A new type of IRES within gag coding region recruits three initiation complexes on HIV-2 genomic RNA
A new type of IRES within gag coding region recruits three initiation complexes on HIV-2 genomic RNA
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DOI：
10.1093/nar/gkp1109
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发表时间：
2010-03-01
影响因子：
14.9
通讯作者：
Sargueil, Bruno
中科院分区：
文献类型：
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作者：
Weill, Laure;James, Laurie;Sargueil, Bruno
灵长类慢病毒的基因组 RNA 既可作为编码 Gag 和 Gag-Pol 多蛋白的 mRNA，又可作为增殖的基因组。该 RNA 的翻译是通过标准帽子依赖性机制或通过核糖体的内部进入启动的。基因组 RNA 的两个区域能够吸引起始复合物，即 5' 非翻译区和 gag 编码区本身。依靠探测数据和系统发育研究，我们对 HIV-1、HIV-2 和 SIVMac 编码区的二级结构进行了建模。这种方法揭示了保守的二级结构元件，突变表明这些元件是核糖体内部进入所必需的。无法鉴定与其他描述的病毒或细胞 IRES 的结构同源性，并且慢病毒 IRES 显示出许多独特的特性。最值得注意的是，HIV-2 gag 编码区中存在的 IRES 具有在单个 RNA 分子上招募多达三个起始复合物的独特能力。 gag编码序列的结构和功能特性定义了一种新型IRES。尽管其确切作用尚不清楚，但 IRES 在快速进化的慢病毒中的保守性表明其具有重要的生理作用。
Genomic RNA of primate lentiviruses serves both as an mRNA that encodes Gag and Gag-Pol polyproteins and as a propagated genome. Translation of this RNA is initiated by standard cap dependant mechanism or by internal entry of the ribosome. Two regions of the genomic RNA are able to attract initiation complexes, the 5' untranslated region and the gag coding region itself. Relying on probing data and a phylogenetic study, we have modelled the secondary structure of HIV-1, HIV-2 and SIVMac coding region. This approach brings to light conserved secondary-structure elements that were shown by mutations to be required for internal entry of the ribosome. No structural homologies with other described viral or cellular IRES can be identified and lentiviral IRESes show many peculiar properties. Most notably, the IRES present in HIV-2 gag coding region is endowed with the unique ability to recruit up to three initiation complexes on a single RNA molecule. The structural and functional properties of gag coding sequence define a new type of IRES. Although its precise role is unknown, the conservation of the IRES among fast evolving lentiviruses suggests an important physiological role.