tetano
Editor, Senior Moderator
Sci Adv
. 2024 Aug 9;10(32):eadn9519.
doi: 10.1126/sciadv.adn9519. Epub 2024 Aug 7. Epitranscriptomic m[SUP]5[/SUP]C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection
Hongyun Wang[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Zhiying Fu[SUP] 1 [/SUP], Tianmo Xu[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Shimin Yang[SUP] 1 [/SUP], Yingjian Li[SUP] 1 [/SUP], Jikai Deng[SUP] 1 [/SUP], Yuzhen Zhang[SUP] 1 [/SUP], Ming Guo[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 2 [/SUP], Zhixiang Huang[SUP] 1 2 [/SUP], Ke Lan[SUP] 1 2 [/SUP], Li Zhou[SUP] 1 2 [/SUP], Yu Chen[SUP] 1 2 [/SUP]
Affiliations
While the significance of N6-methyladenosine (m[SUP]6[/SUP]A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m[SUP]5[/SUP]C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m[SUP]5[/SUP]C is more abundant than m[SUP]6[/SUP]A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m[SUP]5[/SUP]C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m[SUP]5[/SUP]C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m[SUP]5[/SUP]C-MeRIP-seq identified the NSUN2-dependent m[SUP]5[/SUP]C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m[SUP]5[/SUP]C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m[SUP]5[/SUP]C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m[SUP]5[/SUP]C methylation to SARS-CoV-2 RNA.
. 2024 Aug 9;10(32):eadn9519.
doi: 10.1126/sciadv.adn9519. Epub 2024 Aug 7. Epitranscriptomic m[SUP]5[/SUP]C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection
Hongyun Wang[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Zhiying Fu[SUP] 1 [/SUP], Tianmo Xu[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Shimin Yang[SUP] 1 [/SUP], Yingjian Li[SUP] 1 [/SUP], Jikai Deng[SUP] 1 [/SUP], Yuzhen Zhang[SUP] 1 [/SUP], Ming Guo[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 2 [/SUP], Zhixiang Huang[SUP] 1 2 [/SUP], Ke Lan[SUP] 1 2 [/SUP], Li Zhou[SUP] 1 2 [/SUP], Yu Chen[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39110796
- PMCID: PMC11305390
- DOI: 10.1126/sciadv.adn9519
While the significance of N6-methyladenosine (m[SUP]6[/SUP]A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m[SUP]5[/SUP]C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m[SUP]5[/SUP]C is more abundant than m[SUP]6[/SUP]A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m[SUP]5[/SUP]C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m[SUP]5[/SUP]C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m[SUP]5[/SUP]C-MeRIP-seq identified the NSUN2-dependent m[SUP]5[/SUP]C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m[SUP]5[/SUP]C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m[SUP]5[/SUP]C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m[SUP]5[/SUP]C methylation to SARS-CoV-2 RNA.