Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome.

ABSTRACT: Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu_1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1^-/y) hippocampus, which exhibit exaggerated mGlu_1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M₄) is excessively translated, and synthesis of M₄ downstream of mGlu₅ activation is mimicked and occluded. Surprisingly, enhancement

SUBMITTER: Thomson SR 

PROVIDER: S-EPMC5548955 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature