Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage

EMBO J. 2010 May 19;29(10):1674-87. doi: 10.1038/emboj.2010.59. Epub 2010 Apr 8.

Abstract

We previously showed that mRNA 3' end cleavage reaction in cell extracts is strongly but transiently inhibited under DNA-damaging conditions. The cleavage stimulation factor-50 (CstF-50) has a role in this response, providing a link between transcription-coupled RNA processing and DNA repair. In this study, we show that CstF-50 interacts with nuclear poly(A)-specific ribonuclease (PARN) using in vitro and in extracts of UV-exposed cells. The CstF-50/PARN complex formation has a role in the inhibition of 3' cleavage and activation of deadenylation upon DNA damage. Extending these results, we found that the tumour suppressor BARD1, which is involved in the UV-induced inhibition of 3' cleavage, strongly activates deadenylation by PARN in the presence of CstF-50, and that CstF-50/BARD1 can revert the cap-binding protein-80 (CBP80)-mediated inhibition of PARN activity. We also provide evidence that PARN along with the CstF/BARD1 complex participates in the regulation of endogenous transcripts under DNA-damaging conditions. We speculate that the interplay between polyadenylation, deadenylation and tumour-suppressor factors might prevent the expression of prematurely terminated messengers, contributing to control of gene expression under different cellular conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism*
  • DNA Damage*
  • DNA Repair
  • Exoribonucleases / metabolism
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • Models, Biological
  • Polyadenylation*
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Recombinant Proteins / chemistry
  • Ultraviolet Rays
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • RNA, Messenger
  • Recombinant Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • RNA
  • Glutathione Transferase
  • Exoribonucleases
  • poly(A)-specific ribonuclease