Reconstitution of RNA cap methylation reveals different features of SARS‐CoV‐2 and SARS‐CoV methyltransferases
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...
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| creator | He, Miao Cao, Liu Liu, Lihong Jin, Xu Zheng, Birong Liu, Xue Zhuang, Jiaxin Zhang, Fushi Yang, Zixiao Ji, Yanxi Xu, Tiefeng Huang, Siyao Chen, Junhai Xie, Luyang Li, Kun Hou, Panpan Pan, Jian Guo, Deyin Li, Chunmei |
| description | 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. |
| doi_str_mv | 10.1002/jmv.29411 |
| format | Article |
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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.</description><identifier>ISSN: 0146-6615</identifier><identifier>ISSN: 1096-9071</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.29411</identifier><identifier>PMID: 38285434</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>coronavirus ; Coronaviruses ; COVID-19 ; Methylation ; methyltransferases ; Nucleotide sequence ; Pathogenesis ; Ribonucleic acid ; Ribose ; RNA ; SARS‐CoV‐2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; substrate selectivity ; Substrates</subject><ispartof>Journal of medical virology, 2024-02, Vol.96 (2), p.e29411-n/a</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3131-2d68ccb877233889ffa9ebdb3a595ded8ce2f93e6d2ecc77a679c7564777b7363</cites><orcidid>0009-0009-9980-9662</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.29411$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.29411$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38285434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Miao</creatorcontrib><creatorcontrib>Cao, Liu</creatorcontrib><creatorcontrib>Liu, Lihong</creatorcontrib><creatorcontrib>Jin, Xu</creatorcontrib><creatorcontrib>Zheng, Birong</creatorcontrib><creatorcontrib>Liu, Xue</creatorcontrib><creatorcontrib>Zhuang, Jiaxin</creatorcontrib><creatorcontrib>Zhang, Fushi</creatorcontrib><creatorcontrib>Yang, Zixiao</creatorcontrib><creatorcontrib>Ji, Yanxi</creatorcontrib><creatorcontrib>Xu, Tiefeng</creatorcontrib><creatorcontrib>Huang, Siyao</creatorcontrib><creatorcontrib>Chen, Junhai</creatorcontrib><creatorcontrib>Xie, Luyang</creatorcontrib><creatorcontrib>Li, Kun</creatorcontrib><creatorcontrib>Hou, Panpan</creatorcontrib><creatorcontrib>Pan, Jian</creatorcontrib><creatorcontrib>Guo, Deyin</creatorcontrib><creatorcontrib>Li, Chunmei</creatorcontrib><title>Reconstitution of RNA cap methylation reveals different features of SARS‐CoV‐2 and SARS‐CoV methyltransferases</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>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. 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Cao, Liu ; Liu, Lihong ; Jin, Xu ; Zheng, Birong ; Liu, Xue ; Zhuang, Jiaxin ; Zhang, Fushi ; Yang, Zixiao ; Ji, Yanxi ; Xu, Tiefeng ; Huang, Siyao ; Chen, Junhai ; Xie, Luyang ; Li, Kun ; Hou, Panpan ; Pan, Jian ; Guo, Deyin ; Li, Chunmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3131-2d68ccb877233889ffa9ebdb3a595ded8ce2f93e6d2ecc77a679c7564777b7363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>coronavirus</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Methylation</topic><topic>methyltransferases</topic><topic>Nucleotide sequence</topic><topic>Pathogenesis</topic><topic>Ribonucleic acid</topic><topic>Ribose</topic><topic>RNA</topic><topic>SARS‐CoV‐2</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>substrate selectivity</topic><topic>Substrates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Miao</creatorcontrib><creatorcontrib>Cao, Liu</creatorcontrib><creatorcontrib>Liu, Lihong</creatorcontrib><creatorcontrib>Jin, Xu</creatorcontrib><creatorcontrib>Zheng, Birong</creatorcontrib><creatorcontrib>Liu, Xue</creatorcontrib><creatorcontrib>Zhuang, Jiaxin</creatorcontrib><creatorcontrib>Zhang, Fushi</creatorcontrib><creatorcontrib>Yang, Zixiao</creatorcontrib><creatorcontrib>Ji, Yanxi</creatorcontrib><creatorcontrib>Xu, Tiefeng</creatorcontrib><creatorcontrib>Huang, Siyao</creatorcontrib><creatorcontrib>Chen, Junhai</creatorcontrib><creatorcontrib>Xie, Luyang</creatorcontrib><creatorcontrib>Li, Kun</creatorcontrib><creatorcontrib>Hou, Panpan</creatorcontrib><creatorcontrib>Pan, Jian</creatorcontrib><creatorcontrib>Guo, Deyin</creatorcontrib><creatorcontrib>Li, Chunmei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Miao</au><au>Cao, Liu</au><au>Liu, Lihong</au><au>Jin, Xu</au><au>Zheng, Birong</au><au>Liu, Xue</au><au>Zhuang, Jiaxin</au><au>Zhang, Fushi</au><au>Yang, Zixiao</au><au>Ji, Yanxi</au><au>Xu, Tiefeng</au><au>Huang, Siyao</au><au>Chen, Junhai</au><au>Xie, Luyang</au><au>Li, Kun</au><au>Hou, Panpan</au><au>Pan, Jian</au><au>Guo, Deyin</au><au>Li, Chunmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reconstitution of RNA cap methylation reveals different features of SARS‐CoV‐2 and SARS‐CoV methyltransferases</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2024-02</date><risdate>2024</risdate><volume>96</volume><issue>2</issue><spage>e29411</spage><epage>n/a</epage><pages>e29411-n/a</pages><issn>0146-6615</issn><issn>1096-9071</issn><eissn>1096-9071</eissn><abstract>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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38285434</pmid><doi>10.1002/jmv.29411</doi><tpages>15</tpages><orcidid>https://orcid.org/0009-0009-9980-9662</orcidid></addata></record> |
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| subjects | coronavirus Coronaviruses COVID-19 Methylation methyltransferases Nucleotide sequence Pathogenesis Ribonucleic acid Ribose RNA SARS‐CoV‐2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 substrate selectivity Substrates |
| title | Reconstitution of RNA cap methylation reveals different features of SARS‐CoV‐2 and SARS‐CoV methyltransferases |
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