Tools for the Analysis of MicroRNA Function

MicroRNA 功能分析工具

• 批准号: 6885055
• 负责人: LANCE P FORD
• 金额: $ 26.51万
• 依托单位: AMBION, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2006-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885055
• 关键词: DNA repair; angiogenesis; apoptosis; cell cycle; cell differentiation; cell proliferation; chemical synthesis; gene expression; microRNAs; reagent /indicator; reporter genes; technology /technique development

DESCRIPTION (provided by applicant): RNA molecules known as microRNA (miRNA) can influence the expression of target genes. It is thought that mammalian miRNA change the expression of their targets protein while leaving the expression of the cognate mRNA unmodified. These non-protein-encoding miRNA are not only differently expressed but are directly involved in important biological processes such as development and B-cell differentiation. Between 200-255 mammalian miRNA genes are predicted to exist (a number that corresponds to 1 % of all protein encoding genes). Interestingly over 52% of miRNA genes are located in chromosomal fragile sitessome of which are associated with disease. Since each miRNA has the potential to function on several cellular targets their regulatory complexity is potentially enormous. While many of the predicted miRNA have been cloned, the predicted miRNA targets have not yet been evaluated and most mammalian miRNA currently have no identified biological role. We propose to develop the tools that will facilitate the identification of miRNA function and confirm/identify endogenous miRNA targets. We propose to develop a miRNA reporter system, library of miRNA inhibitors and library of miRNA expression vectors or chemically synthesized miRNA corresponding to the known human miRNA. Using these reagents, we will begin to analyze miRNA regulated gene pathways and identify miRNA that participate in a variety of cellular processes, including apoptosis, cell cycle, angiogenesis, proliferation, differentiation, and DNA repair. Combining the resulting data will provide a global view of how miRNA influence human cells and might reveal potential therapeutic targets.

描述（由申请人提供）：称为microRNA（miRNA）的RNA分子可以影响靶基因的表达。据认为，哺乳动物miRNA会改变其靶标的蛋白的表达，同时离开未修饰的同源mRNA的表达。 这些非蛋白质编码的miRNA不仅表达了不同，而且直接参与了重要的生物学过程，例如发育和B细胞分化。预计存在200-255个哺乳动物miRNA基因（这一数字对应于所有蛋白质编码基因的1％）。有趣的是，超过52％的miRNA基因位于与疾病有关的染色体脆弱的坐骨体中。由于每个miRNA具有在几个细胞靶标上发挥作用的潜力，它们的调节复杂性可能是巨大的。 尽管已经克隆了许多预测的miRNA，但尚未评估预测的miRNA靶标，并且大多数哺乳动物miRNA目前尚无生物学作用。 我们建议开发将有助于识别miRNA功能并确认/识别内源miRNA靶标的工具。我们建议开发一个miRNA报告基因系统，miRNA抑制剂库和miRNA表达载体的库或与已知人miRNA相对应的化学合成miRNA。 使用这些试剂，我们将开始分析miRNA调节的基因途径，并确定参与多种细胞过程的miRNA，包括凋亡，细胞周期，血管生成，增殖，分化和DNA修复。结合产生的数据将为miRNA如何影响人类细胞的全球视图，并可能揭示潜在的治疗靶标。