Pasternak Alexander O, Spaan Willy J M, Snijder Eric J
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.
J Gen Virol. 2006 Jun;87(Pt 6):1403-1421. doi: 10.1099/vir.0.81611-0.
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.
许多正链RNA病毒利用亚基因组mRNA来表达其部分遗传信息。为了产生结构蛋白和辅助蛋白，尼多病毒目（冠状病毒、圆环病毒、动脉炎病毒和罗尼病毒）的成员会产生一组3' 共末端的嵌套mRNA，至少有三个，通常为七到九个。冠状病毒和动脉炎病毒的亚基因组转录本不仅3' 共末端，还包含一个共同的5' 前导序列，该序列源自基因组的5' 末端。它们的合成涉及一个不连续RNA合成过程，类似于相似性辅助RNA重组。在过去25年中提出的大多数模型都假定亚基因组RNA前导序列和主体序列是共转录融合的，但对于这一过程是发生在正链还是负链合成期间一直存在争议。在现在已获得相当多支持的后一种模型中，亚基因组mRNA合成发生在一组互补的亚基因组大小的负链RNA上，这些负链RNA是由不连续的负链合成产生的。短保守序列之间的正义-反义碱基配对相互作用在这一过程中起关键调节作用。鉴于假定的尼多病毒共同祖先，最近发现罗尼病毒和圆环病毒的mRNA不包含共同的5' 前导序列这一结果令人惊讶。显然，尼多病毒之间一定存在主要的机制差异，这就引发了关于共同前导序列和尼多病毒转录酶蛋白的功能以及尼多病毒转录进化的问题。在这篇综述中，对尼多病毒转录机制进行了比较，对所使用的实验系统进行了批判性评估，尤其讨论了最近开发的反向遗传系统的影响。
