A Conserved 3′-Untranslated Element Mediates Growth Regulation of DNA Methyltransferase 1 and Inhibits Its Transforming Activity
Bibliographic record
Abstract
Ectopic expression of DNA methyltransferase 1 (DNMT1) has been proposed to play an important role in cancer. dnmt1 mRNA is undetectable in growth-arrested cells but is induced upon entrance into the S phase of the cell cycle, and until now, the mechanisms responsible for this regulation were unknown. In this report, we demonstrate that the 3'-untranslated region (3'-UTR) of the dnmt1 mRNA can confer a growth-dependent regulation on its own message as well as a heterologous beta-globin mRNA. Our results indicate that a 54-nucleotide highly conserved element within the 3'-UTR is necessary and sufficient to mediate this regulation. Cell-free mRNA decay experiments demonstrate that this element increases mRNA turnover rates and does so to a greater extent in the presence of extracts prepared from arrested cells. A specific RNA-protein complex is formed with the 3'-UTR only in growth-arrested cells, and a UV cross-linking analysis revealed a 40-kDa protein (p40), the binding of which is dramatically increased in growth-arrested cells and is inversely correlated with dnmt1 mRNA levels as cells are induced into the cell cycle. Although ectopic expression of human DNMT1 lacking the 3'-UTR can transform NIH-3T3 cells, inclusion of the 3'-UTR prevents transformation. These results support the hypothesis that deregulated expression of DNMT1 with the cell cycle is important for cellular transformation.
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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".