Zymocin-induced cell death in Saccharomyces cerevisiae requires the toxin-target (TOT) effector Elongator, a protein complex with functions in transcription, exocytosis and tRNA modification. In line with the latter, trm9Delta cells lacking a tRNA methylase specific for wobble uridine (U(34)) residues survive zymocin and in excess, the Trm9 substrate tRNA(Glu) copies zymocin protection of Elongator mutants. Phenotypes typical of a tot3/elp3Delta Elongator mutant are absent from trm9Delta cells but copied in a tot3Deltatrm9Delta double mutant suggesting that Elongator acts upstream of Trm9. Consistent with Elongator-dependent tRNA modification being more important to mRNA decoding than Trm9, SUP4 and SOE1TRNA suppressors are highly sensitive to loss of Elongator and tRNA U(34) hypomodification. As Trm9 overexpression counteracts the effect of high-copy tRNA(Glu), zymocin suppression by high-copy tRNA(Glu) may reflect tRNA hypomethylation of trm9Delta cells. Thus, Trm9 methylation may enable recognition of tRNA by zymocin, a notion supported by a dramatic reduction of tRNA(Glu) levels in zymocin-treated cells and by cytotoxic zymocin residues conserved between bacterial nucleases and a tRNA modifying GTPase. In sum, Trm9 is a bona fideTOT pathway component whose methylation may be hijacked by zymocin to target tRNA function and eventually, mRNA translation.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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