Structure and function of RNase P

描述（由申请人提供）：人类细胞依赖RNA在信息传递和其他生物分子的合成中发挥核心作用。在这些过程的几个关键点上，RNA本身起着催化剂的作用。由于它们的重要作用，这些分子是抗癌和抗病毒治疗的重要靶点。然而，细胞和病毒中的rna需要结合特定的蛋白质才能发挥作用。因此，要全面了解RNA的生理学，不仅需要了解RNA分子本身的结构和催化特性，还需要了解蛋白质结合在激活和调节其生物活性中的作用。然而，我们对RNA催化机制的理解仍处于起步阶段，大多数RNA-蛋白复合物组装过程中构象变化的范围和功能影响尚难以实现。

DESCRIPTION (provided by applicant): Human cells depend on RNA to perform central roles in information transfer and the synthesis of other biomolecules. At several critical points in these processes RNA itself acts as a catalyst. Because of their essential role, these molecules are important targets for anti-cancer and anti-viral therapies. However, the RNAs in cells and viruses require the binding of specific proteins to function. Thus, a complete understanding of physiology of RNA requires both an understanding of the structural and catalytic features of the RNA molecules themselves, as well as the roles that protein binding plays in activating and modulating their biological activity. However, our understanding of RNA catalytic mechanism is still emerging and the range and functional effects of conformational changes in the assembly of most RNA-protein complexes has been difficult to achieve. Our investigations focus on understanding how the RNA and protein subunits of bacterial RNase P work together to achieve biological catalysis. RNase P is a ubiquitous and highly conserved ribonucleoprotein enzyme that generates the mature 5' ends of tRNAs. This ribonucleoprotein consists of a single protein bound to a larger catalytic RNA subunit termed P RNA, and is thus an excellent model system for exploring fundamental aspects of RNA catalysis and the coordinated biological function of RNA and protein. We are using this system to address three fundamental questions: 1. What is the mechanism of RNase P catalyzed phosphodiester hydrolysis?; 2. How do the RNA and protein subunits collaborate to achieve catalysis?; and, 3. What is the pathway by which the RNA and protein subunits fold into a functional complex? The answers to these questions will contribute to our understanding of biological catalysis and ribonucleoprotein function and in the long term provide the basis for inhibitor-based therapeutics that target RNAs.