Dicer is regulated by cellular stresses and interferons

Mol Immunol. 2009 Mar;46(6):1222-8. doi: 10.1016/j.molimm.2008.11.012. Epub 2008 Dec 31.

Abstract

The generation of microRNAs is dependent on the RNase III enzyme Dicer, the levels of which vary in different normal cells and in disease states. We demonstrate that Dicer protein expression in JAR trophoblast cells, and several other cell types, was inhibited by multiple stresses including reactive oxygen species, phorbol esters and the Ras oncogene. Additionally, double-stranded RNA and Type I interferons repress Dicer protein in contrast to IFN-gamma which induces Dicer. The effects of stresses and interferons are primarily post-transcriptional. The findings suggest that Dicer is a stress response component and identifies interferons as potentially important regulators of Dicer expression.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids / pharmacology
  • Interferon Type I / pharmacology
  • Interferon Type I / physiology*
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Mice
  • MicroRNAs / metabolism
  • Phorbol Esters / pharmacology
  • Poly I-C / pharmacology
  • Reactive Oxygen Species / metabolism
  • Ribonuclease III / antagonists & inhibitors
  • Ribonuclease III / biosynthesis*
  • Trophoblasts / metabolism
  • ras Proteins / metabolism

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Interferon Type I
  • MicroRNAs
  • Phorbol Esters
  • Reactive Oxygen Species
  • trichostatin A
  • Interferon-gamma
  • Ribonuclease III
  • ras Proteins
  • Poly I-C