The role of poly ADP ribosylation in mRNA export

为了让有机体的细胞存活，它们需要合成蛋白质。在细胞内，一种名为信使RNA(信使RNA)的特殊模板充当了制造蛋白质的蓝图。信使核糖核酸是在细胞内一种称为核的特殊结构中产生的，它被一层被称为核孔的膜包裹着。信使核糖核酸从细胞核通过核孔运输到围绕着细胞核的细胞质。在细胞质中，转移RNA(TRNA)对mRNA进行解码以合成蛋白质，这一过程是细胞生存所必需的。一种名为TREX的蛋白质复合体决定了mRNA何时被完全加工并准备离开细胞核，然后帮助将其运输到细胞质。我们发现，当DNA受损时，TREX内的蛋白质会以一种特殊的方式修改，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这种情况会发生在TREX身上，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损伤后存活所需的mRNAs是如何从细胞核运输到细胞质的。这些研究很重要，因为我们细胞中的DNA不断受到破坏，如果我们想要健康长寿，就必须修复它们。由于TREX复合体从酵母到人类都是保守的，我们的研究可能会在许多影响社会的领域产生广泛影响，包括食品生产、生物制药生产和了解是什么保持人类健康。

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.