Dec 9, 2016

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

Genome Research
Marta MeléJohn L Rinn

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 mRN...Continue Reading

  • References51
  • Citations43

References

Mentioned in this Paper

U2AF2
Biochemical Pathway
Conserved Sequence
Transcriptional Regulation
Post-Transcriptional Regulation
Regulation of Biological Process
3'-splice Site Cleavage, Exon Ligation
Transcription, Genetic
Tissue Specificity
Environment

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