The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression

TLDR

The human genome harbors thousands of lncRNAs, yet comprehensive annotation has been lacking, limiting systematic study of their biological roles. The study presents and analyzes the most complete human lncRNA annotation to date, comprising 9,277 genes and 14,880 transcripts. The annotation was generated by the GENCODE consortium under ENCODE, using manual curation to identify 9,277 genes and 14,880 transcripts. Analyses reveal that lncRNAs share protein‑coding gene features—such as histone marks, splicing signals, and exon/intron lengths—but are biased toward two‑exon, chromatin‑localized transcripts, often processed into small RNAs, exhibit stronger promoter conservation, arose largely in primates, are expressed at lower but more tissue‑specific levels (especially in brain), and positively correlate with antisense coding genes, underscoring the annotation’s value for future studies.

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.