PROCESSING AND FUNCTION OF POLYOMA RNA

多瘤病毒将继续作为模型系统来研究 哺乳动物核糖核酸分子的合成和加工。申请人计划 进行多项研究，主要从以下几个方面了解交换 病毒DNA合成开始前的早期链mRNAs大多 之后的晚期链mrna。早期和晚期链RNA的调节 水平不在启动子水平，而是转录后水平。后链 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。他将决定什么 序列对DNA后晚期基因表达的激活至关重要 复制启动。A基因对早链基因表达的调控 新的机制(来自晚期链的核反义RNA)可能会 通常被细胞用来调节自己的许多基因的表达 基因。这种病毒提供了一个强大的遗传和生化系统，在其中 学习反义调控并学习如何利用这一知识来 调节其他基因的表达，包括病毒和细胞基因。他已经表现出 在晚期链反义分子存在的情况下，许多核 早期链RNA被双链RNA腺苷酶修饰 脱氨酶(ADAR1)。这似乎是下调监管的一个主要方面 病毒生命周期后期的早期基因表达。编辑过的RNA是 滞留在细胞核内。他将使用各种方法来了解更多 关于含有肌苷的RNA的核滞留，并将进行调查 ADAR1在多发性肿瘤感染中的作用及感染对ADAR1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.