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Janowski, R. ; Heinz, G.A. ; Schlundt, A. ; Wommelsdorf, N. ; Brenner, S. ; Gruber, A.R.* ; Blank, M.* ; Buch, T.* ; Buhmann, R.* ; Zavolan, M.* ; Niessing, D. ; Heissmeyer, V. ; Sattler, M.

Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40.

Nat. Commun. 7:11032 (2016)
Verlagsversion Anhang DOI PMC
Open Access Gold
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The RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 3'-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Costimulator Messenger-rna; Constitutive-decay Element; Helper T-cells; Nmr-spectroscopy; Binding Proteins; Differentiation; Autoimmunity; Regnase-1; Family; Inflammation
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 11032 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Research Unit Molecular Immune Regulation (AMIR)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
Immune Response and Infection
PSP-Element(e) G-503091-001
G-501712-001
G-503000-001
PubMed ID 27010430
DOI 10.1038/ncomms11032
WOS ID WOS:000372887400001
Scopus ID 84962258959
Erfassungsdatum 2016-04-20
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