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Mechanisms of Nascent Polypeptide-Mediated Translational Regulation

新生多肽介导的翻译调控机制

基本信息

批准号：
8586895
负责人：
Mee-Ngan F Yap
金额：
$ 24.19万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-05 至 2015-11-30
项目状态：
已结题

项目摘要

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本上的运动在mRNA质量控制和翻译法规。令人惊讶的是，一些受调控的新生多肽在以下情况下会停止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一条路径，离开大的核糖体亚基。尽管隧道具有普遍性和结构保育性，但其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并区分非监管机构来自调节性多肽的多肽。在K99阶段，我使用E.coliSECM作为模型来研究如何逮捕序列模体在隧道内被识别，以及如何释放逮捕的时机已实现。在Roo阶段，我们的目标是通过以下方式推进我们对翻译声学衰减的理解通过表征Small的调节作用来研究核糖体隧道的生物学活性通过识别较大蛋白质中促进核糖体停顿/停顿的多肽序列。具体地说，我们将使用一种综合方法，将比较蛋白质组学、细菌遗传学、生物化学方法和全基因组核糖体图谱以阐明这些的基本原理流程。这项工作不仅将提供有关隧道分子响应的新信息完全不同的新生链条，但也将提供对翻译控制系统多样性的更广泛的看法以及在所有生物系统中都保存的翻译机器。