The study investigates the role of Fragile X Mental Retardation Protein (FMRP) in regulating neuronal translation, particularly in synaptic function and autism. Using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP), the researchers identified FMRP interactions with mouse brain polyribosomal mRNAs. FMRP was found to interact with coding regions of transcripts encoding pre- and postsynaptic proteins, as well as transcripts implicated in autism spectrum disorders (ASD). The study developed a brain polyribosome-programmed translation system to show that FMRP reversibly stalls ribosomes on its target mRNAs. The results suggest that loss of FMRP's translational brake on a subset of synaptic proteins may contribute to Fragile X Syndrome (FXS). Additionally, the findings provide insights into the molecular basis of cognitive and behavioral deficits in FXS and ASD, suggesting multiple targets for clinical intervention. The study also highlights the overlap between FMRP targets and genes linked to ASD, particularly overexpressed genes, providing a new connection between FMRP loss-of-function and autistic symptoms.The study investigates the role of Fragile X Mental Retardation Protein (FMRP) in regulating neuronal translation, particularly in synaptic function and autism. Using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP), the researchers identified FMRP interactions with mouse brain polyribosomal mRNAs. FMRP was found to interact with coding regions of transcripts encoding pre- and postsynaptic proteins, as well as transcripts implicated in autism spectrum disorders (ASD). The study developed a brain polyribosome-programmed translation system to show that FMRP reversibly stalls ribosomes on its target mRNAs. The results suggest that loss of FMRP's translational brake on a subset of synaptic proteins may contribute to Fragile X Syndrome (FXS). Additionally, the findings provide insights into the molecular basis of cognitive and behavioral deficits in FXS and ASD, suggesting multiple targets for clinical intervention. The study also highlights the overlap between FMRP targets and genes linked to ASD, particularly overexpressed genes, providing a new connection between FMRP loss-of-function and autistic symptoms.