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Published on: October 23, 2018
miR-29c Increases Protein Synthesis in Skeletal Muscle Independently of AKT/mTOR
Paula Ketilly Nascimento Alves1, André Cruz1, William J Silva1
1Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil.
Abstract:
microRNAs negatively regulate gene expression by blocking translation or increasing mRNA degradation. In skeletal muscle, these molecules play important roles in adaptive responses, and ongoing investigations are necessary to understand the fine-tune regulation of skeletal muscle mass. Herein we showed that skeletal muscle overexpression of miR-29c increased fiber size and force at 7 and 30 days after electrotransfer. At both time points, AKT/mTOR pathway components were downregulated, and, surprisingly, overall protein synthesis was strongly elevated at day 7, which normalized by day 30 after pCMVmiR-29c electrotransfer. These results indicate that miR-29c expression induces skeletal muscle hypertrophy and gain of function, which involves increased overall protein synthesis in spite of the deactivation of the AKT/mTOR pathway.
Insights
MicroRNA-29c (miR-29c) enhances skeletal muscle growth and function by increasing fiber size and force. This occurs through elevated protein synthesis despite AKT/mTOR pathway downregulation.
Area of Science:
- Molecular Biology
- Muscle Physiology
- Gene Regulation
Background:
- microRNAs (miRNAs) are key regulators of gene expression, impacting cellular processes.
- Skeletal muscle mass regulation is complex and involves fine-tuning by miRNAs.
- Understanding miRNA roles is crucial for muscle adaptation and health.
Purpose of the Study:
- To investigate the effect of miR-29c overexpression on skeletal muscle mass and function.
- To elucidate the molecular mechanisms underlying miR-29c-mediated skeletal muscle adaptations.
- To explore the interplay between miR-29c, protein synthesis, and the AKT/mTOR pathway.
Main Methods:
- Skeletal muscle-specific overexpression of miR-29c using electrotransfer.
- Assessment of muscle fiber size and force production.
- Analysis of AKT/mTOR pathway components and overall protein synthesis rates.
Main Results:
- miR-29c overexpression led to increased skeletal muscle fiber size and force at 7 and 30 days post-electrotransfer.
- AKT/mTOR pathway components were downregulated following miR-29c electrotransfer.
- Overall protein synthesis was significantly elevated at day 7, normalizing by day 30.
Conclusions:
- miR-29c induces skeletal muscle hypertrophy and functional gains.
- These effects are associated with increased protein synthesis, independent of AKT/mTOR pathway activation.
- miR-29c represents a potential therapeutic target for muscle-related disorders.
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