Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element.
Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element.
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DOI：
10.1093/nar/gkl349
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发表时间：
2006
影响因子：
14.9
通讯作者：
Melchers WJ
中科院分区：
文献类型：
--
作者：
van Ooij MJ;Polacek C;Glaudemans DH;Kuijpers J;van Kuppeveld FJ;Andino R;Agol VI;Melchers WJ
许多正链RNA病毒的基因组和抗原基因组分别含有3′-poly（A）和5′-poly（U）片段，作为共同的模板。控制这些均聚物链段的长度的机制还没有很好地理解。在这里，我们发现，在柯萨奇病毒B3（CVB 3）和其他三种肠道病毒的聚（A）道是80-90和聚（U）道是20 nt长。突变分析表明，CVB 3 3′-poly（A）的长度由病毒RNA 3′-非编码区的顺式元件oriR决定。相反，虽然oriR的突变抑制了（−）RNA合成的起始，但它们不影响5′-poly（U）的长度。Poly（A）缺失的基因组能够获得遗传上不稳定的富含AU的Poly（A）终止的3′-尾，其可能通过与同源病毒RNA聚腺苷酸化不同的机制产生。异常的尾部只能确保低效的复制。RNA复制不依赖于oriR和poly（A）的可能性表明，高度衰弱的病毒能够通过利用“出现”（可能是返祖）机制存活。
Genomes and antigenomes of many positive-strand RNA viruses contain 3′-poly(A) and 5′-poly(U) tracts, respectively, serving as mutual templates. Mechanism(s) controlling the length of these homopolymeric stretches are not well understood. Here, we show that in coxsackievirus B3 (CVB3) and three other enteroviruses the poly(A) tract is ∼80–90 and the poly(U) tract is ∼20 nt-long. Mutagenesis analysis indicate that the length of the CVB3 3′-poly(A) is determined by the oriR, a cis-element in the 3′-noncoding region of viral RNA. In contrast, while mutations of the oriR inhibit initiation of (−) RNA synthesis, they do not affect the 5′-poly(U) length. Poly(A)-lacking genomes are able to acquire genetically unstable AU-rich poly(A)-terminated 3′-tails, which may be generated by a mechanism distinct from the cognate viral RNA polyadenylation. The aberrant tails ensure only inefficient replication. The possibility of RNA replication independent of oriR and poly(A) demonstrate that highly debilitated viruses are able to survive by utilizing ‘emergence’, perhaps atavistic, mechanisms.
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