiotic life revolved around {RNA} instead of {DNA} and proteins. Although modern cells have changed significantly in 4 billion years, {RNA} has maintained its central role in cell biology. Since the discovery of {DNA} at the end of the nineteenth century, {RNA} has been extensively studied. Many discoveries such as housekeeping {RNAs} ({rRNA}, {tRNA}, etc.) supported the messenger {RNA} model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding {RNAs} ({ncRNAs}) were initially identified in bacteria and then in most eukaryotic organisms. A few long {ncRNAs} ({lncRNAs}) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2\% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many {ncRNAs}, but their functionality remained controversial. Since then, regulatory {lncRNAs} have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on {lncRNAs}, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of {lncRNAs}, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during {lncRNA} evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of {lncRNA} classes, thus illustrating the vast complexity of eukaryotic transcriptomes.},
	pages = {1--46},
	journaltitle = {Advances in Experimental Medicine and Biology},
	shortjournal = {Adv. Exp. Med. Biol.},
	author = {Jarroux, Julien and Morillon, Antonin and Pinskaya, Marina},
	date = {2017},
	pmid = {28815535},
	keywords = {Transcriptome, Animals, Humans, High-Throughput Nucleotide Sequencing, {RNA}, Long Noncoding, Non-coding {RNA}, Genome, Human, History, 21st Century, History, 20th Century, Central dogma, Classification, {RNA} World}
}

@article{gelbart_drosophila_2009,
	title = {Drosophila dosage compensation: a complex voyage to the X chromosome},
	volume = {136},
	issn = {0950-1991},
	doi = {10.1242/dev.029645},
	shorttitle = {Drosophila dosage compensation},
	abstract = {Dosage compensation is the crucial process that equalizes gene expression from the X chromosome between males ({XY}) and females ({XX}). In Drosophila, the male-specific lethal ({MSL}) ribonucleoprotein complex mediates dosage compensation by upregulating transcription from the single male X chromosome approximately twofold. A key challenge is to understand how the {MSL} complex distinguishes the X chromosome from autosomes. Recent studies suggest that this occurs through a multi-step targeting mechanism that involves {DNA} sequence elements and epigenetic marks associated with transcription. This review will discuss the relative contributions of sequence elements and transcriptional marks to the complete pattern of {MSL} complex binding.},
	pages = {1399--1410},
	number = {9},
	journaltitle = {Development (Cambridge, England)},
	shortjournal = {Development},
	author = {Gelbart, Marnie E. and Kuroda, Mitzi I.},
	date = {2009-05},
	pmid = {19363150},
	pmcid = {PMC2674252},
	keywords = {Animals, Drosophila, X Chromosome, Models, Genetic, Dosage Compensation, Genetic, Genes, Lethal},
	file = {Full Text:/home/jlagarde/Zotero/storage/WXNVNSJ5/Gelbart and Kuroda - 2009 - Drosophila dosage compensation a complex voyage t.pdf:application/pdf}
}

@article{wang_long_2017,
	title = {Long Noncoding {RNAs} in Plants},
	volume = {1008},
	issn = {0065-2598},
	doi = {10.1007/978-981-10-5203-3_5},
	abstract = {The eukaryotic genomes are pervasively transcribed. In addition to protein-coding {RNAs}, thousands of long noncoding {RNAs} ({lncRNAs}) modulate key molecular and biological processes. Most {lncRNAs} are found in the nucleus and associate with chromatin, but {lncRNAs} can function in both nuclear and cytoplasmic compartments. Emerging work has found that many {lncRNAs} regulate gene expression and can affect genome stability and nuclear domain organization both in plant and in the animal kingdom. Here, we describe the major plant {lncRNAs} and how they act, with a focus on research in Arabidopsis thaliana and our emerging understanding of {lncRNA} functions in serving as molecular sponges and decoys, functioning in regulation of transcription and silencing, particularly in {RNA}-directed {DNA} methylation, and in epigenetic regulation of flowering time.},
	pages = {133--154},
	journaltitle = {Advances in Experimental Medicine and Biology},
	shortjournal = {Adv. Exp. Med. Biol.},
	author = {Wang, Hsiao-Lin V. and Chekanova, Julia A.},
	date = {2017},
	pmid = {28815539},
	pmcid = {PMC6689229},
	keywords = {Arabidopsis, Gene Silencing, {RNA}, Long Noncoding, Transcription, Genetic, Gene Expression Regulation, Plant, Epigenetics, Exosome, {FLC}, Noncoding {RNAs}, Plant {lncRNAs}, {RNA}, Plant, Transcriptional regulation}
}

@article{brown_human_1992,
	title = {The human {XIST} gene: analysis of a 17 kb inactive X-specific {RNA} that contains conserved repeats and is highly localized within the nucleus},
	volume = {71},
	issn = {0092-8674},
	doi = {10.1016/0092-8674(92)90520-m},
	shorttitle = {The human {XIST} gene},
	abstract = {X chromosome inactivation in mammalian females results in the cis-limited transcriptional inactivity of most of the genes on one X chromosome. The {XIST} gene is unique among X-linked genes in being expressed exclusively from the inactive X chromosome. Human {XIST} {cDNAs} containing at least eight exons and totaling 17 kb have been isolated and sequenced within the region on the X chromosome known to contain the X inactivation center. The {XIST} gene includes several tandem repeats, the most 5' of which are evolutionarily conserved. The gene does not contain any significant conserved {ORFs} and thus does not appear to encode a protein, suggesting that {XIST} may function as a structural {RNA} within the nucleus. Consistent with this, fluorescence in situ hybridization experiments demonstrate localization of {XIST} {RNA} within the nucleus to a position indistinguishable from the X inactivation-associated Barr body.},
	pages = {527--542},
	number = {3},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Brown, C. J. and Hendrich, B. D. and Rupert, J. L. and Lafrenière, R. G. and Xing, Y. and Lawrence, J. and Willard, H. F.},
	date = {1992-10-30},
	pmid = {1423611},
	keywords = {Base Sequence, Conserved Sequence, Humans, Exons, Cell Nucleus, Introns, Female, Molecular Sequence Data, Sequence Alignment, Transcription Factors, X Chromosome, {RNA}, Long Noncoding, {RNA}, Messenger, {RNA}, Untranslated, Repetitive Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Dosage Compensation, Genetic, Sex Chromatin}
}

@article{gabory_h19_2009,
	title = {H19 acts as a trans regulator of the imprinted gene network controlling growth in mice},
	volume = {136},
	issn = {1477-9129},
	doi = {10.1242/dev.036061},
	abstract = {The imprinted H19 gene produces a non-coding {RNA} of unknown function. Mice lacking H19 show an overgrowth phenotype, due to a cis effect of the H19 locus on the adjacent Igf2 gene. To explore the function of the {RNA} itself, we produced transgenic mice overexpressing H19. We observed postnatal growth reduction in two independent transgenic lines and detected a decrease of Igf2 expression in embryos. An extensive analysis of several other genes from the newly described imprinted gene network ({IGN}) was performed in both loss- and gain-of-function animals. We found that H19 deletion leads to the upregulation of several genes of the {IGN}. This overexpression is restored to the wild-type level by transgenic expression of H19. We therefore propose that the H19 gene participates as a trans regulator in the fine-tuning of this {IGN} in the mouse embryo. This is the first in vivo evidence of a functional role for the H19 {RNA}. Our results also bring further experimental evidence for the existence of the {IGN} and open new perspectives in the comprehension of the role of genomic imprinting in embryonic growth and in human imprinting pathologies.},
	pages = {3413--3421},
	number = {20},
	journaltitle = {Development (Cambridge, England)},
	shortjournal = {Development},
	author = {Gabory, Anne and Ripoche, Marie-Anne and Le Digarcher, Anne and Watrin, Françoise and Ziyyat, Ahmed and Forné, Thierry and Jammes, Hélène and Ainscough, Justin F. X. and Surani, M. Azim and Journot, Laurent and Dandolo, Luisa},
	date = {2009-10},
	pmid = {19762426},
	keywords = {Animals, Mice, Female, Gene Regulatory Networks, Male, Phenotype, {RNA}, Long Noncoding, {RNA}, Untranslated, Mice, Transgenic, Regulatory Sequences, Nucleic Acid, Gene Expression Regulation, Developmental, Insulin-Like Growth Factor {II}},
	file = {Full Text:/home/jlagarde/Zotero/storage/XIJMTM43/Gabory et al. - 2009 - H19 acts as a trans regulator of the imprinted gen.pdf:application/pdf}
}

@article{chureau_comparative_2002,
	title = {Comparative Sequence Analysis of the X-Inactivation Center Region in Mouse, Human, and Bovine},
	volume = {12},
	issn = {1088-9051},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383731/},
	doi = {10.1101/gr.152902},
	abstract = {We have sequenced to high levels of accuracy 714-kb and 233-kb regions of the mouse and bovine X-inactivation centers (Xic), respectively, centered on the Xist gene. This has provided the basis for a fully annotated comparative analysis of the mouse Xic with the 2.3-Mb orthologous region in human and has allowed a three-way species comparison of the core central region, including the Xist gene. These comparisons have revealed conserved genes, both coding and noncoding, conserved {CpG} islands and, more surprisingly, conserved pseudogenes. The distribution of repeated elements, especially {LINE} repeats, in the mouse Xic region when compared to the rest of the genome does not support the hypothesis of a role for these repeat elements in the spreading of X inactivation. Interestingly, an asymmetric distribution of {LINE} elements on the two {DNA} strands was observed in the three species, not only within introns but also in intergenic regions. This feature is suggestive of important transcriptional activity within these intergenic regions. In silico prediction followed by experimental analysis has allowed four new genes, Cnbp2, Ftx, Jpx, and Ppnx, to be identified and novel, widespread, complex, and apparently noncoding transcriptional activity to be characterized in a region 5′ of Xist that was recently shown to attract histone modification early after the onset of X inactivation., [The sequence data described in this paper have been submitted to the {EMBL} data library under accession nos. {AJ}421478, {AJ}421479, {AJ}421480, and {AJ}421481. Online supplemental data are available at http://pbil.univ-lyon1.fr/datasets/Xic2002/data.html and www.genome.org.]},
	pages = {894--908},
	number = {6},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res},
	author = {Chureau, Corinne and Prissette, Marine and Bourdet, Agnès and Barbe, Valérie and Cattolico, Laurence and Jones, Louis and Eggen, André and Avner, Philip and Duret, Laurent},
	urldate = {2019-08-27},
	date = {2002-06},
	pmid = {12045143},
	pmcid = {PMC1383731},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/EE9GJ5KR/Chureau et al. - 2002 - Comparative Sequence Analysis of the X-Inactivatio.pdf:application/pdf}
}

@article{nesterova_characterization_2001,
	title = {Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence},
	volume = {11},
	issn = {1088-9051},
	doi = {10.1101/gr.174901},
	abstract = {The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/{XIST}. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution.},
	pages = {833--849},
	number = {5},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Nesterova, T. B. and Slobodyanyuk, S. Y. and Elisaphenko, E. A. and Shevchenko, A. I. and Johnston, C. and Pavlova, M. E. and Rogozin, I. B. and Kolesnikov, N. N. and Brockdorff, N. and Zakian, S. M.},
	date = {2001-05},
	pmid = {11337478},
	pmcid = {PMC311126},
	keywords = {{DNA}, 3' Untranslated Regions, Animals, Base Sequence, Conserved Sequence, Humans, Mice, 5' Untranslated Regions, Chromosome Mapping, Female, Genes, Genetic Markers, Male, Molecular Sequence Data, Tandem Repeat Sequences, Transcription Factors, X Chromosome, Evolution, Molecular, {RNA}, Long Noncoding, Transcription, Genetic, Cells, Cultured, {RNA}, Untranslated, Animals, Wild, Arvicolinae},
	file = {Full Text:/home/jlagarde/Zotero/storage/INL5BGM4/Nesterova et al. - 2001 - Characterization of the genomic Xist locus in rode.pdf:application/pdf}
}

@article{wutz_shift_2000,
	title = {A shift from reversible to irreversible X inactivation is triggered during {ES} cell differentiation},
	volume = {5},
	issn = {1097-2765},
	abstract = {Xist is required for X inactivation. To study the initiation of X inactivation, we have generated a full-length mouse Xist {cDNA} transgene and an inducible expression system facilitating controlled Xist expression in {ES} cells and differentiated cultures. In {ES} cells, transgenic Xist {RNA} was stable and caused long-range transcriptional repression in cis. Repression was reversible and dependent on continued Xist expression in {ES} cells and early {ES} cell differentiation. By 72 hr of differentiation, inactivation became irreversible and independent of Xist. Upon differentiation, autosomal transgenes did not effect counting, but transgenic Xist {RNA} induced late replication and histone H4 hypoacetylation. Xist had to be activated within 48 hr of differentiation to effect silencing, suggesting that reversible repression by Xist is a required initiation step that might occur during normal X inactivation in female cells.},
	pages = {695--705},
	number = {4},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Wutz, A. and Jaenisch, R.},
	date = {2000-04},
	pmid = {10882105},
	keywords = {Animals, Mice, Cell Differentiation, Gene Silencing, {RNA} Stability, Stem Cells, Transcription Factors, Transgenes, {RNA}, Long Noncoding, {RNA}, Messenger, Models, Genetic, {RNA}, Untranslated, {DNA}, Complementary, Embryo, Mammalian, Dosage Compensation, Genetic}
}

@article{gabory_h19_2006,
	title = {The H19 gene: regulation and function of a non-coding {RNA}},
	volume = {113},
	issn = {1424-859X},
	doi = {10.1159/000090831},
	shorttitle = {The H19 gene},
	abstract = {The H19 gene encodes a 2.3-kb non-coding {mRNA} which is strongly expressed during embryogenesis. This gene belongs to an imprinted cluster, conserved on mouse chromosome 7 and human chromosome 11p15. H19 is maternally expressed and the neighbouring Igf2 gene is transcribed from the paternal allele. These two genes are co-expressed in endoderm- and mesoderm-derived tissues during embryonic development, which suggests a common mechanism of regulation. The regulatory elements (imprinted control region, {CTCF} insulation, different enhancer sequences, promoters of the two genes, matrix attachment regions) confer a differential chromatin architecture to the two parental alleles leading to reciprocal expression. The role of the H19 gene is unclear but different aspects have been proposed. H19 influences growth by way of a cis control on Igf2 expression. Although H19(-/-) mice are viable, a role for this gene during development has been suggested by viable H19(-/-) parthenogenetic mice. Finally it has been described as a putative tumour suppressor gene. H19 has been studied by numerous laboratories over the last fifteen years, nevertheless the function of this non-coding {RNA} remains to be elucidated.},
	pages = {188--193},
	number = {1},
	journaltitle = {Cytogenetic and Genome Research},
	shortjournal = {Cytogenet. Genome Res.},
	author = {Gabory, A. and Ripoche, M.-A. and Yoshimizu, T. and Dandolo, L.},
	date = {2006},
	pmid = {16575179},
	keywords = {Animals, Humans, Mice, Gene Expression Regulation, Chromosome Mapping, Genetic Code, {RNA}, Long Noncoding, {RNA}, Untranslated, Genetic Diseases, Inborn, Gene Expression Regulation, Developmental, Insulin-Like Growth Factor {II}, Germ-Line Mutation, Micronucleus, Germline}
}

@article{okazaki_analysis_2002,
	title = {Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length {cDNAs}},
	volume = {420},
	issn = {0028-0836},
	doi = {10.1038/nature01266},
	abstract = {Only a small proportion of the mouse genome is transcribed into mature messenger {RNA} transcripts. There is an international collaborative effort to identify all full-length {mRNA} transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary {DNA} sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1\% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding {RNA} is a major component of the transcriptome. 41\% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79\% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.},
	pages = {563--573},
	number = {6915},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Okazaki, Y. and Furuno, M. and Kasukawa, T. and Adachi, J. and Bono, H. and Kondo, S. and Nikaido, I. and Osato, N. and Saito, R. and Suzuki, H. and Yamanaka, I. and Kiyosawa, H. and Yagi, K. and Tomaru, Y. and Hasegawa, Y. and Nogami, A. and Schönbach, C. and Gojobori, T. and Baldarelli, R. and Hill, D. P. and Bult, C. and Hume, D. A. and Quackenbush, J. and Schriml, L. M. and Kanapin, A. and Matsuda, H. and Batalov, S. and Beisel, K. W. and Blake, J. A. and Bradt, D. and Brusic, V. and Chothia, C. and Corbani, L. E. and Cousins, S. and Dalla, E. and Dragani, T. A. and Fletcher, C. F. and Forrest, A. and Frazer, K. S. and Gaasterland, T. and Gariboldi, M. and Gissi, C. and Godzik, A. and Gough, J. and Grimmond, S. and Gustincich, S. and Hirokawa, N. and Jackson, I. J. and Jarvis, E. D. and Kanai, A. and Kawaji, H. and Kawasawa, Y. and Kedzierski, R. M. and King, B. L. and Konagaya, A. and Kurochkin, I. V. and Lee, Y. and Lenhard, B. and Lyons, P. A. and Maglott, D. R. and Maltais, L. and Marchionni, L. and McKenzie, L. and Miki, H. and Nagashima, T. and Numata, K. and Okido, T. and Pavan, W. J. and Pertea, G. and Pesole, G. and Petrovsky, N. and Pillai, R. and Pontius, J. U. and Qi, D. and Ramachandran, S. and Ravasi, T. and Reed, J. C. and Reed, D. J. and Reid, J. and Ring, B. Z. and Ringwald, M. and Sandelin, A. and Schneider, C. and Semple, C. a. M. and Setou, M. and Shimada, K. and Sultana, R. and Takenaka, Y. and Taylor, M. S. and Teasdale, R. D. and Tomita, M. and Verardo, R. and Wagner, L. and Wahlestedt, C. and Wang, Y. and Watanabe, Y. and Wells, C. and Wilming, L. G. and Wynshaw-Boris, A. and Yanagisawa, M. and Yang, I. and Yang, L. and Yuan, Z. and Zavolan, M. and Zhu, Y. and Zimmer, A. and Carninci, P. and Hayatsu, N. and Hirozane-Kishikawa, T. and Konno, H. and Nakamura, M. and Sakazume, N. and Sato, K. and Shiraki, T. and Waki, K. and Kawai, J. and Aizawa, K. and Arakawa, T. and Fukuda, S. and Hara, A. and Hashizume, W. and Imotani, K. and Ishii, Y. and Itoh, M. and Kagawa, I. and Miyazaki, A. and Sakai, K. and Sasaki, D. and Shibata, K. and Shinagawa, A. and Yasunishi, A. and Yoshino, M. and Waterston, R. and Lander, E. S. and Rogers, J. and Birney, E. and Hayashizaki, Y. and {FANTOM Consortium} and {RIKEN Genome Exploration Research Group Phase I \& II Team}},
	date = {2002-12-05},
	pmid = {12466851},
	keywords = {Genomics, Animals, Humans, Mice, Transcription Initiation Site, Alternative Splicing, Amino Acid Motifs, Expressed Sequence Tags, Genes, Proteome, Databases, Genetic, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated, Cloning, Molecular, Chromosomes, Mammalian, Physical Chromosome Mapping, {RNA}, Antisense, {DNA}, Complementary, Protein Structure, Tertiary, Membrane Proteins},
	file = {Full Text:/home/jlagarde/Zotero/storage/AV5LZG9B/Okazaki et al. - 2002 - Analysis of the mouse transcriptome based on funct.pdf:application/pdf}
}

@article{sotomaru_unregulated_2002,
	title = {Unregulated expression of the imprinted genes H19 and Igf2r in mouse uniparental fetuses},
	volume = {277},
	issn = {0021-9258},
	doi = {10.1074/jbc.M109212200},
	abstract = {The present study shows that the H19 and Igf2r genes, which are imprinted and expressed solely from maternal alleles, are expressed in an unregulatable manner in mouse uniparental, androgenetic, and parthenogenetic fetuses at day 9.5 of gestation. In the androgenetic fetuses, the H19 and Igf2r genes were respectively expressed at 12 and 40\% of the levels in biparental fetuses. In addition, the expression of both genes was excessive (1259 and 482\%, respectively) in the parthenotes. These expressions of the imprinted genes were not regulated by methylation in the regulatory regions. Moreover, the expression of the antisense Igf2r {RNA} (Air) was also excessive and was not correlated with Igf2r gene expression in the uniparental fetuses. Taken together, these results indicate that the parental specific expression of imprinted genes is not maintained in particular genes in uniparental embryos, which in turn suggests that both parental genomes are required to establish maternal specific expression of the H19 and Igf2r genes by trans-acting mechanisms.},
	pages = {12474--12478},
	number = {14},
	journaltitle = {The Journal of Biological Chemistry},
	shortjournal = {J. Biol. Chem.},
	author = {Sotomaru, Yusuke and Katsuzawa, Yukiko and Hatada, Izuho and Obata, Yayoi and Sasaki, Hiroyuki and Kono, Tomohiro},
	date = {2002-04-05},
	pmid = {11805093},
	keywords = {Animals, Mice, Proteins, Gene Expression Regulation, Alleles, {CpG} Islands, {DNA} Methylation, Female, Genomic Imprinting, Male, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, {RNA}, Long Noncoding, {RNA}, Untranslated, Mice, Inbred C57BL, Fetus, Blotting, Southern, Oligonucleotides, Antisense},
	file = {Full Text:/home/jlagarde/Zotero/storage/I2LGY4XU/Sotomaru et al. - 2002 - Unregulated expression of the imprinted genes H19 .pdf:application/pdf}
}

@article{willingham_strategy_2005,
	title = {A strategy for probing the function of noncoding {RNAs} finds a repressor of {NFAT}},
	volume = {309},
	issn = {1095-9203},
	doi = {10.1126/science.1115901},
	abstract = {Noncoding {RNA} molecules ({ncRNAs}) have been implicated in numerous biological processes including transcriptional regulation and the modulation of protein function. Yet, in spite of the apparent abundance of {ncRNA}, little is known about the biological role of the projected thousands of {ncRNA} genes present in the human genome. To facilitate functional analysis of these {RNAs}, we have created an arrayed library of short hairpin {RNAs} ({shRNAs}) directed against 512 evolutionarily conserved putative {ncRNAs} and, via cell-based assays, we have begun to determine their roles in cellular pathways. Using this system, we have identified an {ncRNA} repressor of the nuclear factor of activated T cells ({NFAT}), which interacts with multiple proteins including members of the importin-beta superfamily and likely functions as a specific regulator of {NFAT} nuclear trafficking.},
	pages = {1570--1573},
	number = {5740},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Willingham, A. T. and Orth, A. P. and Batalov, S. and Peters, E. C. and Wen, B. G. and Aza-Blanc, P. and Hogenesch, J. B. and Schultz, P. G.},
	date = {2005-09-02},
	pmid = {16141075},
	keywords = {Animals, Humans, Mice, Cell Line, {DNA}-Binding Proteins, {RNA} Interference, Transcription Factors, Nuclear Proteins, {RNA}, Long Noncoding, {RNA}, Untranslated, beta Karyopherins, {NFATC} Transcription Factors}
}

@article{mikkelsen_genome-wide_2007,
	title = {Genome-wide maps of chromatin state in pluripotent and lineage-committed cells},
	volume = {448},
	issn = {1476-4687},
	doi = {10.1038/nature06008},
	abstract = {We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated {DNA}, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.},
	pages = {553--560},
	number = {7153},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Mikkelsen, Tarjei S. and Ku, Manching and Jaffe, David B. and Issac, Biju and Lieberman, Erez and Giannoukos, Georgia and Alvarez, Pablo and Brockman, William and Kim, Tae-Kyung and Koche, Richard P. and Lee, William and Mendenhall, Eric and O'Donovan, Aisling and Presser, Aviva and Russ, Carsten and Xie, Xiaohui and Meissner, Alexander and Wernig, Marius and Jaenisch, Rudolf and Nusbaum, Chad and Lander, Eric S. and Bernstein, Bradley E.},
	date = {2007-08-02},
	pmid = {17603471},
	pmcid = {PMC2921165},
	keywords = {Animals, Genome, Mice, Alleles, Cell Lineage, Chromatin, {CpG} Islands, Fibroblasts, Genomic Imprinting, Histones, Male, Methylation, Transcription, Genetic, Promoter Regions, Genetic, Gene Expression Regulation, Developmental, Pluripotent Stem Cells},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/PZRZJKHD/Mikkelsen et al. - 2007 - Genome-wide maps of chromatin state in pluripotent.pdf:application/pdf}
}

@article{wood_hidden_2019,
	title = {Hidden in plain sight: what remains to be discovered in the eukaryotic proteome?},
	volume = {9},
	issn = {2046-2441},
	doi = {10.1098/rsob.180241},
	shorttitle = {Hidden in plain sight},
	abstract = {The first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20\% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes ({BP}). To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences. We use a simple yet powerful metric based on Gene Ontology {BP} terms to define characterized and uncharacterized proteins for human, budding yeast and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalogue of proteins' biological roles.},
	pages = {180241},
	number = {2},
	journaltitle = {Open Biology},
	shortjournal = {Open Biol},
	author = {Wood, Valerie and Lock, Antonia and Harris, Midori A. and Rutherford, Kim and Bähler, Jürg and Oliver, Stephen G.},
	date = {2019-02-28},
	pmid = {30938578},
	pmcid = {PMC6395881},
	keywords = {biocuration, budding yeast, fission yeast, gene ontology, human, unknown proteins},
	file = {Full Text:/home/jlagarde/Zotero/storage/DG62Y9FV/Wood et al. - 2019 - Hidden in plain sight what remains to be discover.pdf:application/pdf}
}

@article{mercer_specific_2008,
	title = {Specific expression of long noncoding {RNAs} in the mouse brain},
	volume = {105},
	issn = {0027-8424},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206602/},
	doi = {10.1073/pnas.0706729105},
	abstract = {A major proportion of the mammalian transcriptome comprises long {RNAs} that have little or no protein-coding capacity ({ncRNAs}). Only a handful of such transcripts have been examined in detail, and it is unknown whether this class of transcript is generally functional or merely artifact. Using in situ hybridization data from the Allen Brain Atlas, we identified 849 {ncRNAs} (of 1,328 examined) that are expressed in the adult mouse brain and found that the majority were associated with specific neuroanatomical regions, cell types, or subcellular compartments. Examination of their genomic context revealed that the {ncRNAs} were expressed from diverse places including intergenic, intronic, and imprinted loci and that many overlap with, or are transcribed antisense to, protein-coding genes of neurological importance. Comparisons between the expression profiles of {ncRNAs} and their associated protein-coding genes revealed complex relationships that, in combination with the specific expression profiles exhibited at both regional and subcellular levels, are inconsistent with the notion that they are transcriptional noise or artifacts of chromatin remodeling. Our results show that the majority of {ncRNAs} are expressed in the brain and provide strong evidence that the majority of processed transcripts with no protein-coding capacity function intrinsically as {RNAs}.},
	pages = {716--721},
	number = {2},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc Natl Acad Sci U S A},
	author = {Mercer, Tim R. and Dinger, Marcel E. and Sunkin, Susan M. and Mehler, Mark F. and Mattick, John S.},
	urldate = {2019-08-29},
	date = {2008-01-15},
	pmid = {18184812},
	pmcid = {PMC2206602},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/GPWXREXV/Mercer et al. - 2008 - Specific expression of long noncoding RNAs in the .pdf:application/pdf}
}

@article{joung_genome-scale_2017,
	title = {Genome-scale activation screen identifies a {lncRNA} locus regulating a gene neighbourhood},
	volume = {548},
	issn = {1476-4687},
	doi = {10.1038/nature23451},
	abstract = {Mammalian genomes contain thousands of loci that transcribe long noncoding {RNAs} ({lncRNAs}), some of which are known to carry out critical roles in diverse cellular processes through a variety of mechanisms. Although some {lncRNA} loci encode {RNAs} that act non-locally (in trans), there is emerging evidence that many {lncRNA} loci act locally (in cis) to regulate the expression of nearby genes-for example, through functions of the {lncRNA} promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional {lncRNA} loci and distinguish among these and other mechanisms. Here, to address these challenges, we developed a genome-scale {CRISPR}-Cas9 activation screen that targets more than 10,000 {lncRNA} transcriptional start sites to identify noncoding loci that influence a phenotype of interest. We found 11 {lncRNA} loci that, upon recruitment of an activator, mediate resistance to {BRAF} inhibitors in human melanoma cells. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed {EMICERI}, revealed that its transcriptional activation resulted in dosage-dependent activation of four neighbouring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a {CRISPR} toolkit with which to systematically discover the functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function.},
	pages = {343--346},
	number = {7667},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Joung, Julia and Engreitz, Jesse M. and Konermann, Silvana and Abudayyeh, Omar O. and Verdine, Vanessa K. and Aguet, Francois and Gootenberg, Jonathan S. and Sanjana, Neville E. and Wright, Jason B. and Fulco, Charles P. and Tseng, Yuen-Yi and Yoon, Charles H. and Boehm, Jesse S. and Lander, Eric S. and Zhang, Feng},
	date = {2017},
	pmid = {28792927},
	pmcid = {PMC5706657},
	keywords = {Humans, Transcription Initiation Site, Genetic Loci, Phenotype, Signal Transduction, Transcriptional Activation, {RNA}, Long Noncoding, Promoter Regions, Genetic, Genome, Human, Cell Line, Tumor, {CRISPR}-Cas Systems, Drug Resistance, Neoplasm, Indoles, Melanoma, Microtubule-Associated Proteins, Protein Kinase Inhibitors, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins B-raf, Sulfonamides, Vemurafenib},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/MQ7W3GJK/Joung et al. - 2017 - Genome-scale activation screen identifies a lncRNA.pdf:application/pdf}
}

@article{schaefer_revolutions_1995,
	title = {Revolutions in rapid amplification of {cDNA} ends: new strategies for polymerase chain reaction cloning of full-length {cDNA} ends},
	volume = {227},
	issn = {0003-2697},
	doi = {10.1006/abio.1995.1279},
	shorttitle = {Revolutions in rapid amplification of {cDNA} ends},
	abstract = {Rapid amplification of {cDNA} ends ({RACE}) is a polymerase chain reaction ({PCR})-based technique which was developed to facilitate the cloning of full-length {cDNA} 5'- and 3'-ends after a partial {cDNA} sequence has been obtained by other methods. While {RACE} can yield complete sequences of {cDNA} ends in only a few days, the {RACE} procedure frequently results in the exclusive amplification of truncated {cDNA} ends, undermining efforts to generate full-length clones. Many investigators have suggested modifications to the {RACE} protocol to improve the effectiveness of the technique. Based on first-hand experience with {RACE}, a critical review of numerous published variations of the key steps in the {RACE} method is presented. Also included is a detailed, effective protocol based on {RNA} ligase-mediated {RACE}/reverse ligation-mediated {PCR}, as well as a demonstration of its utility.},
	pages = {255--273},
	number = {2},
	journaltitle = {Analytical Biochemistry},
	shortjournal = {Anal. Biochem.},
	author = {Schaefer, B. C.},
	date = {1995-05-20},
	pmid = {7573945},
	keywords = {Base Sequence, Molecular Sequence Data, Polymerase Chain Reaction, Cloning, Molecular, {DNA}, Complementary}
}

@article{bower_targeted_2010,
	title = {Targeted rapid amplification of {cDNA} ends (T-{RACE})—an improved {RACE} reaction through degradation of non-target sequences},
	volume = {38},
	issn = {0305-1048},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995088/},
	doi = {10.1093/nar/gkq816},
	abstract = {Amplification of the 5′ ends of {cDNA}, although simple in theory, can often be difficult to achieve. We describe a novel method for the specific amplification of {cDNA} ends. An oligo-{dT} adapter incorporating a {dUTP}-containing {PCR} primer primes first-strand {cDNA} synthesis incorporating {dUTP}. Using the Cap finder approach, another distinct {dUTP} containing adapter is added to the 3′ end of the newly synthesized {cDNA}. Second-strand synthesis incorporating {dUTP} is achieved by {PCR}, using {dUTP}-containing primers complimentary to the adapter sequences incorporated in the {cDNA} ends. The double-stranded {cDNA}-containing {dUTP} serves as a universal template for the specific amplification of the 3′ or 5′ end of any gene. To amplify the ends of {cDNA}, asymmetric {PCR} is performed using a single gene-specific primer and standard {dNTPs}. The asymmetric {PCR} product is purified and non-target transcripts containing {dUTP} degraded by Uracil {DNA} glycosylase, leaving only those transcripts produced during the asymmetric {PCR}. Subsequent {PCR} using a nested gene-specific primer and the 3′ or 5′ T-{RACE} primer results in specific amplification of {cDNA} ends. This method can be used to specifically amplify the 3′ and 5′ ends of numerous {cDNAs} from a single {cDNA} synthesis reaction.},
	pages = {e194},
	number = {21},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res},
	author = {Bower, Neil I. and Johnston, Ian A.},
	urldate = {2019-08-30},
	date = {2010-11},
	pmid = {20846956},
	pmcid = {PMC2995088},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/DRBSA3G7/Bower and Johnston - 2010 - Targeted rapid amplification of cDNA ends (T-RACE).pdf:application/pdf}
}

@article{latos_airn_2012,
	title = {Airn transcriptional overlap, but not its {lncRNA} products, induces imprinted Igf2r silencing},
	volume = {338},
	issn = {1095-9203},
	doi = {10.1126/science.1228110},
	abstract = {Mammalian imprinted genes often cluster with long noncoding (lnc) {RNAs}. Three {lncRNAs} that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous {lncRNA} to different lengths. The results excluded a role for spliced and unspliced Airn {lncRNA} products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with {RNA} polymerase {II} recruitment in the absence of repressive chromatin. Such a repressor function for {lncRNA} transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of {lncRNA} transcripts.},
	pages = {1469--1472},
	number = {6113},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Latos, Paulina A. and Pauler, Florian M. and Koerner, Martha V. and Şenergin, H. Başak and Hudson, Quanah J. and Stocsits, Roman R. and Allhoff, Wolfgang and Stricker, Stefan H. and Klement, Ruth M. and Warczok, Katarzyna E. and Aumayr, Karin and Pasierbek, Pawel and Barlow, Denise P.},
	date = {2012-12-14},
	pmid = {23239737},
	keywords = {Animals, Mice, Alternative Splicing, Gene Silencing, Genomic Imprinting, Multigene Family, {RNA} Polymerase {II}, {RNA}, Long Noncoding, Transcription, Genetic, Cells, Cultured, Promoter Regions, Genetic, Receptor, {IGF} Type 2}
}

@article{sleutels_non-coding_2002,
	title = {The non-coding Air {RNA} is required for silencing autosomal imprinted genes},
	volume = {415},
	issn = {0028-0836},
	doi = {10.1038/415810a},
	abstract = {In genomic imprinting, one of the two parental alleles of an autosomal gene is silenced epigenetically by a cis-acting mechanism. A bidirectional silencer for a 400-kilobase region that contains three imprinted, maternally expressed protein-coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be located in a sequence of 3.7 kilobases, which also contains the promoter for the imprinted, paternally expressed non-coding Air {RNA}. Expression of Air is correlated with repression of all three genes on the paternal allele; however, Air {RNA} overlaps just one of these genes in an antisense orientation. Here we show, by inserting a polyadenylation signal that truncates 96\% of the {RNA} transcript, that Air {RNA} is required for silencing. The truncated Air allele maintains imprinted expression and methylation of the Air promoter, but shows complete loss of silencing of the Igf2r/Slc22a2/Slc22a3 gene cluster on the paternal chromosome. Our results indicate that non-coding {RNAs} have an active role in genomic imprinting.},
	pages = {810--813},
	number = {6873},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Sleutels, Frank and Zwart, Ronald and Barlow, Denise P.},
	date = {2002-02-14},
	pmid = {11845212},
	keywords = {Animals, Mice, Alleles, Chromosomes, {DNA} Methylation, Female, Gene Silencing, Genomic Imprinting, Male, Multigene Family, Poly A, Polyadenylation, Reverse Transcriptase Polymerase Chain Reaction, Sequence Deletion, Promoter Regions, Genetic, {RNA}, Untranslated, {RNA}, Antisense, Globins}
}

@article{anderson_transcription_2016,
	title = {Transcription of the non-coding {RNA} upperhand controls Hand2 expression and heart development},
	volume = {539},
	issn = {1476-4687},
	doi = {10.1038/nature20128},
	abstract = {{HAND}2 is an ancestral regulator of heart development and one of four transcription factors that control the reprogramming of fibroblasts into cardiomyocytes. Deletion of Hand2 in mice results in right ventricle hypoplasia and embryonic lethality. Hand2 expression is tightly regulated by upstream enhancers that reside within a super-enhancer delineated by histone H3 acetyl Lys27 (H3K27ac) modifications. Here we show that transcription of a Hand2-associated long non-coding {RNA}, which we named upperhand (Uph), is required to maintain the super-enhancer signature and elongation of {RNA} polymerase {II} through the Hand2 enhancer locus. Blockade of Uph transcription, but not knockdown of the mature transcript, abolished Hand2 expression, causing right ventricular hypoplasia and embryonic lethality in mice. Given the substantial number of uncharacterized promoter-associated long non-coding {RNAs} encoded by the mammalian genome, the Uph-Hand2 regulatory partnership offers a mechanism by which divergent non-coding transcription can establish a permissive chromatin environment.},
	pages = {433--436},
	number = {7629},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Anderson, Kelly M. and Anderson, Douglas M. and {McAnally}, John R. and Shelton, John M. and Bassel-Duby, Rhonda and Olson, Eric N.},
	date = {2016},
	pmid = {27783597},
	pmcid = {PMC5261552},
	keywords = {Animals, Mice, Chromatin, Gene Knockout Techniques, Organogenesis, {RNA} Polymerase {II}, {RNA}, Long Noncoding, Transcription, Genetic, Promoter Regions, Genetic, Enhancer Elements, Genetic, Mice, Knockout, Basic Helix-Loop-Helix Transcription Factors, Heart, Embryo Loss, Heart Defects, Congenital, Heart Ventricles, Transcription Elongation, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/76RUZ4Y5/Anderson et al. - 2016 - Transcription of the non-coding RNA upperhand cont.pdf:application/pdf}
}

@article{hu_long_2011,
	title = {Long noncoding {RNA}-mediated anti-apoptotic activity in murine erythroid terminal differentiation},
	volume = {25},
	issn = {1549-5477},
	doi = {10.1101/gad.178780.111},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are differentially expressed under both normal and pathological conditions, implying that they may play important biological functions. Here we examined the expression of {lncRNAs} during erythropoiesis and identified an erythroid-specific {lncRNA} with anti-apoptotic activity. Inhibition of this {lncRNA} blocks erythroid differentiation and promotes apoptosis. Conversely, ectopic expression of this {lncRNA} can inhibit apoptosis in mouse erythroid cells. This {lncRNA} represses expression of Pycard, a proapoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a {lncRNA}.},
	pages = {2573--2578},
	number = {24},
	journaltitle = {Genes \& Development},
	shortjournal = {Genes Dev.},
	author = {Hu, Wenqian and Yuan, Bingbing and Flygare, Johan and Lodish, Harvey F.},
	date = {2011-12-15},
	pmid = {22155924},
	pmcid = {PMC3248679},
	keywords = {Animals, Humans, Mice, Gene Expression Profiling, Apoptosis, Cell Differentiation, Gene Knockdown Techniques, {HEK}293 Cells, Cells, Cultured, {RNA}, Untranslated, Mice, Inbred C57BL, Cytoskeletal Proteins, Gene Expression Regulation, Developmental, Apoptosis Regulatory Proteins, {CARD} Signaling Adaptor Proteins, Erythroid Cells, Erythropoiesis},
	file = {Full Text:/home/jlagarde/Zotero/storage/SXR9CHJL/Hu et al. - 2011 - Long noncoding RNA-mediated anti-apoptotic activit.pdf:application/pdf}
}

@article{atianand_long_2016,
	title = {A Long Noncoding {RNA} {lincRNA}-{EPS} Acts as a Transcriptional Brake to Restrain Inflammation},
	volume = {165},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2016.05.075},
	abstract = {Long intergenic noncoding {RNAs} ({lincRNAs}) are important regulators of gene expression. Although {lincRNAs} are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory {lincRNA}, {lincRNA}-{EPS}, that is precisely regulated in macrophages to control the expression of immune response genes ({IRGs}). Transcriptome analysis of macrophages from {lincRNA}-{EPS}-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this {lincRNA} in restraining {IRG} expression. Consistently, {lincRNA}-{EPS}-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. {lincRNA}-{EPS} localizes at regulatory regions of {IRGs} to control nucleosome positioning and repress transcription. Further, {lincRNA}-{EPS} mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a {CANACA} motif located in its 3' end. Together, these findings identify {lincRNA}-{EPS} as a repressor of inflammatory responses, highlighting the importance of {lincRNAs} in the immune system.},
	pages = {1672--1685},
	number = {7},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Atianand, Maninjay K. and Hu, Wenqian and Satpathy, Ansuman T. and Shen, Ying and Ricci, Emiliano P. and Alvarez-Dominguez, Juan R. and Bhatta, Ankit and Schattgen, Stefan A. and {McGowan}, Jason D. and Blin, Juliana and Braun, Joerg E. and Gandhi, Pallavi and Moore, Melissa J. and Chang, Howard Y. and Lodish, Harvey F. and Caffrey, Daniel R. and Fitzgerald, Katherine A.},
	date = {2016-06-16},
	pmid = {27315481},
	pmcid = {PMC5289747},
	keywords = {Transcriptome, Animals, Humans, Mice, Gene Expression Regulation, Gene Deletion, Inflammation, Macrophages, {RNA}, Long Noncoding, Mice, Inbred C57BL, Chromatids, Listeria monocytogenes, Listeriosis, Respirovirus Infections, Sendai virus, Toll-Like Receptors},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/UKK7ZPB7/Atianand et al. - 2016 - A Long Noncoding RNA lincRNA-EPS Acts as a Transcr.pdf:application/pdf}
}

@article{west_long_2014,
	title = {The long noncoding {RNAs} {NEAT}1 and {MALAT}1 bind active chromatin sites},
	volume = {55},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2014.07.012},
	abstract = {Mechanistic roles for many {lncRNAs} are poorly understood, in part because their direct interactions with genomic loci and proteins are difficult to assess. Using a method to purify endogenous {RNAs} and their associated factors, we mapped the genomic binding sites for two highly expressed human {lncRNAs}, {NEAT}1 and {MALAT}1. We show that {NEAT}1 and {MALAT}1 localize to hundreds of genomic sites in human cells, primarily over active genes. {NEAT}1 and {MALAT}1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these {RNAs}. We also identified numerous proteins enriched by both {lncRNAs}, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation alters localization of {NEAT}1 on active chromatin sites, implying that underlying {DNA} sequence does not target {NEAT}1 to chromatin, and that localization responds to cues involved in the transcription process.},
	pages = {791--802},
	number = {5},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {West, Jason A. and Davis, Christopher P. and Sunwoo, Hongjae and Simon, Matthew D. and Sadreyev, Ruslan I. and Wang, Peggy I. and Tolstorukov, Michael Y. and Kingston, Robert E.},
	date = {2014-09-04},
	pmid = {25155612},
	pmcid = {PMC4428586},
	keywords = {Humans, Binding Sites, Chromatin, Nucleic Acid Hybridization, {RNA}, Long Noncoding, Transcription, Genetic, Models, Genetic},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/GIBIHE9M/West et al. - 2014 - The long noncoding RNAs NEAT1 and MALAT1 bind acti.pdf:application/pdf}
}

@article{hutchinson_screen_2007,
	title = {A screen for nuclear transcripts identifies two linked noncoding {RNAs} associated with {SC}35 splicing domains},
	volume = {8},
	issn = {1471-2164},
	doi = {10.1186/1471-2164-8-39},
	abstract = {{BACKGROUND}: Noncoding {RNA} species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller {RNA} species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding {RNAs} that might control gene expression or {mRNA} metabolism, we used Affymetrix expression arrays to identify polyadenylated {RNA} transcripts displaying nuclear enrichment.
{RESULTS}: This screen identified no more than three transcripts; {XIST}, and two unique noncoding nuclear enriched abundant transcripts ({NEAT}) {RNAs} strikingly located less than 70 kb apart on human chromosome 11: {NEAT}1, a noncoding {RNA} from the locus encoding for {TncRNA}, and {NEAT}2 (also known as {MALAT}-1). While the two {NEAT} transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding {RNAs}. {NEAT}2 is extraordinarily well conserved for a noncoding {RNA}, more so than even {XIST}. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding {RNAs} are also nuclear enriched. {RNA} {FISH} analyses suggest that these noncoding {RNAs} function in {mRNA} metabolism as they demonstrate an intimate association of these {RNA} species with {SC}35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, {NEAT}1 localizes to the periphery of such domains, whereas the neighboring transcript, {NEAT}2, is part of the long-sought polyadenylated component of nuclear speckles.
{CONCLUSION}: Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated {RNAs} in the nucleus; the canonical large noncoding {RNA} {XIST} and {NEAT}1 and {NEAT}2. The function of these noncoding {RNAs} in {mRNA} metabolism is suggested by their high levels of conservation and their intimate association with {SC}35 splicing domains in multiple mammalian species.},
	pages = {39},
	journaltitle = {{BMC} genomics},
	shortjournal = {{BMC} Genomics},
	author = {Hutchinson, John N. and Ensminger, Alexander W. and Clemson, Christine M. and Lynch, Christopher R. and Lawrence, Jeanne B. and Chess, Andrew},
	date = {2007-02-01},
	pmid = {17270048},
	pmcid = {PMC1800850},
	keywords = {Animals, Base Sequence, Humans, Mice, {RNA} Splicing, Oligonucleotide Array Sequence Analysis, Cell Nucleus, Introns, Chromosome Mapping, {DNA} Primers, Subcellular Fractions, Evolution, Molecular, {RNA}, Messenger},
	file = {Full Text:/home/jlagarde/Zotero/storage/URVFGMEG/Hutchinson et al. - 2007 - A screen for nuclear transcripts identifies two li.pdf:application/pdf}
}

@article{pauli_systematic_2012,
	title = {Systematic identification of long noncoding {RNAs} expressed during zebrafish embryogenesis},
	volume = {22},
	issn = {1549-5469},
	doi = {10.1101/gr.133009.111},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) comprise a diverse class of transcripts that structurally resemble {mRNAs} but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated {lncRNAs} expressed in cell lines and adult tissues, but a systematic analysis of {lncRNAs} expressed during vertebrate embryogenesis has been elusive. To identify {lncRNAs} with potential functions in vertebrate embryogenesis, we performed a time-series of {RNA}-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed {RefSeq} transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic {ncRNAs} ({lincRNAs}), intronic overlapping {lncRNAs}, exonic antisense overlapping {lncRNAs}, and precursors for small {RNAs} ({sRNAs}). Zebrafish {lncRNAs} share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of {lncRNAs} carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of {lncRNAs} revealed two novel properties: {lncRNAs} are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several {lncRNAs} show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual {lncRNAs} with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of {lncRNAs} in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.},
	pages = {577--591},
	number = {3},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Pauli, Andrea and Valen, Eivind and Lin, Michael F. and Garber, Manuel and Vastenhouw, Nadine L. and Levin, Joshua Z. and Fan, Lin and Sandelin, Albin and Rinn, John L. and Regev, Aviv and Schier, Alexander F.},
	date = {2012-03},
	pmid = {22110045},
	pmcid = {PMC3290793},
	keywords = {Genomics, Animals, Mice, Computational Biology, Gene Expression Profiling, Organ Specificity, Open Reading Frames, Chromatin, Cluster Analysis, Embryonic Development, Gene Expression, Zebrafish, Transcription, Genetic, {RNA}, Untranslated, Gene Expression Regulation, Developmental},
	file = {Full Text:/home/jlagarde/Zotero/storage/DNFPDICW/Pauli et al. - 2012 - Systematic identification of long noncoding RNAs e.pdf:application/pdf}
}

@article{bernard_long_2010,
	title = {A long nuclear-retained non-coding {RNA} regulates synaptogenesis by modulating gene expression},
	volume = {29},
	issn = {1460-2075},
	doi = {10.1038/emboj.2010.199},
	abstract = {A growing number of long nuclear-retained non-coding {RNAs} ({ncRNAs}) have recently been described. However, few functions have been elucidated for these {ncRNAs}. Here, we have characterized the function of one such {ncRNA}, identified as metastasis-associated lung adenocarcinoma transcript 1 (Malat1). Malat1 {RNA} is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when {RNA} polymerase {II}-dependent transcription is active. Knock-down studies revealed that Malat1 modulates the recruitment of {SR} family pre-{mRNA}-splicing factors to the transcription site of a transgene array. {DNA} microarray analysis in Malat1-depleted neuroblastoma cells indicates that Malat1 controls the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippocampal neurons, knock-down of Malat1 decreases synaptic density, whereas its over-expression results in a cell-autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance.},
	pages = {3082--3093},
	number = {18},
	journaltitle = {The {EMBO} journal},
	shortjournal = {{EMBO} J.},
	author = {Bernard, Delphine and Prasanth, Kannanganattu V. and Tripathi, Vidisha and Colasse, Sabrina and Nakamura, Tetsuya and Xuan, Zhenyu and Zhang, Michael Q. and Sedel, Frédéric and Jourdren, Laurent and Coulpier, Fanny and Triller, Antoine and Spector, David L. and Bessis, Alain},
	date = {2010-09-15},
	pmid = {20729808},
	pmcid = {PMC2944070},
	keywords = {Animals, Humans, Mice, {RNA} Splicing, Gene Expression Regulation, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Cell Nucleus, Biomarkers, Neurogenesis, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Precursors, Transcription Factors, {RNA}, Messenger, Cells, Cultured, Neurons, Blotting, Northern, Bone Neoplasms, Hippocampus, Neuroblastoma, Osteosarcoma, {RNA}, Nuclear, Synapses},
	file = {Full Text:/home/jlagarde/Zotero/storage/4KFDAMLP/Bernard et al. - 2010 - A long nuclear-retained non-coding RNA regulates s.pdf:application/pdf}
}

@article{tripathi_nuclear-retained_2010,
	title = {The nuclear-retained noncoding {RNA} {MALAT}1 regulates alternative splicing by modulating {SR} splicing factor phosphorylation},
	volume = {39},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2010.08.011},
	abstract = {Alternative splicing ({AS}) of pre-{mRNA} is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine ({SR}) splicing factors regulate tissue- or cell-type-specific {AS} in a concentration- and phosphorylation-dependent manner. However, the mechanisms that modulate the cellular levels of active {SR} proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory {RNA} ({nrRNA}), {MALAT}1 in {AS} regulation. {MALAT}1 interacts with {SR} proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of {MALAT}1 or overexpression of an {SR} protein changes the {AS} of a similar set of endogenous pre-{mRNAs}. Furthermore, {MALAT}1 regulates cellular levels of phosphorylated forms of {SR} proteins. Taken together, our results suggest that {MALAT}1 regulates {AS} by modulating the levels of active {SR} proteins. Our results further highlight the role for an {nrRNA} in the regulation of gene expression.},
	pages = {925--938},
	number = {6},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Tripathi, Vidisha and Ellis, Jonathan D. and Shen, Zhen and Song, David Y. and Pan, Qun and Watt, Andrew T. and Freier, Susan M. and Bennett, C. Frank and Sharma, Alok and Bubulya, Paula A. and Blencowe, Benjamin J. and Prasanth, Supriya G. and Prasanth, Kannanganattu V.},
	date = {2010-09-24},
	pmid = {20797886},
	pmcid = {PMC4158944},
	keywords = {Animals, Humans, Mice, Binding Sites, Protein Binding, Cell Nucleus, Alternative Splicing, Cell Line, {DNA}-Binding Proteins, {HeLa} Cells, Mitosis, Phosphorylation, {RNA} Precursors, {RNA}-Binding Proteins, Transcription Factors, Nuclear Proteins, {RNA}, Untranslated, {RNA} Splicing Factors, Regulatory Sequences, Ribonucleic Acid, Intranuclear Space, Minor Histocompatibility Antigens, Protein Interaction Domains and Motifs, Serine-Arginine Splicing Factors},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/ZKKAT7LB/Tripathi et al. - 2010 - The nuclear-retained noncoding RNA MALAT1 regulate.pdf:application/pdf}
}

@article{clemson_architectural_2009,
	title = {An architectural role for a nuclear noncoding {RNA}: {NEAT}1 {RNA} is essential for the structure of paraspeckles},
	volume = {33},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2009.01.026},
	shorttitle = {An architectural role for a nuclear noncoding {RNA}},
	abstract = {{NEAT}1 {RNA}, a highly abundant 4 kb {ncRNA}, is retained in nuclei in approximately 10 to 20 large foci that we show are completely coincident with paraspeckles, nuclear domains implicated in {mRNA} nuclear retention. Depletion of {NEAT}1 {RNA} via {RNAi} eradicates paraspeckles, suggesting that it controls sequestration of the paraspeckle proteins {PSP}1 and p54, factors linked to A-I editing. Unlike overexpression of {PSP}1, {NEAT}1 overexpression increases paraspeckle number, and paraspeckles emanate exclusively from the {NEAT}1 transcription site. The {PSP}-1 {RNA} binding domain is required for its colocalization with {NEAT}1 {RNA} in paraspeckles, and biochemical analyses support that {NEAT}1 {RNA} binds with paraspeckle proteins. Unlike other nuclear-retained {RNAs}, {NEAT}1 {RNA} is not A-I edited, consistent with a structural role in paraspeckles. Collectively, results demonstrate that {NEAT}1 functions as an essential structural determinant of paraspeckles, providing a precedent for a {ncRNA} as the foundation of a nuclear domain.},
	pages = {717--726},
	number = {6},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Clemson, Christine M. and Hutchinson, John N. and Sara, Sergio A. and Ensminger, Alexander W. and Fox, Archa H. and Chess, Andrew and Lawrence, Jeanne B.},
	date = {2009-03-27},
	pmid = {19217333},
	pmcid = {PMC2696186},
	keywords = {Animals, Humans, Mice, Cell Nucleus, Gene Knockdown Techniques, Immunoprecipitation, {RNA} Interference, {RNA}-Binding Proteins, Nuclear Proteins, Cells, Cultured, {RNA}, Small Nuclear, Endoribonucleases, Chloroplast Proteins, Intranuclear Inclusion Bodies},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/B8TLNW7Z/Clemson et al. - 2009 - An architectural role for a nuclear noncoding RNA.pdf:application/pdf}
}

@article{mao_direct_2011,
	title = {Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding {RNAs}},
	volume = {13},
	issn = {1476-4679},
	doi = {10.1038/ncb2140},
	abstract = {The cell nucleus is a highly compartmentalized organelle harbouring a variety of dynamic membraneless nuclear bodies. How these subnuclear domains are established and maintained is not well understood. Here, we investigate the molecular mechanism of how one nuclear body, the paraspeckle, is assembled and organized. Paraspeckles are discrete ribonucleoprotein bodies found in mammalian cells and implicated in nuclear retention of hyperedited {mRNAs}. We developed a live-cell imaging system that allows for the inducible transcription of Men ɛ/β (also known as Neat1; ref. 12) noncoding {RNAs} ({ncRNAs}) and the direct visualization of the recruitment of paraspeckle proteins. Using this system, we demonstrate that Men ɛ/β {ncRNAs} are essential to initiate the de novo assembly of paraspeckles. These newly formed structures effectively harbour nuclear-retained {mRNAs} confirming that they are bona fide functional paraspeckles. By three independent approaches, we show that it is the act of Men ɛ/β transcription, but not {ncRNAs} alone, that regulates paraspeckle maintenance. Finally, fluorescence recovery after photobleaching ({FRAP}) analyses supported a critical structural role for Men ɛ/β {ncRNAs} in paraspeckle organization. This study establishes a model in which Men ɛ/β {ncRNAs} serve as a platform to recruit proteins to assemble paraspeckles.},
	pages = {95--101},
	number = {1},
	journaltitle = {Nature Cell Biology},
	shortjournal = {Nat. Cell Biol.},
	author = {Mao, Yuntao S. and Sunwoo, Hongjae and Zhang, Bin and Spector, David L.},
	date = {2011-01},
	pmid = {21170033},
	pmcid = {PMC3007124},
	keywords = {Animals, Humans, Mice, Cell Nucleus, Cell Line, Fluorescence Recovery After Photobleaching, Kinetics, Reverse Transcriptase Polymerase Chain Reaction, {RNA}-Binding Proteins, Nuclear Proteins, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated, Microscopy, Fluorescence, Luminescent Proteins, In Situ Hybridization, Fluorescence, Intranuclear Inclusion Bodies},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/YMCJLSFB/Mao et al. - 2011 - Direct visualization of the co-transcriptional ass.pdf:application/pdf}
}

@article{sunwoo_men_2009,
	title = {{MEN} epsilon/beta nuclear-retained non-coding {RNAs} are up-regulated upon muscle differentiation and are essential components of paraspeckles},
	volume = {19},
	issn = {1088-9051},
	doi = {10.1101/gr.087775.108},
	abstract = {Studies of the transcriptional output of the human and mouse genomes have revealed that there are many more transcripts produced than can be accounted for by predicted protein-coding genes. Using a custom microarray, we have identified 184 non-coding {RNAs} that exhibit more than twofold up- or down-regulation upon differentiation of C2C12 myoblasts into myotubes. Here, we focus on the Men epsilon/beta locus, which is up-regulated 3.3-fold during differentiation. Two non-coding {RNA} isoforms are produced from a single {RNA} polymerase {II} promoter, differing in the location of their 3' ends. Men epsilon is a 3.2-kb polyadenylated {RNA}, whereas Men beta is an approximately 20-kb transcript containing a genomically encoded poly(A)-rich tract at its 3'-end. The 3'-end of Men beta is generated by {RNase} P cleavage. The Men epsilon/beta transcripts are localized to nuclear paraspeckles and directly interact with {NONO}. Knockdown of {MEN} epsilon/beta expression results in the disruption of nuclear paraspeckles. Furthermore, the formation of paraspeckles, after release from transcriptional inhibition by {DRB} treatment, was suppressed in {MEN} epsilon/beta-depleted cells. Our findings indicate that the {MEN} epsilon/beta non-coding {RNAs} are essential structural/organizational components of paraspeckles.},
	pages = {347--359},
	number = {3},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Sunwoo, Hongjae and Dinger, Marcel E. and Wilusz, Jeremy E. and Amaral, Paulo P. and Mattick, John S. and Spector, David L.},
	date = {2009-03},
	pmid = {19106332},
	pmcid = {PMC2661813},
	keywords = {Animals, Base Sequence, Humans, Mice, Cell Nucleus, Cell Differentiation, {HeLa} Cells, Molecular Sequence Data, Muscle Development, Protein Isoforms, Up-Regulation, Cells, Cultured, {RNA}, Untranslated, Active Transport, Cell Nucleus, Gene Expression Regulation, Developmental, Intranuclear Inclusion Bodies, Muscle Fibers, Skeletal, Proto-Oncogene Proteins, Ribonuclease P},
	file = {Full Text:/home/jlagarde/Zotero/storage/WUMCE4B9/Sunwoo et al. - 2009 - MEN epsilonbeta nuclear-retained non-coding RNAs .pdf:application/pdf}
}

@article{lee_noncoding_2016,
	title = {Noncoding {RNA} {NORAD} Regulates Genomic Stability by Sequestering {PUMILIO} Proteins},
	volume = {164},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2015.12.017},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) have emerged as regulators of diverse biological processes. Here, we describe the initial functional analysis of a poorly characterized human {lncRNA} ({LINC}00657) that is induced after {DNA} damage, which we termed "noncoding {RNA} activated by {DNA} damage", or {NORAD}. {NORAD} is highly conserved and abundant, with expression levels of approximately 500-1,000 copies per cell. Remarkably, inactivation of {NORAD} triggers dramatic aneuploidy in previously karyotypically stable cell lines. {NORAD} maintains genomic stability by sequestering {PUMILIO} proteins, which repress the stability and translation of {mRNAs} to which they bind. In the absence of {NORAD}, {PUMILIO} proteins drive chromosomal instability by hyperactively repressing mitotic, {DNA} repair, and {DNA} replication factors. These findings introduce a mechanism that regulates the activity of a deeply conserved and highly dosage-sensitive family of {RNA} binding proteins and reveal unanticipated roles for a {lncRNA} and {PUMILIO} proteins in the maintenance of genomic stability.},
	pages = {69--80},
	number = {1},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Lee, Sungyul and Kopp, Florian and Chang, Tsung-Cheng and Sataluri, Anupama and Chen, Beibei and Sivakumar, Sushama and Yu, Hongtao and Xie, Yang and Mendell, Joshua T.},
	date = {2016-01-14},
	pmid = {26724866},
	pmcid = {PMC4715682},
	keywords = {Animals, Base Sequence, Humans, Mice, Genomic Instability, {HCT}116 Cells, Ploidies, {RNA}-Binding Proteins, {RNA}, Long Noncoding, Chromosomal Instability},
	file = {Full Text:/home/jlagarde/Zotero/storage/UTKZNZ8F/Lee et al. - 2016 - Noncoding RNA NORAD Regulates Genomic Stability by.pdf:application/pdf}
}

@article{tichon_conserved_2016,
	title = {A conserved abundant cytoplasmic long noncoding {RNA} modulates repression by Pumilio proteins in human cells},
	volume = {7},
	issn = {2041-1723},
	doi = {10.1038/ncomms12209},
	abstract = {Thousands of long noncoding {RNA} ({lncRNA}) genes are encoded in the human genome, and hundreds of them are evolutionarily conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic {lncRNAs} are those that are exported to the cytoplasm, including {NORAD}-an abundant and highly conserved cytoplasmic {lncRNA}. Here we show that most of the sequence of {NORAD} is comprised of repetitive units that together contain at least 17 functional binding sites for the two mammalian Pumilio homologues. Through binding to {PUM}1 and {PUM}2, {NORAD} modulates the {mRNA} levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic {lncRNAs} function by modulating the activities of {RNA}-binding proteins, an activity which positions them at key junctions of cellular signalling pathways.},
	pages = {12209},
	journaltitle = {Nature Communications},
	shortjournal = {Nat Commun},
	author = {Tichon, Ailone and Gil, Noa and Lubelsky, Yoav and Havkin Solomon, Tal and Lemze, Doron and Itzkovitz, Shalev and Stern-Ginossar, Noam and Ulitsky, Igor},
	date = {2016},
	pmid = {27406171},
	pmcid = {PMC4947167},
	keywords = {Humans, Gene Expression Regulation, Cell Division, {HeLa} Cells, {RNA}-Binding Proteins, {RNA}, Long Noncoding, {RNA}, Messenger, Cell Line, Tumor, Chromosome Segregation},
	file = {Full Text:/home/jlagarde/Zotero/storage/FLMZTCUW/Tichon et al. - 2016 - A conserved abundant cytoplasmic long noncoding RN.pdf:application/pdf}
}

@article{hansen_natural_2013,
	title = {Natural {RNA} circles function as efficient {microRNA} sponges},
	volume = {495},
	issn = {1476-4687},
	doi = {10.1038/nature11993},
	abstract = {{MicroRNAs} ({miRNAs}) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger {RNAs}. Recently, {miRNA} activity has been shown to be affected by the presence of {miRNA} sponge transcripts, the so-called competing endogenous {RNA} in humans and target mimicry in plants. We previously identified a highly expressed circular {RNA} ({circRNA}) in human and mouse brain. Here we show that this {circRNA} acts as a {miR}-7 sponge; we term this circular transcript {ciRS}-7 (circular {RNA} sponge for {miR}-7). {ciRS}-7 contains more than 70 selectively conserved {miRNA} target sites, and it is highly and widely associated with Argonaute ({AGO}) proteins in a {miR}-7-dependent manner. Although the {circRNA} is completely resistant to {miRNA}-mediated target destabilization, it strongly suppresses {miR}-7 activity, resulting in increased levels of {miR}-7 targets. In the mouse brain, we observe overlapping co-expression of {ciRS}-7 and {miR}-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific {circRNA}, sex-determining region Y (Sry), serves as a {miR}-138 sponge, suggesting that {miRNA} sponge effects achieved by {circRNA} formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed {circRNA}.},
	pages = {384--388},
	number = {7441},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Hansen, Thomas B. and Jensen, Trine I. and Clausen, Bettina H. and Bramsen, Jesper B. and Finsen, Bente and Damgaard, Christian K. and Kjems, Jørgen},
	date = {2013-03-21},
	pmid = {23446346},
	keywords = {Animals, Humans, Mice, {RNA}, Gene Expression Regulation, Argonaute Proteins, Brain, {HEK}293 Cells, {HeLa} Cells, Male, {MicroRNAs}, Mice, Inbred C57BL, Sex-Determining Region Y Protein}
}

@article{memczak_circular_2013,
	title = {Circular {RNAs} are a large class of animal {RNAs} with regulatory potency},
	volume = {495},
	issn = {1476-4687},
	doi = {10.1038/nature11928},
	abstract = {Circular {RNAs} ({circRNAs}) in animals are an enigmatic class of {RNA} with unknown function. To explore {circRNAs} systematically, we sequenced and computationally analysed human, mouse and nematode {RNA}. We detected thousands of well-expressed, stable {circRNAs}, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for {circRNAs}. We found that a human {circRNA}, antisense to the cerebellar degeneration-related protein 1 transcript ({CDR}1as), is densely bound by {microRNA} ({miRNA}) effector complexes and harbours 63 conserved binding sites for the ancient {miRNA} {miR}-7. Further analyses indicated that {CDR}1as functions to bind {miR}-7 in neuronal tissues. Human {CDR}1as expression in zebrafish impaired midbrain development, similar to knocking down {miR}-7, suggesting that {CDR}1as is a {miRNA} antagonist with a {miRNA}-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that {circRNAs} form a large class of post-transcriptional regulators. Numerous {circRNAs} form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.},
	pages = {333--338},
	number = {7441},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Memczak, Sebastian and Jens, Marvin and Elefsinioti, Antigoni and Torti, Francesca and Krueger, Janna and Rybak, Agnieszka and Maier, Luisa and Mackowiak, Sebastian D. and Gregersen, Lea H. and Munschauer, Mathias and Loewer, Alexander and Ziebold, Ulrike and Landthaler, Markus and Kocks, Christine and le Noble, Ferdinand and Rajewsky, Nikolaus},
	date = {2013-03-21},
	pmid = {23446348},
	keywords = {Animals, Conserved Sequence, Humans, Mice, {RNA}, Binding Sites, Gene Expression Regulation, Caenorhabditis elegans, Brain, Cell Line, Female, {HEK}293 Cells, Male, {MicroRNAs}, Zebrafish, Nerve Tissue Proteins, Autoantigens}
}

@article{smits_conservation_2008,
	title = {Conservation of the H19 noncoding {RNA} and H19-{IGF}2 imprinting mechanism in therians},
	volume = {40},
	issn = {1546-1718},
	doi = {10.1038/ng.168},
	abstract = {Comparisons between eutherians and marsupials suggest limited conservation of the molecular mechanisms that control genomic imprinting in mammals. We have studied the evolution of the imprinted {IGF}2-H19 locus in therians. Although marsupial orthologs of protein-coding exons were easily identified, the use of evolutionarily conserved regions and low-stringency Bl2seq comparisons was required to delineate a candidate H19 noncoding {RNA} sequence. The therian H19 orthologs show {miR}-675 and exon structure conservation, suggesting functional selection on both features. Transcription start site sequences and poly(A) signals are also conserved. As in eutherians, marsupial H19 is maternally expressed and paternal methylation upstream of the gene originates in the male germline, encompasses a {CTCF} insulator, and spreads somatically into the H19 gene. The conservation in all therians of the mechanism controlling imprinting of the {IGF}2-H19 locus suggests a sequential model of imprinting evolution.},
	pages = {971--976},
	number = {8},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Smits, Guillaume and Mungall, Andrew J. and Griffiths-Jones, Sam and Smith, Paul and Beury, Delphine and Matthews, Lucy and Rogers, Jane and Pask, Andrew J. and Shaw, Geoff and VandeBerg, John L. and McCarrey, John R. and {SAVOIR Consortium} and Renfree, Marilyn B. and Reik, Wolf and Dunham, Ian},
	date = {2008-08},
	pmid = {18587395},
	keywords = {Animals, Base Sequence, Humans, Mice, {DNA} Methylation, Female, Genomic Imprinting, Male, Molecular Sequence Data, Nucleic Acid Conformation, Sequence Alignment, Evolution, Molecular, {RNA}, Long Noncoding, {RNA}, Untranslated, Insulin-Like Growth Factor {II}, Macropodidae}
}

@article{matsumoto_mtorc1_2017,
	title = {{mTORC}1 and muscle regeneration are regulated by the {LINC}00961-encoded {SPAR} polypeptide},
	volume = {541},
	issn = {1476-4687},
	doi = {10.1038/nature21034},
	abstract = {Although long non-coding {RNAs} ({lncRNAs}) are non-protein-coding transcripts by definition, recent studies have shown that a fraction of putative small open reading frames within {lncRNAs} are translated. However, the biological significance of these hidden polypeptides is still unclear. Here we identify and functionally characterize a novel polypeptide encoded by the {lncRNA} {LINC}00961. This polypeptide is conserved between human and mouse, is localized to the late endosome/lysosome and interacts with the lysosomal v-{ATPase} to negatively regulate {mTORC}1 activation. This regulation of {mTORC}1 is specific to activation of {mTORC}1 by amino acid stimulation, rather than by growth factors. Hence, we termed this polypeptide 'small regulatory polypeptide of amino acid response' ({SPAR}). We show that the {SPAR}-encoding {lncRNA} is highly expressed in a subset of tissues and use {CRISPR}/Cas9 engineering to develop a {SPAR}-polypeptide-specific knockout mouse while maintaining expression of the host {lncRNA}. We find that the {SPAR}-encoding {lncRNA} is downregulated in skeletal muscle upon acute injury, and using this in vivo model we establish that {SPAR} downregulation enables efficient activation of {mTORC}1 and promotes muscle regeneration. Our data provide a mechanism by which {mTORC}1 activation may be finely regulated in a tissue-specific manner in response to injury, and a paradigm by which {lncRNAs} encoding small polypeptides can modulate general biological pathways and processes to facilitate tissue-specific requirements, consistent with their restricted and highly regulated expression profile.},
	pages = {228--232},
	number = {7636},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Matsumoto, Akinobu and Pasut, Alessandra and Matsumoto, Masaki and Yamashita, Riu and Fung, Jacqueline and Monteleone, Emanuele and Saghatelian, Alan and Nakayama, Keiichi I. and Clohessy, John G. and Pandolfi, Pier Paolo},
	date = {2017},
	pmid = {28024296},
	keywords = {Animals, Humans, Mice, Organ Specificity, {HEK}293 Cells, Male, Multiprotein Complexes, Muscles, Regeneration, Signal Transduction, {TOR} Serine-Threonine Kinases, {RNA}, Long Noncoding, {CRISPR}-Cas Systems, Adenosine Triphosphatases, Amino Acids, Endosomes, Gene Editing, Lysosomes, Mechanistic Target of Rapamycin Complex 1, Peptides}
}

@article{ingolia_ribosome_2014-1,
	title = {Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes},
	volume = {8},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2014.07.045},
	abstract = {Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding, including 5' {UTRs} and long noncoding {RNAs} ({lncRNAs}). Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames ({ORFs}). Here, we show hallmarks of translation in these footprints: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early {AUGs}. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including the induction of immune responses following human cytomegalovirus ({HCMV}) infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts at understanding how cells manage and exploit its consequences.},
	pages = {1365--1379},
	number = {5},
	journaltitle = {Cell Reports},
	shortjournal = {Cell Rep},
	author = {Ingolia, Nicholas T. and Brar, Gloria A. and Stern-Ginossar, Noam and Harris, Michael S. and Talhouarne, Gaëlle J. S. and Jackson, Sarah E. and Wills, Mark R. and Weissman, Jonathan S.},
	date = {2014-09-11},
	pmid = {25159147},
	pmcid = {PMC4216110},
	keywords = {Transcriptome, Animals, Conserved Sequence, Humans, Mice, Protein Binding, Algorithms, 5' Untranslated Regions, {HEK}293 Cells, Molecular Sequence Annotation, Protein Biosynthesis, Ribosomes, {RNA}, Long Noncoding, Codon, Initiator, Ecthyma, Contagious, Protein Footprinting},
	file = {Full Text:/home/jlagarde/Zotero/storage/2QUZWYDP/Ingolia et al. - 2014 - Ribosome profiling reveals pervasive translation o.pdf:application/pdf}
}

@article{pauli_toddler:_2014,
	title = {Toddler: an embryonic signal that promotes cell movement via Apelin receptors},
	volume = {343},
	issn = {1095-9203},
	doi = {10.1126/science.1248636},
	shorttitle = {Toddler},
	abstract = {It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled {APJ}/Apelin receptors, and activation of {APJ}/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of {APJ}/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.},
	pages = {1248636},
	number = {6172},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Pauli, Andrea and Norris, Megan L. and Valen, Eivind and Chew, Guo-Liang and Gagnon, James A. and Zimmerman, Steven and Mitchell, Andrew and Ma, Jiao and Dubrulle, Julien and Reyon, Deepak and Tsai, Shengdar Q. and Joung, J. Keith and Saghatelian, Alan and Schier, Alexander F.},
	date = {2014-02-14},
	pmid = {24407481},
	pmcid = {PMC4107353},
	keywords = {Animals, Amino Acid Sequence, Cell Movement, Frameshift Mutation, Molecular Sequence Data, Signal Transduction, Zebrafish, Apelin Receptors, Chemokine {CXCL}12, Gastrulation, Receptors, G-Protein-Coupled, Zebrafish Proteins},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/W5H6JIBW/Pauli et al. - 2014 - Toddler an embryonic signal that promotes cell mo.pdf:application/pdf}
}

@article{magny_conserved_2013,
	title = {Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames},
	volume = {341},
	issn = {1095-9203},
	doi = {10.1126/science.1238802},
	abstract = {Small open reading frames ({smORFs}) are short {DNA} sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that {smORFs} may be a fundamental genome component that should be studied systematically.},
	pages = {1116--1120},
	number = {6150},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Magny, Emile G. and Pueyo, Jose Ignacio and Pearl, Frances M. G. and Cespedes, Miguel Angel and Niven, Jeremy E. and Bishop, Sarah A. and Couso, Juan Pablo},
	date = {2013-09-06},
	pmid = {23970561},
	keywords = {Animals, Conserved Sequence, Open Reading Frames, Drosophila melanogaster, Amino Acid Sequence, Molecular Sequence Data, Myocardium, Evolution, Molecular, Drosophila Proteins, Calcium, Muscle Proteins, Muscle, Skeletal, Protein Structure, Secondary, Peptides, Ion Transport, Myocardial Contraction, Transaldolase}
}

@article{choi_small_2018,
	title = {The small peptide world in long noncoding {RNAs}},
	issn = {1477-4054},
	doi = {10.1093/bib/bby055},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) are a group of transcripts that are longer than 200 nucleotides (nt) without coding potential. Over the past decade, tens of thousands of novel {lncRNAs} have been annotated in animal and plant genomes because of advanced high-throughput {RNA} sequencing technologies and with the aid of coding transcript classifiers. Further, a considerable number of reports have revealed the existence of stable, functional small peptides (also known as micropeptides), translated from {lncRNAs}. In this review, we discuss the methods of {lncRNA} classification, the investigations regarding their coding potential and the functional significance of the peptides they encode.},
	journaltitle = {Briefings in Bioinformatics},
	shortjournal = {Brief. Bioinformatics},
	author = {Choi, Seo-Won and Kim, Hyun-Woo and Nam, Jin-Wu},
	date = {2018-06-29},
	pmid = {30010717},
	file = {Full Text:/home/jlagarde/Zotero/storage/AAS6L2K2/Choi et al. - 2018 - The small peptide world in long noncoding RNAs.pdf:application/pdf}
}

@article{dinger_pervasive_2009,
	title = {Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications},
	volume = {8},
	issn = {1477-4062},
	doi = {10.1093/bfgp/elp038},
	shorttitle = {Pervasive transcription of the eukaryotic genome},
	abstract = {Genome-wide analyses of the eukaryotic transcriptome have revealed that the majority of the genome is transcribed, producing large numbers of non-protein-coding {RNAs} ({ncRNAs}). This surprising observation challenges many assumptions about the genetic programming of higher organisms and how information is stored and organized within the genome. Moreover, the rapid advances in genomics have given little opportunity for biologists to integrate these emerging findings into their intellectual and experimental frameworks. This problem has been compounded by the perception that genome-wide studies often generate more questions than answers, which in turn has led to confusion and controversy. In this article, we address common questions associated with the phenomenon of pervasive transcription and consider the indices that can be used to evaluate the function (or lack thereof) of the resulting {ncRNAs}. We suggest that many lines of evidence, including expression profiles, conservation signatures, chromatin modification patterns and examination of increasing numbers of individual cases, argue in favour of the widespread functionality of non-coding transcription. We also discuss how informatic and experimental approaches used to analyse protein-coding genes may not be applicable to {ncRNAs} and how the general perception that protein-coding genes form the main informational output of the genome has resulted in much of the misunderstanding surrounding pervasive transcription and its potential significance. Finally, we present the conceptual implications of the majority of the eukaryotic genome being functional and describe how appreciating this perspective will provide considerable opportunity to further understand the molecular basis of development and complex diseases.},
	pages = {407--423},
	number = {6},
	journaltitle = {Briefings in Functional Genomics \& Proteomics},
	shortjournal = {Brief Funct Genomic Proteomic},
	author = {Dinger, Marcel E. and Amaral, Paulo P. and Mercer, Timothy R. and Mattick, John S.},
	date = {2009-11},
	pmid = {19770204},
	keywords = {Animals, Genome, Humans, Gene Expression Profiling, Eukaryotic Cells, {RNA}, Messenger, Transcription, Genetic, {RNA}, Untranslated},
	file = {Full Text:/home/jlagarde/Zotero/storage/C8JL8VBI/Dinger et al. - 2009 - Pervasive transcription of the eukaryotic genome .pdf:application/pdf}
}

@article{torarinsson_thousands_2006,
	title = {Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common {RNA} structure},
	volume = {16},
	issn = {1088-9051},
	doi = {10.1101/gr.5226606},
	abstract = {Human and mouse genome sequences contain roughly 100,000 regions that are unalignable in primary sequence and neighbor corresponding alignable regions between both organisms. These pairs are generally assumed to be nonconserved, although the level of structural conservation between these has never been investigated. Owing to the limitations in computational methods, comparative genomics has been lacking the ability to compare such nonconserved sequence regions for conserved structural {RNA} elements. We have investigated the presence of structural {RNA} elements by conducting a local structural alignment, using {FOLDALIGN}, on a subset of these 100,000 corresponding regions and estimate that 1800 contain common {RNA} structures. Comparing our results with the recent mapping of transcribed fragments (transfrags) in human, we find that high-scoring candidates are twice as likely to be found in regions overlapped by transfrags than regions that are not overlapped by transfrags. To verify the coexpression between predicted candidates in human and mouse, we conducted expression studies by {RT}-{PCR} and Northern blotting on mouse candidates, which overlap with transfrags on human chromosome 20. {RT}-{PCR} results confirmed expression of 32 out of 36 candidates, whereas Northern blots confirmed four out of 12 candidates. Furthermore, many {RT}-{PCR} results indicate differential expression in different tissues. Hence, our findings suggest that there are corresponding regions between human and mouse, which contain expressed non-coding {RNA} sequences not alignable in primary sequence.},
	pages = {885--889},
	number = {7},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Torarinsson, Elfar and Sawera, Milena and Havgaard, Jakob H. and Fredholm, Merete and Gorodkin, Jan},
	date = {2006-07},
	pmid = {16751343},
	pmcid = {PMC1484455},
	keywords = {Animals, Base Sequence, Conserved Sequence, Genome, Humans, Mice, {RNA}, Software, Base Pairing, Chickens, Chromosome Mapping, Dogs, Nucleic Acid Conformation, Rats, Transcription, Genetic, Sequence Analysis, {RNA}, Genome, Human, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 20},
	file = {Full Text:/home/jlagarde/Zotero/storage/W3PDI7XF/Torarinsson et al. - 2006 - Thousands of corresponding human and mouse genomic.pdf:application/pdf}
}

@article{kent_human_2002,
	title = {The Human Genome Browser at {UCSC}},
	volume = {12},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/12/6/996},
	doi = {10.1101/gr.229102},
	abstract = {As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided athttp://genome.ucsc.edu. This browser displays assembly contigs and gaps, {mRNA} and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying {MYSQL} database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.},
	pages = {996--1006},
	number = {6},
	journaltitle = {Genome Research},
	shortjournal = {Genome Res.},
	author = {Kent, W. James and Sugnet, Charles W. and Furey, Terrence S. and Roskin, Krishna M. and Pringle, Tom H. and Zahler, Alan M. and Haussler, \{and\} David},
	urldate = {2019-09-02},
	date = {2002-06-01},
	langid = {english},
	pmid = {12045153},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/DEMFCABE/Kent et al. - 2002 - The Human Genome Browser at UCSC.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/VBALMCUS/996.html:text/html}
}

@article{yang_likelihood_1998,
	title = {Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution},
	volume = {15},
	issn = {0737-4038},
	doi = {10.1093/oxfordjournals.molbev.a025957},
	abstract = {An excess of nonsynonymous substitutions over synonymous ones is an important indicator of positive selection at the molecular level. A lineage that underwent Darwinian selection may have a nonsynonymous/synonymous rate ratio ({dN}/{dS}) that is different from those of other lineages or greater than one. In this paper, several codon-based likelihood models that allow for variable {dN}/{dS} ratios among lineages were developed. They were then used to construct likelihood ratio tests to examine whether the {dN}/{dS} ratio is variable among evolutionary lineages, whether the ratio for a few lineages of interest is different from the background ratio for other lineages in the phylogeny, and whether the {dN}/{dS} ratio for the lineages of interest is greater than one. The tests were applied to the lysozyme genes of 24 primate species. The {dN}/{dS} ratios were found to differ significantly among lineages, indicating that the evolution of primate lysozymes is episodic, which is incompatible with the neutral theory. Maximum-likelihood estimates of parameters suggested that about nine nonsynonymous and zero synonymous nucleotide substitutions occurred in the lineage leading to hominoids, and the {dN}/{dS} ratio for that lineage is significantly greater than one. The corresponding estimates for the lineage ancestral to colobine monkeys were nine and one, and the {dN}/{dS} ratio for the lineage is not significantly greater than one, although it is significantly higher than the background ratio. The likelihood analysis thus confirmed most, but not all, conclusions Messier and Stewart reached using reconstructed ancestral sequences to estimate synonymous and nonsynonymous rates for different lineages.},
	pages = {568--573},
	number = {5},
	journaltitle = {Molecular Biology and Evolution},
	shortjournal = {Mol. Biol. Evol.},
	author = {Yang, Z.},
	date = {1998-05},
	pmid = {9580986},
	keywords = {Animals, Genetic Variation, Likelihood Functions, Primates, Evolution, Molecular, Selection, Genetic, Models, Biological, Muramidase},
	file = {Full Text:/home/jlagarde/Zotero/storage/4IIH9KXZ/Yang - 1998 - Likelihood ratio tests for detecting positive sele.pdf:application/pdf}
}

@article{kelley_transposable_2012,
	title = {Transposable elements reveal a stem cell-specific class of long noncoding {RNAs}},
	volume = {13},
	issn = {1474-760X},
	doi = {10.1186/gb-2012-13-11-r107},
	abstract = {{BACKGROUND}: Numerous studies over the past decade have elucidated a large set of long intergenic noncoding {RNAs} ({lincRNAs}) in the human genome. Research since has shown that {lincRNAs} constitute an important layer of genome regulation across a wide spectrum of species. However, the factors governing their evolution and origins remain relatively unexplored. One possible factor driving {lincRNA} evolution and biological function is transposable element ({TE}) insertions. Here, we comprehensively characterize the {TE} content of {lincRNAs} relative to genomic averages and protein coding transcripts.
{RESULTS}: Our analysis of the {TE} composition of 9,241 human {lincRNAs} revealed that, in sharp contrast to protein coding genes, 83\% of {lincRNAs} contain a {TE}, and {TEs} comprise 42\% of {lincRNA} sequence. {lincRNA} {TE} composition varies significantly from genomic averages - L1 and Alu elements are depleted and broad classes of endogenous retroviruses are enriched. {TEs} occur in biased positions and orientations within {lincRNAs}, particularly at their transcription start sites, suggesting a role in {lincRNA} transcriptional regulation. Accordingly, we observed a dramatic example of {HERVH} transcriptional regulatory signals correlating strongly with stem cell-specific expression of {lincRNAs}. Conversely, {lincRNAs} devoid of {TEs} are expressed at greater levels than {lincRNAs} with {TEs} in all tissues and cell lines, particularly in the testis.
{CONCLUSIONS}: {TEs} pervade {lincRNAs}, dividing them into classes, and may have shaped {lincRNA} evolution and function by conferring tissue-specific expression from extant transcriptional regulatory signals.},
	pages = {R107},
	number = {11},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol.},
	author = {Kelley, David and Rinn, John},
	date = {2012-11-26},
	pmid = {23181609},
	pmcid = {PMC3580499},
	keywords = {Humans, Gene Expression Regulation, Organ Specificity, Stem Cells, {RNA}, Long Noncoding, Genome, Human, Endogenous Retroviruses, Retroelements},
	file = {Full Text:/home/jlagarde/Zotero/storage/9W6UZZFX/Kelley and Rinn - 2012 - Transposable elements reveal a stem cell-specific .pdf:application/pdf}
}

@article{seiler_lncrna_2017,
	title = {The {lncRNA} {VELUCT} strongly regulates viability of lung cancer cells despite its extremely low abundance},
	volume = {45},
	issn = {1362-4962},
	doi = {10.1093/nar/gkx076},
	abstract = {Little is known about the function of most non-coding {RNAs} ({ncRNAs}). The majority of long {ncRNAs} ({lncRNAs}) is expressed at very low levels and it is a matter of intense debate whether these can be of functional relevance. Here, we identified {lncRNAs} regulating the viability of lung cancer cells in a high-throughput {RNA} interference screen. Based on our previous expression profiling, we designed an {siRNA} library targeting 638 {lncRNAs} upregulated in human cancer. In a functional {siRNA} screen analyzing the viability of lung cancer cells, the most prominent hit was a novel {lncRNA} which we called Viability Enhancing {LUng} Cancer Transcript ({VELUCT}). In silico analyses confirmed the non-coding properties of the transcript. Surprisingly, {VELUCT} was below the detection limit in total {RNA} from {NCI}-H460 cells by {RT}-{qPCR} as well as {RNA}-Seq, but was robustly detected in the chromatin-associated {RNA} fraction. It is an extremely low abundant {lncRNA} with an {RNA} copy number of less than one copy per cell. Blocking transcription with actinomycin D revealed that {VELUCT} {RNA} was highly unstable which may partially explain its low steady-state concentration. Despite its extremely low abundance, loss-of-function of {VELUCT} with three independent experimental approaches in three different lung cancer cell lines led to a significant reduction of cell viability: Next to four individual {siRNAs}, also two complex {siPOOLs} as well as two antisense oligonucleotides confirmed the strong and specific phenotype. In summary, the extremely low abundant {lncRNA} {VELUCT} is essential for regulation of cell viability in several lung cancer cell lines. Hence, {VELUCT} is the first example for a {lncRNA} that is expressed at a very low level, but has a strong loss-of-function phenotype. Thus, our study proves that at least individual low-abundant {lncRNAs} can play an important functional role.},
	pages = {5458--5469},
	number = {9},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Res.},
	author = {Seiler, Jana and Breinig, Marco and Caudron-Herger, Maïwen and Polycarpou-Schwarz, Maria and Boutros, Michael and Diederichs, Sven},
	date = {2017-05-19},
	pmid = {28160600},
	pmcid = {PMC5435915},
	keywords = {Humans, Cell Proliferation, Cell Survival, Chromatin, Gene Knockdown Techniques, Gene Silencing, Lung Neoplasms, {RNA} Stability, {RNA}, Long Noncoding, {RNA}, Messenger, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, {RNA}, Small Interfering},
	file = {Full Text:/home/jlagarde/Zotero/storage/RAUWKSHP/Seiler et al. - 2017 - The lncRNA VELUCT strongly regulates viability of .pdf:application/pdf}
}

@article{cong_multiplex_2013,
	title = {Multiplex genome engineering using {CRISPR}/Cas systems},
	volume = {339},
	issn = {1095-9203},
	doi = {10.1126/science.1231143},
	abstract = {Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type {II} prokaryotic {CRISPR} (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate {RNA}-guided site-specific {DNA} cleavage. We engineered two different type {II} {CRISPR}/Cas systems and demonstrate that Cas9 nucleases can be directed by short {RNAs} to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single {CRISPR} array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the {RNA}-guided nuclease technology.},
	pages = {819--823},
	number = {6121},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Cong, Le and Ran, F. Ann and Cox, David and Lin, Shuailiang and Barretto, Robert and Habib, Naomi and Hsu, Patrick D. and Wu, Xuebing and Jiang, Wenyan and Marraffini, Luciano A. and Zhang, Feng},
	date = {2013-02-15},
	pmid = {23287718},
	pmcid = {PMC3795411},
	keywords = {{DNA}, Animals, Base Sequence, Genome, Humans, Mice, {RNA}, Genetic Loci, Microarray Analysis, Molecular Sequence Data, Mutagenesis, {CRISPR}-Cas Systems, {DNA} Cleavage, Genetic Engineering, Inverted Repeat Sequences, Recombinational {DNA} Repair, Streptococcus pyogenes},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/VS38VNQS/Cong et al. - 2013 - Multiplex genome engineering using CRISPRCas syst.pdf:application/pdf}
}

@article{mali_rna-guided_2013,
	title = {{RNA}-guided human genome engineering via Cas9},
	volume = {339},
	issn = {1095-9203},
	doi = {10.1126/science.1232033},
	abstract = {Bacteria and archaea have evolved adaptive immune defenses, termed clustered regularly interspaced short palindromic repeats ({CRISPR})/{CRISPR}-associated (Cas) systems, that use short {RNA} to direct degradation of foreign nucleic acids. Here, we engineer the type {II} bacterial {CRISPR} system to function with custom guide {RNA} ({gRNA}) in human cells. For the endogenous {AAVS}1 locus, we obtained targeting rates of 10 to 25\% in 293T cells, 13 to 8\% in K562 cells, and 2 to 4\% in induced pluripotent stem cells. We show that this process relies on {CRISPR} components; is sequence-specific; and, upon simultaneous introduction of multiple {gRNAs}, can effect multiplex editing of target loci. We also compute a genome-wide resource of {\textasciitilde}190 K unique {gRNAs} targeting {\textasciitilde}40.5\% of human exons. Our results establish an {RNA}-guided editing tool for facile, robust, and multiplexable human genome engineering.},
	pages = {823--826},
	number = {6121},
	journaltitle = {Science (New York, N.Y.)},
	shortjournal = {Science},
	author = {Mali, Prashant and Yang, Luhan and Esvelt, Kevin M. and Aach, John and Guell, Marc and {DiCarlo}, James E. and Norville, Julie E. and Church, George M.},
	date = {2013-02-15},
	pmid = {23287722},
	pmcid = {PMC3712628},
	keywords = {Humans, {RNA}, Exons, Codon, Gene Targeting, Genetic Loci, K562 Cells, Genome, Human, Induced Pluripotent Stem Cells, Chromosomes, Human, Pair 19, Clustered Regularly Interspaced Short Palindromic Repeats, {DNA} Cleavage, Genetic Engineering, Inverted Repeat Sequences},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/42N4LCPX/Mali et al. - 2013 - RNA-guided human genome engineering via Cas9.pdf:application/pdf}
}

@article{mohr_rnai_2014,
	title = {{RNAi} screening comes of age: improved techniques and complementary approaches},
	volume = {15},
	issn = {1471-0080},
	doi = {10.1038/nrm3860},
	shorttitle = {{RNAi} screening comes of age},
	abstract = {Gene silencing through sequence-specific targeting of {mRNAs} by {RNAi} has enabled genome-wide functional screens in cultured cells and in vivo in model organisms. These screens have resulted in the identification of new cellular pathways and potential drug targets. Considerable progress has been made to improve the quality of {RNAi} screen data through the development of new experimental and bioinformatics approaches. The recent availability of genome-editing strategies, such as the {CRISPR} (clustered regularly interspaced short palindromic repeats)-Cas9 system, when combined with {RNAi}, could lead to further improvements in screen data quality and follow-up experiments, thus promoting our understanding of gene function and gene regulatory networks.},
	pages = {591--600},
	number = {9},
	journaltitle = {Nature Reviews. Molecular Cell Biology},
	shortjournal = {Nat. Rev. Mol. Cell Biol.},
	author = {Mohr, Stephanie E. and Smith, Jennifer A. and Shamu, Caroline E. and Neumüller, Ralph A. and Perrimon, Norbert},
	date = {2014-09},
	pmid = {25145850},
	pmcid = {PMC4204798},
	keywords = {Animals, Humans, Gene Regulatory Networks, {RNA} Interference, Genetic Testing, {RNA}, Small Interfering, Inverted Repeat Sequences},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/SEGBXYI6/Mohr et al. - 2014 - RNAi screening comes of age improved techniques a.pdf:application/pdf}
}

@article{lagarde_capturing_2018,
	title = {Capturing a Long Look at Our Genetic Library},
	volume = {6},
	issn = {2405-4712},
	doi = {10.1016/j.cels.2018.02.003},
	abstract = {Long-read sequencing, coupled to {cDNA} capture, provides an unrivaled view of the transcriptome of chromosome 21, revealing surprises about the splicing of long noncoding {RNAs}.},
	pages = {153--155},
	number = {2},
	journaltitle = {Cell Systems},
	shortjournal = {Cell Syst},
	author = {Lagarde, Julien and Johnson, Rory},
	date = {2018},
	pmid = {29494803},
	keywords = {Exons, Alternative Splicing, Gene Library, High-Throughput Nucleotide Sequencing, Sequence Analysis, {RNA}}
}

@article{hirabayashi_net-cage_2019,
	title = {{NET}-{CAGE} characterizes the dynamics and topology of human transcribed cis-regulatory elements},
	volume = {51},
	issn = {1546-1718},
	doi = {10.1038/s41588-019-0485-9},
	abstract = {Promoters and enhancers are key cis-regulatory elements, but how they operate to generate cell type-specific transcriptomes is not fully understood. We developed a simple and robust method, native elongating transcript-cap analysis of gene expression ({NET}-{CAGE}), to sensitively detect 5' ends of nascent {RNAs} in diverse cells and tissues, including unstable transcripts such as enhancer-derived {RNAs}. We studied {RNA} synthesis and degradation at the transcription start site level, characterizing the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without the influence of {RNA} turnover, and show that enhancer-promoter pairs are generally activated simultaneously on stimulation. By integrating {NET}-{CAGE} data with chromatin interaction maps, we show that cis-regulatory elements are topologically connected according to their cell type specificity. We identified new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our {NET}-{CAGE} dataset derived from human and mouse cells expands the {FANTOM}5 atlas of transcribed enhancers, with broad applicability to biomedical research.},
	pages = {1369--1379},
	number = {9},
	journaltitle = {Nature Genetics},
	shortjournal = {Nat. Genet.},
	author = {Hirabayashi, Shigeki and Bhagat, Shruti and Matsuki, Yu and Takegami, Yujiro and Uehata, Takuya and Kanemaru, Ai and Itoh, Masayoshi and Shirakawa, Kotaro and Takaori-Kondo, Akifumi and Takeuchi, Osamu and Carninci, Piero and Katayama, Shintaro and Hayashizaki, Yoshihide and Kere, Juha and Kawaji, Hideya and Murakawa, Yasuhiro},
	date = {2019-09},
	pmid = {31477927}
}

@article{brummer_lincrna_2019,
	title = {{LincRNA} sequences are biased to counteract their translation},
	rights = {© 2019, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
	url = {https://www.biorxiv.org/content/10.1101/737890v1},
	doi = {10.1101/737890},
	abstract = {{\textless}p{\textgreater}Long intergenic non-coding {RNAs} ({lincRNAs}) account for a large fraction of transcribed loci in the human genome. While many {lincRNAs} are retained in the cell nucleus, preventing their association with ribosomes, binding of cytosolic {lincRNAs} to ribosomes has been observed, but rarely results in translation. This raises the question of how translation of short open reading frames ({ORFs}) within cytosolic {lincRNAs} is hindered. Here, we investigate the content of nucleotide triplets in {lincRNA} putative {ORFs} (i.e. 9codons9) and its potential impact on ribosome binding and translation. We find that {lincRNA} and {mRNA} {ORFs} have distinct codon frequencies, that are well conserved between human and mouse. In {lincRNAs}, codon frequencies are less correlated with the corresponding {tRNA} abundance measures than in {mRNAs}. This correlation is weaker for cytoplasmic {lincRNAs} and lowest for those without experimental evidence for ribosome binding. Our results suggest that putative {lincRNA} codons are a substrate of evolutionary forces modulating them to counteract unwanted ribosomal binding and translation. The resulting sequence signatures may help in distinguishing bona-fide {lincRNAs} with regulatory roles in the cytoplasm from transcripts coding for peptides.{\textless}/p{\textgreater}},
	pages = {737890},
	journaltitle = {{bioRxiv}},
	author = {Brümmer, Anneke and Dreos, Rene and Marques, Ana Claudia and Bergmann, Sven},
	urldate = {2019-09-10},
	date = {2019-08-16},
	langid = {english},
	file = {Full Text PDF:/home/jlagarde/Zotero/storage/HESECEG6/Brümmer et al. - 2019 - LincRNA sequences are biased to counteract their t.pdf:application/pdf;Snapshot:/home/jlagarde/Zotero/storage/BPT4X3Y9/737890v1.html:text/html}
}

@article{ku_genomewide_2008,
	title = {Genomewide analysis of {PRC}1 and {PRC}2 occupancy identifies two classes of bivalent domains},
	volume = {4},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1000242},
	abstract = {In embryonic stem ({ES}) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 ({PRC}1 and {PRC}2) genomewide in human and mouse {ES} cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes -- the first occupied by both {PRC}2 and {PRC}1 ({PRC}1-positive) and the second specifically bound by {PRC}2 ({PRC}2-only). {PRC}1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of {PRC}2 and {PRC}1 can be largely predicted from the locations, sizes, and underlying motif contents of {CpG} islands. We propose that large {CpG} islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells.},
	pages = {e1000242},
	number = {10},
	journaltitle = {{PLoS} genetics},
	shortjournal = {{PLoS} Genet.},
	author = {Ku, Manching and Koche, Richard P. and Rheinbay, Esther and Mendenhall, Eric M. and Endoh, Mitsuhiro and Mikkelsen, Tarjei S. and Presser, Aviva and Nusbaum, Chad and Xie, Xiaohui and Chi, Andrew S. and Adli, Mazhar and Kasif, Simon and Ptaszek, Leon M. and Cowan, Chad A. and Lander, Eric S. and Koseki, Haruhiko and Bernstein, Bradley E.},
	date = {2008-10},
	pmid = {18974828},
	pmcid = {PMC2567431},
	keywords = {Animals, Genome, Humans, Mice, Computational Biology, Chromatin, Chromatin Immunoprecipitation, Chromosome Mapping, {CpG} Islands, Embryonic Stem Cells, Histones, Methylation, Polycomb-Group Proteins, Repressor Proteins, Promoter Regions, Genetic, Genome, Human, Protein Structure, Tertiary, Pluripotent Stem Cells, Epigenesis, Genetic, Jumonji Domain-Containing Histone Demethylases, Oxidoreductases, N-Demethylating},
	file = {Full Text:/home/jlagarde/Zotero/storage/BMJ8U37P/Ku et al. - 2008 - Genomewide analysis of PRC1 and PRC2 occupancy ide.pdf:application/pdf}
}

@article{cao_functions_2004,
	title = {The functions of E(Z)/{EZH}2-mediated methylation of lysine 27 in histone H3},
	volume = {14},
	issn = {0959-437X},
	doi = {10.1016/j.gde.2004.02.001},
	abstract = {Polycomb group ({PcG}) proteins are important for maintaining the silenced state of homeotic genes. Biochemical and genetic studies in Drosophila and mammalian cells indicate that {PcG} proteins function in at least two distinct protein complexes: the {ESC}-E(Z) or {EED}-{EZH}2 complex, and the {PRC}1 complex. Recent work has shown that at least part of the silencing function of the {ESC}-E(Z) complex is mediated by its intrinsic activity for methylating histone H3 on lysine 27. In addition to being involved in Hox gene silencing, the complex and its associated histone methyltransferase activity are important in other biological processes including X-inactivation, germline development, stem cell pluripotency and cancer metastasis.},
	pages = {155--164},
	number = {2},
	journaltitle = {Current Opinion in Genetics \& Development},
	shortjournal = {Curr. Opin. Genet. Dev.},
	author = {Cao, Ru and Zhang, Yi},
	date = {2004-04},
	pmid = {15196462},
	keywords = {Animals, Gene Expression Regulation, Drosophila, Gene Silencing, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Methylation, Polycomb Repressive Complex 2, Nuclear Proteins, Repressor Proteins, Drosophila Proteins, Dosage Compensation, Genetic, Lysine, Polycomb Repressive Complex 1}
}

@article{phillips_ctcf:_2009,
	title = {{CTCF}: master weaver of the genome},
	volume = {137},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2009.06.001},
	shorttitle = {{CTCF}},
	abstract = {{CTCF} is a highly conserved zinc finger protein implicated in diverse regulatory functions, including transcriptional activation/repression, insulation, imprinting, and X chromosome inactivation. Here we re-evaluate data supporting these roles in the context of mechanistic insights provided by recent genome-wide studies and highlight evidence for {CTCF}-mediated intra- and interchromosomal contacts at several developmentally regulated genomic loci. These analyses support a primary role for {CTCF} in the global organization of chromatin architecture and suggest that {CTCF} may be a heritable component of an epigenetic system regulating the interplay between {DNA} methylation, higher-order chromatin structure, and lineage-specific gene expression.},
	pages = {1194--1211},
	number = {7},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Phillips, Jennifer E. and Corces, Victor G.},
	date = {2009-06-26},
	pmid = {19563753},
	pmcid = {PMC3040116},
	keywords = {Animals, Genome, Humans, Gene Expression Regulation, Chromatin, Repressor Proteins, {CCCTC}-Binding Factor},
	file = {Accepted Version:/home/jlagarde/Zotero/storage/T64YWKY7/Phillips and Corces - 2009 - CTCF master weaver of the genome.pdf:application/pdf}
}

@article{zhang_interplay_2015,
	title = {The interplay of histone modifications – writers that read},
	volume = {16},
	issn = {1469-221X},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641500/},
	doi = {10.15252/embr.201540945},
	abstract = {Histones are subject to a vast array of posttranslational modifications including acetylation, methylation, phosphorylation, and ubiquitylation. The writers of these modifications play important roles in normal development and their mutation or misregulation is linked with both genetic disorders and various cancers. Readers of these marks contain protein domains that allow their recruitment to chromatin. Interestingly, writers often contain domains which can read chromatin marks, allowing the reinforcement of modifications through a positive feedback loop or inhibition of their activity by other modifications. We discuss how such positive reinforcement can result in chromatin states that are robust and can be epigenetically maintained through cell division. We describe the implications of these regulatory systems in relation to modifications including H3K4me3, H3K79me3, and H3K36me3 that are associated with active genes and H3K27me3 and H3K9me3 that have been linked to transcriptional repression. We also review the crosstalk between active and repressive modifications, illustrated by the interplay between the Polycomb and Trithorax histone-modifying proteins, and discuss how this may be important in defining gene expression states during development.},
	pages = {1467--1481},
	number = {11},
	journaltitle = {{EMBO} Reports},
	shortjournal = {{EMBO} Rep},
	author = {Zhang, Tianyi and Cooper, Sarah and Brockdorff, Neil},
	urldate = {2019-09-10},
	date = {2015-11},
	pmid = {26474904},
	pmcid = {PMC4641500},
	file = {PubMed Central Full Text PDF:/home/jlagarde/Zotero/storage/RSJRK2ZQ/Zhang et al. - 2015 - The interplay of histone modifications – writers t.pdf:application/pdf}
}

@article{schmitges_histone_2011,
	title = {Histone methylation by {PRC}2 is inhibited by active chromatin marks},
	volume = {42},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2011.03.025},
	abstract = {The Polycomb repressive complex 2 ({PRC}2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how {PRC}2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the {PRC}2 Nurf55-Su(z)12 submodule. Binding of H3 is lost if lysine 4 in H3 is trimethylated. We find that H3K4me3 inhibits {PRC}2 activity in an allosteric fashion assisted by the Su(z)12 C terminus. In addition to H3K4me3, {PRC}2 is inhibited by H3K36me2/3 (i.e., both H3K36me2 and H3K36me3). Direct {PRC}2 inhibition by H3K4me3 and H3K36me2/3 active marks is conserved in humans, mouse, and fly, rendering transcriptionally active chromatin refractory to {PRC}2 H3K27 trimethylation. While inhibition is present in plant {PRC}2, it can be modulated through exchange of the Su(z)12 subunit. Inhibition by active chromatin marks, coupled to stimulation by transcriptionally repressive H3K27me3, enables {PRC}2 to autonomously template repressive H3K27me3 without overwriting active chromatin domains.},
	pages = {330--341},
	number = {3},
	journaltitle = {Molecular Cell},
	shortjournal = {Mol. Cell},
	author = {Schmitges, Frank W. and Prusty, Archana B. and Faty, Mahamadou and Stützer, Alexandra and Lingaraju, Gondichatnahalli M. and Aiwazian, Jonathan and Sack, Ragna and Hess, Daniel and Li, Ling and Zhou, Shaolian and Bunker, Richard D. and Wirth, Urs and Bouwmeester, Tewis and Bauer, Andreas and Ly-Hartig, Nga and Zhao, Kehao and Chan, Homan and Gu, Justin and Gut, Heinz and Fischle, Wolfgang and Müller, Jürg and Thomä, Nicolas H.},
	date = {2011-05-06},
	pmid = {21549310},
	keywords = {Animals, Humans, Mice, Protein Binding, Amino Acid Sequence, Cell Line, Chromatin, Drosophila, Histone-Lysine N-Methyltransferase, Histones, Methylation, Molecular Sequence Data, Mutation, Polycomb Repressive Complex 2, Polycomb-Group Proteins, Repressor Proteins, Transcription, Genetic, Protein Structure, Tertiary, Models, Molecular, Drosophila Proteins, Lysine, Blotting, Western, Crystallography, X-Ray, Retinoblastoma-Binding Protein 4},
	file = {Submitted Version:/home/jlagarde/Zotero/storage/WFZSDQUS/Schmitges et al. - 2011 - Histone methylation by PRC2 is inhibited by active.pdf:application/pdf}
}

@article{yang_genomewide_2011,
	title = {Genomewide characterization of non-polyadenylated {RNAs}},
	volume = {12},
	issn = {1474-760X},
	doi = {10.1186/gb-2011-12-2-r16},
	abstract = {{BACKGROUND}: {RNAs} can be physically classified into poly(A)+ or poly(A)- transcripts according to the presence or absence of a poly(A) tail at their 3' ends. Current deep sequencing approaches largely depend on the enrichment of transcripts with a poly(A) tail, and therefore offer little insight into the nature and expression of transcripts that lack poly(A) tails.
{RESULTS}: We have used deep sequencing to explore the repertoire of both poly(A)+ and poly(A)- {RNAs} from {HeLa} cells and H9 human embryonic stem cells ({hESCs}). Using stringent criteria, we found that while the majority of transcripts are poly(A)+, a significant portion of transcripts are either poly(A)- or bimorphic, being found in both the poly(A)+ and poly(A)- populations. Further analyses revealed that many {mRNAs} may not contain classical long poly(A) tails and such messages are overrepresented in specific functional categories. In addition, we surprisingly found that a few excised introns accumulate in cells and thus constitute a new class of non-polyadenylated long non-coding {RNAs}. Finally, we have identified a specific subset of poly(A)- histone {mRNAs}, including two histone H1 variants, that are expressed in undifferentiated {hESCs} and are rapidly diminished upon differentiation; further, these same histone genes are induced upon reprogramming of fibroblasts to induced pluripotent stem cells.
{CONCLUSIONS}: We offer a rich source of data that allows a deeper exploration of the poly(A)- landscape of the eukaryotic transcriptome. The approach we present here also applies to the analysis of the poly(A)- transcriptomes of other organisms.},
	pages = {R16},
	number = {2},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biol.},
	author = {Yang, Li and Duff, Michael O. and Graveley, Brenton R. and Carmichael, Gordon G. and Chen, Ling-Ling},
	date = {2011},
	pmid = {21324177},
	pmcid = {PMC3188798},
	keywords = {Transcriptome, Animals, Genome, Humans, {RNA}, Gene Expression Regulation, Computational Biology, Introns, Cell Differentiation, Embryonic Stem Cells, {HeLa} Cells, High-Throughput Nucleotide Sequencing, Histones, Poly A, Protein Isoforms, Eukaryota},
	file = {Full Text:/home/jlagarde/Zotero/storage/GTQ4KI6D/Yang et al. - 2011 - Genomewide characterization of non-polyadenylated .pdf:application/pdf}
}

@article{sarropoulos_developmental_2019,
	title = {Developmental dynamics of {lncRNAs} across mammalian organs and species},
	volume = {571},
	issn = {1476-4687},
	doi = {10.1038/s41586-019-1341-x},
	abstract = {Although many long noncoding {RNAs} ({lncRNAs}) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. In particular, the contribution of {lncRNAs} to organ development remains largely unexplored. Here we analyse the expression patterns of {lncRNAs} across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chicken). Our analyses identified approximately 15,000 to 35,000 candidate {lncRNAs} in each species, most of which show species specificity. We characterized the expression patterns of {lncRNAs} across developmental stages, and found many with dynamic expression patterns across time that show signatures of enrichment for functionality. During development, there is a transition from broadly expressed and conserved {lncRNAs} towards an increasing number of lineage- and organ-specific {lncRNAs}. Our study provides a resource of candidate {lncRNAs} and their patterns of expression and evolutionary conservation across mammalian organ development.},
	pages = {510--514},
	number = {7766},
	journaltitle = {Nature},
	shortjournal = {Nature},
	author = {Sarropoulos, Ioannis and Marin, Ray and Cardoso-Moreira, Margarida and Kaessmann, Henrik},
	date = {2019},
	pmid = {31243368},
	pmcid = {PMC6660317}
}