P38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage

Marina E. Borisova, Andrea Voigt, Maxim A.X. Tollenaere, Sanjeeb Kumar Sahu, Thomas Juretschke, Nastasja Kreim, Niels Mailand, Chunaram Choudhary, Simon Bekker-Jensen, Masato Akutsu, Sebastian A. Wagner, Petra Beli

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA-binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation.

Original languageEnglish
Article number1017
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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