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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Messenger-rna Decay; Target Rna; T-cells; Proteins; Degradation; Domain; Autoimmunity; Recognition; Repression; Expression
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 6253 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) 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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