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Widespread Alterations in Translation Elongation in the Brain of Fmr1 Knock-Out Mice

ABSTRACT: FMRP is a polysome-associated RNA-binding protein encoded by Fmr1 and lost in Fragile X syndrome. Increasing evidence suggests that FMRP regulates both translation initiation and elongation, but the gene-specificity of these effects is unclear. To elucidate the effects of FMRP loss on translation, we used ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in the cortex of Fmr1 knock-out mice. We found a remarkably coherent reduction in ribosome footprint abundance per mRNA for previously identified, high-affinity mRNA binding partners of FMRP, and an increase for terminal oligo-pyrimidine (TOP) motif-containing genes canonically controlled by mTOR-4EBP-eIF4E signaling. Amino acid motif- and gene-level analyses both showed a widespread reduction of translational pausing in Fmr1 knock-out mice. Our findings are consistent with a model of FMRP-mediated regulation of both translation initiation through eIF4E and elongation that is disrupted in Fragile X syndrome.

ORGANISM(S): Mus musculus

PROVIDER: GSE114064 | GEO | 2019/03/10

REPOSITORIES: GEO

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Ribosome profiling and RNA-seq of Fragile X mouse brain cortex

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