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Srivastava, M.* ; Duan, G.* ; Kershaw, N.J.* ; Athanasopoulos, V.* ; Yeo, J.H.* ; Ose, T.* ; Hu, D. ; Brown, S.H.* ; Jergic, S.* ; Patel, H.R.* ; Pratama, A.* ; Richards, S.* ; Verma, A.* ; Jones, E.Y.* ; Heissmeyer, V. ; Preiss, T.* ; Dixon, N.E.* ; Chong, M.M.* ; Babon, J.J.* ; Vinuesa, C.G.*

Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis.

Nat. Commun. 6:6253 (2015)
Verlagsversion DOI PMC
Open Access Gold
Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquin(san)), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3' end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Messenger-rna Decay; Target Rna; T-cells; Proteins; Degradation; Domain; Autoimmunity; Recognition; Repression; Expression
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 6, Heft: , Seiten: , Artikelnummer: 6253 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501792-001
PubMed ID 25697406
DOI 10.1038/ncomms7253
WOS ID WOS:000350202800003
Scopus ID 84923345886
Erfassungsdatum 2015-02-25
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