Matrix metalloproteinase‐2 mediates ribosomal RNA transcription by cleaving nucleolar histones
Bibliographic record
Abstract
Cell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 was previously detected in the nucleus, however, its role there is elusive. Herein we report that matrix metalloproteinase-2 resides within the nucleolus to regulate ribosomal RNA transcription. Matrix metalloproteinase-2 is enriched at the promoter region of ribosomal RNA gene repeats, and its inhibition downregulates preribosomal RNA transcription. The N-terminal tail of histone H3 is clipped by matrix metalloproteinase-2 in the nucleolus, which is associated with increased ribosomal RNA transcription. Knocking down/out matrix metalloproteinase-2, or inhibiting its activity, prevents histone H3 cleavage and reduces both ribosomal RNA transcription and cell proliferation. In addition to the known extracellular roles of matrix metalloproteinase-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar matrix metalloproteinase-2 regulates cell proliferation through histone clipping and facilitation of ribosomal RNA transcription.
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How this classification was reachedexpand
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 | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".