ArticleGenes & development2014
Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
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- RNA Folding Nearest Neighbor Parameters Including the Modification 1-Methyl-Pseudouridine.bioRxiv : the preprint server for biology · 2026Article
- Nanopore sequencing of intact aminoacylated tRNAs.Nature communications · 2025Article
- Mammalian tRNA acetylation determines translation efficiency and tRNA quality control.Nature communications · 2025Article
- Human TRMT1 and TRMT1L paralogs ensure the proper modification state, stability, and function of tRNAs.Cell reports · 2025Article
- Sequence modeling and design from molecular to genome scale with Evo.Science (New York, N.Y.) · 2024Article
- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Advances in the Structural and Functional Understanding of mAccounts of chemical research · 2024Article
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- Hypoxia induces alterations in tRNA modifications involved in translational control.BMC biology · 2023Article
- Initiator tRNA lacking 1-methyladenosine is targeted by the rapid tRNA decay pathway in evolutionarily distant yeast species.PLoS genetics · 2022Article
- Site-Specific Synthesis ofJournal of the American Chemical Society · 2022Article
- Effects of sequence motifs in the yeast 3' untranslated region determined from massively parallel assays of random sequences.Genome biology · 2021Article
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- HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization.Cell host & microbe · 2021Article
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- Transfer RNAs: diversity in form and function.RNA biology · 2021Review
- Fitness landscape of a dynamic RNA structure.PLoS genetics · 2021Article
- RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 5' ends, mutations that sensitize SUP4oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.
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Registered trials
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