Role of HIV-1 RNA and protein determinants for the selective packaging of spliced and unspliced viral RNA and host U6 and 7SL RNA in virus particles.
Role of HIV-1 RNA and protein determinants for the selective packaging of spliced and unspliced viral RNA and host U6 and 7SL RNA in virus particles.
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DOI：
10.1093/nar/gkr577
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发表时间：
2011-11-01
影响因子：
14.9
通讯作者：
Mougel M
中科院分区：
文献类型：
--
作者：
Didierlaurent L;Racine PJ;Houzet L;Chamontin C;Berkhout B;Mougel M
HIV-1颗粒含有非剪接病毒RNA基因组的RNA物种。例如，病毒剪接rna和宿主7SL和U6 rna是非随机结合的天然成分。为了了解包装选择性的机制，我们分析了大量在病毒RNA的5'UTR结构或gag -核衣壳蛋白（GagNC）中突变的HIV-1变异体的含量。同时，我们确定宿主7SL和U6 RNA的选择是否依赖于病毒RNA和/或GagNC。我们的研究结果表明，5'UTR中的多聚a发夹是剪接和未剪接的病毒rna的主要包装决定因素。相比之下，5'UTR RNA结构对U6和7SL RNA的影响很小，这表明这些宿主RNA的包装与病毒RNA的包装无关。对GagNC突变体的实验表明，两个锌指和n端碱基残基限制了剪接RNA的掺入，而有利于未剪接RNA的包装。通过锌指基序的GagNC也限制了7SL和U6 rna的包装。因此，GagNC是包装选择性的主要贡献者。总之，我们的结果为HIV如何选择不同的RNA物种整合到颗粒中提供了新的分子见解。
HIV-1 particles contain RNA species other than the unspliced viral RNA genome. For instance, viral spliced RNAs and host 7SL and U6 RNAs are natural components that are non-randomly incorporated. To understand the mechanism of packaging selectivity, we analyzed the content of a large panel of HIV-1 variants mutated either in the 5′UTR structures of the viral RNA or in the Gag-nucleocapsid protein (GagNC). In parallel, we determined whether the selection of host 7SL and U6 RNAs is dependent or not on viral RNA and/or GagNC. Our results reveal that the polyA hairpin in the 5′UTR is a major packaging determinant for both spliced and unspliced viral RNAs. In contrast, 5′UTR RNA structures have little influence on the U6 and 7SL RNAs, indicating that packaging of these host RNAs is independent of viral RNA packaging. Experiments with GagNC mutants indicated that the two zinc-fingers and N-terminal basic residues restrict the incorporation of the spliced RNAs, while favoring unspliced RNA packaging. GagNC through the zinc-finger motifs also restricts the packaging of 7SL and U6 RNAs. Thus, GagNC is a major contributor to the packaging selectivity. Altogether our results provide new molecular insight on how HIV selects distinct RNA species for incorporation into particles.
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