title: The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
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.
authors.affiliation: Bioinformatics and Genomics, Centre for Genomic Regulation and UPF, 08003 Barcelona, Catalonia, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Derrien
authors.forename: Rory
authors.initials: R
authors.lastname: Johnson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Tanzer
authors.forename: Sarah
authors.initials: S
authors.lastname: Djebali
authors.forename: Hagen
authors.initials: H
authors.lastname: Tilgner
authors.forename: Gregory
authors.initials: G
authors.lastname: Guernec
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Angelika
authors.initials: A
authors.lastname: Merkel
authors.forename: David G
authors.initials: DG
authors.lastname: Knowles
authors.forename: Julien
authors.initials: J
authors.lastname: Lagarde
authors.forename: Lavanya
authors.initials: L
authors.lastname: Veeravalli
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: James B
authors.initials: JB
authors.lastname: Brown
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gonzalez
authors.forename: Mark
authors.initials: M
authors.lastname: Thomas
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Davis
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Hubbard
authors.forename: Cedric
authors.initials: C
authors.lastname: Notredame
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D058977:Molecular Sequence Annotation; D016366:Open Reading Frames; D009928:Organ Specificity / Q000235:genetics; D011323:Primates / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D022821:RNA Splice Sites; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012641:Selection, Genetic; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D022821:RNA Splice Sites; D062085:RNA, Long Noncoding; D012333:RNA, Messenger