ArticleNucleic acids research2022
Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Resurrecting tRNAs of the Last Universal Common Ancestor (Commonote) Toward Rebuilding the Ancient Translation System.Journal of molecular evolution · 2026Article
- Anticodon loop remodeling and D-stem shape drive the specific recognition of ANN-decoding tRNAs for t6A modification.Nucleic acids research · 2026Article
- Catalytic and regulatory basis of tRNA tNature communications · 2026Article
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response.Nature communications · 2026Article
- WDR5-H3K4me3 Epigenetic Axis Promotes TRMT6-Dependent tRNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetically Predicted tClinical, cosmetic and investigational dermatology · 2026Article
- Serine tRNAs compete to regulate the mRNA translation of serine-sensitive codons.Science advances · 2025Article
- Connecting tRNA Charging and Decoding through the Axis of Nucleotide Modifications at Position 37.Journal of molecular biology · 2025Review
- Galloway-mowat syndrome 3 (GAMOS3): a novel disease-causing variant in OSGEP gene and expansion of the clinical spectrum.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- OSGEP, A Negative Ferroptotic Regulator, Alleviates Cerebral Ischemia-Reperfusion Injury Through Modulating mNeurochemical research · 2025Article
- Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.Nature communications · 2024Article
- OSGEP regulates islet β-cell function by modulating proinsulin translation and maintaining ER stress homeostasis in mice.Nature communications · 2024Article
- Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming.Nature cancer · 2024Article
- Activity reconstitution of Kre33 and Tan1 reveals a molecular ruler mechanism in eukaryotic tRNA acetylation.Nucleic acids research · 2024Article
- Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.Nucleic acids research · 2024Article
- Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression.Nucleic acids research · 2024Article
- 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
- Unravelling Strain-Specific Modifications of Toxoplasma gondii tRNA and sncRNA Using LC-MS/MS.Microbiology spectrum · 2023Article
- The tRNA identity landscape for aminoacylation and beyond.Nucleic acids research · 2023Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N 6-Threonylcarbamoyladenosine (t6A) is a universal and pivotal tRNA modification. KEOPS in eukaryotes participates in its biogenesis, whose mutations are connected with Galloway-Mowat syndrome. However, the tRNA substrate selection mechanism by KEOPS and t6A modification function in mammalian cells remain unclear. Here, we confirmed that all ANN-decoding human cytoplasmic tRNAs harbor a t6A moiety. Using t6A modification systems from various eukaryotes, we proposed the possible coevolution of position 33 of initiator tRNAMet and modification enzymes. The role of the universal CCA end in t6A biogenesis varied among species. However, all KEOPSs critically depended on C32 and two base pairs in the D-stem. Knockdown of the catalytic subunit OSGEP in HEK293T cells had no effect on the steady-state abundance of cytoplasmic tRNAs but selectively inhibited tRNAIle aminoacylation. Combined with in vitro aminoacylation assays, we revealed that t6A functions as a tRNAIle isoacceptor-specific positive determinant for human cytoplasmic isoleucyl-tRNA synthetase (IARS1). t6A deficiency had divergent effects on decoding efficiency at ANN codons and promoted +1 frameshifting. Altogether, our results shed light on the tRNA recognition mechanism, revealing both commonality and diversity in substrate recognition by eukaryotic KEOPSs, and elucidated the critical role of t6A in tRNAIle aminoacylation and codon decoding in human cells.
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