Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.

Genome Res
Authors
Abstract

While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre- and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3-a histone modification typically associated with transcriptional repression-is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers but may be partially attributed to lower U2AF65 binding and weaker splicing-related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs and are enriched in lincRNAs that have been functionally characterized.

Year of Publication
2017
Journal
Genome Res
Volume
27
Issue
1
Pages
27-37
Date Published
2017 Jan
ISSN
1549-5469
DOI
10.1101/gr.214205.116
PubMed ID
27927715
PubMed Central ID
PMC5204342
Links
Grant list
P01 GM099117 / GM / NIGMS NIH HHS / United States
R01 ES020260 / ES / NIEHS NIH HHS / United States
R01 MH102416 / MH / NIMH NIH HHS / United States