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VIRMA modulates function of photoreceptor cells through m6A modification and alternative splicing

Wenjing Liu1,2, Xiaojing Wu1, Rong Zou2

  • 1Department of Orthopedics and.

JCI Insight
|March 20, 2026
PubMed

Insights

VIRMA-mediated N6-methyladenosine (m6A) modification is crucial for retinal homeostasis and photoreceptor function. Its depletion impairs vision and causes degeneration, highlighting epigenetic targets for blinding diseases.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Neuroscience

Background:

  • N6-methyladenosine (m6A) is a prevalent mRNA modification regulating gene expression.
  • VIRMA is a key component of the m6A methyltransferase complex, essential for its stability.
  • m6A modification plays a vital role in nervous system development and retinal homeostasis.

Purpose of the Study:

  • To investigate the role of VIRMA-mediated m6A modification in retinal homeostasis and photoreceptor function.
  • To elucidate the molecular mechanisms underlying VIRMA's function in the retina.

Main Methods:

  • Utilized genetic manipulation to deplete Virma in retinal rod cells.
  • Assessed m6A methylation levels, photoreceptor function, and retinal histology.
  • Investigated the interaction of VIRMA with splicing factors and its effect on gene splicing.

Main Results:

  • Loss of Virma led to reduced m6A levels, impaired photoreceptor function, and degeneration.
  • Virma depletion affected the m6A modification of visual perception-associated genes.
  • Virma interacts with splicing factors to regulate alternative splicing of retina-related genes, contributing to photoreceptor damage.
  • Reintroduction of Virma rescued photoreceptor degeneration.

Conclusions:

  • VIRMA-mediated m6A modification is essential for maintaining photoreceptor function and retinal homeostasis.
  • Dysregulation of VIRMA contributes to photoreceptor degeneration and vision impairment.
  • Epigenetic modulation targeting VIRMA presents a potential therapeutic strategy for blinding diseases.
Keywords:
EpigeneticsNeurodegenerationNeuroscienceOphthalmologyRNA processing

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