Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis
- Author(s)
- Srivastava, M; Duan, G; Kershaw, NJ; Athanasopoulos, V; Yeo, JH; Ose, T; Hu, D; Brown, SH; Jergic, S; Patel, HR; Pratama, A; Richards, S; Verma, A; Jones, EY; Heissmeyer, V; Preiss, T; Dixon, NE; Chong, MM; Babon, JJ; Vinuesa, CG;
- Journal Title
- Nat Commun
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Structural Biology
- PubMed ID
- 25697406
- Publisher's Version
- https://doi.org/10.1038/ncomms7253
- Open Access at Publisher's Site
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Creation Date: 2015-02-25 01:47:26
Last Modified: 2016-02-03 08:17:21