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Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation

Author

Listed:
  • Kai P. Hoefig

    (Helmholtz Center Munich)

  • Alexander Reim

    (Max-Planck-Institute of Biochemistry)

  • Christian Gallus

    (Helmholtz Center Munich)

  • Elaine H. Wong

    (Ludwig Maximilians University Munich)

  • Gesine Behrens

    (Helmholtz Center Munich)

  • Christine Conrad

    (Ludwig Maximilians University Munich)

  • Meng Xu

    (Helmholtz Center Munich)

  • Lisa Kifinger

    (Ludwig Maximilians University Munich)

  • Taku Ito-Kureha

    (Ludwig Maximilians University Munich)

  • Kyra A. Y. Defourny

    (Ludwig Maximilians University Munich
    Utrecht University)

  • Arie Geerlof

    (Helmholtz Center Munich)

  • Josef Mautner

    (TU Munich)

  • Stefanie M. Hauck

    (Helmholtz Center Munich)

  • Dirk Baumjohann

    (Ludwig Maximilians University Munich
    University of Bonn)

  • Regina Feederle

    (Helmholtz Center Munich)

  • Matthias Mann

    (Max-Planck-Institute of Biochemistry)

  • Michael Wierer

    (Max-Planck-Institute of Biochemistry
    University of Copenhagen)

  • Elke Glasmacher

    (Helmholtz Center Munich
    Roche Innovation Center Munich)

  • Vigo Heissmeyer

    (Helmholtz Center Munich
    Ludwig Maximilians University Munich)

Abstract

Post-transcriptional gene regulation in T cells is dynamic and complex as targeted transcripts respond to various factors. This is evident for the Icos mRNA encoding an essential costimulatory receptor that is regulated by several RNA-binding proteins (RBP), including Roquin-1 and Roquin-2. Here, we identify a core RBPome of 798 mouse and 801 human T cell proteins by utilizing global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS). The RBPome includes Stat1, Stat4 and Vav1 proteins suggesting unexpected functions for these transcription factors and signal transducers. Based on proximity to Roquin-1, we select ~50 RBPs for testing coregulation of Roquin-1/2 targets by induced expression in wild-type or Roquin-1/2-deficient T cells. Besides Roquin-independent contributions from Rbms1 and Cpeb4 we also show Roquin-1/2-dependent and target-specific coregulation of Icos by Celf1 and Igf2bp3. Connecting the cellular RBPome in a post-transcriptional context, we find contributions from multiple RBPs to the prototypic regulation of mRNA targets by individual trans-acting factors.

Suggested Citation

  • Kai P. Hoefig & Alexander Reim & Christian Gallus & Elaine H. Wong & Gesine Behrens & Christine Conrad & Meng Xu & Lisa Kifinger & Taku Ito-Kureha & Kyra A. Y. Defourny & Arie Geerlof & Josef Mautner , 2021. "Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25345-5
    DOI: 10.1038/s41467-021-25345-5
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