The role of poly(A) metabolism in growth factor induced gene expression

相对少量的基因可以对细胞内和细胞周围的变化迅速作出反应，并调节其他基因以协调适当的细胞反应。这些主控基因对医学非常重要，因为它们的失调通常与癌症、哮喘和中风等疾病有关。此外，生产用于医疗和工业应用的蛋白质也需要基因活性的类似快速变化。由于主控基因也需要能够快速关闭，因此它们的产物必须快速降解。然而，这产生了一个问题，因为如果它迅速降解，就很难积累足够的产品（如果有人吃你的煎饼，因为你烤它们的速度很快，你自己永远不会得到任何东西）。我们最近已经证明，对基因产物的修饰可以在降解发生之前延迟，从而可以积累产物并快速去除它（如果你同意只有在每个人（包括你）都在餐桌上之后才开始吃煎饼，那么一堆煎饼可以积累，然后更快地被去除）。在这个项目中，我们将在用生长因子刺激细胞生长的过程中测量这种延迟，并确定它是否确实起着如此大的作用。我们将研究哪些基因使用延迟衰变，以及是什么导致基因之间延迟的差异。有趣的是，我们发现一种来自传统药用蘑菇虫草的化合物，虫草素，降低了许多炎症和细胞生长的主控制基因的活性。它抑制了导致其产物延迟腐烂的过程，这可能解释了药物如何起作用。因此，我们想知道虫草素是否真的以这种方式工作，以及它是否是一类新型癌症药物的良好候选者（通过抑制大多数生长因子激活的基因）或如果它对太多其他基因有影响，我们的发现对于理解主控基因的调控具有重要意义，因此可能有利于医学研究和工业生产。生产蛋白质。对虫草素的研究可能最终导致癌症和炎症疾病的新药。

A relatively small number of genes can react rapidly to changes in and around the cell and regulate other genes to coordinate an appropriate cellular response. These master control genes are very important for medicine as their misregulation is often involved in diseases such as cancer, asthma and stroke. In addition, a similar rapid change in the activity of genes is required for the production of proteins for medical and industrial applications. Because the master control genes also need to be able to turn off quickly, their products have to be degraded fast. However, this creates a problem, as it is hard to accumulate sufficient product if it degrades quickly (if someone is eating your pancakes as quickly you bake them, you never get any yourself). We have recently shown that a modification to the gene product allows a delay before degradation occurs, making it possible to both accumulate product and remove it quickly (if you agree that pancake eating only starts after everyone, including you, is at the table, a pile of pancakes can accumulate and then be removed even faster). In this project, we will measure this delay during the stimulation of cell growth with growth factor and determine if it indeed plays such a big role. We will investigate which genes use a delayed decay and what causes differences in the delay between genes. Interestingly, we found that a compound from the traditional medicinal mushroom Cordyceps, cordycepin, reduced the activity of many master control genes for inflammation and cell growth. It inhibits the process that causes delay in decay of their products, which may explain how the drug works. We therefore want to find out if cordycepin indeed works this way and if it is a good candidate for a novel class of cancer drugs (by inhibiting mostly growth factor activated genes) or if it has effects on too many other genes, which would lead to nasty side effects.Our findings will be important for the understanding of the regulation of master control genes and are therefore likely to benefit medical research and the industrial production of proteins. The work on cordycepin may ultimately lead to new medicines for cancer and inflammatory disease.