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

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

Nature communications (2015-02-24)

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

PMID25697406

RESUMEN

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.

MATERIALES

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F1804

Sigma-Aldrich

ANTI-FLAG^® M2 monoclonal antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)