Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA388412 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional derepression uncovers cryptic higher-order genetic interactions
| PRJNA292735 | ENA
Project description:A central question in genetics and evolution is the extent to which mutations have outcomes that change depending on the genetic context in which they occur. Pairwise interactions between mutations have been systematically mapped within and between genes, and contribute substantially to phenotypic variation amongst individuals. However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear. Here we quantify >45,000 genetic interactions between the same 87 pairs of mutations across >500 closely related genotypes of a yeast tRNA. Strikingly, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (FDR<0.1). Higher order interactions are also abundant and dynamic across genotypes. The epistasis in this molecule means that all individual mutations switch from detrimental to beneficial in even closely-related genotypes. As a consequence, accurate genetic prediction requires mutation effects to be measured across different genetic backgrounds and the use of higher order epistatic terms.
2018-03-06 | GSE99418 | GEO
Project description:Histone H3 N-terminus Regulates Higher Order Structure of Yeast Heterochromatin
| PRJNA117439 | ENA
Project description:Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that a C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, directed-evolution of the C268A mutant result in intragenic mutations that restore heat resistance but not editing. C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, and the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in ThrRS aminoacylation or editing alone is not sufficient to cause heat sensitivity, and that C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.
2024-01-26 | PXD042145 | Pride
Project description:The canonical role of eEF1A is to deliver the aminoacyl tRNA to the ribosome, we have used the yeast model system to investigate further roles for this protein. We used microarray to study the transcriptomic effects of elevated levels of eEF1A on yeast cells during log phase growth
2016-10-29 | GSE89286 | GEO
Project description:Use of Pleiotropy to Model Genetic Interactions in a Population
| PRJNA151043 | ENA
Project description:The polyploid S. cerevisiae karyotypes were analyzed by array-CGH to identify the deletion or duplication of gene or chromosome during the strain construction and after experimental evolution.
2016-10-11 | GSE76595 | GEO
Project description:Altering the genetic code for applications in synthetic biology and genetic code expansion involves engineered tRNAs that incorporate amino acids that differ from what is defined by the “standard” genetic code. Since these engineered tRNA variants can be lethal due to proteotoxic stress, regulating their expression is necessary to achieve high levels of the resulting novel proteins. Mechanisms to positively regulate transcription with exogenous activator proteins like those often used to regulate RNA polymerase II (RNAP II) transcribed genes are not applicable to tRNAs as their expression by RNA polymerase III requires elements internal to the tRNA. Here, we show that tRNA expression is repressed by overlapping transcription from an adjacent RNAP II promoter. Regulating the expression of the RNAP II promoter allows inverse regulation of the tRNA. Placing either Gal4 or TetR-VP16 activated promoters downstream of a mistranslating tRNA serine variant that mis-incorporates serine at proline codons in Saccharomyces cerevisiae allows mistranslation at a level not otherwise possible because of the toxicity of the unregulated tRNA. Using mass spectrometry, we determine th frequency of mistranslation in both the induced and repressed conditions of the galactose inducible and tetracycline inducible systems.
2021-11-03 | PXD028496 | Pride
Project description:To characterize the ecological interactions among S. cerevisiae strains coming from the same geographical area, we examined the fitness of two natural isolates from San Giovese grapes, alone or in competition, in synthetic wine must (SWM). We performed genome-wide analyses in order to identify the genes involved in yeast competition and cooperation.
2015-07-07 | GSE49550 | GEO