Studies of protein synthesis in the Bacteroidetes

拟杆菌门蛋白质合成的研究

• 批准号: 2029502
• 负责人: Kurt Fredrick
• 金额: $ 85万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029502&HistoricalAwards=false
• 关键词: Studies; protein; synthesis; Bacteroidetes

The Bacteroidetes represent an important group of bacteria, well represented in intestinal tracts of mammals, including humans. Gene expression in the Bacteroidetes differs substantially from that of well-studied bacteria, such as Escherichia coli. This project will reveal the distinct manner in which proteins are made in the Bacteroidetes. The knowledge gained may spur advances in biotechnology and medicine. This project will also provide (i) research training for undergraduate, graduate, and postdoctoral students, (ii) summer research opportunities for local high school students (Columbus Public Schools), and (iii) mentorship training for junior faculty at Ohio State University.In all cells, ribosomes translate the genetic code, synthesizing proteins based on the information content of mRNA. The rate of translation varies dramatically, depending on the translation initiation region (TIR) of mRNA. How intrinsic features of the TIR govern the rate of translation initiation remains an important open question. In bacteria such as E. coli, one well-known feature of the TIR is the Shine-Dalgarno (SD) sequence, a purine-rich element that lies just upstream from the start codon. The SD pairs with the anti-SD (ASD), a pyrimidine-rich element at the 3’ end of the 16S rRNA, to promote initiation. Recent studies have shown that certain taxonomic groups of bacteria, such as the Bacteroidetes, lack SD sequences in their mRNA. Yet, their ribosomes retain the conserved ASD. The project aims to elucidate the unique aspects of protein synthesis in the Bacteroidetes, using Flavobacterium johnsoniae as a model organism. Specifically, the work will address (i) which components of the ribosome govern ASD-mRNA pairing, (ii) how initiation complex formation occurs in F. johnsoniae, (iii) whether the ASD plays a role in ribosome assembly, and (iv) how autoregulation of release factor RF2 occurs in F. johnsoniae. The results will provide fundamental insight on mechanisms of translation initiation, programmed frameshifting, and ribosome assembly in diverse bacteria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

拟杆菌属代表了一组重要的细菌，在哺乳动物包括人类的肠道中有很好的代表性。拟杆菌中的基因表达与研究充分的细菌如大肠杆菌的基因表达有很大不同。该项目将揭示拟杆菌中蛋白质的独特方式。所获得的知识可能会刺激生物技术和医学的进步。该项目还将提供（i）对本科生、研究生和博士后的研究培训，（ii）为当地高中生（哥伦布公立学校）提供夏季研究机会，（iii）为俄亥俄州州立大学的初级教师提供导师培训。在所有细胞中，核糖体翻译遗传密码，根据mRNA的信息内容合成蛋白质。翻译的速率根据mRNA的翻译起始区（TIR）而显著变化。TIR的内在特征如何支配翻译起始的速率仍然是一个重要的悬而未决的问题。在细菌如E.在大肠杆菌中，TIR的一个众所周知的特征是Shine-Dalgarno（SD）序列，这是位于起始密码子上游的富含嘌呤的元件。SD与anti-SD（ASD）配对，anti-SD是16 S rRNA 3'端的富含嘧啶的元件，以促进起始。最近的研究表明，某些分类群的细菌，如拟杆菌，缺乏SD序列在其mRNA。然而，它们的核糖体保留了保守的ASD。该项目旨在阐明拟杆菌中蛋白质合成的独特方面，使用约氏黄杆菌作为模式生物。具体来说，这项工作将解决（i）哪些组成部分的核糖体管理ASD-mRNA配对，（ii）如何启动复合物的形成发生在F。johnsoniae中，（iii）ASD是否在核糖体组装中起作用，以及（iv）释放因子RF 2的自动调节如何在F.约翰逊氏菌。研究结果将为不同细菌中的翻译起始、程序化移码和核糖体组装机制提供基本的见解。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。