ArticleNucleic acids research2017
Editing of misaminoacylated tRNA controls the sensitivity of amino acid stress responses in Saccharomyces cerevisiae.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Natural human tRNARNA (New York, N.Y.) · 2025Article
- Serine mistranslation induces the integrated stress response through the P stalk.The Journal of biological chemistry · 2025Article
- Transfer RNA supplementation rescues HARS deficiency in a humanized yeast model of Charcot-Marie-Tooth disease.Nucleic acids research · 2024Article
- Article
- Global profiling of ribosomal protein acetylation reveals essentiality of acetylation homeostasis in maintaining ribosome assembly and function.Nucleic acids research · 2023Article
- System-wide optimization of an orthogonal translation system with enhanced biological tolerance.Molecular systems biology · 2023Article
- Impact of alanyl-tRNA synthetase editing deficiency in yeast.Nucleic acids research · 2021Article
- Chemical-Genetic Interactions with the Proline Analog L-Azetidine-2-Carboxylic Acid inG3 (Bethesda, Md.) · 2020Article
- Fine-Tuning of Alanyl-tRNA Synthetase Quality Control Alleviates Global Dysregulation of the Proteome.Genes · 2020Article
- Aminoacyl-tRNA synthetases.RNA (New York, N.Y.) · 2020Review
- The mechanism of β-The Journal of biological chemistry · 2020Article
- A Synthetic Reporter for Probing Mistranslation in Living Cells.Frontiers in bioengineering and biotechnology · 2020Article
- Loss of protein synthesis quality control in host-restricted organisms.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Review
- Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae.Microbiology and molecular biology reviews : MMBR · 2018Review
- Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway.PLoS genetics · 2018Article
- A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.Nature communications · 2018Article
- Visualizing tRNA-dependent mistranslation in human cells.RNA biology · 2018Article
- Aminoacyl-tRNA quality control is required for efficient activation of the TOR pathway regulator Gln3p.RNA biology · 2018Review
- Translational fidelity and mistranslation in the cellular response to stress.Nature microbiology · 2017Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation is limited by lack of substrates or inhibition of synthesis. Pairing of amino acids and deacylated tRNAs is catalyzed by aminoacyl-tRNA synthetases, which use quality control pathways to maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNAPhe. While the primary role of aaRS editing is to prevent misaminoacylation, we demonstrate editing of misaminoacylated tRNA is also required for detection of amino acid starvation by Gcn2p. Ablation of PheRS editing caused accumulation of Tyr-tRNAPhe (5%), but not deacylated tRNAPhe during amino acid starvation, limiting Gcn2p kinase activity and suppressing Gcn4p-dependent gene expression. While the PheRS-editing ablated strain grew 50% slower and displayed a 27-fold increase in the rate of mistranslation of Phe codons as Tyr compared to wild type, the increase in mistranslation was insufficient to activate an unfolded protein stress response. These findings show that during amino acid starvation a primary role of aaRS quality control is to help the cell mount an effective stress response, independent of the role of editing in maintaining translational accuracy.
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