An atlas of human long non-coding RNAs with accurate 5′ ends

Abstract

Long non-coding RNAs (lncRNAs) are largely heterogeneous and functionally uncharacterized. Here, using FANTOM5 cap analysis of gene expression (CAGE) data, we integrate multiple transcript collections to generate a comprehensive atlas of 27,919 human lncRNA genes with high-confidence 5' ends and expression profiles across 1,829 samples from the major human primary cell types and tissues. Genomic and epigenomic classification of these lncRNAs reveals that most intergenic lncRNAs originate from enhancers rather than from promoters. Incorporating genetic and expression data, we show that lncRNAs overlapping trait-associated single nucleotide polymorphisms are specifically expressed in cell types relevant to the traits, implicating these lncRNAs in multiple diseases. We further demonstrate that lncRNAs overlapping expression quantitative trait loci (eQTL)-associated single nucleotide polymorphisms of messenger RNAs are co-expressed with the corresponding messenger RNAs, suggesting their potential roles in transcriptional regulation. Combining these findings with conservation data, we identify 19,175 potentially functional lncRNAs in the human genome.

The functions and unique features of long intergenic non-coding RNA

“…The fraction of identical bases between lncRNAs that are mapped to different genomic regions is lower than that between orthologous coding gene pairs, greater than random genomic regions and similar to syntenic blocks 28 . Greater conservation at lincRNA promoters than at their downstream regions 44 suggests selective pressure for enhancer-like functions 7,27,45 , which has indeed been predicted for a substantial subset of lincRNAs 46 , termed e-lincRNAs (TABLE 1). …”

JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states

“…Each CAGE library was sequenced at least 15 million reads. The expression levels of genes were calculated based on the annotations from FANTOM CAT [66] as described [21]. Briefly, the numbers of CAGE read 5' ends (CAGE TSS) falling within the ±50 nt region of the prominent TSS of all CAGE clusters in FANTOM CAT were counted in all samples.…”

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

“…Until recently, serious efforts have been made to gather human lncRNA transcript models with accurate 5 ′ ends by integration of various CAGE-seq data (Hon et al 2017). In order to identify the more accurate transcription start sites (TSSs), we used a modified CAGE-seq technology to analyze lncRNAs identified by RNA sequencing assembly in macaque brains (Fig.…”