The Coronavirus Replicase Gene: Special Enzymes for Special Viruses
John Ziebuhr and Eric J. Snijder
from: Coronaviruses: Molecular and Cellular Biology (Edited by: Volker Thiel). Caister Academic Press, U.K. (2007)
Coronaviruses have single-stranded, positive-sense RNA genomes of about 30 kilobases, by far the largest non-segmented RNA virus genomes currently known. The key functions required for coronavirus RNA synthesis are encoded by the viral replicase gene. The gene comprises more than 20,000 nucleotides and encodes two replicase polyproteins, pp1a and pp1ab, that are proteolytically processed by viral proteases. Over the past years, it has become clear that the unique size of the coronavirus genome and the special mechanism that coronaviruses (and several other nidoviruses) have evolved to produce an extensive set of subgenome-length RNAs is linked to the production of a number of nonstructural proteins (nsps) that is unprecedented among RNA viruses. Many of these replicase cleavage products in fact are multidomain proteins themselves, thus further increasing the complexity of protein functions and interactions. Structural studies suggest that several nsps, following their release from larger precursor molecules, form dimers or even multimers. The various pp1a/pp1ab precursors and processing products are thought to assemble into large, membrane-associated complexes that, in a temporally coordinated manner, catalyze the reactions involved in RNA replication and transcription and, most probably, serve yet other functions in the viral life cycle. This article reviews the expression, maturation and the functional and structural properties and peculiarities of coronavirus replicase gene-encoded enzymic and other functions, including protease, polymerase, helicase, ADP-ribose 1"-phosphatase and RNase activities read more ...