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Impact of intron deletion on starvation dependent repression of gene expression

ABSTRACT: Impact of intron deletion on starvation dependent repression of gene expression

PROVIDER: PRJNA435723 | ENA |

REPOSITORIES: ENA

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Impact of intron deletion on starvation dependent repression of gene expression

Project description:Deleting the introns from either the chromatin remodeling MMS2 gene or the splicing regulator gene YSF3 modified the expression of a common set of genes in the stationary phase of growth.

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Effect of ribosomal protein intron deletion on gene expression

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Intron-mediated induction of phenotypic heterogeneity

Project description:Introns are universally present in the nuclear genomes of eukaryotes. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein (RP) genes differing primarily in their introns. Despite recent findings on the role of RP introns under stress and starvation, understanding the contribution of introns to ribosome regulation remains challenging. Here, combining isogrowth profiling with single-cell protein measurements, we found that introns can mediate inducible phenotypic heterogeneity conferring a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low Rps22B protein levels resulted in prolonged survival under sustained starvation, while high Rps22B levels enabled cells to grow faster after transient starvation. Further, yeast growing at high sugar concentrations – similar to those in ripe grapes – exhibit bimodal Rps22B expression when approaching stationary phase. Differential intron-mediated regulation of RP genes thus provides a way to diversify the population when starvation looms in natural environments. Our findings reveal a new role for introns in inducing phenotypic heterogeneity in changing environments and suggest that duplicated RP genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness.

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A dual-activity topoisomerase complex promotes both transcriptional activation and repression in response to starvation

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Project description:Recent pre-clinical data provide strong evidence that short-term starvation before the administration of cytostatic drugs for the chemotherapy of solid tumors leads to significantly higher efficacy and lower toxicity levels. However, these findings have so far not been validated in patients. The aim of this trial is to provide first clinical evidence regarding the impact of pre-chemotherapeutic short-term starvation on response to therapy (primary endpoint). Additionally, progression-free survival, adverse events, and overall survival will be monitored (secondary endpoints). In perspective, short-term starvation before chemotherapy could represent a simple and secure way to improve both efficacy and tolerance of chemotherapies at low cost.

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