Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage

Genes Dev. 2011 Feb 1;25(3):220-5. doi: 10.1101/gad.607011.

Abstract

Following DNA damage, mRNA 3'-end formation is inhibited, contributing to repression of mRNA synthesis. Here we investigated how DNA-damaged cells accomplish p53 mRNA 3'-end formation when normal mechanisms of pre-mRNA 3'-end processing regulation are inhibited. The underlying mechanism involves the interaction between a G-quadruplex structure located downstream from the p53 cleavage site and hnRNP H/F. Importantly, this interaction is critical for p53 expression and contributes to p53-mediated apoptosis. Our results uncover the existence of a specific rescue mechanism of 3'-end processing regulation allowing stress-induced p53 accumulation and function in apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • G-Quadruplexes*
  • Gene Expression Regulation
  • HCT116 Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism*
  • Humans
  • RNA 3' End Processing / genetics*
  • RNA Precursors / metabolism*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H
  • RNA Precursors
  • Tumor Suppressor Protein p53