Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification
Abstract Mitochondrial antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for antiviral immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especial...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202100606 |
| _version_ | 1818602755206414336 |
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| author | Fei Qin Baoshan Cai Jian Zhao Lei Zhang Yi Zheng Bingyu Liu Chengjiang Gao |
| author_facet | Fei Qin Baoshan Cai Jian Zhao Lei Zhang Yi Zheng Bingyu Liu Chengjiang Gao |
| author_sort | Fei Qin |
| collection | DOAJ |
| description | Abstract Mitochondrial antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for antiviral immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well‐defined. Here, it is reported that the MAVS mRNA undergoes N6‐methyladenosine (m6A) modification through methyltransferase‐like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon‐β production in response to RNA viruses. Compared to wild‐type mice, heterozygotes Mettl14+/− mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post‐transcriptionally through m6A modification. |
| first_indexed | 2024-12-16T13:12:19Z |
| format | Article |
| id | doaj.art-620e0b1815564dbe96cbfdd3817e5f73 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-16T13:12:19Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj.art-620e0b1815564dbe96cbfdd3817e5f732022-12-21T22:30:35ZengWileyAdvanced Science2198-38442021-08-01815n/an/a10.1002/advs.202100606Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine ModificationFei Qin0Baoshan Cai1Jian Zhao2Lei Zhang3Yi Zheng4Bingyu Liu5Chengjiang Gao6Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaKey Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical Sciences Shandong University Jinan Shandong 250012 P. R. ChinaAbstract Mitochondrial antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for antiviral immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well‐defined. Here, it is reported that the MAVS mRNA undergoes N6‐methyladenosine (m6A) modification through methyltransferase‐like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon‐β production in response to RNA viruses. Compared to wild‐type mice, heterozygotes Mettl14+/− mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post‐transcriptionally through m6A modification.https://doi.org/10.1002/advs.202100606antiviral immunityN6‐methyladenosine modificationmethyltransferase‐like protein 14mitochondrial antiviral signaling proteinmRNA stability |
| spellingShingle | Fei Qin Baoshan Cai Jian Zhao Lei Zhang Yi Zheng Bingyu Liu Chengjiang Gao Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification Advanced Science antiviral immunity N6‐methyladenosine modification methyltransferase‐like protein 14 mitochondrial antiviral signaling protein mRNA stability |
| title | Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification |
| title_full | Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification |
| title_fullStr | Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification |
| title_full_unstemmed | Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification |
| title_short | Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification |
| title_sort | methyltransferase like protein 14 attenuates mitochondrial antiviral signaling protein expression to negatively regulate antiviral immunity via n6 methyladenosine modification |
| topic | antiviral immunity N6‐methyladenosine modification methyltransferase‐like protein 14 mitochondrial antiviral signaling protein mRNA stability |
| url | https://doi.org/10.1002/advs.202100606 |
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