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p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage

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 quantit...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845016/
https://www.ncbi.nlm.nih.gov/pubmed/29523821
http://dx.doi.org/10.1038/s41467-018-03417-3
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author 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
author_facet 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
author_sort Borisova, Marina E.
collection PubMed
description 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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spelling pubmed-58450162018-03-13 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 Nat Commun Article 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. Nature Publishing Group UK 2018-03-09 /pmc/articles/PMC5845016/ /pubmed/29523821 http://dx.doi.org/10.1038/s41467-018-03417-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title_full p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title_fullStr p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title_full_unstemmed p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title_short p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
title_sort p38-mk2 signaling axis regulates rna metabolism after uv-light-induced dna damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845016/
https://www.ncbi.nlm.nih.gov/pubmed/29523821
http://dx.doi.org/10.1038/s41467-018-03417-3
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