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Nonsense-mediated mRNA decay promote C2C12 cell proliferation by targeting PIK3R5

Zhenzhou Huang1, Yishu Peng1, Yuhui Wei1

  • 1Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, Shandong, China.

Journal of Muscle Research and Cell Motility
|December 13, 2022
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) regulates myoblast proliferation and muscle repair. NMD targets PIK3R5 to enhance AKT activity, promoting cell growth and offering therapeutic insights for muscle atrophy.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Cellular Biology

Background:

  • Nonsense-mediated mRNA decay (NMD) is a critical RNA surveillance pathway.
  • Myoblast proliferation is vital for skeletal muscle repair and implicated in myosarcoma development.
  • The precise role of NMD in regulating myoblast proliferation remains largely undefined.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which NMD influences myoblast proliferation and apoptosis.
  • To investigate the age-dependent changes in skeletal muscle NMD activity and its correlation with muscle regeneration capacity.
  • To identify NMD target genes involved in the regulation of myoblast growth.

Main Methods:

  • Analysis of NMD activity in skeletal muscle of mice at different ages.
  • Assessment of NMD's role in myoblast proliferation and apoptosis using cell culture models (C2C12 cells).
  • Identification and validation of NMD target genes, including PIK3R5, and their impact on signaling pathways.

Main Results:

  • Skeletal muscle NMD activity is high in young mice and declines with age, correlating with reduced muscle growth and regeneration.
  • NMD significantly impacts myoblast proliferation and apoptosis.
  • PIK3R5 was identified as an NMD substrate that normally inhibits AKT activity and C2C12 cell proliferation.
  • NMD-mediated regulation of PIK3R5 leads to enhanced AKT activity, thereby promoting C2C12 cell proliferation.

Conclusions:

  • NMD plays a crucial role in regulating myoblast proliferation and apoptosis.
  • The NMD-PIK3R5-AKT axis is a key pathway controlling C2C12 cell proliferation.
  • These findings offer novel insights into NMD's function in muscle development and potential therapeutic targets for muscle atrophy.
Keywords:
AKT activityMyoblast proliferationNonsense-mediated mRNA decayPIK3R5

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