Mus musculus Transcriptome or Gene expression. Mus musculus

Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as 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 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 previously unidentified 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.