Role for the MOV10 RNA Helicase in Polycomb-Mediated Repression of the INK4a Tumor Suppressor

Nat Struct Mol Biol. 2010 Jul;17(7):862-8. doi: 10.1038/nsmb.1824. Epub 2010 Jun 13.

Abstract

Several lines of evidence point to a role for noncoding RNA in transcriptional repression by Polycomb group (PcG) proteins, but the precise mechanism remains unclear. Here we show that human MOV10, a putative RNA helicase previously implicated in post-transcriptional gene silencing, co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1) from human cells. Endogenous human MOV10 is mostly nuclear, and a proportion associates with chromatin in an RNA-dependent manner. Small hairpin RNA (shRNA)-mediated knockdown of MOV10 in human fibroblasts leads to the upregulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by the dissociation of PRC1 proteins from the locus and a reduction in trimethylation of histone H3 on Lys27 (H3K27me3). As well as prompting reassessment of MOV10's role in other settings, our findings suggest that it is directly involved in transcriptional silencing by PcG complexes.

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Chromatin / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Fibroblasts / metabolism
  • Gene Knockdown Techniques
  • Gene Silencing*
  • Humans
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • Repressor Proteins / metabolism*

Substances

  • CBX7 protein, human
  • Chromatin
  • Cyclin-Dependent Kinase Inhibitor p16
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1
  • Mov10 protein, human
  • RNA Helicases