The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation
Open accessAbstract
SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set of mRNAs, which presumably are capped at their 5' end and direct the synthesis of all viral proteins in the infected cell. Sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed to nsp14, whereas nsp16 has been predicted to be the AdoMet-dependent (nucleoside-2'O)-methyltransferase. Here, we have reconstituted complete SARS-CoV mRNA cap methylation in vitro. We show that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation. The obligate sequence of methylation events is initiated by nsp14, which first methylates capped RNA transcripts to generate cap-0 (7Me)GpppA-RNAs. The latter are then selectively 2'O-methylated by the 2'O-MTase nsp16 in complex with its activator nsp10 to give rise to cap-1 (7Me)GpppA(2'OMe)-RNAs. Furthermore, sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC(50) values in the micromolar range, providing a validated basis for anti-coronavirus drug design.
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Self-citationNidovirales: Evolving the largest RNA virus genome
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Self-citationStructural classification of zinc fingers: SURVEY AND SUMMARY
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Immunology of COVID-19: Current State of the Science
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Züst, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B. W., Ziebuhr, J., Szretter, K. J., Baker, S. C., Barchet, W., Diamond, M. S., et al. (2011) · Nature Immunology · doi:10.1038/ni.1979 · Cited by 811
Continuous and Discontinuous RNA Synthesis in Coronaviruses
Sola, I., Almazán, F., Zúñiga, S., & Enjuanes, L. (2015) · Annual Review of Virology · doi:10.1146/annurev-virology-100114-055218 · Cited by 643
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Metadata
- Authors
- Bouvet, M., Debarnot, C., Imbert, I., Selisko, B., Snijder, E. J., Canard, B., & Decroly, E.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-04-22
- Volume
- 6
- Issue
- 4
- Pages
- e1000863
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W2045996885
- Cited by
- 406
- References
- 61
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- gold
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