MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 6796256
• 负责人: MARK DEL CAMPO
• 金额: $ 1.14万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6796256
• 关键词: Escherichia coli; bacterial genetics; cell component structure /function; chemical structure function; gene deletion mutation; genetic translation; mutant; predoctoral investigator; ribosomal RNA; ribosomes; uracil nucleoside

DESCRIPTION (provided by applicant): Pseudouridine, the 5-ribosyl isomer of uridine, is the most common post-transcriptional modification known in RNA molecules. The ribosome of the model eubacterum Escherichia coli has eleven pseudouridines; 10 in the 23S RNA and 1 in the 16S RNA. These pseudouridines are formed by 7 site-specific pseudouridine synthases with no overlapping specificity. The effect of deleting any one synthase gene is loss of the pseudouridine(s) that it forms. Thus far, no pseudouridine specific growth defect has been detected. We plan to make a strain carrying 4 synthase gene deletions and lacking 6 pseudouridines to investigate the structural and/or functional differences of these pseudouridine deficient ribosomes from normal ribosomes. These differences may provide insight into the function of pseudouridine in the ribosome. In addition, we plan to map the positions of pseudouridien in the ribosome of deinococcus radiodurans because the cyrstal structure of its 50S ribosomal subunit is available and we can model the positions of pseudouridines in 3D space for possible insights into function based on structure. In ribosomes, pseudouridines tend to cluster around the peptidyl transferase center which may implicate a structural and/or functional role in translation - which is crucial to the well-being of all organisms. If pseudouridines do participate in translation, then we may have a new antibiotic target because the mechanism of ribosomal pseudouridine formation in humans differs from that of bacteria.

描述（由申请人提供）： 假尿苷，尿苷的 5-核糖基异构体，是 RNA 分子中已知的最常见的转录后修饰。 模型真细菌大肠杆菌的核糖体有 11 个假尿苷； 23S RNA 中有 10 个，16S RNA 中有 1 个。 这些假尿苷由 7 个位点特异性假尿苷合酶形成，没有重叠的特异性。 删除任何一种合酶基因都会导致其形成的假尿苷的丢失。 迄今为止，尚未检测到假尿苷特异性生长缺陷。 我们计划制作一个携带 4 个合酶基因缺失并缺乏 6 个假尿苷的菌株，以研究这些假尿苷缺陷核糖体与正常核糖体的结构和/或功能差异。 这些差异可能有助于深入了解核糖体中假尿苷的功能。 此外，我们计划绘制耐辐射球菌核糖体中伪尿苷的位置，因为其 50S 核糖体亚基的晶体结构是可用的，并且我们可以对 3D 空间中的伪尿苷位置进行建模，以便可能了解基于结构的功能。 在核糖体中，假尿苷倾向于聚集在肽基转移酶中心周围，这可能暗示翻译中的结构和/或功能作用——这对所有生物体的健康至关重要。 如果假尿苷确实参与翻译，那么我们可能会有一个新的抗生素靶点，因为人类核糖体假尿苷形成的机制与细菌不同。