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.

虽然细胞的蛋白质是在 DNA（遗传物质）中编码的，但它们是由称为核糖体的细胞器通过从 DNA 转录的中间分子信使 RNA (mRNA) 合成的。 mRNA 的适当末端被送入核糖体，核糖体会一直移动，直到识别出 mRNA 中的三联体起始信号。此时，氨基酸生物合成开始，并且随着每个后续三联体核苷酸“代码”被解码，一个氨基酸被添加到不断增长的氨基酸链中。核糖体继续沿着 mRNA 前进，直到识别出三联体停止信号，此时翻译通常终止，并释放完整的氨基酸聚合物（蛋白质）。然而，在某些情况下，停止信号未被正确识别（据说是“泄漏”），而是添加氨基酸并继续蛋白质合成。这称为终止密码子通读，是我们调查的主题。细胞和病毒使用终止密码子通读以一定的频率制造蛋白质的延长版本，该蛋白质已改变了特性。我们感兴趣的是确定“泄漏”终止密码子附近的 mRNA 结构如何导致核糖体无法有效识别终止密码子。目前，我们对促进通读的 RNA 结构知之甚少。在这个项目中，我们将检查三个不同通读信号的结构，并寻找共同特征，为我们提供有关核糖体如何被误导的线索。对这一过程的更深入的了解将有助于深入了解基因表达的生物学和我们对核糖体功能的了解。