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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms7253

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

Journal article published in 2015 by Monika Srivastava, E. Yvonne Jones, Guowen Duan, Nadia J. Kershaw, Vicki Athanasopoulos, Janet H. C. Yeo, Toyoyuki Ose, Desheng Hu ORCID, Simon H. J. Brown, Slobodan Jergic, Hardip R. Patel, Alvin Pratama, Sashika Richards, Anil Verma, E. Yvonne Jones and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractRoquin 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 (Roquinsan), 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.