Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase.
Identifieur interne : 002B13 ( Main/Exploration ); précédent : 002B12; suivant : 002B14Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase.
Auteurs : Yu Chen [République populaire de Chine] ; Hui Cai ; Ji'An Pan ; Nian Xiang ; Po Tien ; Tero Ahola ; Deyin GuoSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2009.
Descripteurs français
- KwdFr :
- Délétion de gène, Guanosine (analogues et dérivés), Guanosine (métabolisme), Génome viral (génétique), Liaison aux protéines, Methyltransferases (génétique), Methyltransferases (métabolisme), Mutation (génétique), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Réplication virale, Transcription génétique (génétique), Virus du SRAS (enzymologie), Virus du SRAS (génétique).
- MESH :
- analogues et dérivés : Guanosine.
- enzymologie : Virus du SRAS.
- génétique : Génome viral, Methyltransferases, Mutation, Protéines virales non structurales, Transcription génétique, Virus du SRAS.
- métabolisme : Guanosine, Methyltransferases, Protéines virales non structurales.
- Délétion de gène, Liaison aux protéines, Réplication virale.
English descriptors
- KwdEn :
- Gene Deletion, Genome, Viral (genetics), Guanosine (analogs & derivatives), Guanosine (metabolism), Methyltransferases (genetics), Methyltransferases (metabolism), Mutation (genetics), Protein Binding, SARS Virus (enzymology), SARS Virus (genetics), Transcription, Genetic (genetics), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virus Replication.
- MESH :
- chemical , analogs & derivatives : Guanosine.
- enzymology : SARS Virus.
- genetics : Genome, Viral, Methyltransferases, Mutation, SARS Virus, Transcription, Genetic, Viral Nonstructural Proteins.
- chemical , metabolism : Guanosine, Methyltransferases, Viral Nonstructural Proteins.
- Gene Deletion, Protein Binding, Virus Replication.
Abstract
The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
DOI: 10.1073/pnas.0808790106
PubMed: 19208801
Affiliations:
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Le document en format XML
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first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="4"><nlm:affiliation>State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, Peoples Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Cai, Hui" sort="Cai, Hui" uniqKey="Cai H" first="Hui" last="Cai">Hui Cai</name></author><author><name sortKey="Pan, Ji An" sort="Pan, Ji An" uniqKey="Pan J" first="Ji'An" last="Pan">Ji'An Pan</name></author><author><name sortKey="Xiang, Nian" sort="Xiang, Nian" uniqKey="Xiang N" first="Nian" last="Xiang">Nian Xiang</name></author><author><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name></author><author><name sortKey="Ahola, Tero" sort="Ahola, Tero" uniqKey="Ahola T" first="Tero" last="Ahola">Tero Ahola</name></author><author><name sortKey="Guo, Deyin" sort="Guo, Deyin" uniqKey="Guo D" first="Deyin" last="Guo">Deyin Guo</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Gene Deletion</term><term>Genome, Viral (genetics)</term><term>Guanosine (analogs & derivatives)</term><term>Guanosine (metabolism)</term><term>Methyltransferases (genetics)</term><term>Methyltransferases (metabolism)</term><term>Mutation (genetics)</term><term>Protein Binding</term><term>SARS Virus (enzymology)</term><term>SARS Virus (genetics)</term><term>Transcription, Genetic (genetics)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Délétion de gène</term><term>Guanosine (analogues et dérivés)</term><term>Guanosine (métabolisme)</term><term>Génome viral (génétique)</term><term>Liaison aux protéines</term><term>Methyltransferases (génétique)</term><term>Methyltransferases (métabolisme)</term><term>Mutation (génétique)</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Réplication virale</term><term>Transcription génétique (génétique)</term><term>Virus du SRAS (enzymologie)</term><term>Virus du SRAS (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Guanosine</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Guanosine</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genome, Viral</term><term>Methyltransferases</term><term>Mutation</term><term>SARS Virus</term><term>Transcription, Genetic</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome viral</term><term>Methyltransferases</term><term>Mutation</term><term>Protéines virales non structurales</term><term>Transcription génétique</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Guanosine</term><term>Methyltransferases</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Guanosine</term><term>Methyltransferases</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Deletion</term><term>Protein Binding</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Délétion de gène</term><term>Liaison aux protéines</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Hubei</li></region><settlement><li>Wuhan</li></settlement><orgName><li>Université de Wuhan</li></orgName></list><tree><noCountry><name sortKey="Ahola, Tero" sort="Ahola, Tero" uniqKey="Ahola T" first="Tero" last="Ahola">Tero Ahola</name><name sortKey="Cai, Hui" sort="Cai, Hui" uniqKey="Cai H" first="Hui" last="Cai">Hui Cai</name><name sortKey="Guo, Deyin" sort="Guo, Deyin" uniqKey="Guo D" first="Deyin" last="Guo">Deyin Guo</name><name sortKey="Pan, Ji An" sort="Pan, Ji An" uniqKey="Pan J" first="Ji'An" last="Pan">Ji'An Pan</name><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name><name sortKey="Xiang, Nian" sort="Xiang, Nian" uniqKey="Xiang N" first="Nian" last="Xiang">Nian Xiang</name></noCountry><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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