Intracellular targeting of RNAs in virus infection

病毒感染中 RNA 的细胞内靶向

• 批准号: 6320172
• 负责人: Roger Beachy
• 金额: $ 27.14万
• 依托单位: DONALD DANFORTH PLANT SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6320172
• 关键词: Arabidopsis; endoplasmic reticulum; intracellular transport; phosphorylation; tobacco mosaic virus; transport proteins; virus RNA; virus infection mechanism; virus protein

DESCRIPTION: (Adapted from the Investigator's abstract): During development many cellular mRNA are transported from site of synthesis to the site at which they function, and play important roles in determination of cell fate, and a wide range of biochemical activities. Similarly, viral RNAs are targeted to different sites in the host cell where they may take control of cellular functions as they build the 'factories' where virus replication takes place. Often such control results in significant impact on the cell, and in some cases results in apoptosis. Intracellular transport of viral RNAs, and virus replication complexes uses many of the cytoskeletal and membrane components used by host mRNAs. However, the mechanisms of assembly and transport of complexes are not known, and if known may lead to development of chemical or protein therapies that would block virus replication and attendant disease. The research proposed here will isolate and identify the critical components of the cellular membranes that comprise the replication complex for the model plant virus tobacco mosaic virus. The P30 Movement protein encoded by the virus is responsible for recruitment of large bodies of ER membranes to establish the replication factories. After the factories are assembled the membranes are redistributed in the cell. We will identify the host protein factors and processes that are essential for establishing the virus factories and for intracellular transport of the complexes from the perinuclear region, to the cytoplasmic ER, and lastly to the periphery of the cell. Specifically this research project will: I. Determine the topology of the P30 protein in the anchoring viral RNAs; II. Determine the role of MP sequences in aggregation of cellular membranes and for anchoring viral RNAs; Ill. Identify host proteins in membrane bound replication complexes that may be involved in intracellular targeting of viral RNA; IV. Identify and isolate host genes that are essential for function of the MP for intracellular and intercellular transport of RNA, using Arabidopsis thaliana as a model system. These studies will lead to a greater understanding of transport and targeting of RNA complexes within cells, and will increase understanding of regulation of cellular processes. As the system being used involves a virus model system, the knowledge gained by this research may lead to novel therapies and transgenic approaches to control virus replication and disease.

描述：（改编自研究者摘要）：开发期间 许多细胞mRNA从合成位点转运到 它们发挥功能，在决定细胞命运中发挥重要作用， 广泛的生物化学活动。类似地，病毒RNA靶向于 在宿主细胞中的不同位点，它们可以控制细胞内的 在病毒复制的“工厂”中发挥作用。 通常，这种控制对细胞产生显著影响，并且在某些情况下， 导致细胞凋亡。病毒RNA的细胞内转运和病毒 复制复合体使用许多细胞骨架和膜成分 被宿主的mRNA所利用。然而，组装和运输的机制， 复合物是未知的，如果已知，可能会导致化学或 阻止病毒复制和伴随疾病的蛋白质疗法。的 这里提出的研究将分离和确定的关键组成部分， 细胞膜，其包含用于模型植物的复制复合物 烟草花叶病毒该病毒编码的P30运动蛋白是 负责募集大量的内质网膜， 复制工厂工厂组装好后， 在细胞中重新分布。我们将鉴定宿主蛋白因子， 这些过程对于建立病毒工厂和 复合物从核周区向细胞内转运， 细胞质ER，最后到达细胞的外周。具体来说， 研究项目将：I.确定P30蛋白的拓扑结构， 锚定病毒RNA; II.确定MP序列在聚合中的作用 细胞膜和用于锚定病毒RNA; III.鉴定宿主蛋白质 膜结合复制复合物，可能涉及细胞内 病毒RNA的靶向; IV.识别和分离宿主基因， 对于MP用于RNA的细胞内和细胞间转运的功能， 以拟南芥为模型系统。这些研究将导致 更好地理解RNA复合物在细胞内的转运和靶向， 并将增加对细胞过程调节的理解。为 所使用的系统涉及病毒模型系统，由此获得的知识 研究可能导致新的治疗方法和转基因方法来控制病毒 复制和疾病。