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The role of poly ADP ribosylation in mRNA export

聚 ADP 核糖基化在 mRNA 输出中的作用

基本信息

批准号：
BB/N005430/1
负责人：
Stuart Wilson
金额：
$ 50.38万
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN005430%2F1
关键词：
role poly ADP ribosylation mRNA

项目摘要

In order for the cells of an organism to live they need to synthesise proteins. Within cells a special template called messenger RNA (mRNA) acts as a blueprint for making proteins. mRNA is produced in a special structure inside the cell called the nucleus, which is encapsulated by a membrane with holes in it called nuclear pores. The mRNA is transported from the nucleus, through the nuclear pores to the cytoplasm of a cell which surrounds the nucleus. In the cytoplasm mRNA is decoded by transfer RNA (tRNA) to make proteins and this process is essential for cell survival. A complex of proteins called TREX determines when a mRNA is fully processed and ready to leave the nucleus and then helps transport it to the cytoplasm. We have found that when DNA is damaged, the proteins within TREX are modified in a special way and this appears to enhance the way that TREX can assemble in the cell. We do not yet know why this happens to TREX but we suspect that it may allow the cell to make special proteins required to repair damaged DNA. In this project we will dissect how DNA damage modifies the activity of TREX and how the mRNAs required to survive DNA damage are transported from the nucleus to the cytoplasm in the cell. These studies are important because the DNA in our cells is constantly being damaged and must be repaired if we are going to live a long healthy life. Since the TREX complex is conserved from yeast through to man, our studies are likely to have a broad impact in many areas which affect society including food production, production of biopharmaceuticals and understanding what keeps humans healthy.

为了使生物体的细胞存活，它们需要合成蛋白质。在细胞内，一种叫做信使RNA （mRNA）的特殊模板充当了制造蛋白质的蓝图。mRNA是在细胞核内的一个特殊结构中产生的，细胞核被一层膜包裹着，膜上有孔，称为核孔。mRNA通过核孔从细胞核运输到细胞核周围的细胞质。在细胞质中，mRNA被转运RNA （tRNA）解码生成蛋白质，这一过程对细胞存活至关重要。一种叫做TREX的蛋白质复合体决定mRNA何时被完全加工并准备离开细胞核，然后帮助将其运送到细胞质。我们发现，当DNA受损时，TREX中的蛋白质会以一种特殊的方式进行修饰，这似乎增强了TREX在细胞中组装的方式。我们还不知道为什么TREX会发生这种情况，但我们怀疑它可能允许细胞制造修复受损DNA所需的特殊蛋白质。在这个项目中，我们将剖析DNA损伤如何改变TREX的活性，以及DNA损伤所需的mrna如何从细胞核转运到细胞内的细胞质。这些研究很重要，因为我们细胞中的DNA不断被破坏，如果我们想要健康长寿，就必须修复。由于TREX复合物从酵母一直保存到人类，我们的研究可能会在影响社会的许多领域产生广泛的影响，包括食品生产、生物制药生产和了解保持人类健康的原因。