Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins.
Ethan J GreenblattAllan C SpradlingPublished in: Science (New York, N.Y.) (2018)
Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.
Keyphrases
- autism spectrum disorder
- intellectual disability
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- attention deficit hyperactivity disorder
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- genome wide
- single cell
- copy number
- genome wide analysis
- gene expression
- early onset
- pluripotent stem cells
- genome wide identification
- case report
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