ArticleNucleic acids research2011
Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 81 citations in OpenAlex.
- Anticodon loop remodeling and D-stem shape drive the specific recognition of ANN-decoding tRNAs for t6A modification.Nucleic acids research · 2026Article
- A novel homozygous in-frame deletion variant in TPRKB causing Galloway-Mowat syndrome 5.Neurogenetics · 2026Article
- Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.Nature communications · 2024Article
- RNA modifying enzymes shape tRNA biogenesis and function.The Journal of biological chemistry · 2024Review
- O-Sialoglycoprotein Endopeptidase Deficiency Impairs Proteostasis and Induces Autophagy in Human Embryonic Stem Cells.International journal of molecular sciences · 2024Article
- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens.Journal of translational medicine · 2024Article
- Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.Nucleic acids research · 2024Article
- Sua5 catalyzing universal tmSphere · 2024Article
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- A paralog of Pcc1 is the fifth core subunit of the KEOPS tRNA-modifying complex in Archaea.Nature communications · 2023Article
- NovelFrontiers in molecular neuroscience · 2023Article
- Unraveling the Pathobiological Role of the Fungal KEOPS Complex in Cryptococcus neoformans.mBio · 2022Article
- 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
- 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
- Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli.Nucleic acids research · 2021Article
- Article
- A substrate binding model for the KEOPS tRNA modifying complex.Nature communications · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
The EKC/KEOPS complex is universally conserved in Archaea and Eukarya and has been implicated in several cellular processes, including transcription, telomere homeostasis and genomic instability. However, the molecular function of the complex has remained elusive so far. We analyzed the transcriptome of EKC/KEOPS mutants and observed a specific profile that is highly enriched in targets of the Gcn4p transcriptional activator. GCN4 expression was found to be activated at the translational level in mutants via the defective recognition of the inhibitory upstream ORFs (uORFs) present in its leader. We show that EKC/KEOPS mutants are defective for the N6-threonylcarbamoyl adenosine modification at position 37 (t(6)A(37)) of tRNAs decoding ANN codons, which affects initiation at the inhibitory uORFs and provokes Gcn4 de-repression. Structural modeling reveals similarities between Kae1 and bacterial enzymes involved in carbamoylation reactions analogous to t(6)A(37) formation, supporting a direct role for the EKC in tRNA modification. These findings are further supported by strong genetic interactions of EKC mutants with a translation initiation factor and with threonine biosynthesis genes. Overall, our data provide a novel twist to understanding the primary function of the EKC/KEOPS and its impact on several essential cellular functions like transcription and telomere homeostasis.
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