The role of mRNA secondary structures in programmed termination codon readthrough

虽然细胞的蛋白质是在DNA(遗传物质)中编码的，但它们是由一个名为核糖体的细胞器通过从DNA转录而来的中间分子信使RNA(MRNA)合成的。MRNA的适当末端被送入核糖体，核糖体沿着核糖体移动，直到识别出mRNA中的三联体开始信号。在这一点上，氨基酸的生物合成开始，随着每个随后的三联体核苷酸‘密码’被破译，一个氨基酸被添加到一个不断增长的氨基酸链中。核糖体继续沿着信使核糖核酸，直到它识别一个三联体停止信号，在这一点上，翻译通常终止，完成的氨基酸聚合物，蛋白质，被释放。然而，在某些情况下，停止信号没有被正确识别(有人说它是“泄漏的”)，而是添加了一个氨基酸，蛋白质合成继续进行。这被称为终止密码子通读，是我们调查的主题。终止密码子通读是细胞和病毒用来以一定的频率制造蛋白质的加长版本，该版本改变了蛋白质的性质。我们感兴趣的是确定“泄漏的”终止密码子附近的mRNA的结构如何导致核糖体无法有效地识别终止。目前，我们对促进通读的RNA结构知之甚少。在这个项目中，我们将研究三种不同的直读信号的结构，并寻找共同的特征来为我们提供核糖体如何被误导的线索。对这一过程的深入了解将为我们深入了解基因表达的生物学和我们对核糖体功能的知识提供帮助。

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.