The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA
The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA
复制标题
DOI：
10.1128/mcb.26.5.1631-1643.2006
复制
发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Stamminger, T
中科院分区：
文献类型：
--
作者：
Lischka, P;Toth, Z;Stamminger, T
人巨细胞病毒的UL 69基因产物属于所有疱疹病毒中保守的调节蛋白家族，其部分特征在于参与RNA核输出的转录后反式激活因子。最近的实验表明，pUL 69也作为一个转录后激活因子，因为它被证明，通过CRM 1-独立的核输出信号的核质穿梭是其对基因表达的刺激作用的先决条件。基于这些发现，我们开始研究pUL 69在mRNA输出中的作用，并证明pUL 69有效地促进未剪接RNA的细胞质积累。此外，我们表明，这种pUL 69活性与细胞mRNA输出机制的直接蛋白质相互作用与高度相关的DEXD/H盒RNA解旋酶UAP 56和URH 49。特别是，我们确定了一个12个氨基酸的结构域内的N末端的pUL 69，这是需要结合到UAP 56和URH 49，我们可以证明，UAP 56的相互作用和核质穿梭都是pUL 69介导的mRNA输出的先决条件。因此，我们确定了一个新的细胞靶点，它提供了一个疱疹病毒调节蛋白与保守的细胞转运系统，以促进核输出的未剪接的RNA。
The UL69 gene product of human cytomegalovirus belongs to a family of regulatory proteins conserved among all herpesviruses that have in part been characterized as posttranscriptional transactivators participating in the nuclear export of RNA. Recent experiments suggested that pUL69 also acts as a posttranscriptional activator since it was demonstrated that nucleocytoplasmic shuttling via a CRM1-independent nuclear export signal is a prerequisite for its stimulatory effect on gene expression. Based on these findings we initiated studies to investigate the role of pUL69 in mRNA export and demonstrate that pUL69 efficiently promotes the cytoplasmic accumulation of unspliced RNA. Furthermore, we show that this pUL69 activity is linked to the cellular mRNA export machinery by direct protein interaction with the highly related DEXD/H-box RNA helicases UAP56 and URH49. Particularly, we identified a 12-amino-acid domain within the N terminus of pUL69 which is required for binding to UAP56 and URH49, and we could demonstrate that UAP56 interaction and nucleocytoplasmic shuttling are both prerequisites for pUL69-mediated mRNA export. Thus, we identified a novel cellular target which provides a herpesviral regulatory protein with access to a conserved cellular transport system in order to promote nuclear export of unspliced RNA.