Does Saccharomyces cerevisiae Require Specific Post-Translational Silencing against Leaky Translation of Hac1up?
Bibliographic record
Abstract
HAC1 encodes a key transcription factor that transmits the unfolded protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus and regulates downstream UPR genes in Saccharomyces cerevisiae. In response to the accumulation of unfolded proteins in the ER, Ire1p oligomers splice HAC1 pre-mRNA (HAC1u) via a non-conventional process and allow the spliced HAC1 (HAC1i) to be translated efficiently. However, leaky splicing and translation of HAC1u may occur in non-UPR cells to induce undesirable UPR. To control accidental UPR activation, multiple fail-safe mechanisms have been proposed to prevent leaky HAC1 splicing and translation and to facilitate rapid degradation of translated Hac1up and Hac1ip. Among proposed regulatory mechanisms is a degron sequence encoded at the 5′ end of the HAC1 intron that silences Hac1up expression. To investigate the necessity of an intron-encoded degron sequence that specifically targets Hac1up for degradation, we employed publicly available transcriptomic data to quantify leaky HAC1 splicing and translation in UPR-induced and non-UPR cells. As expected, we found that HAC1u is only efficiently spliced into HAC1i and efficiently translated into Hac1ip in UPR-induced cells. However, our analysis of ribosome profiling data confirmed frequent occurrence of leaky translation of HAC1u regardless of UPR induction, demonstrating the inability of translation fail-safe to completely inhibit Hac1up production. Additionally, among 32 yeast HAC1 surveyed, the degron sequence is highly conserved by Saccharomyces yeast but is poorly conserved by all other yeast species. Nevertheless, the degron sequence is the most conserved HAC1 intron segment in yeasts. These results suggest that the degron sequence may indeed play an important role in mitigating the accumulation of Hac1up to prevent accidental UPR activation in the Saccharomyces yeast.
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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".