Murphy Eain, Vanícek Jirí, Robins Harlan, Shenk Thomas, Levine Arnold J
Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA.
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5453-8. doi: 10.1073/pnas.0711910105. Epub 2008 Mar 31.
A quantitative algorithm was developed and applied to predict target genes of microRNAs encoded by herpesviruses. Although there is almost no conservation among microRNAs of different herpesvirus subfamilies, a common pattern of regulation emerged. The algorithm predicts that herpes simplex virus 1, human cytomegalovirus, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all employ microRNAs to suppress expression of their own genes, including their immediate-early genes. In the case of human cytomegalovirus, a virus-coded microRNA, miR-112-1, was predicted to target the viral immediate-early protein 1 mRNA. To test this prediction, mutant viruses were generated that were unable to express the microRNA, or encoded an immediate-early 1 mRNA lacking its target site. Analysis of RNA and protein within infected cells demonstrated that miR-UL112-1 inhibits expression of the major immediate-early protein. We propose that herpesviruses use microRNA-mediated suppression of immediate-early genes as part of their strategy to enter and maintain latency.
开发了一种定量算法并将其应用于预测疱疹病毒编码的微小RNA的靶基因。尽管不同疱疹病毒亚科的微小RNA之间几乎没有保守性，但出现了一种共同的调控模式。该算法预测，单纯疱疹病毒1型、人巨细胞病毒、爱泼斯坦-巴尔病毒和卡波西肉瘤相关疱疹病毒都利用微小RNA来抑制自身基因的表达，包括其立即早期基因。就人巨细胞病毒而言，一种病毒编码的微小RNA，即miR-112-1，被预测靶向病毒立即早期蛋白1的mRNA。为了验证这一预测，构建了无法表达该微小RNA或编码缺乏其靶位点的立即早期1 mRNA的突变病毒。对感染细胞内的RNA和蛋白质进行分析表明，miR-UL112-1抑制主要立即早期蛋白的表达。我们提出，疱疹病毒利用微小RNA介导的对立即早期基因的抑制作为其进入和维持潜伏期策略的一部分。
