N6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins

• 成果类型: Article
• 署名作者: Wang, Qian; Xu, Shuai; Shen, Wentao; Wei, Yanli; Han, Lu; Wang, Zhengxiang; Yu, Yingying; Liu, Minxuan; Liu, Junwen; Deng, Guohua; Chen, Hualan; Zhu, Qiyun
• 署名单位: Chinese Academy of Agricultural Sciences; Lanzhou Veterinary Research Institute, CAAS; Lanzhou University; Chinese Academy of Agricultural Sciences; Harbin Veterinary Research Institute, CAAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12942
• DOI: 10.1073/pnas.2411554122
• 发表日期: 2025-03-18
• 关键词: messenger-rna; gene-expression; n-6-methyladenosine; contributes

摘要

N6-methyladnosine (m6A) modification is present in both positive-and negative-strand RNA of influenza A virus (IAV) and affects the replication and pathogenicity of IAV. However, little is known about the regulatory mechanism of m6A in IAV RNA. In the present study, we identified the m6A methylation of the viral RNA of different IAV subtypes and confirmed that m6A modification promotes the polymerase activity and replication of IAV. By mutating m6A motifs on the multiple viral RNAs (vRNAs) of IAV, we revealed that m6A deficiency in vRNA suppresses the expression of viral genes and the replication of the virus in vitro. In addition, m6A deficiency in vRNA reduced the pathogenicity of IAV in a mouse model. Mechanistically, m6A deficiency in vRNA suppresses the assembly of the viral ribonucleoprotein (vRNP) complex by impairing the interaction between vRNA and vRNP proteins in an m6A methyltransferase-dependent manner, but not the m6A reader proteins. Together, our findings reveal an important role for m6A on viral RNAs in facilitating the activity of the polymerase complex and the replication and pathogenicity of IAV, which provides insights for the development of novel anti-influenza strategies.