No role of the 5 ' untranslated region of ornithine decarboxylase mRNA in the feedback control of the enzyme

The polyamines are ubiquitous in nature and appear to fulfil several import ant functions, mostly related to growth, in the cell. The first, and often rate-limiting, step in the biosynthesis of the polyamines is catalysed by o rnithine decarboxylase (ODC), which is subject to a variety of control mech anisms. The polyamines exert a strong feedback regulation of the expression - as well as the degradation of the enzyme. The regulation of ODC expressi on appears to occur at the translational level. The ODC mRNA contains a lon g GC-rich 5' untranslated region (UTR), which has been demonstrated to hamp er the translation of the mRNA. However, it has not yet been conclusively e stablished whether this part of the mRNA fulfils any function in relation t o the polyamine-mediated control of ODC synthesis. In the present study, we have used stable transgenic CHO cells, expressing either full-length ODC m RNA or 5' UTR-truncated ODC mRNA, to elucidate the role, if any, of the 5' UTR in the translational regulation of the enzyme by polyamines. No differe nces in regulatory properties were observed between the cells expressing th e full-length ODC mRNA and those expressing the ODC mRNA devoid of most the 5' UTR. The cell lines down-regulated ODC (synthesis as well as activity) to the same extent upon exposure to an excess of polyamines, demonstrating that the feedback control of ODC mRNA translation occurs by a mechanism ind ependent of the major part of the 5' UTR of the ODC mRNA.