The regulation of protein synthesis by oxygen

氧对蛋白质合成的调节

• 批准号: RGPIN-2015-04807
• 负责人: Uniacke, Jim
• 金额: $ 2.84万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590030
• 关键词: regulation; protein; synthesis; oxygen

Living organisms are characterized by their ability to respond to stimuli and adapt. My research program focuses on these characteristics with regard to the protein synthesis machinery. Also known as translation, protein synthesis is a fundamental biological process in the flow of genetic information from messenger ribonucleic acid (mRNA) into protein. Stressful environmental changes lead to a refocusing of translation efforts away from the maintenance of basic cell functions and toward the production of stress response proteins. This occurs by repressing the primary translation initiation machinery, which accesses mRNAs through their cap structure located at the 5’ end and accounts for >95% of translation (cap-dependent translation). My research program addresses a major question in cell biology: how do cells translate their mRNAs into proteins during periods of stress when cap-dependent translation is repressed? My focus is on hypoxia (low oxygen) in human cells because the acquisition of adequate oxygen is crucial to produce enough ATP for their proper functioning, especially in cells that constitute multicellular animals. It was believed that hypoxic cells switch from canonical cap-dependent translation (mediated by the cap-binding protein eIF4E) to cap-independent processes to translate select mRNAs during stress. I recently demonstrated

活生物体的特征是它们对刺激和适应的反应能力。我的研究计划着重于蛋白质合成机制的这些特征。蛋白质合成也称为翻译，是从信使色碳酸（mRNA）流向蛋白质的遗传信息流中的基本生物学过程。压力的环境变化导致翻译工作的重新集中，从基本细胞功能的维持和压力反应蛋白的产生。这是通过反映主要的翻译计划机制来发生的，该机械通过其位于5'端的帽结构访问mRNA，占翻译的> 95％（依赖CAP依赖性翻译）。我的研究计划解决了细胞生物学中的一个主要问题：在重现帽依赖性翻译时，细胞如何将其mRNA转化为蛋白质？我的重点是人类细胞中缺氧（低氧），因为获得足够的氧气对于产生足够的ATP至关重要，以使其适当的功能，尤其是在构成多细胞动物的细胞中。人们认为，缺氧细胞从规范帽依赖性翻译（由帽结合蛋白EIF4E介导）转换为盖无依赖性过程，以在应力期间翻译精选的mRNA。我最近演示了