RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection
Abstract Introduction N6‐methyladenosine (m6A) is the most prevalent modification that occurs in messenger RNA (mRNA), affecting mRNA splicing, translation, and stability. This modification is reversible, and its related biological functions are mediated by “writers,” “erasers,” and “readers.” The f...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-06-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.396 |
| _version_ | 1797831371929944064 |
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| author | Xiang Zheng Jia Wang Xiaoyue Zhang Yuxin Fu Qiu Peng Jianhong Lu Lingyu Wei Zhengshuo Li Can Liu Yangge Wu Qun Yan Jian Ma |
| author_facet | Xiang Zheng Jia Wang Xiaoyue Zhang Yuxin Fu Qiu Peng Jianhong Lu Lingyu Wei Zhengshuo Li Can Liu Yangge Wu Qun Yan Jian Ma |
| author_sort | Xiang Zheng |
| collection | DOAJ |
| description | Abstract Introduction N6‐methyladenosine (m6A) is the most prevalent modification that occurs in messenger RNA (mRNA), affecting mRNA splicing, translation, and stability. This modification is reversible, and its related biological functions are mediated by “writers,” “erasers,” and “readers.” The field of viral epitranscriptomics and the role of m6A modification in virus–host interaction have attracted much attention recently. When Epstein–Barr virus (EBV) infects a human B lymphocyte, it goes through three phases: the pre‐latent phase, latent phase, and lytic phase. Little is known about the viral and cellular m6A epitranscriptomes in EBV infection, especially in the pre‐latent phase during de novo infection. Methods Methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and MeRIP‐RT‐qPCR were used to determine the m6A‐modified transcripts during de novo EBV infection. RIP assay was used to confirm the binding of EBNA2 and m6A readers. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) and Western blot analysis were performed to test the effect of m6A on the host and viral gene expression. Results Here, we provided mechanistic insights by examining the viral and cellular m6A epitranscriptomes during de novo EBV infection, which is in the pre‐latent phase. EBV EBNA2 and BHRF1 were highly m6A‐modified upon EBV infection. Knockdown of METTL3 (a “writer”) decreased EBNA2 expression levels. The emergent m6A modifications induced by EBV infection preferentially distributed in 3ʹ untranslated regions of cellular transcripts, while the lost m6A modifications induced by EBV infection preferentially distributed in coding sequence regions of mRNAs. EBV infection could influence the host cellular m6A epitranscriptome. Conclusions These results reveal the critical role of m6A modification in the process of de novo EBV infection. |
| first_indexed | 2024-04-09T13:51:59Z |
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| id | doaj.art-06b2fd7075594d6da6e9651df70422dc |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-09T13:51:59Z |
| publishDate | 2021-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-06b2fd7075594d6da6e9651df70422dc2023-05-08T13:20:47ZengWileyImmunity, Inflammation and Disease2050-45272021-06-019235136210.1002/iid3.396RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infectionXiang Zheng0Jia Wang1Xiaoyue Zhang2Yuxin Fu3Qiu Peng4Jianhong Lu5Lingyu Wei6Zhengshuo Li7Can Liu8Yangge Wu9Qun Yan10Jian Ma11Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan ChinaHunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaCancer Research Institute, Department of Microbiology, Department of Pathology, School of Basic Medical Science Central South University Changsha Hunan ChinaDepartment of Pathology Affiliated Hospital of Guilin Medical University Guilin Guangxi ChinaDepartment of Clinical Laboratory, Xiangya Hospital Central South University Changsha Hunan ChinaHunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan ChinaAbstract Introduction N6‐methyladenosine (m6A) is the most prevalent modification that occurs in messenger RNA (mRNA), affecting mRNA splicing, translation, and stability. This modification is reversible, and its related biological functions are mediated by “writers,” “erasers,” and “readers.” The field of viral epitranscriptomics and the role of m6A modification in virus–host interaction have attracted much attention recently. When Epstein–Barr virus (EBV) infects a human B lymphocyte, it goes through three phases: the pre‐latent phase, latent phase, and lytic phase. Little is known about the viral and cellular m6A epitranscriptomes in EBV infection, especially in the pre‐latent phase during de novo infection. Methods Methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and MeRIP‐RT‐qPCR were used to determine the m6A‐modified transcripts during de novo EBV infection. RIP assay was used to confirm the binding of EBNA2 and m6A readers. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) and Western blot analysis were performed to test the effect of m6A on the host and viral gene expression. Results Here, we provided mechanistic insights by examining the viral and cellular m6A epitranscriptomes during de novo EBV infection, which is in the pre‐latent phase. EBV EBNA2 and BHRF1 were highly m6A‐modified upon EBV infection. Knockdown of METTL3 (a “writer”) decreased EBNA2 expression levels. The emergent m6A modifications induced by EBV infection preferentially distributed in 3ʹ untranslated regions of cellular transcripts, while the lost m6A modifications induced by EBV infection preferentially distributed in coding sequence regions of mRNAs. EBV infection could influence the host cellular m6A epitranscriptome. Conclusions These results reveal the critical role of m6A modification in the process of de novo EBV infection.https://doi.org/10.1002/iid3.396BHRF1EBNA2Epstein–Barr virusMETTL3RNA m6A methylation |
| spellingShingle | Xiang Zheng Jia Wang Xiaoyue Zhang Yuxin Fu Qiu Peng Jianhong Lu Lingyu Wei Zhengshuo Li Can Liu Yangge Wu Qun Yan Jian Ma RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection Immunity, Inflammation and Disease BHRF1 EBNA2 Epstein–Barr virus METTL3 RNA m6A methylation |
| title | RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection |
| title_full | RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection |
| title_fullStr | RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection |
| title_full_unstemmed | RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection |
| title_short | RNA m6A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection |
| title_sort | rna m6a methylation regulates virus host interaction and ebna2 expression during epstein barr virus infection |
| topic | BHRF1 EBNA2 Epstein–Barr virus METTL3 RNA m6A methylation |
| url | https://doi.org/10.1002/iid3.396 |
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