Function of the exoribonuclease pacman in cell movement and cell shape change

伤口愈合需要周围的皮肤细胞伸展，聚集在一起并密封以覆盖皮肤细胞层中的孔。这种伤口愈合的过程类似于所有胚胎发育中的其他细胞片运动。我们已经表明，参与破坏信使RNA的酶是必要的细胞片密封过程中的果蝇。这种酶被命名为Pacman，从一端到另一端咀嚼这些信使RNA。信使RNA是指导细胞制造特定蛋白质的分子。我们已经发现，吃豆人很可能是一个大的蛋白质复合体的一部分，一个“死亡星星”，可以有效地摧毁或监禁信使RNA。我们怀疑Pacman必须破坏可能阻止细胞片层密封过程的RNA。该项目的目的是找出如何帕克曼可以控制这个孔关闭过程。控制机制可能涉及靶向特定的mRNA，以被“死亡星星”复合体破坏，我们将测试是否是这种情况。虽然该项目将使用果蝇果蝇进行，但它也与人类伤口愈合等上皮层密封过程有关，因为两种生物体的细胞过程惊人地相似。此外，苍蝇和人类之间的Pacman酶非常相似，因此我们在这个项目中获得的见解可能有助于我们改善伤口的治疗，也有助于我们了解胚胎中的细胞运动过程。本提案中描述的工作也针对RNA水平基因调控的一般问题。最近人们认识到，通过使用RNA本身作为一种工具来抑制特定基因，可以在信使RNA水平上控制基因。在称为RNA干扰的过程中，可以下调细胞中任何特定的RNA。由于Pacman及其同源物已被证明参与RNA干扰，该项目也将为改善这一过程以达到治疗目的提供创新见解。

Wound healing requires the surrounding skin cells to stretch, draw together and seal to cover the hole in the layer of skin cells. This process of wound healing is similar to other cell sheet movements in the development of all embryos. We have shown that an enzyme involved in the destruction of messenger RNAs is necessary for the cell sheet sealing process in the fruit fly Drosophila melanogaster. This enzyme, which is named Pacman, chews up these messenger RNAs from one end to the other. Messenger RNAs are the molecules which instruct the cell to make particular proteins. We have found out that Pacman is likely to be part of a large complex of proteins, a 'Death Star' which can efficiently destroy or imprison messenger RNAs. We suspect that Pacman must destroy RNAs that would potentially stop the cell sheet sealing process. The aim of this project is to find out how Pacman can control this hole closure process. The control mechanism probably involves targeting particular mRNAs for destruction by the 'Death Star' complex and we will test whether this is the case. Although this project will be carried out using the fruit fly Drosophila, it also has relevance for epithelial sheet sealing processes such as wound healing in humans as the cellular processes are surprisingly similar in both organisms. In addition, the Pacman enzyme is extremely similar between flies and humans therefore the insights we gain during this project may help us to improve the treatment for wounds and also help us to understand the cell movement process in embryos. The work described in this proposal is also directed towards the general question of gene regulation at the RNA level. It has recently become recognised that genes can be controlled at the level of the messenger RNA by using RNA itself as a tool to turn down specific genes. In a process termed RNA interference, it is possible to downregulate any particular RNA in the cell. Since Pacman and its homologues have been shown to be involved in RNA interference, this project will also may also provide innovative insights into the improval of this process for therapeutic purposes.