Pluto Bioinformatics

GSE114064: Widespread Alterations in Translation Elongation in the Brain of Fmr1 Knock-Out Mice

Bulk RNA sequencing

FMRP is a polysome-associated RNA-binding protein encoded byFmr1and lost in Fragile X syndrome. Increasing evidence suggests that FMRP regulatesboth translation initiation and elongation, but the gene-specificity of these effects is unclear. To elucidate theeffects of FMRP loss on translation, we used ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in thecortex ofFmr1knock-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.Aminoacid motif- and gene-level analysesbothshowed a widespread reduction of translational pausing inFmr1knock-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. SOURCE: Peter Sims (pas2182@cumc.columbia.edu) - Columbia University