MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes

PLoS One. 2016 Feb 5;11(2):e0148532. doi: 10.1371/journal.pone.0148532. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • MEF2 Transcription Factors / genetics
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Muscle Cells / cytology
  • Muscle Cells / physiology*
  • Nuclear Respiratory Factor 1 / genetics
  • Organelle Biogenesis*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • FoxJ3 protein, mouse
  • MEF2 Transcription Factors
  • Mef2c protein, mouse
  • MicroRNAs
  • Mirn27 microRNA, mouse
  • Nrf1 protein, mouse
  • Nuclear Respiratory Factor 1
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors

Grants and funding

The study was supported by the Sichuan Sci & Tech Support Program (No. 2013NZ0041 and 2013NZ0056), the earmarked fund for China Agriculture Research System (No. CARS-36-05B), and Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13083). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.