Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome.

ABSTRACT: Dysregulated protein synthesis is a core pathogenic mechanism in Fragile X Syndrome (FX). The mGluR Theory of FX predicts that pathological synaptic changes arise from the excessive translation of mRNAs downstream of mGlu_1/5 activation. Here, we use a combination of CA1 pyramidal neuron-specific TRAP-seq and proteomics to identify the overtranslating mRNAs supporting exaggerated mGlu_1/5 -induced long-term synaptic depression (mGluR-LTD) in the FX mouse model (Fmr1^-/y). Our results identify a significant increase in the translation of ribosomal proteins (RPs) upon mGlu_1/5 stimulation that coincides with a reduced translation of long mRNAs encoding synaptic proteins. These changes are mimicked and occluded in Fmr1^-/y neurons. Inhibiting

SUBMITTER: Seo SS 

PROVIDER: S-EPMC9187743 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature