Regulation of methionine metabolism in Bacillus subtilis

枯草芽孢杆菌蛋氨酸代谢的调控

基本信息

批准号：
8450161
负责人：
TINA M. HENKIN
金额：
$ 31.1万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8450161
关键词：
Affect Affinity Animal Model Archaea Bacillus subtilis Bacteria Binding Biochemical Biological Process Boxing Cells Code Complex DNA Sequence Rearrangement Elements Engineering Eukaryota Family Gene Expression Gene Expression Regulation Genes Genetic Transcription Goals Growth Hybrids In Vitro Individual Investigation Laboratories Ligand Binding Ligands Lysine Mediating Metabolic Methionine Metabolism Pathway Molecular Monitor Organism Pathogenicity Physiological Positioning Attribute Property RNA RNA Binding Regulation Regulatory Element Research Role S-Adenosylmethionine Signal Transduction Specificity Structure System Temperature Testing Thiamine Pyrophosphate Trans-Activators Transcript Translation Initiation Variant Virulence Work analog attenuation base cis acting element in vivo insight member methionine adenosyltransferase mutant novel pathogen public health relevance response tool transcription termination

项目摘要

DESCRIPTION (provided by applicant): Riboswitch RNAs represent an important regulatory mechanism in bacteria. RNAs of this type consist of complex elements positioned in the leader region of a transcript, upstream of the regulated coding sequence(s). These RNA elements directly sense a physiological signal that induces a structural change in the RNA, resulting in an effect on downstream gene expression. This project will focus primarily on two classes of S-adenosylmethionine (SAM)-binding riboswitch RNAs, the S box and the SMK box, with additional efforts on the lysine-binding L box, the thiamine pyrophosphate-binding Thi box, and RNA thermosensors that respond to changes in temperature. The first major goal of the project is to investigate the molecular basis for specific ligand recognition by multiple riboswitch RNAs, and the features responsible for differential SAM sensitivity in natural variants of the S box riboswitch. These efforts will also include using the information obtained to engineer novel classes of riboswitches with the goal of testing the predictive power of these analyses. The second major goal is to investigate the structural and functional differences between riboswitches that operate at the transcriptional and translational levels, to test the hypothesis that translational riboswitches (like the SMK box) have the potential to operate reversibly in vivo, allowing multiple regulatory decisions within the lifetime of a single RNA transcript. These studies will include detailed analysis of the ligand-free form of the SMK box RNA and the transition between the ligand-free and ligand-bound forms. The third major goal involves analysis of the interplay between riboswitch elements and other regulatory mechanisms, using the Bacillus subtilis metK gene, encoding SAM synthetase, as an example. Overall, 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, the model organism for this work. 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. It is also likely that many new riboswitch-like mechanisms remain to be uncovered, and the proposed work will provide important tools for investigation of these mechanisms, and predicting how they function within the cell.

描述（由申请人提供）：核糖开关RNA代表细菌中的重要调节机制。这种类型的 RNA 由位于转录物前导区、受调控编码序列上游的复杂元件组成。这些 RNA 元件直接感知生理信号，从而诱导 RNA 结构变化，从而影响下游基因表达。该项目将主要关注两类 S-腺苷甲硫氨酸 (SAM) 结合核糖开关 RNA，即 S 盒和 SMK 盒，另外还致力于赖氨酸结合 L 盒、硫胺素焦磷酸结合 Thi 盒和 RNA 热传感器对温度变化做出反应。该项目的第一个主要目标是研究多种核糖开关 RNA 特异性配体识别的分子基础，以及 S 盒核糖开关天然变体中导致 SAM 敏感性差异的特征。这些努力还将包括使用获得的信息来设计新型核糖开关，以测试这些分析的预测能力。第二个主要目标是研究在转录和翻译水平上操作的核糖开关之间的结构和功能差异，以检验翻译核糖开关（如 SMK 盒）具有在体内可逆操作的潜力的假设，从而允许在体内进行多种监管决策。单个RNA转录本的寿命。这些研究将包括对 SMK 盒 RNA 的无配体形式的详细分析以及无配体和配体结合形式之间的转变。第三个主要目标涉及以编码 SAM 合成酶的枯草芽孢杆菌 metK 基因为例，分析核糖开关元件与其他调节机制之间的相互作用。总体而言，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（本研究的模型生物）中发现的调节机制密切相关的机制。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。也有可能许多新的核糖开关样机制仍有待发现，并且拟议的工作将为研究这些机制并预测它们在细胞内如何发挥作用提供重要工具。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Thermodynamics of coupled folding in the interaction of archaeal RNase P proteins RPP21 and RPP29.

古菌 RNase P 蛋白 RPP21 和 RPP29 相互作用中耦合折叠的热力学。

DOI：
发表时间：
2012-01-31
期刊：
影响因子：
2.9
作者：
Xu, Yiren;Oruganti, Sri Vidya;Gopalan, Venkat;Foster, Mark P
通讯作者：
Foster, Mark P

The L box regulon: lysine sensing by leader RNAs of bacterial lysine biosynthesis genes.

L 盒调节子：细菌赖氨酸生物合成基因的前导 RNA 感应赖氨酸。

DOI：
发表时间：
2003-10-14
期刊：
影响因子：
0
作者：
Grundy, Frank J;Lehman, Susan C;Henkin, Tina M
通讯作者：
Henkin, Tina M

Identification of a mutation in the Bacillus subtilis S-adenosylmethionine synthetase gene that results in derepression of S-box gene expression.

枯草芽孢杆菌 S-腺苷甲硫氨酸合成酶基因中导致 S-box 基因表达去抑制的突变的鉴定。

DOI：
发表时间：
2006-05
期刊：
影响因子：
0
作者：
McDaniel, Brooke A;Grundy, Frank J;Kurlekar, Vineeta P;Tomsic, Jerneja;Henkin, Tina M
通讯作者：
Henkin, Tina M

Mechanisms of resistance to an amino acid antibiotic that targets translation.

针对翻译的氨基酸抗生素的耐药机制。

DOI：
发表时间：
2007-12-21
期刊：
影响因子：
4
作者：
Ataide, Sandro F;Wilson, Sharnise N;Dang, Sandy;Rogers, Theresa E;Roy, Bappaditya;Banerjee, Rajat;Henkin, Tina M;Ibba, Michael
通讯作者：
Ibba, Michael

Natural variability in S-adenosylmethionine (SAM)-dependent riboswitches: S-box elements in bacillus subtilis exhibit differential sensitivity to SAM In vivo and in vitro.

S-腺苷甲硫氨酸 (SAM) 依赖性核糖开关的自然变异：枯草芽孢杆菌中的 S-box 元件在体内和体外表现出对 SAM 的不同敏感性。