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

研究成果: Article査読

28 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号1017
ジャーナルNature communications
9
1
DOI
出版ステータスPublished - 2018 12 1
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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