The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression
- Thomas Derrien1,11,
- Rory Johnson1,11,
- Giovanni Bussotti1,
- Andrea Tanzer1,
- Sarah Djebali1,
- Hagen Tilgner1,
- Gregory Guernec2,
- David Martin1,
- Angelika Merkel1,
- David G. Knowles1,
- Julien Lagarde1,
- Lavanya Veeravalli3,
- Xiaoan Ruan3,
- Yijun Ruan3,
- Timo Lassmann4,
- Piero Carninci4,
- James B. Brown5,
- Leonard Lipovich6,
- Jose M. Gonzalez7,
- Mark Thomas7,
- Carrie A. Davis8,
- Ramin Shiekhattar9,
- Thomas R. Gingeras8,
- Tim J. Hubbard7,
- Cedric Notredame1,
- Jennifer Harrow7 and
- Roderic Guigó1,10,12
- 1Bioinformatics and Genomics, Centre for Genomic Regulation (CRG) and UPF, 08003 Barcelona, Catalonia, Spain;
- 2INRA, UR1012 SCRIBE, IFR140, GenOuest, 35000 Rennes, France;
- 3Genome Institute of Singapore, Agency for Science, Technology and Research, Genome 138672, Singapore;
- 4Riken Omics Science Center, Riken Yokohama Institute, Yokohama, Kanagawa 351-0198, Japan;
- 5Department of Statistics, University of California, Berkeley, California 94720, USA;
- 6Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA;
- 7Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, United Kingdom;
- 8Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
- 9The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
- 10Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08002 Barcelona, Catalonia, Spain
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↵11 These authors contributed equally to this work.
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.
Footnotes
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↵12 Corresponding author
E-mail roderic.guigo{at}crg.cat
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[Supplemental material is available for this article.]
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Article and supplemental material are at http://www.genome.org/cgi/doi/10.1101/gr.132159.111.
Freely available online through the Genome Research Open Access option.
- Received September 17, 2011.
- Accepted March 7, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
