tetano
Editor, Senior Moderator
J Med Virol
. 2024 Feb;96(2):e29411.
doi: 10.1002/jmv.29411. Reconstitution of RNA cap methylation reveals different features of SARS-CoV-2 and SARS-CoV methyltransferases
Miao He[SUP] 1 [/SUP], Liu Cao[SUP] 1 [/SUP], Lihong Liu[SUP] 2 3 [/SUP], Xu Jin[SUP] 1 [/SUP], Birong Zheng[SUP] 1 2 [/SUP], Xue Liu[SUP] 1 [/SUP], Jiaxin Zhuang[SUP] 1 [/SUP], Fushi Zhang[SUP] 1 [/SUP], Zixiao Yang[SUP] 1 2 [/SUP], Yanxi Ji[SUP] 1 [/SUP], Tiefeng Xu[SUP] 1 2 [/SUP], Siyao Huang[SUP] 1 2 [/SUP], Junhai Chen[SUP] 1 [/SUP], Luyang Xie[SUP] 1 [/SUP], Kun Li[SUP] 1 2 [/SUP], Panpan Hou[SUP] 1 [/SUP], Jian Pan[SUP] 1 [/SUP], Deyin Guo[SUP] 2 3 [/SUP], Chunmei Li[SUP] 1 [/SUP]
Affiliations
Cap RNA methylations play important roles in the replication, evasion of host RNA sensor recognition, and pathogenesis. Coronaviruses possess both guanine N7- and 2'-O-ribose methyltransferases (N7-MTase and 2'-O-MTase) encoded by nonstructural protein (nsp) 14 and nsp16/10 complex, respectively. In this study, we reconstituted the two-step RNA methylations of N7-MTase and 2'-O-MTase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and demonstrated its common and different features in comparison with that of SARS-CoV. We revealed that the nsp16/10 2'-O-MTase of SARS-CoV-2 has a broader substrate selectivity than the counterpart of SARS-CoV and can accommodate both unmethylated and uncapped RNA substrates in a sequence-independent manner. Most intriguingly, the substrate selectivity of nsp16/10 complex is not determined by the apoenzyme of nsp16 MTase but by its cofactor nsp10. These results provide insight into the unique features of SARS-CoV-2 MTases and may help develop strategies to precisely intervene in the methylation pathway and pathogenesis of SARS-CoV-2.
Keywords: SARS-CoV-2; coronavirus; methyltransferases; substrate selectivity.
. 2024 Feb;96(2):e29411.
doi: 10.1002/jmv.29411. Reconstitution of RNA cap methylation reveals different features of SARS-CoV-2 and SARS-CoV methyltransferases
Miao He[SUP] 1 [/SUP], Liu Cao[SUP] 1 [/SUP], Lihong Liu[SUP] 2 3 [/SUP], Xu Jin[SUP] 1 [/SUP], Birong Zheng[SUP] 1 2 [/SUP], Xue Liu[SUP] 1 [/SUP], Jiaxin Zhuang[SUP] 1 [/SUP], Fushi Zhang[SUP] 1 [/SUP], Zixiao Yang[SUP] 1 2 [/SUP], Yanxi Ji[SUP] 1 [/SUP], Tiefeng Xu[SUP] 1 2 [/SUP], Siyao Huang[SUP] 1 2 [/SUP], Junhai Chen[SUP] 1 [/SUP], Luyang Xie[SUP] 1 [/SUP], Kun Li[SUP] 1 2 [/SUP], Panpan Hou[SUP] 1 [/SUP], Jian Pan[SUP] 1 [/SUP], Deyin Guo[SUP] 2 3 [/SUP], Chunmei Li[SUP] 1 [/SUP]
Affiliations
- PMID: 38285434
- DOI: 10.1002/jmv.29411
Cap RNA methylations play important roles in the replication, evasion of host RNA sensor recognition, and pathogenesis. Coronaviruses possess both guanine N7- and 2'-O-ribose methyltransferases (N7-MTase and 2'-O-MTase) encoded by nonstructural protein (nsp) 14 and nsp16/10 complex, respectively. In this study, we reconstituted the two-step RNA methylations of N7-MTase and 2'-O-MTase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and demonstrated its common and different features in comparison with that of SARS-CoV. We revealed that the nsp16/10 2'-O-MTase of SARS-CoV-2 has a broader substrate selectivity than the counterpart of SARS-CoV and can accommodate both unmethylated and uncapped RNA substrates in a sequence-independent manner. Most intriguingly, the substrate selectivity of nsp16/10 complex is not determined by the apoenzyme of nsp16 MTase but by its cofactor nsp10. These results provide insight into the unique features of SARS-CoV-2 MTases and may help develop strategies to precisely intervene in the methylation pathway and pathogenesis of SARS-CoV-2.
Keywords: SARS-CoV-2; coronavirus; methyltransferases; substrate selectivity.