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Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation

Author

Listed:
  • Katharina Essig

    (Ludwig-Maximilians-Universität München)

  • Nina Kronbeck

    (Ludwig-Maximilians-Universität München)

  • Joao C. Guimaraes

    (Computational and Systems Biology, Biozentrum, University of Basel)

  • Claudia Lohs

    (Research Unit Molecular Immune Regulation, Helmholtz Zentrum München)

  • Andreas Schlundt

    (Institute of Structural Biology, Helmholtz Zentrum München
    Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München)

  • Anne Hoffmann

    (Helmholtz Centre for Environmental Research—UFZ
    Leipzig University)

  • Gesine Behrens

    (Ludwig-Maximilians-Universität München)

  • Sven Brenner

    (Research Unit Molecular Immune Regulation, Helmholtz Zentrum München)

  • Joanna Kowalska

    (Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw)

  • Cristina Lopez-Rodriguez

    (Pompeu Fabra University)

  • Jacek Jemielity

    (University of Warsaw)

  • Helmut Holtmann

    (Institute of Biochemistry, Hannover Medical School)

  • Kristin Reiche

    (Helmholtz Centre for Environmental Research—UFZ
    Fraunhofer Institute for Cell Therapy and Immunology—IZI)

  • Jörg Hackermüller

    (Helmholtz Centre for Environmental Research—UFZ)

  • Michael Sattler

    (Institute of Structural Biology, Helmholtz Zentrum München
    Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München)

  • Mihaela Zavolan

    (Computational and Systems Biology, Biozentrum, University of Basel)

  • Vigo Heissmeyer

    (Ludwig-Maximilians-Universität München
    Research Unit Molecular Immune Regulation, Helmholtz Zentrum München)

Abstract

The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem–loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3′-UTR shows that six stem–loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem–loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3′-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements.

Suggested Citation

  • Katharina Essig & Nina Kronbeck & Joao C. Guimaraes & Claudia Lohs & Andreas Schlundt & Anne Hoffmann & Gesine Behrens & Sven Brenner & Joanna Kowalska & Cristina Lopez-Rodriguez & Jacek Jemielity & H, 2018. "Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06184-3
    DOI: 10.1038/s41467-018-06184-3
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