Investigation of the selective reprogramming of translation during apoptosis

细胞凋亡过程中翻译选择性重编程的研究

• 批准号: BB/F000065/2
• 负责人: Anne Willis
• 金额: $ 9.5万
• 依托单位: MRC Toxicology Unit
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF000065%2F2
• 关键词: Investigation; selective; reprogramming; translation; during

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.

蛋白质合成是指细胞内遗传物质DNA中的信息通过中间底物mRNA转化为蛋白质的过程。为了合成蛋白质，mRNA必须与一种叫做核糖体的大复合物相互作用，核糖体由rna和蛋白质组成。核糖体能够解码mRNA中的遗传信息，并进行蛋白质的合成。mrna可以通过两种不同的机制与核糖体相互作用。最常见的机制需要将蛋白质复合物结合到mRNA的5'端，然后该复合物招募核糖体。然而，某些mrna含有不编码蛋白质片段的5'区（称为非翻译区；utr），这些RNA序列包含形成复杂RNA结构所需的信息。这些RNA结构允许核糖体在距离5'端相当远的地方被招募到mRNA上，因此这种招募核糖体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，在细胞死亡期间，有选择性地使用内部核糖体进入，以允许合成这一过程所需的蛋白质。本研究的总体目标是了解这种机制在细胞凋亡过程中的作用。

项目成果

Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.

• DOI: 10.1038/cdd.2013.135
• 发表时间: 2014-01
• 期刊: Cell death and differentiation
• 影响因子: 12.4