HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis

Cell Death Differ. 2011 Nov;18(11):1692-701. doi: 10.1038/cdd.2011.35. Epub 2011 Apr 29.

Abstract

Of critical importance in the stress response is the post-transcriptional control of the expression of important genes involved in the control of cell survival and apoptosis. Here we report that miR-19, an oncogenic component of the miR-17-92/Oncomir-1 microRNA polycistron, regulates the expression of Ras homolog B (RhoB) in keratinocytes upon exposure to ultraviolet (UV) radiation. Strikingly, we could not find any evidence for deregulated expression of miR-19 during UV treatment. However, we show that miR-19-mediated regulation of antiapoptotic RhoB expression requires the binding of human antigen R (HuR), an AU-rich element binding protein, to the 3'-untranslated region of the rhoB mRNA. We propose that the loss of the interdependent binding between HuR and miR-19 to the rhoB mRNA upon UV exposure relieves this mRNA from miR-19-dependent inhibition of translation and contributes to the apoptotic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / radiation effects*
  • Binding Sites
  • Cell Line
  • ELAV Proteins / antagonists & inhibitors
  • ELAV Proteins / genetics
  • ELAV Proteins / metabolism*
  • Humans
  • Luciferases, Firefly / genetics
  • Luciferases, Firefly / metabolism
  • MicroRNAs / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / metabolism
  • Ultraviolet Rays*
  • rhoB GTP-Binding Protein / genetics
  • rhoB GTP-Binding Protein / metabolism*

Substances

  • 3' Untranslated Regions
  • ELAV Proteins
  • MIRN19 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • Luciferases, Firefly
  • rhoB GTP-Binding Protein