MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

Proc Natl Acad Sci U S A. 2011 May 24;108(21):8686-91. doi: 10.1073/pnas.1014018108. Epub 2011 May 10.

Abstract

General transcription factor IIH (TFIIH) is a complex RNA polymerase II basal transcription factor comprising 10 different polypeptides that display activities involved in transcription and DNA repair processes. Although biochemical studies have uncovered TFIIH importance, little is known about how the mRNAs that code for TFIIH subunits are regulated. Here it is shown that mRNAs encoding seven of the TFIIH subunits (p34, p44, p52, p62, XPB, CDK7, and p8) are regulated at the posttranscriptional level in a Dicer-dependent manner. Indeed, abolition of the miRNA pathway induces abnormal accumulation, stabilization, and translational activation of these seven mRNAs. Herein, miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. This work is unique in providing a demonstration of global transcriptional regulation through the action of a single miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Metabolism*
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • MicroRNAs / physiology*
  • Protein Subunits / genetics
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism
  • Ribonuclease III
  • Transcription Factor TFIIH / genetics*
  • Transcription, Genetic*

Substances

  • MIRN27 microRNA, human
  • MicroRNAs
  • Protein Subunits
  • RNA, Messenger
  • Transcription Factor TFIIH
  • Ribonuclease III