Structural studies on macromolecular complexes in translational control and ribosome biogenesis

翻译控制和核糖体生物合成中大分子复合物的结构研究

• 批准号: G1000520/1
• 负责人: Atlanta Cook
• 金额: $ 155.68万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000520%2F1
• 关键词: Structural; studies; macromolecular; complexes; translational

The ribosome is a large molecular machine central to the survival of all living cells. Genetic information is brought to the ribosome in the form of messenger RNA (mRNA) which is a mobile, molecular copy of a given gene sequence. The ribosome reads the information stored in the mRNA and translates it by synthesising a protein with a specific structure and function. By understanding the structure of a particular protein, we can often gain insights into its function (and malfunction in disease states) in the cell. Producing ribosomes requires a large proportion of a growing cell‘s resources and several genetic diseases are associated with inefficient ribosome production. Ribosome synthesis goes through a number of ordered steps, involving many proteins that ensure synthesis proceeds correctly. My research will examine two related aspects of protein production, firstly how a particular protein recognises certain mRNAs and prevents them from being translated. Interestingly, this protein is also hijacked by hepatitis C virus, which disguises its genes by mimicking cellular mRNA. The virus might use the normal function of this protein to aid its reproduction. Secondly, I will look at proteins involved in producing ribosomes and how they control the final stages of ribosome maturation.

核糖体是一个大的分子机器，对所有活细胞的生存至关重要。遗传信息以信使RNA（mRNA）的形式被带到核糖体，信使RNA是给定基因序列的移动的分子拷贝。核糖体读取存储在mRNA中的信息，并通过合成具有特定结构和功能的蛋白质来翻译它。通过了解特定蛋白质的结构，我们通常可以深入了解其在细胞中的功能（以及疾病状态下的功能障碍）。产生核糖体需要大部分生长细胞的资源，并且几种遗传疾病与低效的核糖体产生有关。核糖体的合成经历了许多有序的步骤，涉及许多蛋白质，以确保合成正确进行。我的研究将研究蛋白质生产的两个相关方面，首先是特定蛋白质如何识别某些mRNA并阻止它们被翻译。有趣的是，这种蛋白质也被丙型肝炎病毒劫持，丙型肝炎病毒通过模仿细胞mRNA来掩盖其基因。病毒可能利用这种蛋白质的正常功能来帮助其繁殖。其次，我将研究参与产生核糖体的蛋白质，以及它们如何控制核糖体成熟的最后阶段。