Loss of nonsense mediated decay suppresses mutations in Saccharomyces cerevisiae TRA1
Bibliographic record
Abstract
BACKGROUND: Tra1 is an essential protein in Saccharomyces cerevisiae. It was first identified in the SAGA and NuA4 complexes, both with functions in multiple aspects of gene regulation and DNA repair, and recently found in the ASTRA complex. Tra1 belongs to the PIKK family of proteins with a C-terminal PI3K domain followed by a FATC domain. Previously we found that mutation of leucine to alanine at position 3733 in the FATC domain of Tra1 (tra1-L3733A) results in transcriptional changes and slow growth under conditions of stress. To further define the regulatory interactions of Tra1 we isolated extragenic suppressors of the tra1-L3733A allele. RESULTS: We screened for suppressors of the ethanol sensitivity caused by tra1-L3733A. Eleven extragenic recessive mutations, belonging to three complementation groups, were identified that partially suppressed a subset of the phenotypes caused by tra1-L3733A. Using whole genome sequencing we identified one of the mutations as an opal mutation at tryptophan 165 of UPF1/NAM7. Partial suppression of the transcriptional defect resulting from tra1-L3733A was observed at GAL10, but not at PHO5. Suppression was due to loss of nonsense mediated decay (NMD) since deletion of any one of the three NMD surveillance components (upf1/nam7, upf2/nmd2, or upf3) mediated the effect. Deletion of upf1 suppressed a second FATC domain mutation, tra1-F3744A, as well as a mutation to the PIK3 domain. In contrast, deletions of SAGA or NuA4 components were not suppressed. CONCLUSIONS: We have demonstrated a genetic interaction between TRA1 and genes of the NMD pathway. The suppression is specific for mutations in TRA1. Since NMD and Tra1 generally act reciprocally to control gene expression, and the FATC domain mutations do not directly affect NMD, we suggest that suppression occurs as the result of overlap and/or crosstalk in these two broad regulatory networks.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".