The heme-regulated inhibitor kinase Hri1 is activated in response to aminolevulinic acid deficiency in Schizosaccharomyces pombe
Bibliographic record
Abstract
A key mechanism for regulating the initiation of protein synthesis in response to various stresses involves the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Schizosaccharomyces pombe possesses three distinct eIF2α kinases: Hri1, Hri2, and Gcn2. Using a strain that is unable to synthesize heme de novo (hem1Δ), global transcriptome analysis reveals that among the genes encoding these kinases, hri1+ is the most strongly induced under δ-aminolevulinate (ALA)-limiting conditions. The induction of hri1+ consistently correlates with increased eIF2α phosphorylation and a reduction in global protein translation in ALA-starved hem1Δ cells. In contrast, hem1Δ cells lacking hri1+ (hri1Δ) exhibit poor eIF2α phosphorylation under the same stress conditions. When ALA-starved hem1Δ hri1Δ cells are subsequently transferred to a medium supplemented with exogenous hemin, they exhibit impaired growth compared to ALA-starved hem1Δ cells expressing the endogenous hri1+ allele or hem1Δ hri1Δ hri2Δ gcn2Δ cells expressing functional hri1+ and hri1+-GFP alleles. Consistent with its role as a heme-sensing eIF2α kinase, further analysis by absorbance spectroscopy demonstrates that Hri1 binds to hemin, with an equilibrium dissociation constant (KD) of 0.11 µM. In contrast, a truncated form of Hri1 (from residues 1-185) fails to interact with hemin. Taken together, these findings provide the first report of a fungal eIF2α kinase being activated in response to stress directly linked to a defect in heme homeostasis.
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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 | 0.000 |
| 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".