One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities
Identifieur interne : 002952 ( Ncbi/Merge ); précédent : 002951; suivant : 002953One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities
Auteurs : Lorenzo Subissi [France] ; Clara C. Posthuma [Pays-Bas] ; Axelle Collet [France] ; Jessika C. Zevenhoven-Dobbe [Pays-Bas] ; Alexander E. Gorbalenya [Pays-Bas, Russie] ; Etienne Decroly [France] ; Eric J. Snijder [Pays-Bas] ; Bruno Canard [France] ; Isabelle Imbert [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Descripteurs français
- KwdFr :
- ARN (métabolisme), ARN viral (biosynthèse), Biocatalyse, Complexes multiprotéiques (métabolisme), DNA-directed RNA polymerases (métabolisme), Données de séquences moléculaires, Exoribonucleases (métabolisme), Génétique inverse, Humains, Liaison aux protéines, Mutation (génétique), Protéines mutantes (métabolisme), Protéines virales non structurales (métabolisme), Reproductibilité des résultats, Réplication virale, Syndrome respiratoire aigu sévère (virologie), Séquence nucléotidique, Virus du SRAS (métabolisme).
- MESH :
- biosynthèse : ARN viral.
- génétique : Mutation.
- métabolisme : ARN, Complexes multiprotéiques, DNA-directed RNA polymerases, Exoribonucleases, Protéines mutantes, Protéines virales non structurales, Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Biocatalyse, Données de séquences moléculaires, Génétique inverse, Humains, Liaison aux protéines, Reproductibilité des résultats, Réplication virale, Séquence nucléotidique.
English descriptors
- KwdEn :
- Base Sequence, Biocatalysis, DNA-Directed RNA Polymerases (metabolism), Exoribonucleases (metabolism), Humans, Molecular Sequence Data, Multiprotein Complexes (metabolism), Mutant Proteins (metabolism), Mutation (genetics), Protein Binding, RNA (metabolism), RNA, Viral (biosynthesis), Reproducibility of Results, Reverse Genetics, SARS Virus (metabolism), Severe Acute Respiratory Syndrome (virology), Viral Nonstructural Proteins (metabolism), Virus Replication.
- MESH :
- chemical , biosynthesis : RNA, Viral.
- chemical , metabolism : DNA-Directed RNA Polymerases, Exoribonucleases, Multiprotein Complexes, Mutant Proteins, RNA, Viral Nonstructural Proteins.
- genetics : Mutation.
- metabolism : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Base Sequence, Biocatalysis, Humans, Molecular Sequence Data, Protein Binding, Reproducibility of Results, Reverse Genetics, Virus Replication.
Abstract
The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.
Url:
DOI: 10.1073/pnas.1323705111
PubMed: 25197083
PubMed Central: 4169972
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000D17
- to stream Pmc, to step Curation: 000D17
- to stream Pmc, to step Checkpoint: 000872
- to stream PubMed, to step Corpus: 000F36
- to stream PubMed, to step Curation: 000F36
- to stream PubMed, to step Checkpoint: 000F60
Links to Exploration step
PMC:4169972Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C." last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E." last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Faculty of Bioengineering and Bioinformatics,<institution>Lomonosov Moscow State University</institution>, Moscow 119899,<country>Russia</country></nlm:aff><country xml:lang="fr">Russie</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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25197083</idno><idno type="pmc">4169972</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169972</idno><idno type="RBID">PMC:4169972</idno><idno type="doi">10.1073/pnas.1323705111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000D17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D17</idno><idno type="wicri:Area/Pmc/Curation">000D17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D17</idno><idno type="wicri:Area/Pmc/Checkpoint">000872</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000872</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:25197083</idno><idno type="wicri:Area/PubMed/Corpus">000F36</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F36</idno><idno type="wicri:Area/PubMed/Curation">000F36</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F36</idno><idno type="wicri:Area/PubMed/Checkpoint">000F60</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000F60</idno><idno type="wicri:Area/Ncbi/Merge">002952</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C." last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E." last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Faculty of Bioengineering and Bioinformatics,<institution>Lomonosov Moscow State University</institution>, Moscow 119899,<country>Russia</country></nlm:aff><country xml:lang="fr">Russie</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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Biocatalysis</term><term>DNA-Directed RNA Polymerases (metabolism)</term><term>Exoribonucleases (metabolism)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Multiprotein Complexes (metabolism)</term><term>Mutant Proteins (metabolism)</term><term>Mutation (genetics)</term><term>Protein Binding</term><term>RNA (metabolism)</term><term>RNA, Viral (biosynthesis)</term><term>Reproducibility of Results</term><term>Reverse Genetics</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN (métabolisme)</term><term>ARN viral (biosynthèse)</term><term>Biocatalyse</term><term>Complexes multiprotéiques (métabolisme)</term><term>DNA-directed RNA polymerases (métabolisme)</term><term>Données de séquences moléculaires</term><term>Exoribonucleases (métabolisme)</term><term>Génétique inverse</term><term>Humains</term><term>Liaison aux protéines</term><term>Mutation (génétique)</term><term>Protéines mutantes (métabolisme)</term><term>Protéines virales non structurales (métabolisme)</term><term>Reproductibilité des résultats</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Séquence nucléotidique</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA-Directed RNA Polymerases</term><term>Exoribonucleases</term><term>Multiprotein Complexes</term><term>Mutant Proteins</term><term>RNA</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN</term><term>Complexes multiprotéiques</term><term>DNA-directed RNA polymerases</term><term>Exoribonucleases</term><term>Protéines mutantes</term><term>Protéines virales non structurales</term><term>Virus du SRAS</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>Base Sequence</term><term>Biocatalysis</term><term>Humans</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Reproducibility of Results</term><term>Reverse Genetics</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biocatalyse</term><term>Données de séquences moléculaires</term><term>Génétique inverse</term><term>Humains</term><term>Liaison aux protéines</term><term>Reproductibilité des résultats</term><term>Réplication virale</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.</p></div></front></TEI><double pmid="25197083"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C." last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E." last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Faculty of Bioengineering and Bioinformatics,<institution>Lomonosov Moscow State University</institution>, Moscow 119899,<country>Russia</country></nlm:aff><country xml:lang="fr">Russie</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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 Marseille,<country>France</country>;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25197083</idno><idno type="pmc">4169972</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169972</idno><idno type="RBID">PMC:4169972</idno><idno type="doi">10.1073/pnas.1323705111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000D17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D17</idno><idno type="wicri:Area/Pmc/Curation">000D17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D17</idno><idno type="wicri:Area/Pmc/Checkpoint">000872</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000872</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="1"><nlm:aff id="aff1">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C." last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E." last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Faculty of Bioengineering and Bioinformatics,<institution>Lomonosov Moscow State University</institution>, Moscow 119899,<country>Russia</country></nlm:aff><country xml:lang="fr">Russie</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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology,<institution>Leiden University Medical Center</institution>, 2300RC, Leiden,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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">Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257,<institution>Aix-Marseille Université</institution>, 13288 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="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C" last="Posthuma">Clara C. Posthuma</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</wicri:noCountry></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C" last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</wicri:noCountry></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119899, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119899</wicri:regionArea><placeName><settlement type="city">Moscou</settlement><region>District fédéral central</region></placeName></affiliation></author><author><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</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="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France; isabelle.imbert@afmb.univ-mrs.fr bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Imbert, Isabelle" sort="Imbert, Isabelle" uniqKey="Imbert I" first="Isabelle" last="Imbert">Isabelle Imbert</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France; isabelle.imbert@afmb.univ-mrs.fr bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25197083</idno><idno type="pmid">25197083</idno><idno type="doi">10.1073/pnas.1323705111</idno><idno type="wicri:Area/PubMed/Corpus">000F36</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F36</idno><idno type="wicri:Area/PubMed/Curation">000F36</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F36</idno><idno type="wicri:Area/PubMed/Checkpoint">000F60</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000F60</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.</title><author><name sortKey="Subissi, Lorenzo" sort="Subissi, Lorenzo" uniqKey="Subissi L" first="Lorenzo" last="Subissi">Lorenzo Subissi</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C" last="Posthuma">Clara C. Posthuma</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</wicri:noCountry></affiliation></author><author><name sortKey="Collet, Axelle" sort="Collet, Axelle" uniqKey="Collet A" first="Axelle" last="Collet">Axelle Collet</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Zevenhoven Dobbe, Jessika C" sort="Zevenhoven Dobbe, Jessika C" uniqKey="Zevenhoven Dobbe J" first="Jessika C" last="Zevenhoven-Dobbe">Jessika C. Zevenhoven-Dobbe</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</wicri:noCountry></affiliation></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119899, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119899</wicri:regionArea><placeName><settlement type="city">Moscou</settlement><region>District fédéral central</region></placeName></affiliation></author><author><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><affiliation><nlm:affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands; and.</nlm:affiliation><wicri:noCountry code="subField">The Netherlands; and</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="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France; isabelle.imbert@afmb.univ-mrs.fr bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Imbert, Isabelle" sort="Imbert, Isabelle" uniqKey="Imbert I" first="Isabelle" last="Imbert">Isabelle Imbert</name><affiliation wicri:level="4"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille, France; isabelle.imbert@afmb.univ-mrs.fr bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7257, Aix-Marseille Université, 13288 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></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="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Biocatalysis</term><term>DNA-Directed RNA Polymerases (metabolism)</term><term>Exoribonucleases (metabolism)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Multiprotein Complexes (metabolism)</term><term>Mutant Proteins (metabolism)</term><term>Mutation (genetics)</term><term>Protein Binding</term><term>RNA (metabolism)</term><term>RNA, Viral (biosynthesis)</term><term>Reproducibility of Results</term><term>Reverse Genetics</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN (métabolisme)</term><term>ARN viral (biosynthèse)</term><term>Biocatalyse</term><term>Complexes multiprotéiques (métabolisme)</term><term>DNA-directed RNA polymerases (métabolisme)</term><term>Données de séquences moléculaires</term><term>Exoribonucleases (métabolisme)</term><term>Génétique inverse</term><term>Humains</term><term>Liaison aux protéines</term><term>Mutation (génétique)</term><term>Protéines mutantes (métabolisme)</term><term>Protéines virales non structurales (métabolisme)</term><term>Reproductibilité des résultats</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Séquence nucléotidique</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA-Directed RNA Polymerases</term><term>Exoribonucleases</term><term>Multiprotein Complexes</term><term>Mutant Proteins</term><term>RNA</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN</term><term>Complexes multiprotéiques</term><term>DNA-directed RNA polymerases</term><term>Exoribonucleases</term><term>Protéines mutantes</term><term>Protéines virales non structurales</term><term>Virus du SRAS</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>Base Sequence</term><term>Biocatalysis</term><term>Humans</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Reproducibility of Results</term><term>Reverse Genetics</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biocatalyse</term><term>Données de séquences moléculaires</term><term>Génétique inverse</term><term>Humains</term><term>Liaison aux protéines</term><term>Reproductibilité des résultats</term><term>Réplication virale</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3'-5' exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5'-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. </div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002952 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 002952 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:4169972
|texte= One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:25197083" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |