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

Abstract

The polyamines are ubiquitous in nature and appear to fulfil several important functions, mostly related to growth, in the cell. The first, and often rate-limiting, step in the biosynthesis of the polyamines is catalysed by ornithine decarboxylase (ODC), which is subject to a variety of control mechanisms. The polyamines exert a strong feedback regulation of the expression - as well as the degradation of the enzyme. The regulation of ODC expression appears to occur at the translational level. The ODC mRNA contains a long GC-rich 5' untranslated region (UTR), which has been demonstrated to hamper the translation of the mRNA. However, it has not yet been conclusively established whether this part of the mRNA fulfils any function in relation to the polyamine-mediated control of ODC synthesis. In the present study, we have used stable transgenic CHO cells, expressing either full-length ODC mRNA 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 differences in regulatory properties were observed between the cells expressing the 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 independent of the major part of the 5' UTR of the ODC mRNA.