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

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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.