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Published on: June 15, 2018
MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes
Linyuan Shen1, Lei Chen2, Shunhua Zhang1
1College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
Abstract:
MicroRNAs (miRNAs) are small, non-coding RNAs that affect the post-transcriptional regulation of various biological pathways. To date, it is not fully understood how miRNAs regulate mitochondrial biogenesis. This study aimed at the identification of the role of miRNA-27b in mitochondria biogenesis. The mitochondria content in C2C12 cells was significantly increased during myogenic differentiation and accompanied by a marked decrease of miRNA-27b expression. Furthermore, the expression of the predicted target gene of miRNA-27b, forkhead box j3 (Foxj3), was also increased during myogenic differentiation. Luciferase activity assays confirmed that miRNA-27b directly targets the 3'-untranslated region (3'-UTR) of Foxj3. Overexpression of miRNA-27b provoked a decrease of mitochondria content and diminished expression of related mitochondrial genes and Foxj3 both at mRNA and protein levels. The expression levels of downstream genes of Foxj3, such as Mef2c, PGC1α, NRF1 and mtTFA, were also decreased in C2C12 cells upon overexpression of miRNA-27b. These results suggested that miRNA-27b may affect mitochondria biogenesis by down-regulation of Foxj3 during myocyte differentiation.
Insights
MicroRNAs (miRNAs) regulate mitochondrial biogenesis. This study found that miRNA-27b down-regulates forkhead box j3 (Foxj3), impacting mitochondria content during myocyte differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcriptional level.
- The precise mechanisms by which miRNAs influence mitochondrial biogenesis remain incompletely understood.
- Mitochondrial biogenesis is crucial for cellular energy production and is tightly regulated during differentiation.
Purpose of the Study:
- To investigate the role of miRNA-27b in the regulation of mitochondrial biogenesis.
- To identify the direct target gene of miRNA-27b involved in this process.
- To elucidate the molecular pathway through which miRNA-27b affects mitochondria content.
Main Methods:
- Utilized C2C12 myoblast cell line for studying myogenic differentiation.
- Quantified mitochondrial content and gene/protein expression levels.
- Performed luciferase activity assays to confirm direct miRNA-target interaction.
- Overexpressed miRNA-27b to assess its functional impact on mitochondrial genes and Foxj3.
Main Results:
- Mitochondrial content increased, while miRNA-27b expression decreased during C2C12 cell differentiation.
- Forkhead box j3 (Foxj3) was identified as a direct target of miRNA-27b.
- Overexpression of miRNA-27b led to reduced mitochondrial content and suppressed expression of Foxj3 and its downstream genes (Mef2c, PGC1α, NRF1, mtTFA).
Conclusions:
- miRNA-27b negatively regulates mitochondrial biogenesis in differentiating myocytes.
- This regulation occurs through the direct targeting and down-regulation of Foxj3.
- The findings reveal a novel miRNA-mediated pathway controlling mitochondria development.
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