Properties of an HSV-1 regulatory protein that appears to impair host cell splicing.
Properties of an HSV-1 regulatory protein that appears to impair host cell splicing.
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发表时间：
1994-04
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通讯作者：
R. Sandri-Goldin
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作者：
R. Sandri-Goldin
单纯疱疹病毒 1 型 (HSV-1) 立即早期 (α) 蛋白 ICP27 是一种重要的调节蛋白，似乎参与裂解病毒感染期间的许多不同过程。 ICP27缺陷的病毒突变体具有多种表型，包括宿主蛋白质合成的关闭缺陷、一些立即早期和早期基因的过度表达、DNA复制水平降低以及晚期基因产物水平严重降低。 ICP27 已被证明在转录后发挥其某些调节作用。它在聚腺苷酸化和剪接水平上影响 mRNA 加工。在聚腺苷酸化过程中，ICP27 似乎会刺激选定的 Poly(A) 位点的 3' RNA 加工。相反的作用发生在宿主细胞剪接上，即在HSV-1感染期间，发现宿主细胞剪接的抑制需要ICP27表达。这种剪接损伤会降低可用于翻译的剪接细胞 mRNA 的水平，从而导致宿主蛋白质合成的停止。还发现了 ICP27 调节的剪接因子的重新分布。突变分析表明，蛋白质的 C 末端阻遏区域是剪接效应所必需的，而包含蛋白质 C 末端一半的激活区域是 3' 加工和病毒感染过程中晚期基因表达诱导的影响所必需的。 ICP27 的核定位需要蛋白质 N 末端一半的高碱性富含精氨酸区域。迄今为止，关于 ICP27 促进这些监管流程的机制的详细信息还没有明确定义。
The herpes simplex virus type 1 (HSV-1) immediate early (alpha) protein ICP27 is an essential regulatory protein that appears to be involved in a number of different processes during lytic viral infection. Viral mutants defective in ICP27 have a variety of phenotypes that include defects in the shutoff of host protein synthesis, overexpression of some immediate early and early genes, reduced levels of DNA replication, and severely reduced levels of late gene products. ICP27 has been shown to act posttranscriptionally in the performance of some of its regulatory roles. It affects mRNA processing at the level of both polyadenylation and splicing. During polyadenylation, ICP27 appears to stimulate 3' RNA processing at selected poly(A) sites. The opposite effect, occurs on host cell splicing, that is, during HSV-1 infection, an inhibition in host cell splicing was found that required ICP27 expression. This impairment of splicing contributes to the shutoff of host protein synthesis by decreasing levels of spliced cellular mRNAs available for translation. A redistribution of splicing factors regulated by ICP27 has also been seen. Mutational analysis has shown that the C-terminal repressor region of the protein is required for the effects seen on splicing, whereas the activator region, encompassing the C-terminal half of the protein is required for the effects on 3' processing and the induction of late gene expression during viral infection. A highly basic arginine-rich region in the N-terminal half of the protein is required for nuclear localization of ICP27. Details on the mechanisms by which ICP27 contributes to these regulatory processes have been poorly defined to date.