Mechanisms of Gene Regulation by MicroRNAs

MicroRNA 的基因调控机制

• 批准号: 7319900
• 负责人: JOEL G BELASCO
• 金额: $ 28.73万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319900
• 关键词: Address; Animals; Awareness; Binding; Biological; Biological Models; Cells; Complex; Congenital Abnormality; Defect; Down-Regulation; Elements; Etiology; Excision; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Goals; Human; Investigation; Knowledge; Language; Malignant Neoplasms; Mammalian Cell; Mediating; Medical; Messenger RNA; Methods; MicroRNAs; Molecular; Play; Poly A; Poly(A) Tail; Protein Isoforms; Proteins; RNA Interference; RNA Recognition Motif; Regulation; Repression; Research; Role; Scanning; Site; Small RNA; Thinking; Time; Translation Initiation; Translational Repression; Translations; Virus Diseases; analytical tool; base; cofactor; improved; improved functioning; insight; interest; mRNA Decay; mRNA Stability; mRNA Transcript Degradation

DESCRIPTION (provided by applicant): These investigations will focus on microRNA-mediated mRNA degradation in mammalian cells, with the goal of understanding the mechanism by which microRNAs expedite deadenylation as an early step in the degradation of their mRNA targets and the contribution of mRNA deadenylation and decay to gene regulation by microRNAs. Using cultured mammalian cells as model systems and molecular biological methods as analytical tools, we will investigate the proteins that contribute to microRNA-directed deadenylation, the manner in which they associate with one another, and the importance of those interactions for miRNA function. In addition, we will examine the impact of mRNA context on the degree to which microRNAs influence mRNA stability. Finally, we will explore the mechanism by which microRNAs identify their target sites in mRNA. The results of these studies should enhance our knowledge of a widespread mechanism of eukaryotic gene regulation that presently is poorly understood. This knowledge should ultimately be of value for understanding the etiology of diseases thought in some instances to be related to defects in microRNA function and for improving the efficacy of RNA interference as a medical therapy. Lay language statement: There is growing awareness that the hundreds of distinct microRNAs in human cells play key roles in gene regulation. Additional evidence suggests that microRNAs are important for viral infection and that defects in microRNA function can contribute to cancer and congenital abnormalities. The proposed research should eventually be of value for understanding the etiology of diseases related to microRNA function or dysfunction and for improving the efficacy of medical therapies based on small RNA molecules.

描述（由申请人提供）：这些研究将集中在哺乳动物细胞中microRNA介导的mRNA降解上，目的是了解microRNAS迅速降解的机制，作为其mRNA靶标降解的早期一步，以及mrodoRORNAS的mRNA Deadenylation and decay decation nylaS的贡献。我们将使用培养的哺乳动物细胞作为模型系统和分子生物学方法作为分析工具，我们将研究有助于microRNA指导的deadenylation的蛋白质，它们相互关联的方式以及这些相互作用对miRNA功能的重要性。此外，我们将研究mRNA环境对microRNA影响mRNA稳定性的程度的影响。最后，我们将探讨microRNA在mRNA中识别其目标位点的机制。这些研究的结果应增强我们对目前知之甚少的真核基因调节机制的知识。在某些情况下，这些知识最终对于理解与microRNA功能缺陷有关的疾病的病因以及提高RNA干扰作为医疗疗法的疗效而具有价值。外行语言陈述：越来越意识到人类细胞中数百个不同的microRNA在基因调节中起关键作用。其他证据表明，microRNA对病毒感染很重要，而microRNA功能的缺陷会导致癌症和先天性异常。拟议的研究最终对于理解与microRNA功能或功能障碍有关的疾病的病因以及改善基于小RNA分子的医疗疗法的功效而具有价值。