ArticleNucleic acids research2023
Coordination between aminoacylation and editing to protect against proteotoxicity.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Mistranslation from an endogenous tRNA variant in human pan-genome cell lines.Nucleic acids research · 2026Article
- Serine mistranslation induces the integrated stress response through the P stalk.The Journal of biological chemistry · 2025Article
- Aminoacyl-tRNA synthetase defects in neurological diseases.IUBMB life · 2025Review
- Role of the epitranscriptome in viral infections: beneficial or detrimental?Memorias do Instituto Oswaldo Cruz · 2025Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, while the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in either ThrRS aminoacylation or editing is insufficient to cause heat sensitivity, and that ths1-C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.
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Registered trials
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