This research will examine the regulation by polyamines of the translational efficiency of ornithine decarboxylase (ODC) mRNA. cDNA and genomic clones for mouse ODC have been isolated, the sequence of the 312 base 5' leader sequence has been determined and it has been established that increasing the polyamine pools of cells decreases the rate of ODC synthesis without changing the level of intracellular ODC mRNA. Because ODC is rate-limiting for polyamine synthesis in animal cells, interaction of polyamines with leader represents a means by which polyamines could contribute to the regulation of their own synthesis. Many laboratories are studying the regulation of gene expression at the level of transcription. Few are characterizing regulation at the secondary level of messenger translation. Dr. Coffino and his associates have been developing this system of regulation of ornithine decarboxylase for a number of years. Ornithine decarboxylase is biologically important, appears to play a significant role in cell growth and is subject to a variety of modes of regulation. The focus in this project is on regulation at the translational level and the results should allow greater insight into the different ways a cell can modulate the amount of product available.
