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副粘病毒mRNA编辑、“六规则”与错误灾难:一种假说

Paramyxovirus mRNA editing, the "rule of six" and error catastrophe: a hypothesis.

作者信息

Kolakofsky Daniel, Roux Laurent, Garcin Dominique, Ruigrok Rob W H

机构信息

Department of Microbiology and Molecular Medicine, Université de Genève, Geneva, Switzerland.

Laboratoire de Virologie Moléculaire et Structurale, FRE 2854 CNRS-Université Joseph Fourier, Grenoble, France.

出版信息

J Gen Virol. 2005 Jul;86(Pt 7):1869-1877. doi: 10.1099/vir.0.80986-0.

DOI:10.1099/vir.0.80986-0
PMID:15958664
Abstract

The order Mononegavirales includes three virus families that replicate in the cytoplasm: the Paramyxoviridae, composed of two subfamilies, the Paramyxovirinae and Pneumovirinae, the Rhabdoviridae and the Filoviridae. These viruses, also called non-segmented negative-strand RNA viruses (NNV), contain five to ten tandemly linked genes, which are separated by conserved junctional sequences that act as mRNA start and poly(A)/stop sites. For the NNV, downstream mRNA synthesis depends on termination of the upstream mRNA, and all NNV RNA-dependent RNA polymerases reiteratively copy ("stutter" on) a short run of template uridylates during transcription to polyadenylate and terminate their mRNAs. The RNA-dependent RNA polymerase of a subset of the NNV, all members of the Paramyxovirinae, also stutter in a very controlled fashion to edit their phosphoprotein gene mRNA, and Ebola virus, a filovirus, carries out a related process on its glycoprotein mRNA. Remarkably, all viruses that edit their phosphoprotein mRNA are also governed by the "rule of six", i.e. their genomes must be of polyhexameric length (6n+0) to replicate efficiently. Why these two seemingly unrelated processes are so tightly linked in the Paramyxovirinae has been an enigma. This paper will review what is presently known about these two processes that are unique to viruses of this subfamily, and will discuss whether this enigmatic linkage could be due to the phenomenon of RNA virus error catastrophe.

摘要

单负链RNA病毒目包括三个在细胞质中复制的病毒科:副粘病毒科,由副粘病毒亚科和肺病毒亚科两个亚科组成;弹状病毒科和丝状病毒科。这些病毒,也被称为非节段性负链RNA病毒(NNV),含有五到十个串联连接的基因,这些基因被保守的连接序列隔开,这些连接序列充当mRNA起始位点和聚腺苷酸/终止位点。对于NNV,下游mRNA合成取决于上游mRNA的终止,并且所有NNV RNA依赖性RNA聚合酶在转录过程中反复复制(“口吃”)一段短的模板尿苷酸以聚腺苷酸化并终止它们的mRNA。NNV的一个亚组(副粘病毒亚科的所有成员)的RNA依赖性RNA聚合酶也以非常受控的方式口吃以编辑其磷蛋白基因mRNA,并且丝状病毒埃博拉病毒在其糖蛋白mRNA上进行相关过程。值得注意的是,所有编辑其磷蛋白mRNA的病毒也受“六规则”支配,即它们的基因组必须是多聚六聚体长度(6n + 0)才能有效复制。为什么这两个看似不相关的过程在副粘病毒亚科中如此紧密地联系在一起一直是个谜。本文将综述目前已知的关于该亚科病毒特有的这两个过程的信息,并将讨论这种神秘的联系是否可能是由于RNA病毒错误灾难现象。

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