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RDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast.

ABSTRACT: rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast.

PROVIDER: PRJNA796823 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17601507_1.fastq.gz	Fastqsanger.gz
	SRR17601507_2.fastq.gz	Fastqsanger.gz
	SRR17601108_1.fastq.gz	Fastqsanger.gz
	SRR17601108_2.fastq.gz	Fastqsanger.gz
	SRR17601508_1.fastq.gz	Fastqsanger.gz

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rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - ATACseq

Project description:In this study we perform ATAC-seq of budding yeast strains with variable copy number of the rRNA genes (rDNA CN). We aim to better understand the relationship between DNA accessibility and replicative lifespan in strains with variable rDNA CN.

2022-04-05 | GSE193598 | GEO

rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - ATACseq

Project description:rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - ATACseq

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rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - RNAseq

Project description:rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - RNAseq

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rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast - RNAseq

Project description:In this study we perform RNA-seq of budding yeast strains with variable copy number of the rRNA genes (rDNA CN) to assess the relationship between rDNA CN and gene expression. RNA-seq was performed on samples both with and without polyA selection (for all transcripts and for rRNA transcripts, respectively).

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rDNA array length is a major determinant of replicative lifespan in budding yeast.

Project description:The complex processes and interactions that regulate aging and determine lifespan are not fully defined for any organism. Here, taking advantage of recent technological advances in studying aging in budding yeast, we discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene present in its chromosomal array and replicative lifespan (RLS). Specifically, the chromosomal ribosomal DNA (rDNA) copy number (rDNA CN) positively correlated with RLS and this interaction explained over 70% of variability in RLS among a series of wild-type strains. In strains with low rDNA CN, SIR2 expression was attenuated and extrachromosomal rDNA circle (ERC) accumulation was increased, leading to shorter lifespan. Suppressing ERC formation by deletion of FOB1 eliminated the relationship between rDNA CN and RLS. These data suggest that previously identified rDNA CN regulatory mechanisms limit lifespan. Importantly, the RLSs of reported lifespan-enhancing mutations were significantly impacted by rDNA CN, suggesting that changes in rDNA CN might explain the magnitude of some of those reported effects. We propose that because rDNA CN is modulated by environmental, genetic, and stochastic factors, considering rDNA CN is a prerequisite for accurate interpretation of lifespan data.

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rDNA Array Length is a Major Determinant of Replicative Lifespan in Budding Yeast.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-04-05 | GSE193600 | GEO

Yeast transcriptome profiling in replicative ageing

Project description:A crucial step towards understanding the mechanisms underlying aging is to obtain an integrated account of the molecular changes during aging. To address this, we mapped the yeast (S. cerevisiae) transcriptome during the replicative lifespan of budding yeast using novel culture and computational methods.

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Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae

Project description:Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality-control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes. These are all CGH arrays comparing DNA content between the indicated strain of interest and a wt control.

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Project description:The involvement of protein chaperones in aging is intriguing and their potential contribution has, so far, been attributed solely to their central role in proteostasis. Here we show that four protein chaperones from different cellular compartments extend replicative lifespan (RLS) in budding yeast by a common mechanism akin to caloric restriction. The RLS extension relies on the increased direct activation of Snf1 kinase by Hsp90, thereby bypassing the signal on the environmental glucose level. The chaperone-related RLS extension is accompanied by the uncoupling of the respiratory chain. A genomic approach confirmed the repression of glycolysis and cytoplasmic translation, and contrary, activation of gluconeogenesis and fatty acid oxidation. Our results set a novel paradigm for the role of protein chaperones: by modulation of the chaperone expression level one can affect metabolic features such as glucose sensing, fatty acid consumption, respiration rate, and, consequently, modify lifespan. We expect the described mechanism to open new avenues for research in aging and age-related diseases.

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