MOV10 and FMRP Regulate AGO2 Association with MicroRNA Recognition Elements
Phillip J. Kenny,
Hongjun Zhou,
Miri Kim,
Geena Skariah,
Radhika S. Khetani,
Jenny Drnevich,
Mary Luz Arcila,
Kenneth S. Kosik,
Stephanie Ceman
Affiliations
Phillip J. Kenny
Cell and Developmental Biology, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA
Hongjun Zhou
Neuroscience Research Institute and Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Miri Kim
College of Medicine, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA; Neuroscience Program, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA
Geena Skariah
Neuroscience Program, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA
Radhika S. Khetani
High-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA
Jenny Drnevich
High-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA
Mary Luz Arcila
Neuroscience Research Institute and Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Kenneth S. Kosik
Neuroscience Research Institute and Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Stephanie Ceman
Cell and Developmental Biology, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA; College of Medicine, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA; Neuroscience Program, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL 61801, USA; Corresponding author
Summary: 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 et al. 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.
