m6A-modified RIOK3 activated the NF-κB-signaling pathway by CDC42, promoting the replication and proliferation of

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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

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Xiaolan Liu1, Hua Wang2, Mengran Yuan2

  • 1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, PR China; Department of Clinical Laboratory, Norinco General Hospital, Xi'an, Shaanxi 710065, PR China.

International Journal of Biological Macromolecules
|February 17, 2025
PubMed

Insights

Enterovirus infections utilize N(6)-methyladenosine (m6A) modification of RIO kinase 3 (RIOK3) to promote viral replication. This process involves suppressing CDC42 and activating NF-κB signaling, driving inflammation and pathogenesis.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Enteroviruses cause inflammatory diseases like myocarditis and meningitis.
  • Viral entry triggers innate and inflammatory immune responses, but mechanisms for inflammation-induced replication are unclear.
  • N(6)-methyladenosine (m6A) is a key mRNA modification regulated by METTL3, influencing gene expression.

Purpose of the Study:

  • To elucidate the role of RIO kinase 3 (RIOK3) in Coxsackievirus B3 (CVB3) infection.
  • To investigate the involvement of m6A modification in enterovirus pathogenesis.
  • To understand how RIOK3 and CDC42 interaction affects viral replication and immune signaling.

Main Methods:

  • Investigated RIOK3 expression in CVB3-infected cells and animal models.
  • Assessed m6A modification levels on RIOK3 mRNA.
  • Analyzed the impact of RIOK3 and METTL3 on CDC42 expression and NF-κB signaling.
  • Studied the effect of CDC42 modulation on CVB3 replication.

Main Results:

  • CVB3 infection significantly upregulated RIOK3 expression and m6A modification of RIOK3 mRNA.
  • METTL3-mediated m6A enhanced RIOK3 transcription, leading to CDC42 downregulation.
  • Suppression of CDC42 promoted CVB3 replication.
  • RIOK3 and CDC42 modulated the NF-κB signaling pathway, impacting inflammatory responses.

Conclusions:

  • m6A-modified RIOK3 promotes enterovirus replication by activating NF-κB signaling through CDC42 suppression.
  • This pathway offers new insights into enterovirus pathogenesis and inflammatory disease mechanisms.
  • RIOK3 is identified as a critical factor in CVB3 infection and innate immunity.
Keywords:
CDC42CVB3EnterovirusRIOK3m(6)A

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