Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging.
Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging.
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DOI：
10.1186/1742-4690-9-59
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发表时间：
2012-07-24
期刊：
影响因子：
3.3
通讯作者：
Berkhout B
中科院分区：
文献类型：
--
作者：
Das AT;Vrolijk MM;Harwig A;Berkhout B
TAR发夹存在于HIV-1RNA基因组的5‘端和3’端。5‘元件与病毒的TAT蛋白结合，是TAT介导的转录激活所必需的。我们最近观察到，在HIV-1变异株的背景下，完全的TAR缺失是允许的，该变异株不依赖于这个Tat-TAR轴进行转录。然而，打开5‘茎环结构的突变确实影响了前导RNA的构象，并导致了严重的复制缺陷。在这项研究中，我们开始分析HIV-1复制周期的哪一步受到先导RNA的这种构象变化的影响。我们证明，通过在茎区域两侧的缺失打开5‘TAR结构会导致异常的二聚化，并减少未拼接的病毒RNA基因组的包装。相反，通过茎两侧的缺失截断焦油发夹并不影响RNA二聚体的形成和包装。这些结果表明，虽然TAR发夹对RNA二聚和包装不是必不可少的，但TAR的突变可以通过相关RNA信号的错误折叠来显著影响这些过程。
The TAR hairpin is present at both the 5′ and 3′ end of the HIV-1 RNA genome. The 5′ element binds the viral Tat protein and is essential for Tat-mediated activation of transcription. We recently observed that complete TAR deletion is allowed in the context of an HIV-1 variant that does not depend on this Tat-TAR axis for transcription. Mutations that open the 5′ stem-loop structure did however affect the leader RNA conformation and resulted in a severe replication defect. In this study, we set out to analyze which step of the HIV-1 replication cycle is affected by this conformational change of the leader RNA. We demonstrate that opening the 5′ TAR structure through a deletion in either side of the stem region caused aberrant dimerization and reduced packaging of the unspliced viral RNA genome. In contrast, truncation of the TAR hairpin through deletions in both sides of the stem did not affect RNA dimer formation and packaging. These results demonstrate that, although the TAR hairpin is not essential for RNA dimerization and packaging, mutations in TAR can significantly affect these processes through misfolding of the relevant RNA signals.
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影响因子：
14.9
作者：
Didierlaurent L;Racine PJ;Houzet L;Chamontin C;Berkhout B;Mougel M
通讯作者：
Mougel M
影响因子：
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影响因子：
5.4
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影响因子：
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影响因子：
4.8
作者：
Abbink, TEM;Berkhout, B
通讯作者：
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