INVESTIGATING THE PROPOSED 'SWITCHING' MECHANISM OF VARIOUS RIBOSWITCHES

研究各种核开关的拟议“转换”机制

• 批准号: 8168631
• 负责人: Nathan Baird
• 金额: $ 1.44万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168631
• 关键词: Bacteria; Binding; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence Rearrangement; Drug Delivery Systems; Elements; Funding; Gene Expression; Genes; Genetic; Global Change; Grant; Institution; Ligands; Literature; Messenger RNA; Molecular Conformation; Nature; RNA; Reporting; Research; Research Personnel; Resources; Second Messenger Systems; Signal Transduction; Source; Structure; Structure-Activity Relationship; United States National Institutes of Health; Work; beamline; interest; novel; second messenger

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Riboswitches are structured mRNA elements found predominantly in bacteria. Upon recognition of specific cellular metabolies these RNAs are directly responsible for regulating gene expression at both the transcriptional and translational levels. Because riboswitches are found predominantly in bacteria and represent potential novel drug targets, these RNAs have been of recent interest for structure-function relationships. A metabolite-induced conformational change is a central part of the proposed mechanism of riboswitch function. Our research has focused on the nature of the structural changes elicited by metabolite-binding. Much discussion in the literature has debated whether ligand recognition results in global changes in the RNA or simply local rearrangements around the binding pocket. Our research at the BioCAT beamline demonstrates that different riboswitches behave idiosyncratically, perhaps indicating that the conformational changes are tuned to the genetic context of each riboswitch. Additionally, our work at BioCAT has allowed direct observation of the metabolite-bound and metabolite-free conformation of a riboswitch that recognizes the second messenger cyclic diguanylate. This is the first riboswitch reported which recongizes a second messenger and is responsible for regulating a wide variety of genes involved in signaling instead of the more common riboswitch targets relating

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 核糖开关是主要存在于细菌中的结构化 mRNA 元件。 在识别特定的细胞代谢后，这些 RNA 直接负责在转录和翻译水平上调节基因表达。 由于核糖开关主要存在于细菌中并且代表潜在的新药物靶标，因此这些 RNA 最近在结构-功能关系方面引起了人们的兴趣。 代谢物诱导的构象变化是所提出的核糖开关功能机制的核心部分。 我们的研究重点是代谢物结合引起的结构变化的性质。 文献中的许多讨论都在争论配体识别是否会导致 RNA 的整体变化，或者仅仅是结合袋周围的局部重排。 我们在 BioCAT 光束线的研究表明，不同的核糖开关具有特殊的行为，这可能表明构象变化是根据每个核糖开关的遗传背景进行调整的。 此外，我们在 BioCAT 的工作允许直接观察识别第二信使环二鸟苷酸的核糖开关的代谢物结合和无代谢物构象。 这是第一个报道的核糖开关，它识别第二信使并负责调节参与信号传导的多种基因，而不是与相关的更常见的核糖开关靶标。