Major genetic marker of nidoviruses encodes a replicative endoribonuclease.
Identifieur interne : 005255 ( Main/Exploration ); précédent : 005254; suivant : 005256Major genetic marker of nidoviruses encodes a replicative endoribonuclease.
Auteurs : Konstantin A. Ivanov [Allemagne] ; Tobias Hertzig ; Mikhail Rozanov ; Sonja Bayer ; Volker Thiel ; Alexander E. Gorbalenya ; John ZiebuhrSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2004.
Descripteurs français
- KwdFr :
- ARN viral (métabolisme), Alignement de séquences, Données de séquences moléculaires, Endoribonucleases (génétique), Endoribonucleases (métabolisme), Humains, Manganèse (métabolisme), Marqueurs génétiques, Méthylation, Nidovirales (enzymologie), Nidovirales (génétique), Phosphates (), Phosphates (métabolisme), Protéines virales (génétique), Protéines virales (métabolisme), Réplication virale, Spécificité du substrat, Séquence d'acides aminés, Uridine monophosphate (métabolisme), Virus du SRAS (génétique).
- MESH :
- enzymologie : Nidovirales.
- génétique : Endoribonucleases, Nidovirales, Protéines virales, Virus du SRAS.
- métabolisme : ARN viral, Endoribonucleases, Manganèse, Phosphates, Protéines virales, Uridine monophosphate.
- Alignement de séquences, Données de séquences moléculaires, Humains, Marqueurs génétiques, Méthylation, Phosphates, Réplication virale, Spécificité du substrat, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Endoribonucleases (genetics), Endoribonucleases (metabolism), Genetic Markers, Humans, Manganese (metabolism), Methylation, Molecular Sequence Data, Nidovirales (enzymology), Nidovirales (genetics), Phosphates (chemistry), Phosphates (metabolism), RNA, Viral (metabolism), SARS Virus (genetics), Sequence Alignment, Substrate Specificity, Uridine Monophosphate (metabolism), Viral Proteins (genetics), Viral Proteins (metabolism), Virus Replication.
- MESH :
- chemical , chemistry : Phosphates.
- chemical , genetics : Endoribonucleases, Viral Proteins.
- chemical , metabolism : Endoribonucleases, Manganese, Phosphates, RNA, Viral, Uridine Monophosphate, Viral Proteins.
- enzymology : Nidovirales.
- genetics : Nidovirales, SARS Virus.
- Amino Acid Sequence, Genetic Markers, Humans, Methylation, Molecular Sequence Data, Sequence Alignment, Substrate Specificity, Virus Replication.
Abstract
Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the approximately 30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn(2+)-dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2'-3' cyclic phosphate ends. 2'-O-ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2'-O-ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.
DOI: 10.1073/pnas.0403127101
PubMed: 15304651
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002C28
- to stream PubMed, to step Curation: 002C28
- to stream PubMed, to step Checkpoint: 002C07
- to stream Ncbi, to step Merge: 000987
- to stream Ncbi, to step Curation: 000987
- to stream Ncbi, to step Checkpoint: 000987
- to stream Main, to step Merge: 005654
- to stream Main, to step Curation: 005255
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Major genetic marker of nidoviruses encodes a replicative endoribonuclease.</title>
<author><name sortKey="Ivanov, Konstantin A" sort="Ivanov, Konstantin A" uniqKey="Ivanov K" first="Konstantin A" last="Ivanov">Konstantin A. Ivanov</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Virology and Immunology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Virology and Immunology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Basse-Franconie</region>
<settlement type="city">Wurtzbourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hertzig, Tobias" sort="Hertzig, Tobias" uniqKey="Hertzig T" first="Tobias" last="Hertzig">Tobias Hertzig</name>
</author>
<author><name sortKey="Rozanov, Mikhail" sort="Rozanov, Mikhail" uniqKey="Rozanov M" first="Mikhail" last="Rozanov">Mikhail Rozanov</name>
</author>
<author><name sortKey="Bayer, Sonja" sort="Bayer, Sonja" uniqKey="Bayer S" first="Sonja" last="Bayer">Sonja Bayer</name>
</author>
<author><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name>
</author>
<author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name>
</author>
<author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2004">2004</date>
<idno type="RBID">pubmed:15304651</idno>
<idno type="pmid">15304651</idno>
<idno type="doi">10.1073/pnas.0403127101</idno>
<idno type="wicri:Area/PubMed/Corpus">002C28</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002C28</idno>
<idno type="wicri:Area/PubMed/Curation">002C28</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002C28</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002C07</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002C07</idno>
<idno type="wicri:Area/Ncbi/Merge">000987</idno>
<idno type="wicri:Area/Ncbi/Curation">000987</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000987</idno>
<idno type="wicri:doubleKey">0027-8424:2004:Ivanov K:major:genetic:marker</idno>
<idno type="wicri:Area/Main/Merge">005654</idno>
<idno type="wicri:Area/Main/Curation">005255</idno>
<idno type="wicri:Area/Main/Exploration">005255</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Major genetic marker of nidoviruses encodes a replicative endoribonuclease.</title>
<author><name sortKey="Ivanov, Konstantin A" sort="Ivanov, Konstantin A" uniqKey="Ivanov K" first="Konstantin A" last="Ivanov">Konstantin A. Ivanov</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Virology and Immunology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Virology and Immunology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Basse-Franconie</region>
<settlement type="city">Wurtzbourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hertzig, Tobias" sort="Hertzig, Tobias" uniqKey="Hertzig T" first="Tobias" last="Hertzig">Tobias Hertzig</name>
</author>
<author><name sortKey="Rozanov, Mikhail" sort="Rozanov, Mikhail" uniqKey="Rozanov M" first="Mikhail" last="Rozanov">Mikhail Rozanov</name>
</author>
<author><name sortKey="Bayer, Sonja" sort="Bayer, Sonja" uniqKey="Bayer S" first="Sonja" last="Bayer">Sonja Bayer</name>
</author>
<author><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name>
</author>
<author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name>
</author>
<author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
</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>
<imprint><date when="2004" type="published">2004</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Endoribonucleases (genetics)</term>
<term>Endoribonucleases (metabolism)</term>
<term>Genetic Markers</term>
<term>Humans</term>
<term>Manganese (metabolism)</term>
<term>Methylation</term>
<term>Molecular Sequence Data</term>
<term>Nidovirales (enzymology)</term>
<term>Nidovirales (genetics)</term>
<term>Phosphates (chemistry)</term>
<term>Phosphates (metabolism)</term>
<term>RNA, Viral (metabolism)</term>
<term>SARS Virus (genetics)</term>
<term>Sequence Alignment</term>
<term>Substrate Specificity</term>
<term>Uridine Monophosphate (metabolism)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (métabolisme)</term>
<term>Alignement de séquences</term>
<term>Données de séquences moléculaires</term>
<term>Endoribonucleases (génétique)</term>
<term>Endoribonucleases (métabolisme)</term>
<term>Humains</term>
<term>Manganèse (métabolisme)</term>
<term>Marqueurs génétiques</term>
<term>Méthylation</term>
<term>Nidovirales (enzymologie)</term>
<term>Nidovirales (génétique)</term>
<term>Phosphates ()</term>
<term>Phosphates (métabolisme)</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Réplication virale</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
<term>Uridine monophosphate (métabolisme)</term>
<term>Virus du SRAS (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Phosphates</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endoribonucleases</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Endoribonucleases</term>
<term>Manganese</term>
<term>Phosphates</term>
<term>RNA, Viral</term>
<term>Uridine Monophosphate</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Nidovirales</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Nidovirales</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Nidovirales</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Endoribonucleases</term>
<term>Nidovirales</term>
<term>Protéines virales</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term>
<term>Endoribonucleases</term>
<term>Manganèse</term>
<term>Phosphates</term>
<term>Protéines virales</term>
<term>Uridine monophosphate</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Genetic Markers</term>
<term>Humans</term>
<term>Methylation</term>
<term>Molecular Sequence Data</term>
<term>Sequence Alignment</term>
<term>Substrate Specificity</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Marqueurs génétiques</term>
<term>Méthylation</term>
<term>Phosphates</term>
<term>Réplication virale</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the approximately 30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn(2+)-dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2'-3' cyclic phosphate ends. 2'-O-ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2'-O-ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Bavière</li>
<li>District de Basse-Franconie</li>
</region>
<settlement><li>Wurtzbourg</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Bayer, Sonja" sort="Bayer, Sonja" uniqKey="Bayer S" first="Sonja" last="Bayer">Sonja Bayer</name>
<name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name>
<name sortKey="Hertzig, Tobias" sort="Hertzig, Tobias" uniqKey="Hertzig T" first="Tobias" last="Hertzig">Tobias Hertzig</name>
<name sortKey="Rozanov, Mikhail" sort="Rozanov, Mikhail" uniqKey="Rozanov M" first="Mikhail" last="Rozanov">Mikhail Rozanov</name>
<name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name>
<name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
</noCountry>
<country name="Allemagne"><region name="Bavière"><name sortKey="Ivanov, Konstantin A" sort="Ivanov, Konstantin A" uniqKey="Ivanov K" first="Konstantin A" last="Ivanov">Konstantin A. Ivanov</name>
</region>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 005255 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 005255 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Main |étape= Exploration |type= RBID |clé= pubmed:15304651 |texte= Major genetic marker of nidoviruses encodes a replicative endoribonuclease. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:15304651" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |