The role of mRNA secondary structures in programmed termination codon readthrough

虽然细胞的蛋白质是由DNA（遗传物质）编码的，但它们是由称为核糖体的细胞器通过中间分子信使RNA（mRNA）合成的，信使RNA（mRNA）是从DNA转录的。mRNA的适当末端被送入核糖体，核糖体沿着移动，直到mRNA中的三联体起始信号被识别。在这一点上，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生长的氨基酸链。核糖体继续沿着mRNA，直到它识别三联体终止信号，此时翻译正常终止，完整的氨基酸聚合物，即蛋白质被释放。然而，在某些情况下，终止信号没有被正确识别（它被称为“泄漏”），相反，添加氨基酸并继续蛋白质合成。这被称为终止密码子通读，是我们研究的主题。终止密码子通读被细胞和病毒用于以一定的频率制造具有改变的性质的蛋白质的延长版本。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。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通读信号的结构，并寻找共同的特征，为我们提供关于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了解提供帮助。

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.