Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication.

Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication.
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ICP27 RGG 盒的精氨酸甲基化调节 ICP27 输出,并且是单纯疱疹病毒 1 有效复制所必需的。

DOI:
10.1128/jvi.00238-09
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发表时间:
2009
影响因子:
5.4
通讯作者:
Sandri-Goldin,RozanneM
Sandri-Goldin,RozanneM
中科院分区:
医学2区
文献类型:
--
作者:
Souki,StuartK;Gershon,PaulD;Sandri-Goldin,RozanneM

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相似文献

单纯疱疹病毒1型(HSV-1)多功能调节蛋白ICP27作为病毒的mRNA输出因子,穿梭于细胞核和细胞质之间。甘氨酸和富含精氨酸的基序上的精氨酸甲基化已被证明调节蛋白质的输出。ICP27含有一个RGG盒,已被证明在病毒感染过程中发生甲基化。我们通过质谱分析发现,RGG盒中的三个精氨酸残基发生了甲基化。用赖氨酸取代精氨酸残基的病毒突变体被创建为单、双和三个突变体。与野生型HSV-1相比,这些突变体的生长受到损害,病毒复制周期被推迟。最引人注目的发现是,在精氨酸替代突变体感染引起的低甲基化条件下,或者用甲基化抑制剂腺苷二醛处理野生型HSV-1感染细胞时,ICP27输出到细胞质的时间比野生型ICP27输出的时间更早,速度更快。我们的结论是,ICP27 RGG盒的精氨酸甲基化调节其出口活性,ICP27的早期出口干扰其核功能的发挥。
The herpes simplex virus 1 (HSV-1) multifunctional regulatory protein ICP27 shuttles between the nucleus and cytoplasm in its role as a viral mRNA export factor. Arginine methylation on glycine- and arginine-rich motifs has been shown to regulate protein export. ICP27 contains an RGG box and has been shown to be methylated during viral infection. We found by mass spectrometric analysis that three arginine residues within the RGG box were methylated. Viral mutants with substitutions of lysine for arginine residues were created as single, double, and triple mutants. Growth of these mutants was impaired and the viral replication cycle was delayed compared to wild-type HSV-1. Most striking was the finding that under conditions of hypomethylation resulting from infection with arginine substitution mutants or treatment of wild-type HSV-1-infected cells with the methylation inhibitor adenosine dialdehyde, ICP27 export to the cytoplasm occurred earlier and was more rapid than wild-type ICP27 export. We conclude that arginine methylation of the ICP27 RGG box regulates its export activity and that early export of ICP27 interferes with the performance of its nuclear functions.
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