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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis.
Nat. Commun. 6:6253 (2015)
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
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 6,
Article Number: 6253
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)