ArticleNucleic acids research2013
In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 82 citations in OpenAlex.
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- Purine Chemistry in the Early RNA World at the Origins of Life: From RNA and Nucleobases Lesions to Current Key Metabolic Routes.Chembiochem : a European journal of chemical biology · 2025Review
- Targeting emerging amino acid dependencies and transporters in cancer therapy.Frontiers in pharmacology · 2025Review
- Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.Nature communications · 2024Article
- Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.Nucleic acids research · 2024Article
- Tyrosine transfer RNA levels and modifications during blood-feeding and vitellogenesis in the mosquito,bioRxiv : the preprint server for biology · 2023Article
- Structure-function analysis of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases.Nucleic acids research · 2023Article
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- Article
- A paralog of Pcc1 is the fifth core subunit of the KEOPS tRNA-modifying complex in Archaea.Nature communications · 2023Article
- The universal Sua5/TsaC family evolved different mechanisms for the synthesis of a key tRNA modification.Frontiers in microbiology · 2023Article
- Epitranscriptome: Review of Top 25 Most-Studied RNA Modifications.International journal of molecular sciences · 2022Review
- Conservation and Diversification of tRNA tInternational journal of molecular sciences · 2022Review
- Nuclear Functions of KaeA, a Subunit of the KEOPS Complex inInternational journal of molecular sciences · 2022Article
- Article
- Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs.Nucleic acids research · 2022Article
- Biallelic variants in YRDC cause a developmental disorder with progeroid features.Human genetics · 2021Article
- The structural and functional workings of KEOPS.Nucleic acids research · 2021Review
- tRNA-modifying enzyme mutations induce codon-specific mistranslation and protein aggregation in yeast.RNA biology · 2021Article
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9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N(6)-threonylcarbamoyladenosine (t(6)A) is a modified nucleotide found in all transfer RNAs (tRNAs) decoding codons starting with adenosine. Its role is to facilitate codon-anticodon pairing and to prevent frameshifting during protein synthesis. Genetic studies demonstrated that two universal proteins, Kae1/YgjD and Sua5/YrdC, are necessary for t(6)A synthesis in Saccharomyces cerevisiae and Escherichia coli. In Archaea and Eukarya, Kae1 is part of a conserved protein complex named kinase, endopeptidase and other proteins of small size (KEOPS), together with three proteins that have no bacterial homologues. Here, we reconstituted for the first time an in vitro system for t(6)A modification in Archaea and Eukarya, using purified KEOPS and Sua5. We demonstrated binding of tRNAs to archaeal KEOPS and detected two distinct adenosine triphosphate (ATP)-dependent steps occurring in the course of the synthesis. Our data, together with recent reconstitution of an in vitro bacterial system, indicated that t(6)A cannot be catalysed by Sua5/YrdC and Kae1/YgjD alone but requires accessory proteins that are not universal. Remarkably, we observed interdomain complementation when bacterial, archaeal and eukaryotic proteins were combined in vitro, suggesting a conserved catalytic mechanism for the biosynthesis of t(6)A in nature. These findings shed light on the reaction mechanism of t(6)A synthesis and evolution of molecular systems that promote translation fidelity in present-day cells.
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