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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Inducible Costimulator; Binding Proteins; Stem-loop; Icos; Differentiation; Expression; Proteome; Events; Identification; Degradation
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 5208 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) 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
Forschungsfeld(er) Immune Response and Infection
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-501712-001
G-501900-226
G-503000-001
G-505700-001
G-502210-001
Förderungen 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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