Mechanisms of bacterial RNA degradation

细菌RNA降解机制

• 批准号: 10621918
• 负责人: JOEL G BELASCO
• 金额: $ 76.83万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-13 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621918
• 关键词: Acceleration; Antibiotics; Bacteria; Bacterial RNA; Biochemical; Biological; Biophysics; Cell physiology; Cells; Diffusion; Environment; Gene Expression; Gene Expression Regulation; Genetic; Goals; Human; Infection; Knowledge; Messenger RNA; Methods; Modification; Molecular; Organism; Pathogenesis; Phylogenetic Analysis; Play; Process; RNA; RNA Degradation; Research; Research Project Grants; Scanning; Site; Stress; Transcript; endonuclease; insight; mRNA Transcript Degradation; mRNA capping; microbial; novel; ribonuclease E

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.

项目摘要 这个研究项目的首要目标是了解管理的基本原则， 信使RNA降解是一个细胞过程，在调节基因表达中起着关键作用。 在所有生物体中表达。近期目标是阐明5′端对 细菌mRNA寿命。特别是，这项研究将侧重于了解影响 5′-末端帽和5′-末端依赖性核酸内切酶切割对mRNA表达速率的影响 细菌降解。长期以来被认为只存在于真核RNA转录物上， 现在已经在细菌RNA 5 '末端发现了各种各样的蛋白质，但许多重要方面 它们的功能仍然无法解释。此外，调节核酸内切酶RNase E具有 最近，通过一种新的扫描方法， 类似于从5′端线性扩散的机制，但它是如何做到这一点是未知的。具体 本研究项目的目的是阐明结构和系统发育的多样性， 细菌mRNA帽和帽之间的相互作用，细胞生理学，和压力， 确定RNase 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，以及其调节的广度， 冲击分子生物学、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 为基因调控的新方面提供了基本的见解，这些方面与 细菌致病性和抗生素敏感性。