ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif
ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif
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DOI：
10.1101/gad.12.6.868
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发表时间：
1998-03-15
影响因子：
10.5
通讯作者：
Sandri-Goldin, RM
中科院分区：
文献类型：
--
作者：
Sandri-Goldin, RM
一些病毒感染后生动物细胞，改变了细胞内信使核糖核酸输出的平衡，有利于病毒核糖核酸的输出，并使细胞转录产物保留在细胞核内。在这里，有证据表明，单纯疱疹病毒1(HSV-1)必需调节蛋白ICP27，它抑制宿主细胞的剪接，导致未剪接的转录本在细胞核中积累，介导病毒无内含子mRNAs的RNA输出。ICP27通过一个富含亮氨酸的核输出信号在细胞核和细胞质之间穿梭，该信号单独能够指导异源绿色荧光蛋白的输出。体内紫外光照射研究表明，ICP27可以与胞核和胞浆中的Poly(A)(+)RNA交联，支持其在出口中的作用。此外，在HSV-1感染的细胞中，与Poly(A)(+)RNA结合的hnRNP A1的数量比未感染的细胞减少。此外，还发现ICP27在胞核和胞浆同时结合了7个无内含子的HSV-1转录本，并且在感染ICP27缺失突变病毒时，这些转录本的输出显著减少。相反，ICP27不与两个经历剪接的HSV-1 mRNAs结合。最后，ICP27在体内与RNA的结合需要一个类似RGG盒的精氨酸-甘氨酸区域。这些结果表明ICP27是一个重要的病毒输出因子，促进HSV-1无内含子RNA的运输。
Infection of metazoan cells with some viruses alters the balance of cellular mRNA export to favor viral RNA export and to retain cellular transcripts in the nucleus. Here, evidence is presented to show that the herpes simplex virus 1 (HSV-1) essential regulatory protein ICP27, which inhibits host cell-splicing, resulting in the accumulation of unspliced transcripts in the nucleus, mediates RNA export of viral intronless mRNAs. ICP27 was shown to shuttle between the nucleus and cytoplasm through a leucine-rich nuclear export signal, which alone was able to direct the export of the heterologous green fluorescent protein. In vivo UV irradiation studies demonstrated that ICP27 could be crosslinked to poly(A)(+) RNA in the nucleus and the cytoplasm, supporting a role in export. Furthermore, the amount of hnRNP A1, which has been implicated in the export of cellular spliced mRNAs, that was bound to poly(A)(+) RNA in HSV-1-infected cells was reduced compared with uninfected cells. In addition, it was demonstrated that ICP27 bound seven intronless HSV-1 transcripts in both the nucleus and the cytoplasm, and export of these transcripts was diminished substantially during infection with an ICP27 null mutant virus. In contrast, ICP27 did not bind to two HSV-1 mRNAs that undergo splicing. Finally, binding of ICP27 to RNA in vivo required an arginine-glycine region that resembles an RGG box. These results indicate that ICP27 is an important viral export factor that promotes the transport of HSV-1 intronless RNAs.