FMRP-associated MOV10 facilitates and antagonizes miRNA-mediated regulation

The fragile X mental retardation protein FMRP is an RNA binding protein that regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway and we show here that it is associated with MOV10, a putative helicase that is also associated with the microRNA pathway. We show that FMRP associates with MOV10 in an RNA-dependent manner and facilitates MOV10-association with RNAs in brain. We identified the RNA sequences recognized by MOV10 using iCLIP and found an increased number of G-quadruplexes in the CLIP sites. We provide evidence that MOV10 facilitates microRNA-mediated translation regulation and also has the novel role of increasing the expression of a subset of RNAs by sterically hindering Argonaute2 association. In summary, we have identified a new mechanism for FMRP-mediated translational regulation through its association with MOV10. Overall design: Comparison of MOV10 siRNA knockdown, irrelevant siRNA control and MOV10 overexpression on total RNA levels

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Kenny PJ, Zhou H, Kim M, Skariah G, Khetani RS, Drnevich J, Arcila ML, Kosik KS, Ceman S