RT Journal A1 Derrien, Thomas A1 Johnson, Rory A1 Bussotti, Giovanni A1 Tanzer, Andrea A1 Djebali, Sarah A1 Tilgner, Hagen A1 Guernec, Gregory A1 Martin, David A1 Merkel, Angelika A1 Knowles, David G. A1 Lagarde, Julien A1 Veeravalli, Lavanya A1 Ruan, Xiaoan A1 Ruan, Yijun A1 Lassmann, Timo A1 Carninci, Piero A1 Brown, James B. A1 Lipovich, Leonard A1 Gonzalez, Jose M. A1 Thomas, Mark A1 Davis, Carrie A. A1 Shiekhattar, Ramin A1 Gingeras, Thomas R. A1 Hubbard, Tim J. A1 Notredame, Cedric A1 Harrow, Jennifer A1 Guigó, Roderic T1 The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression JF Genome Research JO Genome Research YR 2012 FD September 01 VO 22 IS 9 SP 1775 OP 1789 DO 10.1101/gr.132159.111 UL http://genome.cshlp.org/content/22/9/1775.abstract AB 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.