A dynamic ribosomal biogenesis response is not required for IGF‐1–mediated hypertrophy of human primary myotubes
Bibliographic record
Abstract
ABSTRACT Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF‐1–mediated myotube hypertrophy in vitro. Primary skeletal myotubes were treated with IGF‐1 (50 ng/ml) with or without 0.5 μM CX‐5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre‐rRNA expression (−64 ± 5% vs . IGF‐1; P < 0.001) and total RNA content (−16 ± 2% vs. IGF‐1; P < 0.001) in IGF‐1‐treated myotubes. IGF‐1‐mediated increases in myotube diameter (1.27 ± 0.09‐fold, P < 0.05 vs . control) and total protein (+20 ± 2%; P < 0.001 vs . control) were not prevented by CX treatment. Suppression of rRNA synthesis during IGF‐1 treatment did not prevent early increases in AKT (+203 ± 39% vs . CX; P < 0.001) and p70 S6K1 (269 ± 41% vs . CX; P < 0.001) phosphorylation. Despite robust inhibition of the dynamic ribosomal biogenesis response to IGF‐1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF‐1‐induced myotube hypertrophy in vitro. —Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF‐1‐mediated hypertrophy of human primary myotubes. FASEB J. 31, 5196‐5207 (2017). www.fasebj.org
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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 | 0.001 | 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 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".