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Background <p>N6-methyladenosine, the most prevalent post-transcriptional modification in eukaryotes, plays a critical role in regulating gene expression and disease pathogenesis. Concurrently, G-quadruplex structures are implicated in key biological processes, including the regulation of transcription and post-transcriptional events. Emerging evidence suggests that m<sup>6</sup>A modifications and G4 structures colocalize within viral genomes and human pre-mRNAs; however, their functional interplay remains poorly understood.</p> Results <p>Using existing MeRIP-seq data from Marek’s disease virus (MDV)-infected samples, we investigated the colocalization pattern and its potential role in viral infection. Our bioinformatic analyses revealed that the predicted G4 structures were predominantly two G-tetrad G-quadruplexes. Genes with m<sup>6</sup>A-G4 colocalization were significantly enriched in pathways related to immune response and tumorigenesis. Then we verified the presence of co-localization on the <i>CCL4</i>, which inhibited <i>CCL4</i> expression. Co-localization also affected viral replication and regulated <i>ICP4</i> expression.</p> Conclusions <p>We systematically characterized the features of G4 structures co-localized with m<sup>6</sup>A modifications during MDV infection, investigated the role in viral replication and gene regulation, and provided experimental evidence for m<sup>6</sup>A-G4 co-localization. These findings shed new light on the epitranscriptomic regulatory mechanisms employed by an oncogenic virus and may inform the development of novel antiviral and anti-tumor therapeutic strategies.</p>

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Comprehensive analysis and validation of m6A-G4 colocalization and its regulatory role in Marek’s disease virus infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Lulu Yao,
  • Yunzhe Kang,
  • Xuyang Zhao,
  • Lucai Wang,
  • Lijie Lv,
  • Wenhui Zhu,
  • Xiuwen Yang,
  • Guoqing Zhuang,
  • Aijun Sun

摘要

Background

N6-methyladenosine, the most prevalent post-transcriptional modification in eukaryotes, plays a critical role in regulating gene expression and disease pathogenesis. Concurrently, G-quadruplex structures are implicated in key biological processes, including the regulation of transcription and post-transcriptional events. Emerging evidence suggests that m6A modifications and G4 structures colocalize within viral genomes and human pre-mRNAs; however, their functional interplay remains poorly understood.

Results

Using existing MeRIP-seq data from Marek’s disease virus (MDV)-infected samples, we investigated the colocalization pattern and its potential role in viral infection. Our bioinformatic analyses revealed that the predicted G4 structures were predominantly two G-tetrad G-quadruplexes. Genes with m6A-G4 colocalization were significantly enriched in pathways related to immune response and tumorigenesis. Then we verified the presence of co-localization on the CCL4, which inhibited CCL4 expression. Co-localization also affected viral replication and regulated ICP4 expression.

Conclusions

We systematically characterized the features of G4 structures co-localized with m6A modifications during MDV infection, investigated the role in viral replication and gene regulation, and provided experimental evidence for m6A-G4 co-localization. These findings shed new light on the epitranscriptomic regulatory mechanisms employed by an oncogenic virus and may inform the development of novel antiviral and anti-tumor therapeutic strategies.