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RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway

Author

Listed:
  • Yasuhiro Murakawa

    (RNA Biology and Posttranscriptional Regulation, Berlin Institute of Medical Systems Biology at the Max-Delbrück Center for Molecular Medicine)

  • Michael Hinz

    (Signal Transduction in Tumor Cells, Max-Delbrück Center for Molecular Medicine)

  • Janina Mothes

    (Mathematical Modelling of Cellular Processes, Max-Delbrück Center for Molecular Medicine)

  • Anja Schuetz

    (Macromolecular Structure and Interaction, Max-Delbrück Center for Molecular Medicine
    Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine)

  • Michael Uhl

    (Albert-Ludwigs-Universität Freiburg)

  • Emanuel Wyler

    (RNA Biology and Posttranscriptional Regulation, Berlin Institute of Medical Systems Biology at the Max-Delbrück Center for Molecular Medicine)

  • Tomoharu Yasuda

    (Immune Regulation and Cancer, Max-Delbrück Center for Molecular Medicine)

  • Guido Mastrobuoni

    (Integrative Proteomics and Metabolomics Platform, Berlin Institute of Medical Systems Biology at the Max-Delbrück Center for Molecular)

  • Caroline C. Friedel

    (Institut für Informatik, Ludwig-Maximilians-Universität)

  • Lars Dölken

    (Institute for Virology and Immunobiology, University of Würzburg)

  • Stefan Kempa

    (Integrative Proteomics and Metabolomics Platform, Berlin Institute of Medical Systems Biology at the Max-Delbrück Center for Molecular)

  • Marc Schmidt-Supprian

    (Technische Universität)

  • Nils Blüthgen

    (Institute of Pathology, Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany
    Integrative Research Institute (IRI) for the Life Sciences and Institute for Theoretical Biology, Humboldt-Universität zu Berlin)

  • Rolf Backofen

    (Albert-Ludwigs-Universität Freiburg)

  • Udo Heinemann

    (Macromolecular Structure and Interaction, Max-Delbrück Center for Molecular Medicine
    Chemistry and Biochemistry Institute, Freie Universität Berlin)

  • Jana Wolf

    (Mathematical Modelling of Cellular Processes, Max-Delbrück Center for Molecular Medicine)

  • Claus Scheidereit

    (Signal Transduction in Tumor Cells, Max-Delbrück Center for Molecular Medicine)

  • Markus Landthaler

    (RNA Biology and Posttranscriptional Regulation, Berlin Institute of Medical Systems Biology at the Max-Delbrück Center for Molecular Medicine)

Abstract

The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFα mRNA decay via a 3′UTR constitutive decay element (CDE). Here we applied PAR-CLIP to human RC3H1 to identify ∼3,800 mRNA targets with >16,000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage-induced mRNAs, indicating a role of this RNA-binding protein in the post-transcriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of the NF-κB pathway regulators such as IκBα and A20. RC3H1 uses ROQ and Zn-finger domains to contact a binding site in the A20 3′UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IκB kinase and NF-κB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κB pathway.

Suggested Citation

  • Yasuhiro Murakawa & Michael Hinz & Janina Mothes & Anja Schuetz & Michael Uhl & Emanuel Wyler & Tomoharu Yasuda & Guido Mastrobuoni & Caroline C. Friedel & Lars Dölken & Stefan Kempa & Marc Schmidt-Su, 2015. "RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway," Nature Communications, Nature, vol. 6(1), pages 1-14, July.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8367
    DOI: 10.1038/ncomms8367
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    Cited by:

    1. Anita Rogic & Ila Pant & Luca Grumolato & Ruben Fernandez-Rodriguez & Andrew Edwards & Suvendu Das & Aaron Sun & Shen Yao & Rui Qiao & Shabnam Jaffer & Ravi Sachidanandam & Guray Akturk & Rosa Karlic , 2021. "High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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