Translation efficiency of synaptic proteins and its coding sequence determinants

The synapse is an organized structure that contains synaptic vesicles, mitochondria, receptors, transporters and stored proteins. About 10% of the mRNAs that are express in mammalian neurons are delivered to synaptic sites, where they are subjected to local translation. While neuronal plasticity, learning and memory occur at the synapse, the mechanisms that regulate post-transcriptional events and local translation are mostly unknown. We hypothesized that evolutional signals that govern translational efficiency are encoded in the mRNA of synaptic proteins. Specifically, we applied a measure of tRNA adaptation index (tAI) as an indirect proxy for translation rate and showed that ionic channels and ligand-binding receptors are specified by a global low tAI values. In contrast, the genuine proteins of the synaptic vesicles exhibit significantly higher tAI values. The expression of many of these proteins actually accompanied synaptic plasticity. Furthermore, in human, the local tAI values for the initial segment of mRNA coding differs for synaptic proteins in view of the rest of the human proteome. We propose that the translation of synaptic proteins is a robust solution for compiling with the high metabolic demands of the synapse.