Abstract

To form and modify synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes unique logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of mRNAs near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally1. It is not known, however if, how and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA-seq and Ribo-seq from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies as well as dendrites and axons (neuropil). More than 4800 transcripts were translated in synaptic regions. Thousands of transcripts were differentially translated between somatic and synaptic regions, with scaffold and signaling molecules mostly arising from local sources. Furthermore, specific mRNA features were identified that regulate the efficiency of mRNA translation. The findings overturn the view that local translation is a minor source of synaptic protein2 and indicate that on-site translational control is an important mechanism to control synaptic strength.