NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation
© 2023. Springer Nature Limited..
N-acetyltransferase 10 (NAT10) is an N4-acetylcytidine (ac4C) writer that catalyzes RNA acetylation at cytidine N4 position on tRNAs, rRNAs and mRNAs. Recently, NAT10 and the associated ac4C have been reported to increase the stability of HIV-1 transcripts. Here, we show that NAT10 catalyzes ac4C addition to the polyadenylated nuclear RNA (PAN), a long non-coding RNA encoded by the oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency. Mutagenesis of ac4C sites in PAN RNA in the context of KSHV infection abolishes PAN ac4C modifications, downregulates the expression of viral lytic genes and reduces virion production. NAT10 knockdown or mutagenesis erases ac4C modifications of PAN RNA and increases its instability, and prevents KSHV reactivation. Furthermore, PAN ac4C modification promotes NAT10 recruitment of IFN-γ-inducible protein-16 (IFI16) mRNA, resulting in its ac4C acetylation, mRNA stability and translation, and eventual inflammasome activation. These results reveal a novel mechanism of viral and host ac4C modifications and the associated complexes as a critical switch of KSHV replication and antiviral immunity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 10. Okt., Seite 6327 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Qin [VerfasserIn] |
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| Links: |
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| Themen: |
3768-18-1 |
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| Anmerkungen: |
Date Completed 12.10.2023 Date Revised 12.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-42135-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM363098739 |
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| 245 | 1 | 0 | |a NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation |
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| 520 | |a N-acetyltransferase 10 (NAT10) is an N4-acetylcytidine (ac4C) writer that catalyzes RNA acetylation at cytidine N4 position on tRNAs, rRNAs and mRNAs. Recently, NAT10 and the associated ac4C have been reported to increase the stability of HIV-1 transcripts. Here, we show that NAT10 catalyzes ac4C addition to the polyadenylated nuclear RNA (PAN), a long non-coding RNA encoded by the oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency. Mutagenesis of ac4C sites in PAN RNA in the context of KSHV infection abolishes PAN ac4C modifications, downregulates the expression of viral lytic genes and reduces virion production. NAT10 knockdown or mutagenesis erases ac4C modifications of PAN RNA and increases its instability, and prevents KSHV reactivation. Furthermore, PAN ac4C modification promotes NAT10 recruitment of IFN-γ-inducible protein-16 (IFI16) mRNA, resulting in its ac4C acetylation, mRNA stability and translation, and eventual inflammasome activation. These results reveal a novel mechanism of viral and host ac4C modifications and the associated complexes as a critical switch of KSHV replication and antiviral immunity | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Zhou, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ziyu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Xiangya |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xinyue |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wan |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Shou-Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chun |e verfasserin |4 aut | |
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