Yaxu Liang, Xuejiao Zhu, Ruhao Zhuo, Ning Peng, Shuyu Chen, Shimeng Huang, Zhending Gan, Jun Qi, Zhibo Wang, Bin Li, Xiang Zhong
{"title":"m6A RNA甲基化在猪轮状病毒与宿主细胞的爱恨关系中的作用。","authors":"Yaxu Liang, Xuejiao Zhu, Ruhao Zhuo, Ning Peng, Shuyu Chen, Shimeng Huang, Zhending Gan, Jun Qi, Zhibo Wang, Bin Li, Xiang Zhong","doi":"10.1186/s13578-025-01436-4","DOIUrl":null,"url":null,"abstract":"<p><p>N6-methyladenosine (m<sup>6</sup>A), the most abundant mRNA modification, regulates various mRNA metabolism to affect numerous physiological processes, including immune response. Interestingly, many RNA viruses contain internal m<sup>6</sup>A modifications that contribute to viral replication and innate immune escape process, but its mechanisms remain unclear. Porcine rotavirus (PoRV) is a common cause of diarrhea and gastroenteritis in piglets. Here, we first revealed the m<sup>6</sup>A methylation profile on the PoRV genome. PoRV infection significantly reduced methyltransferase METTL3 expression and induced nuclear-cytoplasmic translocation of METTL3. The structural protein VP6 of PoRV can co-localize with METTL3 in the cytoplasm and bind to METTL3 protein, suggesting that PoRV hijacked the host METTL3 to achieve m<sup>6</sup>A methylation. On the contrary, knockdown of Mettl3 or Ythdf2 in IPEC cells inhibited the replication of PoRV. Mechanistically, silencing of Mettl3 or Ythdf2 enhanced the expression of IRF2 and IFI44L via an increase of mRNA stability of Irf2 and Ifi44l. Furthermore, knockdown of Irf2 and Ifi44l promoted viral replication in IPEC cells. In conclusion, PoRV took full advantage of METTL3 to promote replication, in turn, host reduced own m<sup>6</sup>A methylation to enhance IRF2 and IFI44L to restrain virus infection, suggesting a love-hate relationship between virus and host, and providing novel targets for developing antiviral drugs in the pig industry.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"99"},"PeriodicalIF":6.2000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239464/pdf/","citationCount":"0","resultStr":"{\"title\":\"The role of m<sup>6</sup>A RNA methylation in a love-hate relationship between porcine rotavirus and host cells.\",\"authors\":\"Yaxu Liang, Xuejiao Zhu, Ruhao Zhuo, Ning Peng, Shuyu Chen, Shimeng Huang, Zhending Gan, Jun Qi, Zhibo Wang, Bin Li, Xiang Zhong\",\"doi\":\"10.1186/s13578-025-01436-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>N6-methyladenosine (m<sup>6</sup>A), the most abundant mRNA modification, regulates various mRNA metabolism to affect numerous physiological processes, including immune response. Interestingly, many RNA viruses contain internal m<sup>6</sup>A modifications that contribute to viral replication and innate immune escape process, but its mechanisms remain unclear. Porcine rotavirus (PoRV) is a common cause of diarrhea and gastroenteritis in piglets. Here, we first revealed the m<sup>6</sup>A methylation profile on the PoRV genome. PoRV infection significantly reduced methyltransferase METTL3 expression and induced nuclear-cytoplasmic translocation of METTL3. The structural protein VP6 of PoRV can co-localize with METTL3 in the cytoplasm and bind to METTL3 protein, suggesting that PoRV hijacked the host METTL3 to achieve m<sup>6</sup>A methylation. On the contrary, knockdown of Mettl3 or Ythdf2 in IPEC cells inhibited the replication of PoRV. Mechanistically, silencing of Mettl3 or Ythdf2 enhanced the expression of IRF2 and IFI44L via an increase of mRNA stability of Irf2 and Ifi44l. Furthermore, knockdown of Irf2 and Ifi44l promoted viral replication in IPEC cells. In conclusion, PoRV took full advantage of METTL3 to promote replication, in turn, host reduced own m<sup>6</sup>A methylation to enhance IRF2 and IFI44L to restrain virus infection, suggesting a love-hate relationship between virus and host, and providing novel targets for developing antiviral drugs in the pig industry.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"15 1\",\"pages\":\"99\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2025-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239464/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-025-01436-4\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-025-01436-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells.
N6-methyladenosine (m6A), the most abundant mRNA modification, regulates various mRNA metabolism to affect numerous physiological processes, including immune response. Interestingly, many RNA viruses contain internal m6A modifications that contribute to viral replication and innate immune escape process, but its mechanisms remain unclear. Porcine rotavirus (PoRV) is a common cause of diarrhea and gastroenteritis in piglets. Here, we first revealed the m6A methylation profile on the PoRV genome. PoRV infection significantly reduced methyltransferase METTL3 expression and induced nuclear-cytoplasmic translocation of METTL3. The structural protein VP6 of PoRV can co-localize with METTL3 in the cytoplasm and bind to METTL3 protein, suggesting that PoRV hijacked the host METTL3 to achieve m6A methylation. On the contrary, knockdown of Mettl3 or Ythdf2 in IPEC cells inhibited the replication of PoRV. Mechanistically, silencing of Mettl3 or Ythdf2 enhanced the expression of IRF2 and IFI44L via an increase of mRNA stability of Irf2 and Ifi44l. Furthermore, knockdown of Irf2 and Ifi44l promoted viral replication in IPEC cells. In conclusion, PoRV took full advantage of METTL3 to promote replication, in turn, host reduced own m6A methylation to enhance IRF2 and IFI44L to restrain virus infection, suggesting a love-hate relationship between virus and host, and providing novel targets for developing antiviral drugs in the pig industry.
期刊介绍:
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.