A novel role for Vpr of human immunodeficiency virus type 1 as a regulator of the splicing of cellular pre-mRNA
A novel role for Vpr of human immunodeficiency virus type 1 as a regulator of the splicing of cellular pre-mRNA
复制标题
DOI：
10.1016/j.micinf.2005.03.022
复制
发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
Aida, Y
中科院分区：
文献类型：
--
作者：
Kuramitsu, M;Hashizume, C;Aida, Y
Vpr是人类免疫缺陷病毒1型（HIV-1）的辅助基因产物之一，影响病毒和细胞增殖的各个方面，参与长末端重复序列（LTR）激活、细胞周期停滞在G2期和细胞凋亡。我们已经发现了一个新的作用Vpr作为一个调节器的剪接前mRNA在体内和体外。我们发现，通过RT-PCR和RNase保护分析，Vpr引起的积累不完全剪接形式的α-珠蛋白2和β-珠蛋白前mRNA的细胞中，已瞬时转染Vpr表达载体。我们推测Vpr的这种新效应可能是通过一种与G2期细胞周期阻滞不同的途径发生的。通过分析体外剪接反应，我们发现Vpr在体外抑制β-珠蛋白前体mRNA的剪接。Vpr对α-珠蛋白2前体mRNA内含子1的剪接有一定的抑制作用，但对内含子2的剪接无影响。有趣的是，利用高滴度HIV-1/水疱性口炎病毒G蛋白的实验感染系统显示，从HIV-1前病毒表达的Vpr足以积累内源性α-珠蛋白2前mRNA。因此，Vpr可能有助于选择性抑制细胞前mRNA的剪接。(C)2005年，Elsevier SAS。All rights reserved.
Vpr, one of the accessory gene products of human immunodeficiency virus type 1 (HIV-1), affects aspects of both viral and cellular proliferation, being involved in long terminal repeat (LTR) activation, arrest of the cell cycle at the G2 phase, and apoptosis. We have discovered a novel role for Vpr as a regulator of the splicing of pre-mRNA both in vivo and in vitro. We found, by RT-PCR and RNase protection analysis, that Vpr caused the accumulation of incompletely spliced forms of alpha-globin 2 and beta-globin pre-mRNAs in cells that had been transiently transfected with a Vpr expression vector. We postulated that this novel effect of Vpr might occur via a pathway that is distinct from arrest of the cell cycle at G2. By analyzing splicing reactions in vitro, we showed that Vpr inhibited the splicing of beta-globin pre-mRNA in vitro. The splicing of intron 1 of alpha-globin 2 pre-mRNA was modestly inhibited by Vpr but the splicing of intron 2 was unaffected. Interestingly, an experimental infection system which utilizes high-titered HIV-1/vesticular stomatitis virus G protein showed that Vpr expressed from an HIV-1 provirus was sufficient to accumulate endogenous a-globin 2 pre-mRNA. Thus, it is likely that Vpr contributes to selective inhibition of the splicing of cellular pre-mRNA. (C) 2005 Elsevier SAS. All rights reserved.