The environmental stress response causes ribosome loss in aneuploid yeast cells.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA611978 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11289200.fastq.gz | Fastqsanger.gz | |||
| SRR11289300.fastq.gz | Fastqsanger.gz | |||
| SRR11289201.fastq.gz | Fastqsanger.gz | |||
| SRR11289301.fastq.gz | Fastqsanger.gz | |||
| SRR11289202.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 176 |
Similar Datasets
Project description:Aneuploidy, a condition characterized by whole chromosome gains and losses, is often associated with significant cellular stress and decreased fitness. However, whether and how cells respond to the aneuploid state has remained controversial. In aneuploid budding yeast, two opposing gene expression patterns have been reported: an environmental stress response (ESR) and a “common aneuploidy gene-expression” (CAGE) signature, in which many ESR genes are oppositely regulated. Here, we investigate and bring clarity to this controversy. We show that the CAGE signature is not an aneuploidy-specific gene expression signature but is the result of euploid control cells, but not aneuploid cells, having grown into stationary phase. Because growth into stationary phase is amongst the strongest inducers of the ESR, the ESR in aneuploid cells was masked when stationary phase euploid cells were used for normalization in transcriptomic studies. When exponentially growing euploid cells are used in gene expression comparisons with aneuploid cells, the CAGE signature is no longer evident in aneuploid cells. Instead, aneuploid cells are found to exhibit the ESR. We further show that the ESR causes a selective loss of ribosomes in aneuploid cells, providing an explanation for the decreased cellular density in aneuploid cells. We conclude that aneuploid budding yeast cells mount the ESR, rather than a CAGE signature, in response to aneuploidy-induced cellular stresses that results in selective ribosome loss.
2020-06-16 | GSE146791 | GEO
Project description:Aneuploidy, a condition characterized by whole chromosome gains and losses, is often associated with significant cellular stress and decreased fitness. However, how cells respond to the aneuploid state has remained controversial. In aneuploid budding yeast, two opposing gene-expression patterns have been reported: the "environmental stress response" (ESR) and the "common aneuploidy gene-expression" (CAGE) signature, in which many ESR genes are oppositely regulated. Here, we investigate this controversy. We show that the CAGE signature is not an aneuploidy-specific gene-expression signature but the result of normalizing the gene-expression profile of actively proliferating aneuploid cells to that of euploid cells grown into stationary phase. Because growth into stationary phase is among the strongest inducers of the ESR, the ESR in aneuploid cells was masked when stationary phase euploid cells were used for normalization in transcriptomic studies. When exponentially growing euploid cells are used in gene-expression comparisons with aneuploid cells, the CAGE signature is no longer evident in aneuploid cells. Instead, aneuploid cells exhibit the ESR. We further show that the ESR causes selective ribosome loss in aneuploid cells, providing an explanation for the decreased cellular density of aneuploid cells. We conclude that aneuploid budding yeast cells mount the ESR, rather than the CAGE signature, in response to aneuploidy-induced cellular stresses, resulting in selective ribosome loss. We propose that the ESR serves two purposes in aneuploid cells: protecting cells from aneuploidy-induced cellular stresses and preventing excessive cellular enlargement during slowed cell cycles by down-regulating translation capacity.
| S-EPMC7382292 | biostudies-literature
Project description:Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.
2024-07-31 | GSE269238 | GEO
Project description:Premature aging in aneuploid yeast is influenced by aneuploidy-induced defects in Ribosome Quality Control [RiboSeq]
| PRJNA1120791 | ENA
Project description:We generated forty 2n+x aneuploid yeast strains and qualify the proteomes in nine of them using SILAC.
2019-05-23 | PXD007157 | Pride
Project description:Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.
2024-07-31 | GSE269237 | GEO
Project description:Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.
2024-07-31 | GSE269236 | GEO
Project description:In general, RNA-binding proteins act to modulate gene expression at transcript level through degradation or at protein level through translation. To elucidate the effect of Whi3, a yeast RNA binding protein, on gene expression, we performed ribosome profiling experiment on whi3 mutant and wildtype cells. Comparison ribosome profiling and RNA-seq data between whi3 mutant and wildtype cells
2013-09-26 | E-GEOD-51164 | biostudies-arrayexpress
Project description:Aneuploidy, the state in which an organism’s genome contains one or more missing or additional chromosomes, often causes widespread genotypic and phenotypic effects. Most often, aneuploidies are deleterious; the most common examples in humans being Down’s syndrome (Trisomy 21) and Turner’s syndrome (monosomy X). However, aneuploidy is surprisingly common in wild yeast populations. In recent years, there has been debate as to whether yeast contain an innate dosage compensation response on the whole-genome level, or if these natural isolates are robust to aneuploidy without such a mechanism. In this study, we tested for differential gene expression in 20 aneuploid and 18 euploid lines of yeast from two previous mutation accumulation experiments, where selection was low and therefore aneuploidies arose spontaneously. We found no evidence for whole-chromosome dosage compensation in aneuploid yeast but did find some evidence for attenuation of expression on a gene-by-gene basis. We additionally found that aneuploidy has no effect on the expression of the rest of the genome (i.e. “trans” genes), and that very few mutually exclusive aneuploid lines shared differentially expressed genes. However, we found a small common differential expression response in the euploid lines, suggesting an effect of mutation accumulation on gene expression. Our findings contribute to our understanding of aneuploidy in yeast and support the hypothesis that there is no innate dosage compensation mechanism at the whole-chromosome level.
2021-03-11 | GSE168674 | GEO
Project description:To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability.
2012-06-27 | GSE36454 | GEO