The roles of biologically relevant ncRNAs

生物学相关的 ncRNA 的作用

• 批准号: 8738902
• 负责人: STEVEN A CARR
• 金额: $ 28.32万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8738902
• 关键词: Affect; Antisense RNA; Bacteria; Bacterial Genome; Bacterial Physiology; Bacterial RNA; Binding; Biochemical; Biological; Biological Assay; Biological Process; Cell physiology; Cells; Code; Complement; Environment; Eukaryotic Cell; Family; Fortune; Functional RNA; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genetic Translation; Genomics; Goals; Growth; Instruction; Lead; Messenger RNA; Methods; Mycobacterium tuberculosis; Organism; Pharmaceutical Preparations; Phenotype; Play; Prokaryotic Cells; Proteome; Regulation; Regulator Genes; Regulon; Role; Series; Signal Transduction; Small RNA; Specificity; Structure; System; Time; Transact; Transcript; Transfer RNA; Tuberculosis Vaccines; Untranslated RNA; Work; cis acting element; global health; in vivo; insight; novel; protein function

The goal of this project is to define the function of biologically important noncoding RNAs in Mycobacterium tuberculosis. It has recently become clear that noncoding RNAs play important regulatory roles in many prokaryotes. However, in Mtb, like most bacteria, the vast majority of them remain completely uncharacterized. We have experimentally identified over 1000 noncoding RNAs in Mtb, of which only 5 have been experimentally characterized to any extent. In this proposal, we will focus on one class of noncoding RNAs, trans-acting, intergenic regulatory RNAs, commonly termed small RNAs (sRNAs). While some sRNAs interact with and affect the function of proteins, the vast majority of sRNAs characterized to date influence the stability and/or translation of mRNAs. Thus, the critical steps in defining the biological function a regRNA are to identify the mRNA(s) it regulates and the biological consequences of this regulation—first at the level of the transcriptome and proteome (regulon) and then in terms of the cell's physiology. We propose a tiered series of aims in which we will define the function of candidate sRNAs with increasing specificity—first defining the importance of the candidates for Mtb growth under standard and "in vivo-like" growth conditions. We will then define the regulatory network controlled by each sRNA. Finally, we will use a combination of computational and biochemical approaches to identify and validate the target of each sRNA. We anticipate that through these studies, we will provide unprecedented insights into sRNA function in bacteria in general and in Mtb more specifically.

该项目的目的是定义分枝杆菌中生物学上重要的非编码RNA的功能 结核。最近很明显，非编码RNA在许多人中扮演着重要的调节角色 原核生物。但是，在MTB中，像大多数细菌一样，其中绝大多数仍然完全保持 未表征。我们在MTB中实验确定了超过1000多个非编码RNA，其中只有5个 我们在任何程度上都对我们进行了实验表征。在此提案中，我们将重点放在一类非编码上 RNA，反式，基因间调节RNA，通常称为小RNA（SRNA）。而有些 SRNA与蛋白质的功能相互作用并影响蛋白质的功能，这是迄今为止特征的绝大多数SRNA 影响mRNA的稳定性和/或翻译。这，定义生物学功能的关键步骤 regrna旨在确定它调节的mRNA和该调节的生物学后果 - 首先 在转录组和蛋白质组（调节元）的水平上，然后就细胞的生理学而言。我们 提案一系列目标，我们将随着增加而定义候选SRNA的功能 特异性 - 首先定义候选人在标准和“体内样”下对MTB增长的重要性 生长条件。然后，我们将定义每个SRNA控制的调节网络。最后，我们将使用 计算和生化方法的组合，以识别和验证每个SRNA的靶标。 我们预计，通过这些研究，我们将提供对SRNA功能的前所未有的见解 通常，细菌和MTB中更具体地。