Regulation of methionine metabolism in Bacillus subtilis

枯草芽孢杆菌蛋氨酸代谢的调控

• 批准号: 7195069
• 负责人: TINA M. HENKIN
• 金额: $ 27.76万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7195069
• 关键词: Regulation; methionine; metabolism; Bacillus; subtilis

DESCRIPTION (provided by applicant): The S box system is a novel global regulatory mechanism for control of genes involved in methionine metabolism in Gram-positive bacteria. Genes in the S box family contain a complex set of conserved primary sequence and structural elements upstream of the start of the coding sequence. These elements act in the nascent RNA to bind S-adenosylmethionine (SAM), and interaction with SAM results in a structural switch in the RNA that promotes premature termination of transcription. Lysine biosynthesis genes use a similar mechanism, with binding of lysine to nascent RNAs in the L box family to terminate transcription or prevent translation initiation. A new SAM-binding RNA element has now been identified in the upstream region of SAM synthetase genes of certain Gram-positive organisms, and this element, like the S box element, is predicted to regulate expression of the downstream coding sequence in response to SAM. These and related systems are widely used to regulate gene expression in Gram-positive bacteria, including important pathogens. The overall goals of this project are to investigate the molecular basis for specific recognition of effector molecules by the nascent RNA, and for calibration of the affinity of each class of RNA to physiologically relevant concentrations of the effector. A variety of genetic, biochemical, and structural biology approaches will be employed to elucidate both the RNA-effector interaction and the structural rearrangement necessary for the appropriate regulatory response to effector binding. The interaction between methionine gene regulation and the stringent response will also be explored. Work will focus on Bacillus subtilis as a model for analysis of these systems, and will also include analysis of the new SAM binding element from Enterococcus faecalis. This project will provide basic information about novel RNA-based mechanisms of gene regulation, and will also provide insight into metabolic regulation in pathogenic organisms that use these mechanisms. Gram-positive pathogens generally use regulatory mechanisms closely related to those found in Bacillus subtilis. Expression of determinants for pathogenicity are often regulated in response to physiological signals, and understanding how the cell monitors these signals is important for understanding bacterial virulence.

描述（由申请人提供）：S盒系统是一种新颖的全局调节机制，用于控制革兰氏阳性菌中蛋氨酸代谢所涉及的基因。 S盒家族中的基因包含一组复杂的保守一级序列和编码序列起始上游的结构元件。这些元件在新生 RNA 中发挥作用，结合 S-腺苷甲硫氨酸 (SAM)，与 SAM 的相互作用会导致 RNA 中的结构转换，从而促进转录的提前终止。赖氨酸生物合成基因使用类似的机制，赖氨酸与L盒家族中的新生RNA结合以终止转录或阻止翻译起始。现已在某些革兰氏阳性生物体的 SAM 合成酶基因的上游区域中鉴定出一种新的 SAM 结合 RNA 元件，并且该元件与 S 盒元件一样，预计可响应 SAM 调节下游编码序列的表达。这些和相关系统广泛用于调节革兰氏阳性细菌（包括重要病原体）的基因表达。该项目的总体目标是研究新生 RNA 特异性识别效应分子的分子基础，并校准每类 RNA 与效应子生理相关浓度的亲和力。将采用各种遗传、生物化学和结构生物学方法来阐明RNA-效应子相互作用以及对效应子结合的适当调节反应所必需的结构重排。还将探讨蛋氨酸基因调控与严格反应之间的相互作用。工作重点是枯草芽孢杆菌作为分析这些系统的模型，并且还包括对来自粪肠球菌的新 SAM 结合元件的分析。该项目将提供有关基于 RNA 的新型基因调控机制的基本信息，还将深入了解使用这些机制的病原生物体的代谢调控。革兰氏阳性病原体通常使用与枯草芽孢杆菌密切相关的调节机制。致病性决定因素的表达通常根据生理信号进行调节，了解细胞如何监测这些信号对于了解细菌毒力非常重要。