The re-modelling of mRNPs and the regulation of localised mRNA translation during mammalian cell attachment and spreading

在细胞迁移过程中，储存在遗传物质(DNA)中的关键信息必须由细胞解码，以在正确的数量、地点和时间产生各种蛋白质，从而使这一过程发生；肿瘤细胞经常搞错这一点！信息从DNA到蛋白质的一般传递是由信使RNA(信使RNA)执行的，信使RNA是DNA序列的副本。这种信使核糖核酸必须被称为核糖体的复杂的、高度调控的机器解码成蛋白质，这个过程被称为翻译。为了高效、准确地工作，并使核糖体以细胞的最佳利益发挥作用，这一机制需要相互作用的辅助蛋白(翻译启动因子；EIF)，并确保mRNA和核糖体聚集在一起形成高度调控的大型启动复合体，以产生所需的蛋白质。那么细胞是如何控制这一过程的呢？启动因子本身的相互作用是哺乳动物细胞中调节的主要部位。调控蛋白，如4E-BP1和CYFIP，阻止eIF4E与支架蛋白eIF4G的相互作用，阻止mRNA募集到核糖体，停止蛋白质合成。当需要蛋白质合成时，细胞发出信号，从被抑制的复合体中释放eIF4E/mRNA，使其在需要的时间和地点工作。然而，我们仍然不知道细胞是如何确切地控制处于扩散和迁移过程中的细胞中蛋白质合成被激活的位置。通过使用特殊的显微镜技术“观察”细胞内部，我们知道启动因子和它们的调节蛋白分散地定位在细胞的边缘，沿着它们移动的方向；它们不仅仅是漂浮着。在这里描述的工作中，我们想要研究细胞用来调节局部蛋白质合成的特殊信号的性质，观察在这些部位发现的蛋白质和信使核糖核酸的复合体，并了解信使它的哪些部分对这些位于细胞边缘的信使核糖核酸结合蛋白具有吸引力。这些研究将大大增加我们对控制蛋白质合成在调节细胞生长和迁移中的重要性的总体理解，为控制已经获得在体内移动能力的癌细胞开辟新的潜在途径。

During cell migration, critical information stored in the genetic material (DNA) has to be decoded by the cell to produce a wide variety of proteins in the right amount, place and time to allow for this process occur; tumour cells often get this wrong! The general transfer of information from DNA to protein is carried out by the messenger RNA (mRNA), which is a copy of the DNA sequence. This mRNA has to be decoded into protein by a complex, highly regulated machine termed a ribosome, in a process known as translation. To work efficiently, accurately, and to allow the ribosome to function in the best interests of the cell, this machinery requires helper proteins (translation initiation factors; eIF) that interact with each other, and also make sure that the mRNA and the ribosome come together into a highly regulated, large initiation complex to make the proteins required. So how does the cell control this? The interaction of the initiation factors themselves is a major site for regulation in mammalian cells. Regulatory proteins, such as 4E-BP1 and CYFIP, prevent the interaction of eIF4E with the scaffold protein, eIF4G, and stop the recruitment of mRNA to the ribosome and halt protein synthesis. When protein synthesis is needed, the cell signals for the release the eIF4E/mRNA from the inhibited complex to let it work when and where it is needed. However, we still do not know how the cell controls exactly where protein synthesis is activated in cells which are in the process of spreading and migrating. From "looking" inside the cell with specialised microscopy techniques, we know that the initiation factors and their regulatory proteins are discretely localised to the edge of cells in the direction that they are moving; they are not just floating about. In the work described here we want to investigate the nature of the specialised signals used by the cell to regulate localised protein synthesis, look at the complexes of proteins and mRNA found at such sites and understand what parts of the mRNA make it attractive to these mRNA binding proteins at the edge of cells.These studies will substantially increase our general understanding of the significance of the control of protein synthesis in the regulation of cell growth and migration, opening up new potential avenues for controlling cancer cells which have acquired the ability to move about the body.