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Unveiling the potential impact of RNA m5C methyltransferases NSUN2 and NSUN6 on cellular aging

Jiale Zhou1,2, Yang Han3, Fuxi Ji4

  • 1Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Frontiers in Genetics
|May 1, 2025
PubMed

Insights

The study reveals that NSUN2 and NSUN6 proteins are crucial for cellular aging. Their absence accelerates aging markers and impairs cell proliferation, suggesting roles in age-related diseases.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • NSUN2 and NSUN6 are NOL1/NSUN proteins catalyzing RNA 5-methylcytosine (m5C) formation.
  • These proteins are implicated in various physiological and pathological processes, including disease development.

Purpose of the Study:

  • To investigate the biological functions of NSUN2 and NSUN6 in cellular processes.
  • To explore the role of NSUN2 and NSUN6 in cellular aging and senescence.

Main Methods:

  • CRISPR/Cas9 technology was used to create NSUN2 knockout (NSUN2-/-) and NSUN6 knockout (NSUN6-/-) HEK293T cell lines.
  • Cell proliferation, senescence-associated markers (P27, β-galactosidase), and protein expression were analyzed.
  • Analysis was conducted in both knockout cell lines and Hutchinson-Gilford Progeria Syndrome (HGPS) premature aging cell lines.

Main Results:

  • No significant interaction was observed between NSUN2 and NSUN6 protein expression.
  • Ablation of NSUN2 or NSUN6 led to reduced cell proliferation and increased P27 expression.
  • NSUN2/NSUN6 knockout cells exhibited increased susceptibility to oxidative stress, indicated by higher β-galactosidase activity.
  • Expression of NSUN2 and NSUN6 was significantly decreased in HGPS premature aging cell lines.

Conclusions:

  • NSUN2 and NSUN6 play a significant role in regulating cellular aging.
  • The findings suggest a potential link between NSUN2/NSUN6 function and the aging process.
  • These proteins may represent novel therapeutic targets for aging and age-associated diseases.
Keywords:
5-methylcytosineNSUN6NSun2RNA methylationaging

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