BIOGENESIS OF DNA TUMOR VIRAL MRNAS

DNA 肿瘤病毒 MRNAS 的生物发生

• 批准号: 6493039
• 负责人: Janet Elaine Mertz
• 金额: $ 25.41万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6493039
• 关键词: Xenopus oocyte; gene expression; genetic enhancer element; genetic transcription; hepatitis B virus group; herpes simplex virus 1; intermolecular interaction; laboratory mouse; laboratory rabbit; messenger RNA; nucleic acid biosynthesis; nucleic acid sequence; oncogenic virus; oncoproteins; posttranscriptional RNA processing; protein purification; simian virus 40; tissue /cell culture; transcription factor; tumor antigens; virus genetics; virus protein; virus replication

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.

目的是了解分子水平的一些 转录和转录后机制， 猴病毒40（SV 40），单纯疱疹病毒型 1（HSV-1），B肝炎病毒（HBV），并最终，其他临床 相关肿瘤病毒。第一个具体目标是确定 前体mRNA加工的功能和作用机制 HSV的胸苷激酶基因的增强子（PPE），HSV是人类的一种 免疫缺陷病毒（HIV）Rev-反应样元件，及其HIV Rev- 与细胞反式作用因子一样， 蛋白（hnRNP）L，在前体mRNA的加工和核输出中， 它们在互补DNA表达中的效用，通过（a）鉴定 前体mRNA的核输出及其在表达 通过（a）鉴定参与PPE功能的碱基， (b)确定hnRNP L介导的功能和机制 通过结合该PPE的内向非依赖性mRNA生物发生，（c）鉴定 在其它无内含子基因中的其它PPE样元件，和（d） 确定PPE的通用性， 在哺乳动物细胞中的基因表达。第二和第三个具体目标是 以确定类固醇/甲状腺的成员 激素受体超家族及其配体影响表达， 类固醇/甲状腺激素受体超家族SV 40的复制 及其配体通过以下方式影响SV 40和HBV的表达和复制：（a） 研究对转录和病毒体产生的影响， 结合这两种病毒的启动子和配体的核受体 对于这些受体，和（B）确定特异性的 核受体，它们的配体，SV 40编码的癌蛋白大T- 抗原和细胞因子DAP调节SV 40的转录， 主要晚期启动子。各种生物化学、分子学、遗传学和 将使用蜂窝技术。这些研究的结果应该 不仅增加了我们对基本机制的理解， 调节病毒和哺乳动物中的mRNA生物合成，但也可能导致 用于治疗由以下疾病引起的疾病的新药的开发 用于基因治疗的病毒和改进的载体及其制备方法 生物有用的蛋白质。