title: To charge or not to charge: mechanistic insights into neuropathy-associated tRNA synthetase mutations.
abstract: Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for the first step of protein translation--attaching amino acids to cognate tRNA molecules. Interestingly, ARS gene mutations have been implicated in tissue-specific human diseases, including inherited peripheral neuropathies. To date, five loci encoding an ARS have been implicated in peripheral neuropathy, and alleles at each locus show loss-of-function characteristics. The majority of the phenotypes are autosomal dominant, and each of the implicated enzymes acts as an oligomer, indicating that a dominant-negative effect should be considered. On the basis of current data, impaired tRNA charging is likely to be a central component of ARS-related neuropathy. Future efforts should focus on testing this notion and developing strategies for restoring ARS function in the peripheral nerve.
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
authors: Rachel C
authors: RC
authors: Wallen
authors: Anthony
authors: A
authors: Antonellis
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010525:Peripheral Nerves / Q000201:enzymology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics*
chemical_list: D000604:Amino Acyl-tRNA Synthetases