Translational and pretranslational control of ornithine aminotransferase synthesis in rat liver.
The mitochondrial matrix enzyme, ornithine aminotransferase, is induced in rat liver by the administration of a diet high in protein and by glucagon. The rate of synthesis of the enzyme is increased 100-fold in the livers of rats maintained on a 60% relative to a 0% protein diet, whereas the levels of functional and hybridizable mRNA measured by in vitro translation and through the use of a cloned cDNA probe increased by only 2- to 6-fold and 2- to 3-fold, respectively. Under conditions of glucagon induction that resulted in a 10- to 12-fold increase in the rate of enzyme synthesis, the relative level of functional ornithine aminotransferase mRNA increased by only 2-fold, and the level of hybridizable mRNA actually decreased. The rate of polypeptide chain elongation and the relative number of ornithine aminotransferase nascent chains on polysomes were 2-fold and 23-fold greater, respectively, in hepatocytes derived from 60% relative to 0% protein-fed rats. Using these data, a 23-fold increase in the translational efficiency of the mRNA was calculated. This increase, along with a 2-fold increase in the mRNA level, completely account for the 40-fold increase in the rate of ornithine aminotransferase synthesis observed in hepatocytes derived from 60% protein-fed rats. We conclude that ornithine aminotransferase synthesis is regulated at both a translational and a pretranslational level in rat liver.
D000818:Animals; D004247:DNA; D004044:Dietary Proteins / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D009693:Nucleic Acid Hybridization; D009953:Ornithine-Oxo-Acid Transaminase / Q000096:biosynthesis*; D011061:Poly A / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000637:Transaminases / Q000096:biosynthesis*
D004044:Dietary Proteins; D012333:RNA, Messenger; D011061:Poly A; D004247:DNA; D000637:Transaminases; D009953:Ornithine-Oxo-Acid Transaminase