Intracellular targeting of RNAs in virus infection

描述：(改编自调查者摘要)：在开发过程中 许多细胞信使核糖核酸从合成部位运输到 它们的功能，并在决定细胞命运中发挥重要作用，并且 广泛的生化活动。同样，病毒RNA的目标是 宿主细胞中的不同位置，在那里它们可能控制细胞 在他们建造病毒复制发生的‘工厂’时发挥作用。 通常，这种控制会对细胞产生重大影响，在某些情况下 会导致细胞凋亡。病毒RNA的细胞内运输，以及病毒 复制复合体使用许多细胞骨架和膜组件 由宿主mRNA使用。然而，组装和运输的机制 络合物是未知的，如果已知，可能会导致化学或 蛋白质疗法可以阻止病毒复制和伴随的疾病。这个 这里提出的研究将分离和确定关键组件 构成模式植物复制复合体的细胞膜 烟草花叶病毒。该病毒编码的P30运动蛋白是 负责招募大量ER膜以建立 复制工厂。在工厂组装完成后，膜被 在细胞内重新分布。我们将确定宿主蛋白因子并 对于建立病毒工厂和 络合物从核周区到细胞内的转运 胞质内质网，最后到达细胞的外围。具体来说就是这个 研究项目将：I.确定P30蛋白在细胞中的拓扑结构 锚定病毒RNA；II.确定MP序列在聚集中的作用 细胞膜和锚定病毒RNA；伊利诺伊州。鉴定寄主蛋白 可能参与细胞内的膜结合复制复合体 靶向病毒RNA；IV.鉴定和分离必需的宿主基因 对于MP在细胞内和细胞间转运RNA的功能， 以拟南芥为模型系统。这些研究将导致 更好地了解RNA复合体在细胞内的运输和靶向， 并将增加对细胞过程调控的理解。作为 正在使用的系统涉及病毒模型系统，由此获得的知识 研究可能导致控制病毒的新疗法和转基因方法 复制和疾病。

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.