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PMID:25464849

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Citation

Kenny, PJ, Zhou, H, Kim, M, Skariah, G, Khetani, RS, Drnevich, J, Arcila, ML, Kosik, KS and Ceman, S (2014) MOV10 and FMRP regulate AGO2 association with microRNA recognition elements. Cell Rep 9:1729-1741

Abstract

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.

Links

PubMed PMC4268400 Online version:10.1016/j.celrep.2014.10.054

Keywords

3' Untranslated Regions; Animals; Argonaute Proteins/metabolism; Binding Sites; Brain/metabolism; Fragile X Mental Retardation Protein/physiology; GC Rich Sequence; HEK293 Cells; Humans; Mice; Mice, Knockout; MicroRNAs/metabolism; Protein Binding; RNA Helicases/physiology; RNA Interference; Transcriptome

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MOV10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35922

F

Seeded From UniProt

complete

MOUSE:FMR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23249

F

Seeded From UniProt

complete

HUMAN:FMR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9HCE1

F

Seeded From UniProt

complete

HUMAN:MOV10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q06787

F

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:0060964: regulation of gene silencing by miRNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FMR1

enables

GO:0002151: G-quadruplex RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:1902416: positive regulation of mRNA binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FMR1

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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