数字农科院2.0

N6-methyladenosine within transmissible gastroenteritis virus genomic RNA inhibits its replication via efficient recognition by RNA sensor RIG-I

文献类型： 外文期刊

作者： Chen, Jianing;Lin, Shengyu;Liu, Qianzi;Gao, Mengling;Wang, Zemei;Tang, Jiao;Cui, Yaru;Tan, Chen;Liu, Guangliang

作者机构：

关键词： N6-methyladenosine;transmissible gastroenteritis virus;coronavirus;RIG-I;post-transcriptional modification

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and plays diverse roles in RNA metabolism. Increasing evidence indicates that m6A is also present in viral RNAs, where it exerts virus-specific effects. While several studies have shown that m6A can facilitate viral replication, its antiviral mechanisms remain less understood. In this study, we used transmissible gastroenteritis virus (TGEV) as a model to investigate the inhibitory role of m6A in viral infection. We demonstrated that m6A modification is present in the TGEV genome and suppresses viral replication. The m6A reader proteins bind to viral RNA and reduce the stability of m6A-modified transcripts. Notably, TGEV infection increased global m6A levels in host RNA, particularly in interferon (IFN)-associated genes. Inhibition of m6A methylation significantly diminished IFN gene expression. Furthermore, compared to other viruses, TGEV genomic RNA displayed an abnormally higher m6A ratio, which can be distinguished by RIG-I to promote an immune response. Collectively, our findings reveal that high m6A modification enhances RIG-I-mediated sensing of TGEV RNA, leading to the activation of IFN responses and inhibition of viral replication. This study provides new insights into the complex regulatory functions of m6A during viral infection and host antiviral defense.IMPORTANCEN6-methyladenosine (m6A) is one of the most prevalent RNA modifications in viral genomes, but its functional impact varies widely across viruses. While m6A often promotes viral replication, it can exert inhibitory effects in certain viruses, particularly within the Flaviviridae and Coronaviridae families. Despite growing evidence of this antiviral role, the underlying mechanisms remain largely unclear. Here, we used transmissible gastroenteritis virus (TGEV), a swine coronavirus, as a model to explore the inhibitory function of m6A. We show that the TGEV genome harbors a relatively high density of m6A modification compared to other viruses and host mRNA, which are efficiently detected by the host pattern recognition receptor RIG-I. This interaction enhances innate immune activation and restricts viral replication. Our findings uncover the mechanism by which abnormal m6A modification can be sensed to activate antiviral immunity and provide deeper insight into the multifaceted role of m6A in host-virus interactions.

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