Coronavirus: how a large RNA viral genome is replicated and transcribed

Coronaviruses are important human and animal pathogens and contain an extraordinarily long (27-31 kb) RNA genome. Its RNA synthesis involves complex mechanisms of regulation, similar to those of DNA viruses. In this treatise, mouse hepatitis virus (MHV) is used as a model for the discussion of the mechanism of viral RNA synthesis. We show that MHV RNA synthesis requires interactions of multiple RNA components, which are likely mediated by protein-RNA and protein-protein, as well as RNA-RNA, interactions. This virus also provides a unique example of a discontinuous transcription mechanism, which involves a trans-acting RNA component. Finally, study of the cis-acting signals for the various steps of RNA synthesis revealed an insight into the regulation of viral RNA synthesis. This discussion suggests that the regulation of RNA synthesis in coronavirus is more complex than previously thought possible for RNA viruses. Coronavirus RNA transcription and replication may serve as a paradigm of RNA synthesis for RNA viruses in general.