明确卡波氏肉瘤相关疱疹病毒 ORF57 结合和活性所需的核心 RNA 元件。
Delineation of a core RNA element required for Kaposi's sarcoma-associated herpesvirus ORF57 binding and activity.
机构信息
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9048, USA.
出版信息
Virology. 2011 Oct 25;419(2):107-16. doi: 10.1016/j.virol.2011.08.006. Epub 2011 Sep 1.
Abstract
The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is an essential multifunctional regulator of gene expression. ORF57 interaction with RNA is necessary for ORF57-mediated posttranscriptional functions, but little is known about the RNA elements that drive ORF57-RNA specificity. Here, we investigate the cis-acting factors on the KSHV PAN RNA that dictate ORF57 binding and activity. We show that ORF57 binds directly to the 5' end of PAN RNA in KSHV-infected cells. Furthermore, we employ in vitro and cell-based assays to define a 30-nucleotide (nt) core ORF57-responsive element (ORE) that is necessary and sufficient for ORF57 binding and activity. Mutational analysis of the core ORE further suggests that a 9-nt sequence is a specific binding site for ORF57. These studies provide insight into ORF57 specificity determinants and lay a foundation for future analyses of cellular and viral ORF57 targets.
摘要
卡波氏肉瘤相关疱疹病毒（KSHV）ORF57 蛋白是一种重要的多功能基因表达调控因子。ORF57 与 RNA 的相互作用对于 ORF57 介导的转录后功能是必需的，但对于驱动 ORF57-RNA 特异性的 RNA 元件知之甚少。在这里，我们研究了 KSHV PAN RNA 上的顺式作用因子，这些因子决定了 ORF57 的结合和活性。我们发现，ORF57 在感染 KSHV 的细胞中直接结合 PAN RNA 的 5'端。此外，我们利用体外和基于细胞的测定来定义一个 30 个核苷酸（nt）的核心 ORF57 反应元件（ORE），该元件对于 ORF57 的结合和活性是必需且充分的。核心 ORE 的突变分析进一步表明，一个 9-nt 序列是 ORF57 的特异性结合位点。这些研究为 ORF57 的特异性决定因素提供了深入的了解，并为未来对细胞和病毒 ORF57 靶标的分析奠定了基础。
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