Widespread Alterations in Translation Elongation in the Brain of Juvenile Fmr1 Knock-Out Mice [article]

Sohani Das Sharma, Jordan B. Metz, Hongyu Li, Benjamin D. Hobson, Nicholas Hornstein, David Sulzer, Guomei Tang, Peter A. Sims
2018 bioRxiv   pre-print
FMRP is a polysome-associated RNA-binding protein encoded by Fmr1 that is 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 impact of Fmr1 loss on translation, we used ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in the cortex of 24 day-old Fmr1 knock-out mice. We found a remarkably coherent reduction in ribosome
more » ... ootprint 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.
doi:10.1101/319368 fatcat:2el7nj2tn5ga5ie2odklxgl7ou