Abstract
The effect of the 5'-untranslated region of ornithine decarboxylase (ODC) mRNA and of spermidine on the translation of ODC mRNA was studied in a rabbit reticulocyte cell-free system. The ODC mRNAs, possessing different sizes of the 5'-untranslated region and named mODC241, mODC188, mODC85, and mODC24 according to the number of nucleotides in the 5'-untranslated region, were synthesized by in vitro transcription techniques through the use of plasmids containing various sizes of mouse ODC cDNA. As the size of the 5'-untranslated region of ODC mRNA increased, the efficiency of the translation decreased and the degree of stimulation of the translation by 0.2 mM spermidine increased. The inhibition of ODC mRNA translation by high concentrations of spermidine (0.6-1 mM) also increased with an increase in the size of the 5'-untranslated region. The spermidine effects were increased greatly when the size of the 5'-untranslated region of ODC mRNA was increased from 85 to 188 nucleotides. These results suggest that the nucleotides 70-220 upstream from the initiator AUG are involved in the decrease in translational efficiency. In addition, at least the nucleotides in the 70-170 region upstream from the initiator AUG are important in the strong stimulation of ODC synthesis by low spermidine concentrations and in the inhibition of ODC synthesis at high spermidine concentrations.
Highlights
The effect of the 5’-untranslated region of ornithine decarboxylase (ODC) mRNA and of spermidine on the translation of ODC mRNA was studied in a rabbit reticulocyte cell-free system
Spermidine stimulation at 0.2 mM was 17.1-fold, and the inhibitory effect by 0.8-l mM spermidine was clearly observed (Fig. 8). These results show that the nucleotide sequence in the 5’-untranslated region (5’-UTR) itself is involved in the decrease of translational efficiency and the spermidine effect
Mouse ODC mRNA has an unusually long 5’-UTR, which consists of 313 nucleotides [33, 34]
Summary
The spermidine effects were increased greatly when the size of the 5’-untranslated region of ODC mRNA was increased from 85 to 188 nucleotides. Higher concentrations of spermidine were inhibitory, and its inhibitory effect on ODC synthesis was greater than on protein synthesis in general [17,18,19] This indicates that at least part of the feedback regulation of ODC synthesis exerted by polyamines is due to their direct inhibition of ODC mRNA translation. The results suggest that the size of the 5’-UTR is inversely correlated to ODC synthetic activity and that at least the nucleotides in the 70-170 region upstream from the initiator AUG are important for polyamine stimulation and inhibition of ODC synthesis
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