Nuclear Organization and Adenovirus Gene Expression

核组织和腺病毒基因表达

• 批准号: 6505308
• 负责人: Eileen K BRIDGE
• 金额: $ 14万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2005-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6505308
• 关键词: Adenoviridae; DNA replication; HeLa cells; cell nucleus; gene expression; host organism interaction; intracellular transport; tissue /cell culture; virus infection mechanism; virus protein; virus replication

DESCRIPTION (provided by applicant): The in vivo organization of gene expression is a major challenge in cell biology research. We will study the functional significance of nuclear organization in HeLa cells infected by the human DNA virus, Adenovirus (Ad). This research plan is focused Ad induced changes in two nuclear structures, nuclear domain 10 (ND 10) and interchromatin granule clusters (IGCs), and on the transport activities of viral shuttle proteins that move between the nucleus and the cytoplasm. ND10 is a nuclear structure that is disrupted in some human cancer cells, and following infection by different DNA viruses. IGCs contain splicing factors, poly(A) RNA, and in infected cells, virus RNA. IGCs may have an important role in RNA production or trafficking. The long-term goal of the project is to understand how activities such as DNA replication and gene expression are coordinated with the structural organization of the nucleus. We will make a step toward achieving this goal by studying virus reorganization of ND10 and IGCs and nucleocytoplasmic transport. In the first specific aim we will study the production and localization viral and cellular RNA relative to IGCs in infections by wild-type and mutant viruses. In the second specific aim we will investigate the roles of Ad shuttle proteins in promoting viral DNA replication and gene expression. We will analyze mutant viral proteins, and test the effect of inhibiting a specific transport pathway on the function of these proteins. In the third specific aim we will investigate the significance of ND10 reorganization by studying viral mutants. These studies are important because they will provide valuable information about how nuclear organization is related to function. By clarifying the role of nuclear organization in viral replication and gene expression we will gain important insights into its significance for replication and gene expression of the host cell. This will serve as a valuable platform for studying the inter-relationship between nuclear organization and aspects of replication and gene expression in development, cell differentiation, and cancer.

描述（由申请人提供）：基因表达的体内组织是细胞生物学研究的主要挑战。我们将研究被人类 DNA 病毒腺病毒 (Ad) 感染的 HeLa 细胞中核组织的功能意义。该研究计划的重点是 Ad 诱导的两个核结构、核结构域 10 (ND 10) 和染色质间颗粒簇 (IGC) 的变化，以及在细胞核和细胞质之间移动的病毒穿梭蛋白的转运活动。 ND10 是一种核结构，在某些人类癌细胞中以及在被不同 DNA 病毒感染后被破坏。 IGC 含有剪接因子、poly(A) RNA，在受感染的细胞中含有病毒 RNA。 IGC 可能在 RNA 生产或运输中发挥重要作用。该项目的长期目标是了解 DNA 复制和基因表达等活动如何与细胞核的结构组织相协调。我们将通过研究 ND10 和 IGC 的病毒重组以及核细胞质运输，朝着实现这一目标迈出一步。 在第一个具体目标中，我们将研究野生型和突变病毒感染中与 IGC 相关的病毒和细胞 RNA 的产生和定位。在第二个具体目标中，我们将研究 Ad 穿梭蛋白在促进病毒 DNA 复制和基因表达中的作用。我们将分析突变病毒蛋白，并测试抑制特定转运途径对这些蛋白功能的影响。在第三个具体目标中，我们将通过研究病毒突变体来研究 ND10 重组的意义。这些研究很重要，因为它们将提供有关核组织与功能如何相关的有价值的信息。通过阐明核组织在病毒复制和基因表达中的作用，我们将深入了解其对宿主细胞复制和基因表达的重要性。这将成为研究核组织与发育、细胞分化和癌症中复制和基因表达方面之间相互关系的宝贵平台。