BIOGENESIS OF DNA TUMOR VIRAL MRNAS

目标是了解分子水平上的一些 转录和转录后调控机制 猴病毒40(SV40)单纯疱疹病毒型基因的表达 1(单纯疱疹病毒1型)，乙肝病毒(乙肝病毒)，并最终在临床上 相关的肿瘤病毒。第一个具体目标是确定 前信使核糖核酸加工的功能和作用机制 人单纯疱疹病毒胸苷激酶基因增强子(PPE) 免疫缺陷病毒(HIV)Rev-Response样元件及其HIV Rev-... 与细胞反式作用因子一样，异质核-核糖核 蛋白质(HnRNP)L，在加工和核输出的前mRNAs和 它们通过(A)识别它们在互补DNA的表达中的效用 Pre-mRNAs的核输出及其在表达中的作用 互补DNA通过(A)鉴定参与PPE功能的碱基， (二)确定HNRNP L调解的职能和机制 通过结合该PPE实现内含子独立的mRNA生物发生，(C)鉴定 其他无内含子基因中的额外PPE样元件，以及(D) 确定实现有效内含子无关的PPE的共性 哺乳动物细胞中的基因表达。第二和第三个具体目标是 为了确定类固醇/甲状腺激素成员 激素受体超家族及其配体影响基因的表达和 类固醇/甲状腺激素受体超家族SV40的复制 它们的配体通过(A)影响SV40和乙肝病毒的表达和复制。 检测几种病毒对转录和病毒粒子产生的影响 结合这两种病毒启动子和配体的核受体 对于这些受体，以及(B)确定通过哪些机制特异性 核受体及其配体，SV40编码的癌蛋白大T- 抗原和细胞因子DAP调节SV40的转录 主要的已故发起人。各种生化的、分子的、遗传的和 将使用细胞技术。这些研究的发现应该是 不仅增加了我们对涉及的基本机制的了解 调节病毒和哺乳动物中的信使核糖核酸生物发生，但也可能导致 治疗传染性非典型肺炎疾病的新药开发 用于基因治疗和制造的病毒和改进的载体 生物有用的蛋白质。

The objectives are to understand the molecular level some of the transcriptional and post-transcriptional mechanisms that regulate expression of genes of simian virus 40 (SV40), herpes simplex virus type 1 (HSV-1), hepatitis B virus (HBV) and, eventually, other clinically relevant tumor viruses. The first specific aim is to determine the functions and mechanisms of action of action of the pre-mRNA processing enhancer (PPE) of the thymidine kinase gene of HSV, a human immunodeficiency virus (HIV) Rev-response-like element, and its HIV Rev- like cellular trans-acting factor, the heterogeneous nuclear-ribonuclear protein (hnRNP) L, in the processing and nuclear export of pre-mRNAs and their utility in the expression of complementary DNAs by (a) identifying the nuclear export of pre-mRNAs and their utility in the expression of complementary DNAs by (a) identifying the bases involved in PPE function, (b) determining the functions and mechanisms by which hnRNP L mediates intro-independent mRNA biogenesis via binding this PPE, (c) identifying additional PPE-like elements in other intronless genes, and (d) determining the generality of PPEs enabling efficient intron-independent gene expression in mammalian cells. The second and third specific aims are to determine the mechanisms by which members of the steroid/thyroid hormone receptor superfamily and their ligands affect expression and replication of SV40 of the steroid/thyroid hormone receptor superfamily and their ligands affect expression and replication of SV40 and HBV by (a) examining the effects on transcription and virion production of some nuclear receptors that bind promoters of these two viruses and the ligands for these receptors, and (b) determining the mechanisms by which specific nuclear receptors, their ligands, the SV40 encoded oncoprotein large T- antigen, and a cellular factor, DAP, regulated transcription from the SV40 major late promoter. A variety of biochemical, molecular, genetical, and cellular techniques will be used. The findings from these studies should not only increase our understanding of fundamental mechanisms involved in regulation of mRNA biogenesis in viruses and mammals, but may also lead to the development of novel drugs for the treatment of diseases caused by viruses and improved vectors for use in gene therapy and the manufacture of biologically useful proteins.