Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity

Nat Commun. 2011 Oct 25;2:513. doi: 10.1038/ncomms1519.

Abstract

MicroRNAs (miRNAs) interact with 3'-untranslated regions of messenger RNAs to restrict expression of most protein-coding genes during normal development and cancer. RNA-binding proteins (RBPs) can control the biogenesis, stability and activity of miRNAs. Here we identify RBM38 in a genetic screen for RBPs whose expression controls miRNA access to target mRNAs. RBM38 is induced by p53 and its ability to modulate miRNA-mediated repression is required for proper p53 function. In contrast, RBM38 shows lower propensity to block the action of the p53-controlled miR-34a on SIRT1. Target selectivity is determined by the interaction of RBM38 with uridine-rich regions near miRNA target sequences. Furthermore, in large cohorts of human breast cancer, reduced RBM38 expression by promoter hypermethylation correlates with wild-type p53 status. Thus, our results indicate a novel layer of p53 gene regulation, which is required for its tumour suppressive function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cell Cycle
  • Cell Line, Tumor
  • DNA Methylation
  • Flow Cytometry
  • Humans
  • Magnetic Resonance Spectroscopy
  • MicroRNAs / genetics*
  • Microscopy, Fluorescence
  • Promoter Regions, Genetic
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RBM38 protein, human
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53

Associated data

  • GEO/GSE32301