Investigation of the selective reprogramming of translation during apoptosis

蛋白质合成是细胞中遗传物质中的信息，DNA通过中间底物mRNA转化为蛋白质的过程。为了合成蛋白质，mRNA必须与一个由RNA和蛋白质组成的称为核糖体的大复合体相互作用。核糖体能够解码mRNA中保存的遗传信息并进行蛋白质的合成。mRNA与核糖体相互作用有两种不同的机制。最常见的机制需要蛋白质复合物与mRNA的5'端结合，然后该复合物募集核糖体。然而，某些mRNA含有不编码蛋白质部分的5'区域（称为非翻译区; UTR），并且这些RNA序列含有形成复杂RNA结构所需的信息。这些RNA结构允许核糖体被募集到mRNA中，通常距离5'端相当远，因此这种核糖体募集的方法被称为内部核糖体进入。有趣的是，使用内部核糖体进入的信息通常编码参与细胞生长和细胞死亡过程的蛋白质。我们已经证明，在细胞死亡过程中，有选择性地使用内部核糖体进入，以允许合成该过程所需的蛋白质。这项建议的总体目标是了解这种机制如何在细胞凋亡过程中发挥作用。

Protein synthesis is the process by which the information in the genetic material in the cell, DNA is converted via an intermediary substrate mRNA, into proteins. For proteins to be synthesised the mRNA must interact with a large complex called the ribosome which consists of RNAs and proteins. Ribosomes are able to decode the genetic information that is held in the mRNA and carry out the synthesis of the proteins. There are two distinct mechanisms by which mRNAs can interact with the ribosomes. The most common mechanism requires the binding of a protein complex to the 5' end of the mRNA and this complex then recruits the ribosome. However, certain mRNAs contain 5' regions that do not code for sections of proteins (termed untranslated regions; UTRs) and these sequences of RNA harbour the information that is required to form a complex RNA structure. These RNA structures allow the ribosome to be recruited to the mRNA generally a considerable distance from the 5' end and so this method of ribosome recruitment has been termed internal ribosome entry. Interestingly, messages that use internal ribosome entry generally encode proteins that are involved in the processes of cell growth and cell death. We have shown that during cell death there is selective use of internal ribosome entry to allow synthesis of the proteins that are required for this process to proceed. The overall aim of this proposal is to understand how this mechanism functions during apoptosis.