Virus-Mosquito mRNA Stability

病毒-蚊子 mRNA 稳定性

• 批准号: 7379942
• 负责人: Jeffrey Wilusz
• 金额: $ 33.72万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379942
• 关键词: 3' Untranslated Regions; Address; Aedes; Arboviruses; Area; Biological Assay; Biology; Bunyaviridae; Cell Extracts; Cells; Culicidae; Cytoplasm; Data; Dengue; Development; Disease Vectors; Elements; Enzymes; Exonuclease; Family; Flaviviridae; Gene Expression; Genomics; Goals; Hand; In Vitro; Indium; Insecta; Kinetics; Knowledge; Lacrosse; Life Cycle Stages; Mammalian Cell; Mediating; Messenger RNA; Modeling; Molecular Biology; Numbers; Organism; Pathway interactions; Play; Poly A; Post-Transcriptional Regulation; Process; Quality Control; RNA Viruses; Regulation; Regulatory Element; Role; Series; Sindbis Virus; System; Therapeutic; Togaviridae; Transcript; Untranslated Regions; Viral; Virus; Work; base; comparative; experience; in vivo; insight; mRNA Decay; mRNA Stability; novel; pathogen; research study; therapeutic target; vector; vector mosquito; viral RNA; virus host interaction

DESCRIPTION (provided by applicant): Mosquitoes are vectors of multiple viral pathogens, a large number of which are RNA viruses. Strategies for viral control may target the vector itself or the interaction between the virus and the vector. This application is based upon the hypothesis that RNA viruses have evolved specific mechanisms for evading the mRNA turnover machineries of the mosquito cell and therefore mRNA decay factors may represent a novel target for therapeutics. Our current knowledge of mRNA decay in insects is minimal thus the primary goals of this proposal must be to elucidate the factors and pathways involved in mRNA turnover in the Aedes mosquito and characterize their regulation. Using an in vitro approach that we have successfully adapted to mosquito cell extracts along with in vivo assays, the goal of Aim I is to characterize the processes of mRNA deadenylation, decapping and decay in mosquitoes. In Aim II we will use this knowledge to gain insights into mechanisms of regulated mRNA decay mediated by togavirus 3' untranslated regions that we have observed. The final aim of the application will address the underlying mechanisms responsible for how non- polyadenylated viral RNAs avoid degradation upon entry into the mosquito cell. In summary, this information will provide fundamental insights into insect molecular biology and virus-host interactions that will provide the groundwork for novel avenues of arbovirus control.

描述（申请人提供）：蚊子是多种病毒病原体的载体，其中大量是RNA病毒。病毒控制策略可以针对载体本身或病毒与载体之间的相互作用。该应用基于这样的假设：RNA 病毒已经进化出逃避蚊子细胞 mRNA 转换机制的特定机制，因此 mRNA 衰减因子可能代表治疗的新靶标。我们目前对昆虫 mRNA 衰减的了解很少，因此该提案的主要目标必须是阐明伊蚊中 mRNA 更新所涉及的因素和途径，并描述其调节特征。使用我们已成功适应蚊子细胞提取物的体外方法以及体内测定，Aim I 的目标是表征蚊子中 mRNA 脱腺苷化、脱帽和腐烂的过程。在 Aim II 中，我们将利用这些知识来深入了解我们观察到的披膜病毒 3' 非翻译区介导的 mRNA 衰变调节机制。该应用的最终目标将解决非聚腺苷酸化病毒 RNA 在进入蚊子细胞后如何避免降解的潜在机制。总之，这些信息将为昆虫分子生物学和病毒与宿主相互作用提供基本见解，从而为虫媒病毒控制的新途径奠定基础。