METTL3-Mediated m6A Modification of TRIF and MyD88 mRNAs Suppresses Innate Immunity in Teleost Fish, Miichthys miiuy
Copyright © 2023 by The American Association of Immunologists, Inc..
Methyltransferase (METTL3), the most important N6-methyladenosine (m6A) writer, plays a vital role in regulating immune-related signaling pathways. However, the underlying mechanism of METTL3 action remains largely unknown, especially in lower vertebrates. The results of this study show that METTL3 inhibits innate immune response and promotes the infection of miiuy croaker, Miichthys miiuy, by Siniperca chuatsi rhabdovirus and Vibrio anguillarum. Significantly, the function of METTL3 in inhibiting immunity depends on its methylase activity. Mechanistically, METTL3 increases the methylation level of trif and myd88 mRNA, rendering them sensitive to degradation by the YTHDF2/3 reader proteins. By contrast, we found that the YTHDF1 reader protein promotes the translation of myd88 mRNA. In summary, these results indicate that METTL3-mediated m6A modification of trif and myd88 mRNAs suppresses innate immunity by inhibiting the TLR pathway, unveiling a molecular mechanism by which RNA methylation controls innate immunity to pathogens in the teleost fish.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:211 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 211(2023), 1 vom: 01. Juli, Seite 130-139 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Geng, Shang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.06.2023 Date Revised 26.06.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.2300033 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356578224 |
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| 245 | 1 | 0 | |a METTL3-Mediated m6A Modification of TRIF and MyD88 mRNAs Suppresses Innate Immunity in Teleost Fish, Miichthys miiuy |
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| 500 | |a Date Completed 22.06.2023 | ||
| 500 | |a Date Revised 26.06.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 by The American Association of Immunologists, Inc. | ||
| 520 | |a Methyltransferase (METTL3), the most important N6-methyladenosine (m6A) writer, plays a vital role in regulating immune-related signaling pathways. However, the underlying mechanism of METTL3 action remains largely unknown, especially in lower vertebrates. The results of this study show that METTL3 inhibits innate immune response and promotes the infection of miiuy croaker, Miichthys miiuy, by Siniperca chuatsi rhabdovirus and Vibrio anguillarum. Significantly, the function of METTL3 in inhibiting immunity depends on its methylase activity. Mechanistically, METTL3 increases the methylation level of trif and myd88 mRNA, rendering them sensitive to degradation by the YTHDF2/3 reader proteins. By contrast, we found that the YTHDF1 reader protein promotes the translation of myd88 mRNA. In summary, these results indicate that METTL3-mediated m6A modification of trif and myd88 mRNAs suppresses innate immunity by inhibiting the TLR pathway, unveiling a molecular mechanism by which RNA methylation controls innate immunity to pathogens in the teleost fish | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Myeloid Differentiation Factor 88 |2 NLM | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
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| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Adaptor Proteins, Vesicular Transport |2 NLM | |
| 700 | 1 | |a Zheng, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Tianjun |e verfasserin |4 aut | |
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