ArticleRNA biology2014
TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish.
Article in RNA biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Error-prone translation as a driver of proteostasis collapse and neurodegeneration.Neural regeneration research · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- Article
- Mistranslating tRNA variants impact the proteome and phosphoproteome of Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2026Article
- Mistranslating tRNA variants impact the proteome and phosphoproteome ofbioRxiv : the preprint server for biology · 2025Article
- Specific branches of the proteostasis network regulate the toxicity associated with mistranslation.Nucleic acids research · 2025Article
- Mistranslating tRNA variants have anticodon- and sex-specific impacts on Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Impact of tRNA-induced proline-to-serine mistranslation on the transcriptome of Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Mistranslating tRNA variants have anticodon- and sex-specific impacts onbioRxiv : the preprint server for biology · 2024Article
- Impact of tRNA-induced proline-to-serine mistranslation on the transcriptome ofbioRxiv : the preprint server for biology · 2024Article
- Transcriptome Profiling of Etridiazole-Exposed Zebrafish (International journal of molecular sciences · 2023Article
- Transcriptome Analysis of Thiram-Treated Zebrafish (Biology · 2023Article
- Anticodon sequence determines the impact of mistranslating tRNARNA biology · 2023Article
- Genetic background and mistranslation frequency determine the impact of mistranslating tRNASerUGG.G3 (Bethesda, Md.) · 2022Article
- A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects.G3 (Bethesda, Md.) · 2022Article
- Human cells adapt to translational errors by modulating protein synthesis rate and protein turnover.RNA biology · 2020Article
- Polymerase III transcription is necessary for T cell priming by dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Deletion of Gtpbp3 in zebrafish revealed the hypertrophic cardiomyopathy manifested by aberrant mitochondrial tRNA metabolism.Nucleic acids research · 2019Article
- Deletion of Mtu1 (Trmu) in zebrafish revealed the essential role of tRNA modification in mitochondrial biogenesis and hearing function.Nucleic acids research · 2018Article
- Errors in protein synthesis increase the level of saturated fatty acids and affect the overall lipid profiles of yeast.PloS one · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.