Brain‐derived neurotrophic factor expression is repressed during myogenic differentiation by miR‐206
Bibliographic record
Abstract
Brain-derived neurotrophic factor (BDNF) is required for efficient skeletal-muscle regeneration and perturbing its expression causes abnormalities in the proliferation and differentiation of skeletal muscle cells. In this study, we investigated the mechanism of BDNF suppression that occurs during myogenic differentiation. BDNF is expressed at the mRNA level as two isoforms that differ in the length of their 3'UTRs as a result of alternative cleavage and polyadenylation. Sequence analysis revealed the presence of three miR-206 target sites in the long BDNF 3'UTR (BDNF-L), whereas only one site was found in the short mRNA BDNF 3'UTR (BDNF-S). miR-206 is known to regulate the differentiation of C2C12 myoblasts and its expression is induced during the transition from myoblasts to myotubes. We thus examined whether miR-206-mediated suppression is responsible for the expression pattern of BDNF during myogenic differentiation. BDNF-L was suppressed to a greater extent than BDNF-S during differentiation of C2C12 myoblasts. Transfection of a miR-206 precursor decreased activity of reporters representative of the BDNF-L 3'UTR, but not BDNF-S 3'UTR, and repressed endogenous BDNF mRNA levels. This suppression was found to be dependent on the presence of multiple miR-206 target sites in the BDNF-L 3'UTR. Conversely, suppression of miR-206 levels resulted in de-repression of BDNF 3'UTR reporter activity and increased endogenous BDNF-L mRNA levels. A receptor for BDNF, p75(NTR) , was also suppressed during differentiation and in response to miR-206, but this appeared to not be entirely mediated via a miR-206 target site its 3'UTR. Based on these observations, BDNF represents a novel target through which miR-206 controls the initiation and maintenance of the differentiated state of muscle cells. These results further suggest that miR-206 might play a role in regulating retrograde signaling of BDNF at the neuromuscular junction.
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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".