MOV10 and FMRP Regulate AGO2 Association with MicroRNA Recognition Elements

• FMRP and MOV10 associate and regulate the translation of a subset of RNAs
• MOV10 binds G-C-rich secondary structures in close proximity to MREs
• FMRP binds in proximity to MREs, indicating a role in the microRNA pathway
• MOV10 modulates AGO2 function based on the proximity to FMRP binding sites

SummaryThe 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.

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