PROCESSING AND FUNCTION OF POLYOMA RNA

多瘤病毒将继续作为一个模型系统，以研究 哺乳动物RNA分子的合成和加工。申请人计划 进行了大量的研究，旨在了解从大多数 在病毒DNA合成开始之前， 后链mRNA。早链和晚链RNA的调节 水平不是在启动子水平，而是转录后水平。后股 RNA水平以一种意想不到的方式被调节--它们似乎是积极的， 在感染过程中影响自身的积累。他会决定 序列对于DNA后晚期基因表达的激活至关重要， 复制起始。一种新的转录因子对早链基因表达的调控 新的机制（核反义RNA从晚链），这可能是 通常被细胞用来调节许多它们自己的 基因.这种病毒提供了强大的遗传和生化系统， 研究反义调控，并学习如何利用这些知识， 调节其他病毒和细胞基因的表达。他表现出 在后链反义分子的存在下， 早链RNA被双链RNA腺苷酶修饰 脱氨酶（ADAR 1）。这似乎是一个主要方面的下调， 病毒生命周期晚期的早期基因表达。编辑的RNA是 保留在细胞核中。他将使用各种方法来了解更多 关于含肌苷的RNA的核保留，并将研究 ADAR 1在多瘤感染中的作用及感染对ADAR 1的影响 表达、活性和定位。

Polyoma virus will continue to serve as a model system to study the synthesis and processing of mammalian RNA molecules. The applicant plans to perform a number of studies designed to understand the switch from mostly early-strand mRNAs before the initiation of viral DNA synthesis to mostly late-strand mRNAs afterwards. The regulation of both early and late strand RNA levels is not at the promoter level, and is post-transcriptional. Late-strand RNA levels are regulated in an unexpected way-they appear to positively influence their own accumulation during infection. He will determine what sequences are critical for the activation of late gene expression after DNA replication initiation. The regulation of early-strand gene expression by a novel mechanism (nuclear antisense RNA from the late strand) that is likely to be generally used by cells to regulate the expression of many of their own genes. This virus provides a powerful genetic and biochemical system in which to study antisense regulation and to learn how to exploit this knowledge to regulate the expression of other genes, both viral and cellular. He has shown that, in the presence of late-strand antisense molecules, many nuclear early-strand RNAs are modified by the enzyme double strand RNA adenosine deaminase (ADAR1). This appears to be a major aspect of the downregulation of early gene expression at late times in the viral life cycle. Edited RNAs are retained in the nucleus. He will use a variety of approaches to learn more about the nuclear retention of inosine-containing RNAs, and will investigate the role of ADAR1 in polyoma infection, and the influence of infection on ADAR1 expression, activity, and localization.