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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 PMC
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
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 5208 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Immune Regulation (AMIR)
Institute of Diabetes and Obesity (IDO)
Institute of Structural Biology (STB)
CF Metabolomics & Proteomics (CF-MPC)
CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP Element(s) G-501712-001
G-501900-226
G-503000-001
G-505700-001
G-502210-001
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
HE3359/7-1
German Research Foundation
DOI 10.1038/s41467-021-25345-5
WOS ID WOS:000692406100015
Scopus ID 85114163930
PubMed ID 34471108
Erfassungsdatum 2021-10-08
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