A long-range RNA-RNA interaction between the 5′ and 3′ ends of the HCV genome
A long-range RNA-RNA interaction between the 5′ and 3′ ends of the HCV genome
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DOI：
10.1261/rna.1680809
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发表时间：
2009-09-01
期刊：
影响因子：
4.5
通讯作者：
Berzal-Herranz, Alfredo
中科院分区：
文献类型：
--
作者：
Romero-Lopez, Cristina;Berzal-Herranz, Alfredo
丙型肝炎病毒（HCV）的RNA基因组包含多个保守的顺式结构域，这些结构域指导蛋白质的合成、复制和传染性。不可翻译区（utr）在HCV周期中起着至关重要的作用。无帽病毒rna通过位于5' UTR的内部核糖体进入位点（IRES）进行翻译，该位点作为招募多种蛋白质因子的支架。病毒基因组的复制始于3' UTR。生物信息学方法已经确定了其他被认为参与HCV周期的结构RNA元件。5BSL3.2基序嵌入在NS5B编码序列3‘端的十字形结构中，有助于整个基因组3’端的三维折叠。它在复制开始时是必不可少的。本文报道了在基因组的5‘和3’端发现了一种新的、链特异性的、远程RNA-RNA相互作用，涉及5BSL3.2和IRES基序。在结构域IIId的顶端环或5BSL3.2的内部环中含有取代的突变体破坏了该复合体，表明这些区域在启动接吻相互作用中是必不可少的。当使用相关口蹄疫病毒的utr进行结合试验时，没有形成复合物，这表明这种相互作用是HCV序列特有的。目前的数据确凿地表明，存在一种高阶结构，可能介导HCV基因组的蛋白质非依赖性环化。5‘-3’端桥可能在病毒翻译调节和从蛋白质合成到RNA复制的转换中起作用。
The RNA genome of the hepatitis C virus (HCV) contains multiple conserved structural cis domains that direct protein synthesis, replication, and infectivity. The untranslatable regions (UTRs) play essential roles in the HCV cycle. Uncapped viral RNAs are translated via an internal ribosome entry site (IRES) located at the 5' UTR, which acts as a scaffold for recruiting multiple protein factors. Replication of the viral genome is initiated at the 3' UTR. Bioinformatics methods have identified other structural RNA elements thought to be involved in the HCV cycle. The 5BSL3.2 motif, which is embedded in a cruciform structure at the 3' end of the NS5B coding sequence, contributes to the three-dimensional folding of the entire 3' end of the genome. It is essential in the initiation of replication. This paper reports the identification of a novel, strand-specific, long-range RNA-RNA interaction between the 5' and 3' ends of the genome, which involves 5BSL3.2 and IRES motifs. Mutants harboring substitutions in the apical loop of domain IIId or in the internal loop of 5BSL3.2 disrupt the complex, indicating these regions are essential in initiating the kissing interaction. No complex was formed when the UTRs of the related foot and mouth disease virus were used in binding assays, suggesting this interaction is specific for HCV sequences. The present data firmly suggest the existence of a higher-order structure that may mediate a protein-independent circularization of the HCV genome. The 5'-3' end bridge may have a role in viral translation modulation and in the switch from protein synthesis to RNA replication.