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

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, researchers from Harvard University performed an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. They found 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, they found 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, the researchers found 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.

Summary of the similarities and differences between the lincRNA and mRNA life cycles

 lncrna

(A,B) LincRNAs have fewer histone marks (A) and transcription factors (B) bound in their promoter than mRNAs. (C) U1 motif profiles are similar in lincRNAs and mRNAs. (D) Splicing efficiency is lower in lincRNAs than in mRNAs and lincRNAs are depleted for U2AF65-binding. (E) LincRNA and mRNA stability is similar when comparing expression-matched groups. HuR binds equally to both classes but is biased toward 3′ UTR localization in mRNAs alone.

Melé M, Mattioli K, Mallard W, Shechner DM, Gerhardinger C, Rinn JL. (2016) Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs. Genome Res [Epub ahead of print]. [article]

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