STRUCTURE DETERMINATION OF HUMAN RNA FRAGMENT

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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控制着生命各个过程中的基因表达：MicroRNA控制着干细胞维持、细胞分化和生物体发育的过程，这使得它们的失调与多种疾病（例如各种类型的癌症）相关。 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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.