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Schlundt, A. ; Heinz, G.A. ; Janowski, R. ; Geerlof, A. ; Stehle, R.* ; Heissmeyer, V. ; Niessing, D. ; Sattler, M.

Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation.

Nat. Struct. Mol. Biol. 21, 671-678 (2014)
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Open Access Gold
Roquin function in T cells is essential for the prevention of autoimmune disease. Roquin interacts with the 3′ untranslated regions (UTRs) of co-stimulatory receptors and controls T-cell activation and differentiation. Here we show that the N-terminal ROQ domain from mouse roquin adopts an extended winged-helix (WH) fold, which is sufficient for binding to the constitutive decay element (CDE) in the Tnf 3′ UTR. The crystal structure of the ROQ domain in complex with a prototypical CDE RNA stem-loop reveals tight recognition of the RNA stem and its triloop. Surprisingly, roquin uses mainly non-sequence-specific contacts to the RNA, thus suggesting a relaxed CDE consensus and implicating a broader spectrum of target mRNAs than previously anticipated. Consistently with this, NMR and binding experiments with CDE-like stem-loops together with cell-based assays confirm roquin-dependent regulation of relaxed CDE consensus motifs in natural 3′ UTRs.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Costimulator Messenger-rna; Helper T-cells; Crystal-structure; Autoimmunity; Decay; Degradation; Repression; Family; Domain
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Zeitschrift Nature Structural & Molecular Biology
Quellenangaben Band: 21, Heft: 8, Seiten: 671-678 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Institute of Molecular Immunology (IMI)
Research Unit Molecular Immune Regulation (AMIR)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
Immune Response and Infection
PSP-Element(e) G-503000-001
G-503091-001
G-501792-001
G-503000-003
PubMed ID 25026077
DOI 10.1038/nsmb.2855
WOS ID WOS:000340074300007
Scopus ID 84905656367
Scopus ID 84904271377
Erfassungsdatum 2014-07-14
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