Translational regulation of ornithine decarboxylase (ODC), which catalyses the first step in the biosynthesis of polyamines, appears to be an important mechanism in the strong feedback control as well as in the hypotonic induction of the enzyme. However, the exact mechanisms are not yet understood. The ODC mRNA has long 5′ and 3′ untranslated regions (UTRs) which may be involved in the translational control of the enzyme. In the present study we have used a series of stable transfectants of Chinese Hamster ovary cells expressing ODC mRNAs with various truncations in the 5′ and 3′ UTRs to investigate the importance of these regions. It is demonstrated that neither the 5′ UTR nor the 3′ UTR appears to be involved in the polyamine-mediated feedback control of ODC synthesis. The hypotonic induction of ODC, on the other hand, was shown to be highly dependent on the presence of the 3′ UTR, but not on the 5′ UTR, of ODC mRNA. Cells expressing ODC mRNAs lacking the 3′ UTR showed no, or only a very slight, induction of ODC whether the 5′ UTR was present or not, whereas the cell lines expressing ODC mRNAs containing the 3′ UTR (with or without the 5′ UTR) markedly induced ODC after a hypotonic shock. The present finding of a role for the ODC mRNA 3′ UTR in the hypotonic induction of ODC is the first demonstration of a specific effect of the 3′ UTR in the regulation of ODC.
Abbreviations used: ODC, ornithine decarboxylase; UTR, untranslated region; CHO, Chinese Hamster ovary; DFMO, α-difluoromethylornithine; ARE, AU-rich element.
Present addresss: Dipartimento di Medicina e Oncologia Sperimentale, Universita di Torino, I-10126 Torino, Italy.
Present addresss: Department of Women's and Children's Health, Uppsala University Hospital, S-751 85 Uppsala, Sweden.