Cellular adaptation to low oxygen availability by a switch in the protein synthesis machinery
Bibliographic record
Abstract
Protein synthesis is a classic molecular mechanism of cell biology that is taught in introductory biology classrooms. It involves the translation of messenger ribonucleic acid (mRNA) information into proteins, the building blocks of life. The initial step of protein synthesis consists of the eu¬karyotic translation initiation factor 4E (eIF4E) binding to the 5’cap of mRNAs. A variety of stress¬es repress translation to conserve energy because protein synthesis requires over half of a cell’s energy supply. An important stress for multicellular animals is low oxygen availability (hypoxia). This causes a repression of cap-directed translation by inhibiting eIF4E. This raises a fundamental question in cell biology as to how proteins are synthesized in periods of oxygen scarcity and eIF4E inhibition. Here, we describe an oxygen-regulated translation initiation complex that mediates selective cap-dependent protein synthesis. Hypoxia stimulates the formation of a complex that in¬cludes the oxygen-regulated hypoxia-inducible factor 2α (HIF-2α), the RNA binding protein RBM4 and the cap-binding eIF4E2, an eIF4E homologue. We also identified an RNA hypoxia response ele¬ment (rHRE) that recruits this complex to a wide array of mRNAs, including the epidermal growth factor receptor (EGFR), which plays a role in growth signaling and proliferation. Once assembled at the rHRE, HIF-2α/RBM4/eIF4E2 captures the 5’cap and targets mRNAs for active translation thereby evading hypoxia-induced repression of protein synthesis. These findings demonstrate that cells have evolved a program whereby oxygen availability switches the basic translation initiation machinery.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".