Roquin binds ICOS mRNA and effectors of mRNA decay to induce miRNA-independent post-transcriptional repression
Résumé
The molecular mechanism by which Roquin controls ICOS expression to prevent autoimmunity remains unsolved. Here we show that in helper T cells Roquin localized to processing bodies and downregulated ICOS expression. The repression was dependent on Rck, and Roquin interacted with Rck and Edc4, which cooperate in mRNA decapping. Sequences in Roquin that confer P body localization were essential for Roquin-mediated ICOS repression. This process did not require microRNAs or the RISC. Instead, Roquin bound ICOS mRNA directly, exhibiting an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region. Our results support a model in which Roquin controls ICOS expression through binding to the 3'UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.
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