Journal article
Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis
M Srivastava, G Duan, NJ Kershaw, V Athanasopoulos, JHC Yeo, T Ose, D Hu, SHJ Brown, S Jergic, HR Patel, A Pratama, S Richards, A Verma, EY Jones, V Heissmeyer, T Preiss, NE Dixon, MMW Chong, JJ Babon, CG Vinuesa
Nature Communications | Published : 2015
DOI: 10.1038/ncomms7253
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 (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 uridylatio..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank Joseph J. B. Cockburn, Nick S. Berrow, David Alderton, David I. Stuart, Raymond J. Owens for crystallographic work; the JCSMR Microscopy and Cytometry Resource facility (MCRF) for assistance with FACS and microscopy and the Biomolecular Resource Facility (BRF) for sequencing. T.P. acknowledges funding through an NHMRC project grant. J.J.B is funded by ARC future fellowship. This work was funded by an Australian Research Council grant and a NHMRC Elizabeth Blackburn Fellowship awarded to C.G.V.