Mechanisms of bacterial RNA degradation

项目总结 这项研究项目的首要目标是了解 信使RNA降解，这是一种在基因调控中起关键作用的细胞过程 在所有生物体中都有表达。眼下的目标是阐明5‘端对 细菌信使核糖核酸寿命。特别是，这项研究将侧重于了解这一影响 5‘-末端帽和5’-末端依赖的内切核裂解对mRNA速率的影响 细菌的降解。长期以来，人们认为只存在于真核细胞的RNA转录本，CAPS 现在已经在细菌的RNA5‘端发现了各种类型的DNA，但有许多重要的方面 它们的功能仍未得到解释。此外，调节性核酸内切酶RNaseE具有 最近被证明通过一种新的扫描定位单磷酸化RNA中的裂解位点 机制类似于从5‘端的线性扩散，但它如何做到这一点尚不清楚。具体的 本研究项目的目的是阐明该物种的结构和系统发育多样性。 细菌mRNA封顶及其与细胞生理、应激和TO之间的相互作用 确定核糖核酸酶E扫描RNA寻找切割位点的分子机制， 细胞环境对这一过程的影响及其调控的广度 冲击力。分子生物学、生物化学、生物物理学和遗传学方法的结合 将被用来实现这些目标。从这些研究中获得的知识将 提供对基因调控的新方面的基本见解，这些方面已被牵连到 细菌致病机制和抗生素敏感性。

PROJECT SUMMARY The overarching goal of this research project is to understand the basic principles that govern messenger RNA degradation, a cellular process that plays a key role in regulating gene expression in all organisms. The immediate goal is to elucidate the impact of the 5′ end on bacterial mRNA lifetimes. In particular, this research will focus on understanding the influence of 5′-terminal caps and 5′-end-dependent endonucleolytic cleavage on rates of mRNA degradation in bacteria. Long thought to reside exclusively on eukaryotic RNA transcripts, caps of various kinds have now been found on RNA 5′ ends in bacteria, yet many important aspects of their function remain unexplained. In addition, the regulatory endonuclease RNase E has recently been shown to locate cleavage sites in monophosphorylated RNA by a novel scanning mechanism akin to linear diffusion from the 5′ end, but how it does so is unknown. The specific objectives of this research project are to elucidate the structural and phylogenetic diversity of bacterial mRNA capping and the interplay between capping, cell physiology, and stress and to determine the molecular mechanism by which RNase E scans RNA in search of cleavage sites, the influence of the cellular environment on this process, and the breadth of its regulatory impact. A combination of molecular biological, biochemical, biophysical, and genetic methods will be employed to achieve these objectives. The knowledge gained from these studies will provide fundamental insights into novel aspects of gene regulation that have been implicated in bacterial pathogenesis and antibiotic sensitivity.