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Hoefig, K.P. ; Reim, A.* ; Gallus, C. ; Wong, E.H.* ; Behrens, G. ; Conrad, C.* ; Xu, M. ; Kifinger, L.* ; Ito-Kureha, T.* ; Defourny, K.A.Y.* ; Geerlof, A. ; Mautner, J.M.* ; Hauck, S.M. ; Baumjohann, D.* ; Feederle, R. ; Mann, M.* ; Wierer, M.* ; Glasmacher, E. ; Heissmeyer, V.

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

Nat. Commun. 12:5208 (2021)
Publ. Version/Full Text DOI
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Inducible Costimulator; Binding Proteins; Stem-loop; Icos; Differentiation; Expression; Proteome; Events; Identification; Degradation
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 5208 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Grants HE3359/8-1
Wilhelm Sander Foundation
Fritz Thyssen foundation
Else Kroner-Fresenius Foundation
Deutsche Krebshilfe foundation
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)
Germany's Excellence Strategy EXC2151
German Research Foundation