ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export
ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export
复制标题
DOI：
10.1128/jvi.79.7.3949-3961.2005
复制
发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Sandri-Goldin, RM
中科院分区：
文献类型：
--
作者：
Chen, IHB;Li, L;Sandri-Goldin, RM
单纯疱疹病毒1型（HSV-1）蛋白ICP27与细胞输出衔接蛋白Aly/REF相互作用，后者是参与细胞mRNA输出的外显子连接复合体的一部分。我们之前报道Aly/REF在感染期间不再与剪接因子SC35位点相关，而是在不同的结构中与ICP27共定位。我们发现这些结构与ICP4共定位，是HSV-1转录的位点。在与Aly/REF相互作用所需区域出现病变的ICP27突变体无法将Aly/REF招募到病毒转录位点；然而，ICP27向细胞质的输出并未受损，这表明ICP27与Aly/REF的相互作用并不需要ICP27穿梭。ICP27也被证明与细胞mRNA输出受体TAP/NXFI相互作用。我们报告说，ICP27直接与TAP/NXF1相互作用，而不需要Aly/REF来桥接相互作用。需要ICP27的C端；然而，n端富含亮氨酸的区域也有助于ICP27与TAP/NXFI的相互作用。与Aly/REF的结果相反，不能与TAP/NXFI相互作用的突变体不能输出到细胞质中，TAP/NXFI也不能被招募到HSV-1转录位点。因此，ICP27与TAP/NXF1的相互作用发生在ICP27离开病毒转录位点之后。我们得出结论，ICP27及其结合的病毒rna通过TAP/NXFI输出受体输出。
Herpes simplex virus type 1 (HSV-1) protein ICP27 interacts with the cellular export adaptor protein Aly/REF, which is part of the exon junction complex implicated in cellular mRNA export. We previously reported that Aly/REF was no longer associated with splicing factor SC35 sites during infection but instead colocalized with ICP27 in distinct structures. Here we show that these structures colocalize with ICP4 and are sites of HSV-1 transcription. ICP27 mutants with lesions in the region required for the interaction with Aly/REF failed to recruit Aly/REF to viral transcription sites; however, ICP27 export to the cytoplasm was unimpaired, indicating that the interaction of ICP27 with Aly/REF is not required for ICP27 shuttling. ICP27 has also been shown to interact with the cellular mRNA export receptor TAP/NXFI. We report that ICP27 interacts directly with TAP/NXF1 and does not require Aly/REF to bridge the interaction. The C terminus of ICP27 is required; however, the N-terminal leucine-rich region also contributes to the interaction of ICP27 with TAP/NXFI. In contrast to the results found for Aly/REF, mutants that failed to interact with TAP/NXFI were not exported to the cytoplasm, and TAP/NXFI was not recruited to sites of HSV-1 transcription. Therefore, the interaction of ICP27 with TAP/NXF1 occurs after ICP27 leaves viral transcription sites. We conclude that ICP27 and the viral RNAs to which it binds are exported via the TAP/NXFI export receptor.