ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 121 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Locally synthesized glycyl aminoacyl-tRNA synthetase is important for local translation in neurons.Life science alliance · 2026Article
- Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.Amino acids · 2026Review
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- Dominant aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Elusive Trans-Acting Factors Which Operate with Type I (Poliovirus-like) IRES Elements.International journal of molecular sciences · 2022Review
- A missense, loss-of-functionCold Spring Harbor molecular case studies · 2022Article
- Pathogenic missense variants altering codon 336 of GARS1 lead to divergent dominant phenotypes.Human mutation · 2022Article
- Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders.Molecules and cells · 2022Article
- Charcot-Marie-Tooth mutation in glycyl-tRNA synthetase stalls ribosomes in a pre-accommodation state and activates integrated stress response.Nucleic acids research · 2021Article
- Review
- tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase.Science (New York, N.Y.) · 2021Article
- SIRT2-knockdown rescues GARS-induced Charcot-Marie-Tooth neuropathy.Aging cell · 2021Article
- Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: A gain or a loss?Journal of neurochemistry · 2021Review
- Mitochondrial Aminoacyl-tRNA Synthetase and Disease: The Yeast Contribution for Functional Analysis of Novel Variants.International journal of molecular sciences · 2021Review
- CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish.The FEBS journal · 2021Article
- VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy.Annals of clinical and translational neurology · 2020Article
- GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment.American journal of medical genetics. Part A · 2020Article
- Overlapping spectrums: The clinicogenetic commonalities between Charcot-Marie-Tooth and other neurodegenerative diseases.Brain research · 2020Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more severe in the upper extremities. We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is a member of the family of aminoacyl-tRNA synthetases responsible for charging tRNA with cognate amino acids; GARS ligates glycine to tRNA(Gly). Here, we present functional analyses of disease-associated GARS mutations and show that there are not any significant mutation-associated changes in GARS expression levels; that the majority of identified GARS mutations modeled in yeast severely impair viability; and that, in most cases, mutant GARS protein mislocalizes in neuronal cells. Indeed, four of the five mutations studied show loss-of-function features in at least one assay, suggesting that tRNA-charging deficits play a role in disease pathogenesis. Finally, we detected endogenous GARS-associated granules in the neurite projections of cultured neurons and in the peripheral nerve axons of normal human tissue. These data are particularly important in light of the recent identification of CMT-associated mutations in another tRNA synthetase gene [YARS (tyrosyl-tRNA synthetase gene)]. Together, these findings suggest that tRNA-charging enzymes play a key role in maintaining peripheral axons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.