p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex

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  • Christopher Tiedje, Hannover Medical School
  • ,
  • Michal Lubas, Københavns Universitet
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  • Mohammad Tehrani, Hannover Medical School
  • ,
  • Manoj B. Menon, Hannover Medical School
  • ,
  • Natalia Ronkina, Hannover Medical School
  • ,
  • Simon Rousseau, McGill University
  • ,
  • Philip Cohen, MRC Phosphorylation und Ubiquitylation Unit (MRC-PPU)
  • ,
  • Alexey Kotlyarov, Hannover Medical School
  • ,
  • Matthias Gaestel, Hannover Medical School

The nuclear exosome targeting complex (NEXT) directs a major 3'-5' exonuclease, the RNA exosome, for degradation of nuclear noncoding (nc) RNAs. We identified the RNA-binding component of the NEXT complex, RBM7, as a substrate of p38MAPK/MK2-mediated phosphorylation at residue S136. As a result of this phosphorylation, RBM7 displays a strongly decreased RNA-binding capacity, while inhibition of p38MAPK or mutation of S136A in RBM7 increases its RNA association. Interestingly, promoter-upstream transcripts (PROMPTs), such as proRBM39, proEXT1, proDNAJB4, accumulated upon stress stimulation in a p38MAPK/MK2-dependent manner, a process inhibited by overexpression of RBM7S136A. While there are no stress-dependent changes in RNA-polymerase II (RNAPII) occupation of PROMPT regions representing unchanged transcription, stability of PROMPTs is increased. Hence, we propose that phosphorylation of RBM7 by the p38MAPK/MK2 axis increases nuclear ncRNA stability by blocking their RBM7-binding and subsequent RNA exosome targeting to allow stress-dependent modulations of the noncoding transcriptome.

Sider (fra-til)262-278
Antal sider17
StatusUdgivet - 2015

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