Cellular adaptation to low oxygen availability by a switch in the protein synthesis machinery
Why this work is in the frame
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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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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 | 0.002 | 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 | 0.001 | 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 it