Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA
Identifieur interne : 000091 ( France/Analysis ); précédent : 000090; suivant : 000092Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA
Auteurs : François Ferron [France] ; Lorenzo Subissi [France] ; Ana Theresa Silveira De Morais [France] ; Nhung Thi Tuyet Le [France] ; Marion Sevajol [France] ; Laure Gluais [France] ; Etienne Decroly [France] ; Clemens Vonrhein ; Gérard Bricogne ; Bruno Canard [France] ; Isabelle Imbert [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2017.
Descripteurs français
- KwdFr :
- ARN viral (génétique), ARN viral (métabolisme), Antiviraux (métabolisme), Antiviraux (pharmacologie), Coronavirus (), Coronavirus (génétique), Coronavirus (métabolisme), Cristallographie aux rayons X, Domaines protéiques, Exoribonucleases (), Exoribonucleases (génétique), Exoribonucleases (métabolisme), Humains, Liaison aux protéines, Methyltransferases (), Methyltransferases (génétique), Methyltransferases (métabolisme), Modèles moléculaires, Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Ribavirine (métabolisme), Ribavirine (pharmacologie), Réplication virale, Syndrome respiratoire aigu sévère (virologie).
- MESH :
- génétique : ARN viral, Coronavirus, Exoribonucleases, Methyltransferases, Protéines virales non structurales.
- métabolisme : ARN viral, Antiviraux, Coronavirus, Exoribonucleases, Methyltransferases, Protéines virales non structurales, Ribavirine.
- pharmacologie : Antiviraux, Ribavirine.
- virologie : Syndrome respiratoire aigu sévère.
- Coronavirus, Cristallographie aux rayons X, Domaines protéiques, Exoribonucleases, Humains, Liaison aux protéines, Methyltransferases, Modèles moléculaires, Protéines virales non structurales, Réplication virale.
English descriptors
- KwdEn :
- Antiviral Agents (metabolism), Antiviral Agents (pharmacology), Coronavirus (drug effects), Coronavirus (genetics), Coronavirus (metabolism), Crystallography, X-Ray, Exoribonucleases (chemistry), Exoribonucleases (genetics), Exoribonucleases (metabolism), Humans, Methyltransferases (chemistry), Methyltransferases (genetics), Methyltransferases (metabolism), Models, Molecular, Protein Binding, Protein Domains, RNA, Viral (genetics), RNA, Viral (metabolism), Ribavirin (metabolism), Ribavirin (pharmacology), Severe Acute Respiratory Syndrome (virology), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virus Replication.
- MESH :
- chemical , chemistry : Exoribonucleases, Methyltransferases, Viral Nonstructural Proteins.
- chemical , genetics : Exoribonucleases, Methyltransferases, RNA, Viral, Viral Nonstructural Proteins.
- chemical , metabolism : Antiviral Agents, Exoribonucleases, Methyltransferases, RNA, Viral, Ribavirin, Viral Nonstructural Proteins.
- chemical , pharmacology : Antiviral Agents, Ribavirin.
- drug effects : Coronavirus.
- genetics : Coronavirus.
- metabolism : Coronavirus.
- virology : Severe Acute Respiratory Syndrome.
- Crystallography, X-Ray, Humans, Models, Molecular, Protein Binding, Protein Domains, Virus Replication.
- mix :
Abstract
Emerging coronaviruses (CoVs; severe acute respiratory syndrome-CoV and Middle East respiratory syndrome-CoV) pose serious health threats globally, with no specific antiviral treatments available. These viruses are able to faithfully synthesize their large genomic RNA. We report, however, that their main RNA polymerase, nsp12, is not accurate. To achieve accuracy, CoVs have acquired nsp14, a bifunctional enzyme able to methylate the viral RNA cap [methyltransferase (MTase)] and excise erroneous mutagenic nucleotides inserted by nsp12. Strikingly, ribavirin can be excised from the viral genome, thus showing no antiviral activity. The crystal structure of nsp14 shows that it is unique, having been replaced by other MTase types during evolution. This unprecedented RNA correction machinery has allowed RNA genome size expansion, but also provided potential nucleoside drug resistance to these deadly pathogens.
Url:
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777078
- https://hal-amu.archives-ouvertes.fr/hal-02094607
DOI: 10.1073/pnas.1718806115
PubMed: 29279395
PubMed Central: 5777078
Affiliations:
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PMC:5777078Le document en format XML
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Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Silveira De Morais, Ana Theresa" sort="Silveira De Morais, Ana Theresa" uniqKey="Silveira De Morais A" first="Ana Theresa" last="Silveira De Morais">Ana Theresa Silveira De Morais</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Le, Nhung Thi Tuyet" sort="Le, Nhung Thi Tuyet" uniqKey="Le N" first="Nhung Thi Tuyet" last="Le">Nhung Thi Tuyet Le</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sevajol, Marion" sort="Sevajol, Marion" uniqKey="Sevajol M" first="Marion" last="Sevajol">Marion Sevajol</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gluais, Laure" sort="Gluais, Laure" uniqKey="Gluais L" first="Laure" last="Gluais">Laure Gluais</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vonrhein, Clemens" sort="Vonrhein, Clemens" uniqKey="Vonrhein C" first="Clemens" last="Vonrhein">Clemens Vonrhein</name><affiliation><nlm:aff id="aff2"><institution>Global Phasing Ltd.</institution>, Cambridge CB3 0AX,<country>England</country></nlm:aff><wicri:noCountry code="nlm country">England</wicri:noCountry></affiliation></author><author><name sortKey="Bricogne, Gerard" sort="Bricogne, Gerard" uniqKey="Bricogne G" first="Gérard" last="Bricogne">Gérard Bricogne</name><affiliation><nlm:aff id="aff2"><institution>Global Phasing Ltd.</institution>, Cambridge CB3 0AX,<country>England</country></nlm:aff><wicri:noCountry code="nlm country">England</wicri:noCountry></affiliation></author><author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Imbert, Isabelle" sort="Imbert, Isabelle" uniqKey="Imbert I" first="Isabelle" last="Imbert">Isabelle Imbert</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre National de la Recherche Scientifique,<institution>Aix-Marseille Université</institution>, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 13009 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (metabolism)</term><term>Antiviral Agents (pharmacology)</term><term>Coronavirus (drug effects)</term><term>Coronavirus (genetics)</term><term>Coronavirus (metabolism)</term><term>Crystallography, X-Ray</term><term>Exoribonucleases (chemistry)</term><term>Exoribonucleases (genetics)</term><term>Exoribonucleases (metabolism)</term><term>Humans</term><term>Methyltransferases (chemistry)</term><term>Methyltransferases (genetics)</term><term>Methyltransferases (metabolism)</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Domains</term><term>RNA, Viral (genetics)</term><term>RNA, Viral (metabolism)</term><term>Ribavirin (metabolism)</term><term>Ribavirin (pharmacology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Nonstructural Proteins (chemistry)</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>ARN viral (génétique)</term><term>ARN viral (métabolisme)</term><term>Antiviraux (métabolisme)</term><term>Antiviraux (pharmacologie)</term><term>Coronavirus ()</term><term>Coronavirus (génétique)</term><term>Coronavirus (métabolisme)</term><term>Cristallographie aux rayons X</term><term>Domaines protéiques</term><term>Exoribonucleases ()</term><term>Exoribonucleases (génétique)</term><term>Exoribonucleases (métabolisme)</term><term>Humains</term><term>Liaison aux protéines</term><term>Methyltransferases ()</term><term>Methyltransferases (génétique)</term><term>Methyltransferases (métabolisme)</term><term>Modèles moléculaires</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Ribavirine (métabolisme)</term><term>Ribavirine (pharmacologie)</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (virologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Exoribonucleases</term><term>Methyltransferases</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Exoribonucleases</term><term>Methyltransferases</term><term>RNA, Viral</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term><term>Exoribonucleases</term><term>Methyltransferases</term><term>RNA, Viral</term><term>Ribavirin</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Ribavirin</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN viral</term><term>Coronavirus</term><term>Exoribonucleases</term><term>Methyltransferases</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term><term>Antiviraux</term><term>Coronavirus</term><term>Exoribonucleases</term><term>Methyltransferases</term><term>Protéines virales non structurales</term><term>Ribavirine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Ribavirine</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Crystallography, X-Ray</term><term>Humans</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Domains</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coronavirus</term><term>Cristallographie aux rayons X</term><term>Domaines protéiques</term><term>Exoribonucleases</term><term>Humains</term><term>Liaison aux protéines</term><term>Methyltransferases</term><term>Modèles moléculaires</term><term>Protéines virales non structurales</term><term>Réplication virale</term></keywords><keywords scheme="mix" xml:lang="en"><term>RNA virus</term><term>fold evolution</term><term>proofreading</term><term>ribavirin</term><term>virus replication</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Emerging coronaviruses (CoVs; severe acute respiratory syndrome-CoV and Middle East respiratory syndrome-CoV) pose serious health threats globally, with no specific antiviral treatments available. These viruses are able to faithfully synthesize their large genomic RNA. We report, however, that their main RNA polymerase, nsp12, is not accurate. To achieve accuracy, CoVs have acquired nsp14, a bifunctional enzyme able to methylate the viral RNA cap [methyltransferase (MTase)] and excise erroneous mutagenic nucleotides inserted by nsp12. Strikingly, ribavirin can be excised from the viral genome, thus showing no antiviral activity. The crystal structure of nsp14 shows that it is unique, having been replaced by other MTase types during evolution. 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uniqKey="Mansky L">LM Mansky</name></author><author><name sortKey="Belshaw, R" uniqKey="Belshaw R">R Belshaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sidwell, Rw" uniqKey="Sidwell R">RW Sidwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parker, Wb" uniqKey="Parker W">WB Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crotty, S" uniqKey="Crotty S">S Crotty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mchutchison, Jg" uniqKey="Mchutchison J">JG McHutchison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hall, Cb" uniqKey="Hall C">CB Hall</name></author><author><name sortKey="Walsh, Ee" uniqKey="Walsh E">EE Walsh</name></author><author><name sortKey="Hruska, Jf" uniqKey="Hruska J">JF Hruska</name></author><author><name sortKey="Betts, Rf" uniqKey="Betts R">RF 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sortKey="Bricogne, G" uniqKey="Bricogne G">G Bricogne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blanc, E" uniqKey="Blanc E">E Blanc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimaio, F" uniqKey="Dimaio F">F DiMaio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Vb" uniqKey="Chen V">VB Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pettersen, Ef" uniqKey="Pettersen E">EF Pettersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bugl, H" uniqKey="Bugl H">H Bügl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potisopon, S" uniqKey="Potisopon S">S Potisopon</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Bricogne, Gerard" sort="Bricogne, Gerard" uniqKey="Bricogne G" first="Gérard" last="Bricogne">Gérard Bricogne</name><name sortKey="Vonrhein, Clemens" sort="Vonrhein, Clemens" uniqKey="Vonrhein C" first="Clemens" last="Vonrhein">Clemens Vonrhein</name></noCountry><country name="France"><noRegion><name sortKey="Ferron, Francois" sort="Ferron, Francois" uniqKey="Ferron F" first="François" last="Ferron">François Ferron</name></noRegion><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><name sortKey="Gluais, Laure" sort="Gluais, Laure" uniqKey="Gluais L" first="Laure" last="Gluais">Laure Gluais</name><name sortKey="Imbert, Isabelle" sort="Imbert, Isabelle" uniqKey="Imbert I" first="Isabelle" last="Imbert">Isabelle Imbert</name><name sortKey="Le, Nhung Thi Tuyet" sort="Le, Nhung Thi Tuyet" uniqKey="Le N" first="Nhung Thi Tuyet" last="Le">Nhung Thi Tuyet Le</name><name sortKey="Sevajol, Marion" sort="Sevajol, Marion" uniqKey="Sevajol M" first="Marion" last="Sevajol">Marion Sevajol</name><name sortKey="Silveira De Morais, Ana Theresa" sort="Silveira De Morais, Ana Theresa" uniqKey="Silveira De Morais A" first="Ana Theresa" last="Silveira De Morais">Ana Theresa Silveira De Morais</name><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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