A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

Genes Dev. 2014 Sep 15;28(18):1977-82. doi: 10.1101/gad.246272.114. Epub 2014 Sep 4.

Abstract

RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.

Keywords: 14-3-3; DNA damage response; MAPKAPK2; UV; nuclear exosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • DNA Damage / physiology*
  • Exosome Multienzyme Ribonuclease Complex / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MAP Kinase Signaling System
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Untranslated / metabolism
  • Ultraviolet Rays

Substances

  • 14-3-3 Proteins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Untranslated
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Exosome Multienzyme Ribonuclease Complex