Mechanisms of Nascent Polypeptide-Mediated Translational Regulation

新生多肽介导的翻译调控机制

• 批准号: 8393462
• 负责人: Mee-Ngan F Yap
• 金额: $ 23.41万
• 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/8393462
• 关键词: Biochemical; Biochemical Reaction; Biological; Co-Immunoprecipitations; Escherichia coli; Eukaryota; Gene Expression; Goals; Hereditary Disease; Human Genetics; 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.

核糖体在模板转录物上的运动在mRNA质量控制中起着重要作用