Regulation of the hypertonic stress response by the 3’ mRNA cleavage and polyadenylation complex
Bibliographic record
Abstract
Abstract Maintenance of osmotic homeostasis is one of the most aggressively defended homeostatic setpoints in physiology. One major mechanism of osmotic homeostasis involves the upregulation of proteins that catalyze the accumulation of solutes called organic osmolytes. To better understand how osmolyte accumulation proteins are regulated, we conducted forward genetic screen in C. elegans for mutants with no induction of osmolyte biosynthesis gene expression (Nio mutants). nio-3 mutants encoded a missense mutation in cpf-2 /CstF64 while nio-7 mutants encoded a missense mutation in symk-1 /Symplekin. Both cpf-2 and symk-1 are nuclear components of the highly conserved 3’ mRNA cleavage and polyadenylation complex. cpf-2 and symk-1 block the hypertonic induction of gpdh-1 and other osmotically induced mRNAs, suggesting they act at the transcriptional level. We generated a functional auxin-inducible degron (AID) allele for symk-1 and found that acute, post-developmental degradation in the intestine and hypodermis was sufficient to cause the Nio phenotype. symk-1 and cpf-2 exhibit genetic interactions that strongly suggest they function through alterations in 3’ mRNA cleavage and/or alternative polyadenylation. Consistent with this hypothesis, we find that inhibition of several other components of the mRNA cleavage complex also cause a Nio phenotype. cpf-2 and symk-1 specifically affect the osmotic stress response since heat shock-induced upregulation of a hsp-16 . 2::GFP reporter is normal in these mutants. Our data suggest a model in which alternative polyadenylation of one or more mRNAs is essential to regulate the hypertonic stress response.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".