Srivastava, Monika and Duan, Guowen and Kershaw, Nadia J and Athanasopoulos, Vicki and Yeo, Janet H C and Ose, Toyoyuki and Hu, Desheng and Brown, Simon H J and Jergic, Slobodan and Patel, Hardip R and Pratama, Alvin and Richards, Sashika and Verma, Anil and Jones, E Yvonne and Heissmeyer, Vigo and Preiss, Thomas and Dixon, Nicholas E and Chong, Mark M W and Babon, Jeffrey J and Vinuesa, Carola G (2015) Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis. Nature Communications, 6. p. 6253. ISSN 2041-1723 (OA)
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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.
| Item Type: | Article |
|---|---|
| Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | DOAJ Publication |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 Feb 2016 00:22 |
| Last Modified: | 28 Sep 2016 05:52 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/331 |
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