STRUCTURE DETERMINATION OF HUMAN RNA FRAGMENT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 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微小RNA分子如何产生的分子细节。MicroRNA是小的调节RNA分子，其在整个发育过程中内源性产生和调节，在真核生物中特别突出。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在各种生命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，如各种类型的癌症。 我们研究了在细胞中产生microRNA的基本步骤。目前，我们正专注于一个模型microRNA，let-7 microRNA家族。发现microRNA生物发生中的第一个调节分子LIN-28特异性地阻断let-7前体的成熟。LIN 28特异性地与let-7前体相互作用，防止其被Drosha和/或Dicer酶加工。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的相对末端切割的RNA酶的影响仍然不清楚。通过了解LIN 28与前体let-7相互作用的结构细节，我们将深入了解RNA酶如何识别microRNA前体以进行适当的成熟。

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.