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Published on: August 10, 2018
microRNA-151-3p regulates slow muscle gene expression by targeting ATP2a2 in skeletal muscle cells
Huan Wei1, Zhongwen Li, Xiaobin Wang
1Department of Animal Science, Northwest A&F University, Yangling, Shaanxi, China.
Abstract:
MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate the stability or translation of cognate mRNAs at the post-transcriptional level. Accumulating evidence indicates that miRNAs play important roles in many aspects of muscle function, including muscle growth and development, regeneration, contractility, and muscle fiber type plasticity. In the current study, we examined the function of miR-151-3p in myoblast proliferation and differentiation. Results show that overexpression of miR-151-3p not only upregulates myoblast proliferation, but also decreases slow muscle gene expression (such as MHC-β/slow and slow muscle troponin I) in both C2C12 myotubes and in primary cultures. Alternatively, inhibition of miR-151-3p by antisense RNA was found to upregulate MHC-β/slow expression, indicating that miR-151-3p plays a role in muscle fiber type determination. Further investigation into the underlying mechanisms revealed for the first time that miR-151-3p directly targets ATP2a2, a gene encoding for a slow skeletal and cardiac muscle specific Ca(2+) ATPase, SERCA2 thus downregulating slow muscle gene expression. Mechanisms by which the alteration in SERCA2 expression induces changes in other slow muscle gene expression levels needs to be defined in future research.
Insights
MicroRNAs (miRNAs) regulate muscle function. This study shows miR-151-3p promotes myoblast proliferation and influences muscle fiber type by targeting SERCA2, impacting muscle gene expression.
Area of Science:
- Molecular Biology
- Muscle Physiology
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression.
- miRNAs are increasingly recognized for their roles in muscle development, regeneration, and function.
Purpose of the Study:
- To investigate the function of miR-151-3p in myoblast proliferation and differentiation.
- To elucidate the role of miR-151-3p in muscle fiber type determination.
Main Methods:
- Overexpression and inhibition of miR-151-3p in C2C12 myotubes and primary muscle cells.
- Analysis of myoblast proliferation and differentiation markers.
- Target gene validation using molecular assays.
Main Results:
- Overexpression of miR-151-3p enhanced myoblast proliferation.
- miR-151-3p overexpression decreased expression of slow muscle genes (MHC-β/slow, slow muscle troponin I).
- Inhibition of miR-151-3p increased MHC-β/slow expression, suggesting a role in fiber type determination.
- miR-151-3p was found to directly target ATP2a2 (SERCA2), a gene encoding a slow skeletal and cardiac muscle Ca(2+) ATPase.
Conclusions:
- miR-151-3p plays a significant role in regulating myoblast proliferation and muscle fiber type.
- The mechanism involves direct targeting of SERCA2, leading to downregulation of slow muscle gene expression.
- Further research is needed to define how SERCA2 alterations affect other slow muscle genes.
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