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Review article |
Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, LUMC P4-26, PO Box 9600, 2300 RC Leiden, The Netherlands
Correspondence
Eric J. Snijder
e.j.snijder{at}lumc.nl
Many positive-stranded RNA viruses use subgenomic mRNAs to express part of their genetic information. To produce structural and accessory proteins, members of the order Nidovirales (corona-, toro-, arteri- and roniviruses) generate a 3' co-terminal nested set of at least three and often seven to nine mRNAs. Coronavirus and arterivirus subgenomic transcripts are not only 3' co-terminal but also contain a common 5' leader sequence, which is derived from the genomic 5' end. Their synthesis involves a process of discontinuous RNA synthesis that resembles similarity-assisted RNA recombination. Most models proposed over the past 25 years assume co-transcriptional fusion of subgenomic RNA leader and body sequences, but there has been controversy over the question of whether this occurs during plus- or minus-strand synthesis. In the latter model, which has now gained considerable support, subgenomic mRNA synthesis takes place from a complementary set of subgenome-size minus-strand RNAs, produced by discontinuous minus-strand synthesis. Sense–antisense base-pairing interactions between short conserved sequences play a key regulatory role in this process. In view of the presumed common ancestry of nidoviruses, the recent finding that ronivirus and torovirus mRNAs do not contain a common 5' leader sequence is surprising. Apparently, major mechanistic differences must exist between nidoviruses, which raises questions about the functions of the common leader sequence and nidovirus transcriptase proteins and the evolution of nidovirus transcription. In this review, nidovirus transcription mechanisms are compared, the experimental systems used are critically assessed and, in particular, the impact of recently developed reverse genetic systems is discussed.
Published online ahead of print on 23 February 2006 as DOI 10.1099/vir.0.81611-0.
*When its definition is followed to the letter, the term ‘transcription’ (i.e. ‘the process by which genetic information encoded in one strand of DNA is copied into a complementary RNA strand’) does not apply to the synthesis of sg mRNAs by nidoviruses and other RNA viruses. Nevertheless, there is a clear functional parallel (production of RNA templates for protein synthesis) and the term ‘transcription’ has been used in studies on coronavirus sg mRNA synthesis from the very start. Consequently, for the purpose of this review and regardless of the lack of a DNA template, we will use the term ‘transcription’ for the synthesis of sg plus strands (sg mRNAs). Genome amplification, which results in the production of a full-length mRNA, will be referred to as ‘replication’.
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