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 tissuespecific 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.

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

“…Athough the promoters of lncRNAs are mostly well conserved (Johnsson et al, 2014, Derrien et al, 2012, Pang et al, 2006, these lncRNA transcripts tend to be less well conserved than other protein-coding transcripts (Guttman et al, 2009, Ponjavic et al, 2007. Nonetheless, they are largely functionally conserved (Johnsson et al, 2014).…”

The Norway spruce genome sequence and conifer genome evolution

“…Recent ENCODE publications 24,25 characterized numerous long non-coding RNA (lncRNA) loci in the human genome, but this class of RNA remains largely uncharacterized in plants. Using short-read de novo transcript assemblies, 13,031 spruce-specific and 9,686 conserved intergenic lncRNAs were identified (Supplementary Information 2.4.3).…”

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

“…Over the past decade, findings from the ENCODE (Encyclopedia of DNA Elements) consortium have revealed that a great number of noncoding transcripts are transcribed from human genome 6. Interestingly, numerous noncoding RNAs including microRNAs, long noncoding RNAs (lncRNAs), and pseudogenes have been discovered after annotation of these noncoding transcripts 7, 8.…”