Loss of miR-451a enhances SPARC production during myogenesis

Rachel Munk1, Jennifer L Martindale1, Xiaoling Yang1

  • 1Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

Plos One
|March 30, 2019
PubMed

Insights

MicroRNAs (miRNAs) regulate gene expression. In aged muscle, miR-451a increased, and it inhibits muscle cell differentiation by suppressing SPARC biosynthesis, impacting muscle homeostasis.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Muscle Physiology

Background:

  • MicroRNAs (miRNAs) are small noncoding RNAs crucial for gene expression.
  • miRNA abundance and function are linked to physiological and pathological processes.
  • Increased miR-451a and miR-144-3p levels were observed in aged monkey muscle.

Purpose of the Study:

  • To investigate the role of miR-451a and miR-144-3p in myogenesis.
  • To test the hypothesis that these miRNAs influence muscle homeostasis.

Main Methods:

  • Studied miRNA function in the mouse myoblast cell line C2C12.
  • Assessed miRNA levels during myogenesis.
  • Investigated the impact of miR-451a overexpression on C2C12 differentiation.
  • Identified Sparc mRNA as a target of miR-451a.

Main Results:

  • miR-451a and miR-144-3p levels decreased during C2C12 myogenesis.
  • Overexpression of miR-451a, but not miR-144-3p, significantly inhibited C2C12 differentiation.
  • miR-451a was found to suppress Sparc mRNA translation in mouse myoblasts.
  • SPARC (secreted protein acidic and rich in cysteine) is involved in wound healing and cellular differentiation.

Conclusions:

  • miR-451a is downregulated during myoblast differentiation.
  • miR-451a inhibits C2C12 differentiation, partly by suppressing SPARC biosynthesis.
  • These findings suggest miR-451a plays a role in regulating muscle homeostasis.

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