A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus

作者：Imbert Isabelle; Guillemot Jean Claude; Bourhis Jean Marie; Bussetta Cecile; Coutard Bruno; Egloff Marie Pierre; Ferron Francois; Gorbalenya Alexander E; Canard Bruno^*

来源：The EMBO Journal, 2006, 25(20): 4933-4942.

DOI：10.1038/sj.emboj.7601368

• coronavirus
• polymerase
• replication
• RNA
• SARS

In (+) RNA coronaviruses, replication and transcription of the giant similar to 30 kb genome to produce genome- and subgenome-size RNAs of both polarities are mediated by a cognate membrane-bound enzymatic complex. Its RNA-dependent RNA polymerase (RdRp) activity appears to be supplied by non-structural protein 12 (nsp12) that includes an RdRp domain conserved in all RNA viruses. Using SARS coronavirus, we now show that coronaviruses uniquely encode a second RdRp residing in nsp8. This protein strongly prefers the internal 5'-(G/U)CC-3' tri-nucleotides on RNA templates to initiate the synthesis of complementary oligonucleotides of < 6 residues in a reaction whose fidelity is relatively low. Distant structural homology between the C-terminal domain of nsp8 and the catalytic palm subdomain of RdRps of RNA viruses suggests a common origin of the two coronavirus RdRps, which however may have evolved different sets of catalytic residues. A parallel between the nsp8 RdRp and cellular DNA-dependent RNA primases is drawn to propose that the nsp8 RdRp produces primers utilized by the primer-dependent nsp12 RdRp.

• 出版日期2006-10-18