Coronavirus Nsp10, a Critical Co-factor for Activation of Multiple Replicative Enzymes

Bouvet, Mickaël; Lugari, Adrien; Posthuma, Clara C.; Zevenhoven, Jessika C.; Bernard, Stéphanie; Betzi, S.; Imbert, Isabelle; Canard, Bruno; Guillemot, Jean‐Claude; Lécine, Patrick; Pfefferle, Susanne; Drosten, Christian; Snijder, Eric J.; Decroly, Étienne; Morelli, Xavier

doi:10.1074/jbc.m114.577353

Cited by 205 publications

(252 citation statements)

References 66 publications

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“…The involvement of nsp10 in coronavirus RNA synthesis was first reported from the analysis of MHV mutants (153). More recently, it has been shown that nsp10 acts as a cofactor of both nsp14 ExoN and nsp16 methyltransferase (MTase) activities (154). Moreover, as nsp14 and nsp16 bind to overlapping nsp10 sites, nsp10 might act as a molecular switch, mediating interactions between RNA and proteins from both proofreading and mRNA capping machineries.…”

Section: Cellular and Viral Proteins Of The Coronavirus Replication-tmentioning

confidence: 99%

Continuous and Discontinuous RNA Synthesis in Coronaviruses

et al. 2015

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Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.

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Section: Cellular and Viral Proteins Of The Coronavirus Replication-tmentioning

confidence: 99%

Continuous and Discontinuous RNA Synthesis in Coronaviruses

et al. 2015

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“…There are multiple interactions between the individual replicase gene-encoded nsps and the structural basis and functional implications of these interactions have been studied in a few cases. For example, it has been shown that the exoribonuclease and ribose 2 O-methyltransferase activities associated with nsp14 and nsp16, respectively, are each stimulated by specific interactions with nsp10 (Bouvet et al, 2014;Decroly et al, 2011). Also, there is evidence that a heteromultimeric complex formed by nsp7 and nsp8 interacts with (and serves as a processivity factor for) the RNA-dependent RNA polymerase (RdRp, nsp12) (Zhai et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Also, there is evidence that a heteromultimeric complex formed by nsp7 and nsp8 interacts with (and serves as a processivity factor for) the RNA-dependent RNA polymerase (RdRp, nsp12) (Zhai et al, 2005). Additional interactions between individual subunits of the RTC have been suggested on the basis of two-hybrid screening data (Pan et al, 2008;von Brunn et al, 2007) and there is evidence that a substantial number of coronavirus nsps form homo-and/or heterooligomeric complexes (Anand et al, 2002(Anand et al, , 2003Bouvet et al, 2014;Chen et al, 2011;Ricagno et al, 2006;Su et al, 2006;Xiao et al, 2012;Zhai et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

RNA structure analysis of alphacoronavirus terminal genome regions

et al. 2014

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Coronavirus genome replication is mediated by a multi-subunit protein complex that is comprised of more than a dozen virally encoded and several cellular proteins. Interactions of the viral replicase complex with cis-acting RNA elements located in the 5' and 3'-terminal genome regions ensure the specific replication of viral RNA. Over the past years, boundaries and structures of cis-acting RNA elements required for coronavirus genome replication have been extensively characterized in betacoronaviruses and, to a lesser extent, other coronavirus genera. Here, we review our current understanding of coronavirus cis-acting elements located in the terminal genome regions and use a combination of bioinformatic and RNA structure probing studies to identify and characterize putative cis-acting RNA elements in alphacoronaviruses. The study suggests significant RNA structure conservation among members of the genus Alphacoronavirus but also across genus boundaries. Overall, the conservation pattern identified for 5' and 3'-terminal RNA structural elements in the genomes of alpha- and betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements.

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“…The Mpro domain was encoded between TM2 and TM3, a location conserved in all nidoviruses. We also identified a homologue of coronavirus non-structural protein 10 (nsp10), a zinc-binding protein that is involved in RNA synthesis (Bouvet et al, 2014).…”

mentioning

confidence: 99%

Discovery of a novel nidovirus in cattle with respiratory disease

Tokarz

Sameroff

Hesse

et al. 2015

Journal of General Virology

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The family Coronaviridae represents a diverse group of vertebrate RNA viruses, all with genomes greater than 26 000 nt. Here, we report the discovery and genetic characterization of a novel virus present in cattle with respiratory disease. Phylogenetic characterization of this virus revealed that it clusters within the subfamily Torovirinae, in the family Coronaviridae. The complete genome consists of only 20 261 nt and represents the smallest reported coronavirus genome. We identified seven ORFs, including the canonical nidovirus ORF1a and ORF1b. Analysis of polyprotein 1ab revealed that this virus, tentatively named bovine nidovirus (BoNV), shares the highest homology with the recently described python-borne nidoviruses and contains several conserved nidovirus motifs, but does not encode the NendoU or O-MT domains that are present in other viruses within the family Coronaviridae. In concert with its reduced genome, the atypical domain architecture indicates that this virus represents a unique lineage within the order Nidovirales.

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Coronavirus Nsp10, a Critical Co-factor for Activation of Multiple Replicative Enzymes

Cited by 205 publications

References 66 publications

Continuous and Discontinuous RNA Synthesis in Coronaviruses

Continuous and Discontinuous RNA Synthesis in Coronaviruses

RNA structure analysis of alphacoronavirus terminal genome regions

Discovery of a novel nidovirus in cattle with respiratory disease

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