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 and Petra Beli ()
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Marina E. Borisova: Institute of Molecular Biology (IMB)
Andrea Voigt: Institute of Molecular Biology (IMB)
Maxim A. X. Tollenaere: University of Copenhagen
Sanjeeb Kumar Sahu: Institute of Molecular Biology (IMB)
Thomas Juretschke: Institute of Molecular Biology (IMB)
Nastasja Kreim: Institute of Molecular Biology (IMB)
Niels Mailand: University of Copenhagen
Chunaram Choudhary: University of Copenhagen
Simon Bekker-Jensen: University of Copenhagen
Masato Akutsu: Goethe University
Sebastian A. Wagner: Goethe University
Petra Beli: Institute of Molecular Biology (IMB)

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03417-3

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