BIOGENESIS OF DNA TUMOR VIRAL MRNAS

DNA 肿瘤病毒 MRNAS 的生物发生

• 批准号: 6352712
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6352712
• 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.

目标是了解分子水平的某些 调节的转录和转录后机制 Simian病毒40（SV40）的基因的表达，单纯疱疹病毒类型 1（HSV-1），丙型肝炎病毒（HBV），最终在其他临床上 相关的肿瘤病毒。第一个具体目的是确定 前MRNA处理的作用的功能和机制 HSV的胸苷激酶基因的增强剂（PPE），人类 免疫缺陷病毒（HIV）类似响应的元素及其HIV Rev- 像细胞跨作用因子一样，异质性核核核 蛋白质（HNRNP）L，在MRNA的加工和核输出中 他们通过（a）识别它们在补充DNA表达的效用 前MRNA的核出口及其在表达中的效用 互补的DNA通过（a）识别涉及PPE函数的基础， （b）确定HNRNP L介导的功能和机制 通过结合这种PPE，（c）识别独立的独立mRNA生物发生 其他无固有基因中的其他类似PPE的元素，（d） 确定PPE的一般性，实现有效的内含子独立 哺乳动物细胞中的基因表达。第二和第三个特定目标是 确定类固醇/甲状腺成员的机制 激素受体超家族及其配体会影响表达和 类固醇/甲状腺激素受体超家族的SV40复制 它们的配体会影响（a）的SV40和HBV的表达和复制 检查对某些转录和病毒体产生的影响 结合这两种病毒和配体的启动子的核受体 对于这些受体，以及（b）确定特定的机制 核受体，配体，SV40编码大型T- 抗原和细胞因子DAP，从SV40调控转录 主要的晚期发起人。多种生化，分子，遗传和 将使用蜂窝技术。这些研究的发现应该 不仅增加了我们对涉及的基本机制的理解 调节病毒和哺乳动物中的mRNA生物发生，但也可能导致 开发用于治疗疾病的新型药物 病毒和改进的载体用于基因疗法和制造 生物学上有用的蛋白质。