STRUCTURE DETERMINATION OF HUMAN RNA FRAGMENT

人 RNA 片段的结构测定

• 批准号: 8170662
• 负责人: Piotr Sliz
• 金额: $ 0.29万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170662
• 关键词: Binding; Biogenesis; Cell Differentiation process; Cell Maintenance; Cells; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Development; Dicer Enzyme; Disease; Eukaryota; Event; Family; Funding; Gene Expression; Goals; Grant; Human; Institution; Life; Link; MicroRNAs; Modeling; Molecular; Organism; Process; RNA; Research; Research Personnel; Resources; Role; Source; Stem cells; Structure; United States National Institutes of Health; cancer type; insight; member; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our research goal is to elucidate the molecular details of how microRNA molecules are generated. MicroRNAs are small regulatory RNA molecules that are produced and regulated endogenously throughout development, particularly prominent in eukaryotes. Recent advances in microRNA research has only begun to reveal the importance of their role, as microRNAs control gene expression in various processes of life: MicroRNAs govern processes in stem cell maintenance, cell differentiation, and organism development, which makes their dysregulation linked to many diseases such as various types of cancer. We study the basic steps involved in producing microRNAs in cells. Currently we are focusing on a model microRNA, the family of let-7 microRNAs. The first regulatory molecule in microRNA biogenesis, LIN-28, was found to specifically block maturation of precursors of let-7. LIN28 specifically interacts with the let-7 precursor, preventing its processing by Drosha and/or Dicer enzymes. However, how various let-7 members are recognized and how the binding event leads to protection from RNAses that cleave at opposite ends of the precursor is still unclear. By understanding the structural details of the interaction of LIN28 with precursor let-7, we will gain insight into how microRNA precursors are recognized by the RNAses for proper maturation.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们的研究目标是阐明 microRNA 分子如何生成的分子细节。 MicroRNA 是在整个发育过程中内源产生和调节的小调节 RNA 分子，在真核生物中尤其突出。 microRNA 研究的最新进展才刚刚开始揭示其作用的重要性，因为 microRNA 在生命的各个过程中控制基因表达：MicroRNA 控制干细胞维持、细胞分化和生物体发育的过程，这使得它们的失调与许多疾病有关比如各种癌症。 我们研究在细胞中产生 microRNA 的基本步骤。目前我们专注于一个模型 microRNA，即 let-7 microRNA 家族。 microRNA 生物发生中的第一个调节分子 LIN-28，被发现可以特异性阻断 let-7 前体的成熟。 LIN28 与 let-7 前体发生特异性相互作用，阻止 Drosha 和/或 Dicer 酶对其进行加工。然而，各种let-7成员如何被识别以及结合事件如何导致保护免受在前体相反末端切割的RNA酶的影响仍不清楚。通过了解 LIN28 与前体 let-7 相互作用的结构细节，我们将深入了解 microRNA 前体如何被 RNAses 识别以实现适当的成熟。