Genomic instability is a conserved factor in lifespan reduction, although the molecular mechanism is not known. Studies in the yeast Saccharomyces cerevisiae over the past 20 years have found a connection between the ribosomal RNA gene cluster (rDNA) and lifespan. The highly repetitive rDNA exhibits genomic instability, and the antiaging histone deacetylase gene SIR2 regulates this instability. We previously proposed that SIR2 governs lifespan by repressing rDNA noncoding transcription and rDNA instability, but the extent to which lifespan is affected by SIR2 acting at the rDNA versus other genomic regions, and the relationship between rDNA noncoding transcription/rDNA stability and lifespan have remained controversial. To control rDNA noncoding transcription and rDNA instability, we use a strain in which the rDNA noncoding promoter is replaced with an inducible promoter. Here, we show that repression of noncoding transcription extends lifespan and makes SIR2 dispensable for lifespan extension. These results indicate that Sir2 maintains lifespan through repression of E-pro noncoding transcription in the rDNA cluster, rather than pleiotropically at other loci. The observation of rDNA instability in other organisms, including humans, suggests that this may be a conserved aging pathway.
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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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Evidence ID | Analyze ID | File | Description |
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