Locally synthesized glycyl aminoacyl-tRNA synthetase is important for local translation in neurons.

Abstract

Regulation of gene expression is essential for neuronal development and function. A prominent regulatory mechanism involves synthesis of proteins at their activity site. Such local protein synthesis enables neurons to respond rapidly and tightly to stimuli. Key components of the translation machinery, including mRNA and ribosomes, were identified in subcellular regions of neurons. Yet, the role of tRNAs and their charging enzymes, aminoacyl-tRNA synthetases (ARS), in this process remains largely unclear. Here, we demonstrate that glycyl-tRNA synthetase (Gars1) mRNA is abundant in neurites and undergoes local translation, producing GARS1 protein. Notably, Gars1 mRNA colocalizes with mitochondria in a translation-dependent manner, with its coding sequence (CDS) sufficient to direct this association. The localized GARS1 protein is in close proximity to tRNA^Gly, and disrupting their proximity impairs local protein synthesis in neurites. These findings establish the functional importance of GARS1 and tRNA^Gly in neuritic translation and highlight mitochondria as hubs for mRNA transport and translation.