The abstract is read at the publisher; the summary is JClub's.
In Drosophila CMT-YARS1 models and the Yars1E196K mouse model, tyrosyl-tRNA sequestration by mutant TyrRS depletes free tRNATyr, causing ribosome stalling at tyrosine codons.
- Why it matters: CMT-linked mono-allelic mutations in cytosolic aminoacyl-tRNA synthetase genes leave the molecular mechanism unclear, limiting targeted therapies for CMT-YARS1.
- What they did: The study tested three Drosophila CMT-YARS1 models and the Yars1E196K mouse model, using biochemical assays for tRNATyr sequestration, ribosome profiling for tyrosine-codon pausing, and AAV9-mediated tRNATyr overexpression or gene therapy.
- The result: tRNATyr overexpression rescued peripheral neuropathy phenotypes and defective mRNA translation in Drosophila, and in mice it fully rescued motor performance deficits, improved nerve conduction velocity and motor axon calibre while preventing integrated stress response activation in spinal motor neurons.
The findingWhy it mattersWhat they didThe result
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