Molecular Mechanisms Underlying the Activity‐Linked Alterations in Acetylcholinesterase mRNAs in Developing Versus Adult Rat Skeletal Muscles
Bibliographic record
Abstract
The molecular mechanisms underlying the activity-linked plasticity of acetylcholinesterase (AChE) mRNA levels in mammalian skeletal muscle have yet to be established. Here, we demonstrate that denervation of adult muscle induces a dramatic (up to 90%) and rapid (within 24 h) decrease in the abundance of AChE mRNAs. By contrast, denervation of 14-day-old rats leads to a significantly less pronounced reduction (50% of control) in the expression of AChE mRNAs. Assessment of the transcriptional activity of the AChE gene reveals that it remains essentially unchanged in adult denervated muscles, whereas it displays an approximately two- to three-fold increase (p < 0.05) in denervated muscles from 2- to 14-day-old rats. In addition, we observed a higher rate of degradation of in vitro transcribed AChE mRNAs upon incubation with protein extracts from denervated muscles. Finally, UV-crosslinking experiments reveal that denervation increases the abundance of RNA-protein interactions in the 3' untranslated region of AChE transcripts. Taken together, these data suggest that the abundance of AChE transcripts in mature muscles is controlled primarily via posttranscriptional regulatory mechanisms, whereas in neo- and postnatal muscles, both transcriptional and posttranscriptional regulation appears critical in dictating AChE mRNA levels. Accordingly, the activity-linked transcriptional regulation of the AChE gene appears to demonstrate a high level of plasticity during muscle development when maturation of the neuromuscular junctions is still occurring.
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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 | 0.001 |
| 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".