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Dataset | Description | Keywords | Number of Conditions | Reference |
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Air-liquid interfacial biofilm vs planktonic S. cerevisiae cells | Goal was to identify yeast genes whose expression changed as a function of the shift from growth in bulk culture to growth in an air-liquid interfacial biofilm. | fermentation, environmental-sensing | 6 | Zara S, et al. (2010) PMID:20435772 |
Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability II | Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, and as a translational repressor, but their functions in cells are incompletely understood. We have analyzed these questions by a combination of ribosome profiling, RNA-Seq, CAGE analysis of capped mRNAs. | filamentous growth, nutrient utilization, environmental-sensing | 14 | Vijjamarri AK, et al. (2023) PMID:36711592 |
Global repression driven by RNA polymerase II stalling in yeast | In multicellular eukaryotes, RNA polymerase (pol) II pauses transcription ~30-50 bp after initiation, and involves DSIF and other factors. While the budding yeast Saccharomyces has its transcription mechanisms mostly conserved with other eukaryotes, it appears to lack this fundamental promoter-proximal pausing. However, we now discover that acute stress (e.g., peroxide) causes most yeast genes, including constitutive and stress-induced genes, to manifest two distinct pausing or stall sites during the early elongation phase of Pol II transcription. The first stall occurs at the promoter, where Pol II melts the DNA and acquires all tested interactions normally. The second stall occurs 100-200 bp downstream. It too has most, but not all, of the tested interactions. This stall is phenocopied by depletion of DSIF. Our results suggest that similar to other eukaryotes, in yeast stalling globally down regulates nearly all Pol II transcription, but primarily in response to acute stimuli, whereas in other eukaryotes it represents the default state in all cells. | transcriptional regulation, environmental-sensing | 104 | Badjatia N, et al. (2021) PMID:33472084 |
Measurement of mRNA stability during transcriptional memory in mutants for RNA degradation | Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Factors related to chromatin organization and activation of transcription have been shown to play a role in the faster response of those cells previously exposed to a stimulus (primed). However, the contribution of post-transcriptional regulation is not yet explored. Here, we investigate the contribution of cytoplasmic RNA decay to this process, we investigate global changes in mRNA turnover in ski2∆ (component of the cytoplasmic 3’-5’exosome) and xrn1∆ (cytoplasmic 5’-3’exonuclease) strains in S. cerevisiae. | environmental-sensing | 30 | Li B, et al. (2023) PMID:36801853 |
Molecular basis of complex heritability in natural genotype-to-phenotype relationships | The intrinsic complexity of quantitative traits was evident even before the molecular nature of the gene was understood. Yet we still lack a detailed molecular understanding of complex heritability. Here we alleviated statistical roadblocks to high-resolution genetic mapping by using an inbred population of diploid yeast with very low linkage disequilibrium and more individuals than segregating polymorphisms. We mapped over 18,000 quantitative trait loci, resolving more than 3,300 to single nucleotides. This allowed us to explore the molecular origins of complexity, hybrid vigor, pleiotropy, and gene ´ environment interactions and to rigorously estimate the distribution of fitness effects of natural genetic variation. Our results describe a comprehensive, high-resolution genotype-to-phenotype map and define general principles underlying the complexity of heredity. | environmental-sensing, evolution | 18 | |
Multi-environment fitness landscapes of a tRNA gene | A fitness landscape (FL) describes the genotype-fitness relationship in a given environment. To explain and predict evolution, it is imperative to measure the FL in multiple environments because the natural environment changes frequently. Using a high-throughput method that combines precise gene replacement with next-generation sequencing, we determine the in vivo FL of a yeast tRNA gene comprising over 23,000 genotypes in four environments. Although genotype-by-environment interaction (G×E) is abundantly detected, its pattern is so simple that we can transform an existing FL to that in a new environment with fitness measures of only a few genotypes in the new environment. Under each environment, we observe prevalent, negatively biased epistasis between mutations (G×G). Epistasis-by-environment interaction (G×G×E) is also prevalent, but trends in epistasis difference between environments are predictable. Our study thus reveals simple rules underlying seemingly complex FLs, opening the door to understanding and predicting FLs in general. | environmental-sensing, evolution, genome variation | 5 | |
Pbp1 associates with Puf3 and promotes translation of its target mRNAs involved in mitochondrial biogenesis | Pbp1 (polyA-binding protein - binding protein 1) is a stress granule marker and polyglutamine expansions in its mammalian ortholog ataxin-2 have been linked to neurodegenerative conditions. Pbp1 was recently shown to form intracellular assemblies that function in the negative regulation of TORC1 signaling under respiratory conditions. Furthermore, it was observed that loss of Pbp1 leads to mitochondrial dysfunction. Here, we show that loss of Pbp1 leads to a specific decrease in mitochondrial proteins whose encoding mRNAs are targets of the RNA-binding protein Puf3, suggesting a functional relationship between Pbp1 and Puf3. We found that Pbp1 stabilizes and promotes the translation of Puf3-target mRNAs in respiratory conditions, such as those involved in the assembly of cytochrome c oxidase. We further show that Pbp1 and Puf3 associate through their respective low complexity domains, which is required for target mRNA stabilization and translation. Our findings reveal a key role for Pbp1-containing assemblies in enabling the translation of mRNAs critical for mitochondrial biogenesis and respiration under metabolically challenging conditions. They may further explain prior associations of Pbp1/ataxin-2 with stress granule biology and RNA metabolism. | stress, environmental-sensing | 8 | |
Simultaneous estimation of gene regulatory network structure and RNA kinetics from single cell gene expression | Cells respond to environmental and developmental stimuli by changing their transcriptomes through both regulation of transcription rate and regulated mRNA decay. These biophysical properties determine the transcriptional state of a cell, but measuring them requires metabolic RNA labeling (e.g. 4-thiouracil pulse-chase) to separate RNA decay from synthesis rates. We approach this problem by sequencing individual Saccharomyces cerevisiae cell transcriptomes by continuously sampling from a population without metabolic labeling. Using this continuous-sampling system, we measure expression in 180,000 individual cells both prior to and in response to rapamycin treatment. The rates of change for each transcript can be calculated on a per-cell basis to give smooth, biologically relevant, estimates of RNA velocity. We then train deep learning models to use this transcriptomic and velocity information to make time-dependent predictions about RNA biophysics, and to infer causal regulatory relationships between transcription factors and their genes. | chemical stimulus, environmental-sensing | 35 | |
The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae | Prolonged cell cycle arrests occur naturally in differentiated cells and in response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether and how cells survive prolonged cell cycle arrests is not clear. Here, we used S. cerevisiae to compare physiological cell cycle arrests and genetically induced arrests in G1-, meta- and anaphase. Prolonged cell cycle arrest led to growth attenuation in all studied conditions, coincided with activation of the Environmental Stress Response (ESR) and with a reduced ribosome content as determined by whole ribosome purification and TMT mass spectrometry. Suppression of the ESR through hyperactivation of the Ras/PKA pathway reduced cell viability during prolonged arrests, demonstrating a cytoprotective role of the ESR. Attenuation of cell growth and activation of stress induced signaling pathways also occur in arrested human cell lines, raising the possibility that the response to prolonged cell cycle arrest is conserved. | environmental-sensing, stress | 159 | Terhorst A, et al. (2023) PMID:37123399 |
Wild-type yeast vs delta esl1/ delta esl2 mutant strain | Transcript profiling of the double delta esl1/ delta esl2 mutant versus wild-type growning at log phase in rich meda | environmental-sensing | 4 | Lai X, et al. (2013) PMID:23893744 |