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

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, Stefanie M. Hauck, Dirk Baumjohann, Regina Feederle, Matthias Mann, Michael Wierer (), Elke Glasmacher () and Vigo Heissmeyer ()
Additional contact information
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
Arie Geerlof: Helmholtz Center Munich
Josef Mautner: TU Munich
Stefanie M. Hauck: Helmholtz Center Munich
Dirk Baumjohann: Ludwig Maximilians University Munich
Regina Feederle: Helmholtz Center Munich
Matthias Mann: Max-Planck-Institute of Biochemistry
Michael Wierer: Max-Planck-Institute of Biochemistry
Elke Glasmacher: Helmholtz Center Munich
Vigo Heissmeyer: Helmholtz Center Munich

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25345-5

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DOI: 10.1038/s41467-021-25345-5

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