The role of poly ADP ribosylation in mRNA export

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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.