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

Author

Listed:
  • 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
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Petra Beli

    (Institute of Molecular Biology (IMB))

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.

Suggested Citation

  • 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 & Sebast, 2018. "p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03417-3
    DOI: 10.1038/s41467-018-03417-3
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    Cited by:

    1. Seina Ohe & Yuji Kubota & Kiyoshi Yamaguchi & Yusuke Takagi & Junichiro Nashimoto & Hiroko Kozuka-Hata & Masaaki Oyama & Yoichi Furukawa & Mutsuhiro Takekawa, 2022. "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Barbara Steurer & Roel C. Janssens & Marit E. Geijer & Fernando Aprile-Garcia & Bart Geverts & Arjan F. Theil & Barbara Hummel & Martin E. Royen & Bastiaan Evers & René Bernards & Adriaan B. Houtsmull, 2022. "DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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