Decapping of long noncoding RNAs regulates inducible genes

Mol Cell. 2012 Feb 10;45(3):279-91. doi: 10.1016/j.molcel.2011.11.025. Epub 2012 Jan 5.

Abstract

Decapping represents a critical control point in regulating expression of protein coding genes. Here, we demonstrate that decapping also modulates expression of long noncoding RNAs (lncRNAs). Specifically, levels of >100 lncRNAs in yeast are controlled by decapping and are degraded by a pathway that occurs independent of decapping regulators. We find many lncRNAs degraded by DCP2 are expressed proximal to inducible genes. Of these, we show several genes required for galactose utilization are associated with lncRNAs that have expression patterns inversely correlated with their mRNA counterpart. Moreover, decapping of these lncRNAs is critical for rapid and robust induction of GAL gene expression. Failure to destabilize a lncRNA known to exert repressive histone modifications results in perpetuation of a repressive chromatin state that contributes to reduced plasticity of gene activation. We propose that decapping and lncRNA degradation serve a vital role in transcriptional regulation specifically at inducible genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Exoribonucleases / genetics*
  • Exoribonucleases / metabolism
  • Gene Expression Regulation, Fungal*
  • Gene Knockout Techniques
  • Promoter Regions, Genetic
  • RNA Caps / genetics
  • RNA Caps / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Analysis, RNA

Substances

  • RNA Caps
  • RNA, Messenger
  • RNA, Untranslated
  • Saccharomyces cerevisiae Proteins
  • RAT1 protein, S cerevisiae
  • DCP2 protein, S cerevisiae
  • Endoribonucleases
  • Exoribonucleases