Glycyl-tRNA synthetase 1 mRNA (GARS1 mRNA) (GARS1 mRNA)

GARS1 mRNA is the transcript of the Glycyl-tRNA Synthetase 1 gene, which encodes a bifunctional enzyme responsible for charging tRNA with glycine in both the cytoplasm and mitochondria [1]. While the GARS1 protein is essential for global protein synthesis, specific dominant mutations in the GARS1 gene cause Charcot-Marie-Tooth disease type 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V) [4]. These neuropathies are primarily attributed to a toxic gain-of-function where the mutant protein inappropriately interacts with extracellular receptors like Neuropilin-1, disrupting neurotrophic signaling and axonal integrity [2]. Consequently, GARS1 mRNA has emerged as a primary target for gene-silencing therapeutics, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), designed to reduce the cellular burden of the toxic mutant protein [3]. The therapeutic strategy often focuses on allele-specific knockdown to preserve the essential wild-type enzyme function while eliminating the pathogenic variant.

Other names

GARS mRNAGlycine--tRNA ligase mRNACMT2D mRNAHMN5 mRNAGlycyl-tRNA synthetase mRNA

Targeted degradation of mRNA transcripts via RNase H-mediated cleavage (for antisense oligonucleotides) or the RNA-induced silencing complex (for siRNA) to reduce the expression of toxic mutant proteins [3].