The isomerase Rrd1 mediates rapid loss of the Sgs1 helicase in response to rapamycin
Bibliographic record
Abstract
In Saccharomyces cerevisiae , rapamycin exposure inhibits the target of rapamycin (TOR) signaling pathway, causing a profound alteration in the transcription pattern of many genes, including those involved in ribosome biogenesis and nutritional changes. Deletion of the RRD1 gene encoding a peptidyl prolyl isomerase resulted in mutants that are resistant to rapamycin. These rrd1Δ mutants are unable to efficiently downregulate genes such as ribosomal protein genes, or to upregulate genes involved in diauxic shift. It is believed that the isomerase function of Rrd1 plays a role in changing the transcriptional profile upon rapamycin exposure. Herein, we set out to search for genes that when deleted in the rrd1Δ mutant would suppress the rapamycin-resistant phenotype. The analysis revealed that deletion of the SGS1 gene in the rrd1Δ mutant partially suppresses the rapamycin-resistant phenotype of the single rrd1Δ mutant. SGS1 encodes a helicase that functions in many biological processes, including transcriptional regulation. We further show, and for the first time, that Sgs1 is rapidly lost in the parent cells in response to rapamycin, but not by other agents. Interestingly, Sgs1 reduction was completely blocked in the rrd1Δ mutant, suggesting that Rrd1 is required to mediate this process. Genes such as PUT4 and HSP42, known to be upregulated in the parent in response to rapamycin, were not induced in the rrd1Δ mutant if the SGS1 gene was deleted. Since Sgs1 plays a role in transcriptional regulation, we propose that it acts as a repressor of a subset of rapamycin responsive genes. Thus, the observed Rrd1-dependent reduction in Sgs1 level may promote expression of specific classes of genes in response to rapamycin.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".