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mt-Ty 5'tiRNA regulates skeletal muscle cell proliferation and differentiation

Jun Cao1,2, Xin Wang1, Vivek Advani1,3

  • 1Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Cell Proliferation
|February 9, 2023
PubMed

Insights

tRNA-derived fragments (tiRNAs) are crucial for skeletal muscle development. This study shows that mt-Ty 5' tiRNAs regulate myoblast proliferation and differentiation, offering potential therapeutic targets for muscle diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • tRNA-derived fragments (tiRNAs) are emerging as key regulators of gene expression.
  • The specific roles of mitochondrial tRNA-derived fragments (mt-tiRNAs) in skeletal muscle development are not well understood.

Purpose of the Study:

  • To investigate the function of mt-Ty 5' tiRNAs in skeletal muscle cell proliferation and differentiation.
  • To elucidate the regulatory mechanisms of mt-Ty 5' tiRNAs in gene expression during myogenesis.

Main Methods:

  • Cell culture of C2C12 myoblasts.
  • Manipulation of mt-Ty 5' tiRNA levels (inhibition and overexpression).
  • Gene expression analysis using Northern blotting, RT-PCR, and RNA-Seq.
  • Cellular and subcellular structure characterization via electron microscopy (TEM).

Main Results:

  • mt-Ty 5' tiRNAs are enriched in mouse skeletal muscle, with levels increasing during later developmental stages.
  • Inhibition of mt-Ty 5' tiRNAs reduced C2C12 myoblast proliferation and myogenic differentiation.
  • RNA-Seq and RT-PCR confirmed downregulation of proliferation and differentiation pathways upon tiRNA inhibition, with reversal upon overexpression.

Conclusions:

  • mt-Ty 5' tiRNAs are essential regulators of myoblast proliferation and differentiation in skeletal muscle.
  • These findings identify mt-Ty 5' tiRNAs as potential therapeutic targets for muscle-related diseases.

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