The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells
Abstract 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 e...
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BMC
2025-07-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-025-01436-4 |
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| author | Yaxu Liang Xuejiao Zhu Ruhao Zhuo Ning Peng Shuyu Chen Shimeng Huang Zhending Gan Jun Qi Zhibo Wang Bin Li Xiang Zhong |
| author_facet | Yaxu Liang Xuejiao Zhu Ruhao Zhuo Ning Peng Shuyu Chen Shimeng Huang Zhending Gan Jun Qi Zhibo Wang Bin Li Xiang Zhong |
| author_sort | Yaxu Liang |
| collection | DOAJ |
| description | Abstract 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. Graphical abstract |
| format | Article |
| id | doaj-art-9fed0ce7ba6449a1ae1c6b410f84e4b8 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-9fed0ce7ba6449a1ae1c6b410f84e4b82025-08-20T04:02:50ZengBMCCell & Bioscience2045-37012025-07-0115111710.1186/s13578-025-01436-4The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cellsYaxu Liang0Xuejiao Zhu1Ruhao Zhuo2Ning Peng3Shuyu Chen4Shimeng Huang5Zhending Gan6Jun Qi7Zhibo Wang8Bin Li9Xiang Zhong10College of Animal Science and Technology, Nanjing Agricultural UniversityInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Jiangsu Academy of Agricultural Sciences, Ministry of AgricultureCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Jiangsu Academy of Agricultural Sciences, Ministry of AgricultureState Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Jiangsu Academy of Agricultural Sciences, Ministry of AgricultureCollege of Animal Science and Technology, Nanjing Agricultural UniversityAbstract 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. Graphical abstracthttps://doi.org/10.1186/s13578-025-01436-4N6-methyladenosinePorcine rotavirusImmuneIRF2IFI44L |
| spellingShingle | Yaxu Liang Xuejiao Zhu Ruhao Zhuo Ning Peng Shuyu Chen Shimeng Huang Zhending Gan Jun Qi Zhibo Wang Bin Li Xiang Zhong The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells Cell & Bioscience N6-methyladenosine Porcine rotavirus Immune IRF2 IFI44L |
| title | The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells |
| title_full | The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells |
| title_fullStr | The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells |
| title_full_unstemmed | The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells |
| title_short | The role of m6A RNA methylation in a love-hate relationship between porcine rotavirus and host cells |
| title_sort | role of m6a rna methylation in a love hate relationship between porcine rotavirus and host cells |
| topic | N6-methyladenosine Porcine rotavirus Immune IRF2 IFI44L |
| url | https://doi.org/10.1186/s13578-025-01436-4 |
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