Mechanisms of Nascent Polypeptide-Mediated Translational Regulation

新生多肽介导的翻译调控机制

• 批准号: 8318356
• 负责人: Mee-Ngan F Yap
• 金额: $ 24.89万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-05 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318356
• 关键词: Biochemical; Biochemical Reaction; Biological; Co-Immunoprecipitations; Escherichia coli; Eukaryota; Gene Expression; Goals; Hereditary Disease; Human Genetics; Instruction; Lead; Left; Life; Mediating; Messenger RNA; Methods; Modeling; Molecular; Movement; Mutagenesis; Mutation; Open Reading Frames; Organism; Peptides; Phase; Play; Process; Prokaryotic Cells; Protein Biosynthesis; Proteins; Proteome; Proteomics; Quality Control; Ribosomal Proteins; Ribosomes; Role; Signal Transduction; Staging; Stress; System; Techniques; Time; Transcript; Translational Regulation; Translations; Work; attenuation; bacterial genetics; comparative; crosslink; genome-wide; human disease; insight; interest; novel; polypeptide; protein aminoacid sequence; response

Ribosome movement on its template transcript plays an important role in mRNA quality control and translational regulation. Surprisingly, some regulatory nascent polypeptides stall their own translation when they are still inside the ribosome tunnel, a path that every newly synthesized protein traverses to leave the large ribosomal subunit. Despite the universality and structural conservation of the tunnel, its function is still rather mysterious. It is unclear how the tunnel deciphers the arrest signals and discriminates non-regulatory peptides from regulatory peptides. During the K99 phase I used E. coli SecM as a model to investigate how the arrest sequence motif is recognized inside the tunnel and how the timing of the release of arrest is achieved. In the ROO phase, we aim to advance our understanding of translatlonal attenuation by investigating the biological activities of the ribosome tunnel by characterizing the regulatory role of small peptides and by identifying peptide sequences within larger proteins that promote ribosome stalling/pausing. Specifically we will use an Integrative approach that combines comparative proteomics, bacterial genetics, biochemical methods and genome-wide ribosome profiling to elucidate the fundamental principles of these processes. This work will not only provide new information on the molecular responses of the tunnel to disparate nascent chains, but will also offer a broader view of the diversity of translational control systems and the translation machinery that is conserved in all living systems.

核糖体在其模板转录物上的运动在mRNA质量控制中起着重要作用， 翻译调节令人惊讶的是，一些调节性新生多肽在以下情况下会停止它们自己的翻译： 它们仍然在核糖体隧道内，这是每一个新合成的蛋白质穿过的路径， 核糖体大亚基尽管隧道的普遍性和结构保护，它的功能仍然是 相当神秘目前尚不清楚隧道如何破译逮捕信号和歧视非监管 从调节肽的肽。在K99阶段，我使用了E.大肠杆菌SecM作为模型来研究如何 在隧道内识别阻滞序列基序以及阻滞释放的时机如何 办妥了一批在ROO阶段，我们的目标是通过以下方式来提高我们对translatlonal衰减的理解： 研究核糖体隧道的生物活性，通过表征小分子的调节作用， 肽，并通过识别促进核糖体停滞/暂停的较大蛋白质内的肽序列。 具体来说，我们将使用综合方法，结合比较蛋白质组学，细菌遗传学， 生物化学方法和全基因组核糖体分析，以阐明这些基本原则， 流程.这项工作不仅将为隧道的分子响应提供新的信息， 不同的新生链，但也将提供一个更广泛的看法，翻译控制系统的多样性 以及在所有生命系统中保存的翻译机制。