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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.

SUBMITTER: Wallen RC

PROVIDER: S-EPMC3703498 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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To charge or not to charge: mechanistic insights into neuropathy-associated tRNA synthetase mutations.

Wallen Rachel C RC Antonellis Anthony A

Current opinion in genetics & development 20130304 3

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 ...[more]

PMID: 23465884

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