Locally synthesized glycyl aminoacyl tRNA synthetase (GARS1) is important for local translation in neurons
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 (aaRS), 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. Localized GARS1 protein is in close proximity to tRNAGly, and disrupting this interaction impairs local protein synthesis in neurites. Notably, in a neuropathy-causing mutant variant of GARS1, we observed enhanced proximity to tRNAGly, indicating that altered GARS1– tRNAGly interactions may contribute to disease pathogenesis. These findings establish the functional importance of GARS1 and tRNAGly in neuritic translation and suggest a mechanism for peripheral neuropathies due to mutations in GARS1.
