RIBOSOME BIOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 核糖体的生物发生是细胞增殖和肿瘤进展的基础。癌细胞经常含有增大的核仁，这被认为是核糖体RNA(RRNA)增加的结果。因此，降低rRNA的合成速度可能会提供一种阻止癌症进展的方法。从前rRNA转录本合成成熟rRNA(rRNA加工)是一个复杂的顺序过程，最近在真核系统中发现了几个影响因素。对于这些因素中的许多，还没有确定在rRNA加工中的具体作用。我的实验室的目标是利用X射线结晶学结合生化表征和功能研究来阐明rRNA加工因子的分子功能。为此，我们目前的研究集中在RIO激酶和NEP1/Emg1的结构和功能上，RIO激酶是一组古老的非典型丝氨酸激酶，NEP1/Emg1是一种高度保守的rRNA结合的甲基转移酶。这两组蛋白质都是小核糖体亚基rRNA正常成熟所必需的。我们有兴趣从这些蛋白质及其配体的晶体中收集结构信息，以便进行基于结构的功能研究。从这些研究中获得的结构信息有望最终导致核糖体合成抑制剂的基于结构的设计。由UMCP启动基金和NIH支持

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. Ribosome biogenesis is fundamental to cell proliferation and thereby, tumor progression. Cancer cells frequently contain enlarged nucleoli, which are thought to result from increased ribosomal RNA (rRNA). Therefore, decreasing the rate of rRNA synthesis might provide a means of blocking cancer progression. The synthesis of mature rRNA from the pre-rRNA transcript (rRNA processing) is a complex sequential process for which several factors have recently been identified in eukaryotic systems. For many of these factors, the specific role in the rRNA processing has not been determined. The goal of my laboratory is to use X-ray crystallography coupled with biochemical characterization and functional studies to elucidate the molecular functions of rRNA processing factors. To that end, our studies are currently focused on the structure and function of the RIO kinases, which are an ancient group of atypical serine kinases, and Nep1/Emg1, a highly conserved, rRNA-binding, putative methyltransferase. Both groups of proteins are required for the proper maturation of the rRNA of the small ribosomal subunit. We are interested in gathering structural information from crystals of these proteins and their ligands to allow for structure-based functional studies. The structural information obtained from these studies is expected to lead eventually to the structure-based design of inhibitors of ribosome synthesis. Supportted by UMCP start-up funds and NIH