P38-MK2 Signaling Axis Regulates RNA Metabolism After UV-light-induced DNA Damage

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Mar 11

PMID 29523821

Citations 40

Authors

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

Affiliations

Soon will be listed here.

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.

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