| First Author | Srivastava M | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6253 | PubMed ID | 25697406 |
| Mgi Jnum | J:221791 | Mgi Id | MGI:5641569 |
| Doi | 10.1038/ncomms7253 | Citation | Srivastava M, et al. (2015) Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis. Nat Commun 6:6253 |
| abstractText | 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. |
