The role of mRNA secondary structures in programmed termination codon readthrough

mRNA二级结构在程序性终止密码子通读中的作用

基本信息

批准号：
BB/G020272/1
负责人：
Ian Brierley
金额：
$ 42.69万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG020272%2F1
关键词：
role mRNA secondary structures programmed

项目摘要

Whilst a cell's proteins are encoded in DNA (the genetic material), they are synthesised by an organelle called the ribosome through an intermediate molecule, messenger RNA (mRNA), that is transcribed from DNA. The appropriate end of the mRNA is fed into the ribosome which moves along until a triplet start signal in the mRNA is recognised. At this point, amino acid biosynthesis starts and as each subsequent triplet nucleotide 'code' is decoded, one amino acid is added to a growing amino acid chain. The ribosome continues along the mRNA until it recognises a triplet stop signal, at which point translation normally terminates and the completed amino acid polymer, the protein, is released. However in some instances, the stop signal is not recognised correctly (it is said to be 'leaky'), and instead, an amino acid is added and protein synthesis continues. This is called stop codon readthrough and is the subject of our investigation. Stop codon readthrough is used by cells and viruses to make, at a certain frequency, an elongated version of a protein, which has altered properties. We are interested in determining how the structure of the mRNA in the vicinity of the 'leaky' stop codon can cause the ribosome to fail to recognise the stop efficiently. At present, we know little about the RNA structures that promote readthrough. In this project, we will examine the structures from three different readthrough signals and look for common features to give us clues as to how the ribosome is being mislead. A deeper knowledge of this process will provide insights into the biology of gene expression and our knowledge of ribosome function.

虽然A细胞的蛋白质是用DNA（遗传物质）编码的，但它们是由一种称为核糖体的细胞器通过中间分子Messenger RNA（mRNA）合成的，该细胞体从DNA转录。 mRNA的适当末端被送入核糖体中，该核糖体沿着核糖体移动，直到识别mRNA中的三胞胎启动信号为止。在这一点上，氨基酸的生物合成开始，随后将每个随后的三重核苷酸“代码”解码，将一个氨基酸添加到生长的氨基酸链中。核糖体一直沿mRNA持续，直到它识别出三胞胎停止信号为止，此时翻译通常终止，并且释放完整的氨基酸聚合物（蛋白质）。但是，在某些情况下，停止信号未正确识别（据说是“漏水”），而是添加氨基酸并继续蛋白质合成。这称为终止密码子读取，是我们调查的主题。细胞和病毒使用停止密码子读取，以一定的频率使蛋白质的细长版本变化，从而改变了特性。我们有兴趣确定“泄漏”终止密码子附近mRNA的结构如何导致核糖体有效地识别停止。目前，我们对促进读取的RNA结构一无所知。在这个项目中，我们将检查来自三个不同的读取信号的结构，并寻找共同的功能，以使我们有关核糖体如何误导的线索。对这一过程的更深入了解将为基因表达的生物学和我们对核糖体功能的了解提供见解。