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

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-25345-5

2041-1723

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, Vigo Heissmeyer,

RNA and protein synthesis mechanisms

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.