MOV10 and FMRP Regulate AGO2 Association with MicroRNA Recognition Elements

The fragile X mental retardation protein FMRP regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway, and we show here that it associates with the RNA helicase MOV10, also associated with the microRNA pathway. FMRP associates with MOV10 directly and in an RNA-dependent manner and facilitates MOV10's association with RNAs in brain and cells, suggesting a cooperative interaction. We identified the RNAs recognized by MOV10 using RNA immunoprecipitation and iCLIP. Examination of the fate of MOV10 on RNAs revealed a dual function for MOV10 in regulating translation: it facilitates microRNA-mediated translation of some RNAs, but it also increases expression of other RNAs by preventing AGO2 function. The latter subset was also bound by FMRP in close proximity to the MOV10 binding site, suggesting that FMRP prevents MOV10-mediated microRNA suppression. We have identified a mechanism for FMRP-mediated translational regulation through its association with MOV10. Kenny etal. show that FMRP recruits the helicase MOV10 to mRNAs for translation regulation. MOV10 and FMRP modulate AGO association with RNAs, and all three proteins bind near microRNA recognition elements. MOV10 usually facilitates microRNA-mediated regulation; however, proximal binding of FMRP blocks AGO association to allow translation.