COX-2: mechanisms of post-transcriptional regulation

Cyclooxygenases are the key and rate-limiting enzymes in the production of prostaglandins. Prostaglandins play an important role in many diverse biological processes. The goal of this project is to uncover the sequences and factors involved in the regulation of formation and function of the unusually large 3' untranslated region (UTR) of the human cyclooxygenase-2 (COX-2) gene. This ~ 2.5 kb 3' UTR likely contains elements that regulate gene expression by several post-transcriptional mechanisms. COX-2 is a highly regulated gene, and previous studies have shown that transcriptional activation alone cannot account for the sustained induction of the mRNA under abnormal conditions. Therefore, understanding all of the post-transcriptional molecular mechanisms involved in COX-2 gene regulation is critical. First, auxiliary regulatory elements will be identified that play a role in the alternative polyadenylation of COX-2, the process that determines the size of the 3' UTR. Second, protein factor(s) that recognize and bind these auxiliary regulatory elements will be identified. Finally, turnover of the COX-2 mRNA regulated by its 3' UTR will be investigated.

These studies will lead to new insights into mechanisms of gene regulation, with broad applicability to many areas of biology. These investigations will be excellent training for two women who are graduate students in the lab, thereby enhancing the representation of women in experimental science. In addition, the Principal Investigator strives to serve as a role model for women in science. Given the location of the laboratory in an inner-city environment, these investigations will also serve as an outstanding training opportunity for undergraduates and minorities.