The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle

The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle
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DOI:
10.1128/jvi.77.7.3939-3949.2003
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发表时间:
2003-04-01
影响因子:
5.4
通讯作者:
Sonenberg, N
Sonenberg, N
中科院分区:
医学2区
文献类型:
--
作者:
Brasey, A;Lopez-Lastra, M;Sonenberg, N

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人类免疫缺陷病毒1型(HIV-1)基因组RNA的5‘端含有高度结构化的结构域,参与了病毒生命周期的关键步骤。这些RNA结构域抑制帽子依赖的蛋白质合成。在此,我们报道了HIV-15‘端含有一个内部核糖体进入位点(IRES),能够在G(2)/M细胞周期中驱动蛋白质合成,在G(2)/M细胞周期中,帽依赖的启动被抑制。在体外和体外实验中,用双顺反子mRNAs描绘了HIV-1IRES。HIV-1的前导IRES跨越104到336个核苷酸,并与基因组RNA包装的主要决定因素部分重叠。这些数据有力地表明,对于HIV-1的转录,IRES介导的翻译启动在病毒诱导的G(2)/M细胞周期停滞过程中可能在病毒复制中发挥重要作用。
The 5' leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps of the viral life cycle. These RNA domains inhibit cap-dependent protein synthesis. Here we report that the HIV-1 5' leader harbors an internal ribosome entry site (IRES) capable of driving protein synthesis during the G(2)/M cell cycle phase in which cap-dependent initiation is inhibited. The HIV-1 IRES was delineated with bicistronic mRNAs in in vitro and ex vivo assays. The HIV-1 leader IRES spans nucleotides 104 to 336 and partially overlaps the major determinants of genomic RNA packaging. These data strongly suggest that, as for HIV-1 transcription, IRES-mediated translation initiation could play an important role in virus replication during virus-induced G(2)/M cell cycle arrest.