p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
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p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage. / Borisova, Marina E; Voigt, Andrea; Tollenaere, Maxim A.X.; Sahu, Sanjeeb Kumar; Juretschke, Thomas; Kreim, Nastasja; Mailand, Niels; Choudhary, Chunaram; Bekker-Jensen, Simon; Akutsu, Masato; Wagner, Sebastian A; Beli, Petra.
In: Nature Communications, Vol. 9, 1017, 01.12.2018, p. 1-16.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
AU - Borisova, Marina E
AU - Voigt, Andrea
AU - Tollenaere, Maxim A.X.
AU - Sahu, Sanjeeb Kumar
AU - Juretschke, Thomas
AU - Kreim, Nastasja
AU - Mailand, Niels
AU - Choudhary, Chunaram
AU - Bekker-Jensen, Simon
AU - Akutsu, Masato
AU - Wagner, Sebastian A
AU - Beli, Petra
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-03417-3
DO - 10.1038/s41467-018-03417-3
M3 - Journal article
C2 - 29523821
VL - 9
SP - 1
EP - 16
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1017
ER -
ID: 192400297