Journal article

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

Monika Srivastava, Guowen Duan, Nadia J Kershaw, Vicki Athanasopoulos, Janet HC Yeo, Toyoyuki Ose, Desheng Hu, Simon HJ Brown, Slobodan Jergic, Hardip R Patel, Alvin Pratama, Sashika Richards, Anil Verma, E Yvonne Jones, Vigo Heissmeyer, Thomas Preiss, Nicholas E Dixon, Mark MW Chong, Jeffrey J Babon, Carola G Vinuesa

Nature Communications | NATURE PUBLISHING GROUP | Published : 2015

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 uridylat..

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Grants

Awarded by Medical 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.