The expression of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A synthase in neonatal rat intestine and liver is under transcriptional control

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HOMeGlt-CoA) synthase regulates ketogenesis in the liver of adult rat and in the intestine and liver of neonatal animals but whose mechanisms of regulation have not been fully defined. To investigate transcriptional control of this gene in intestine and liver of suckling rats a quantitative PCR amplification of the pre-mRNA (heteronuclear RNA), composed of part of the first exon and of the first intron, was carried out. Results show that the intestinal pre-mRNA for mitochondrial HOMeGlt-CoA synthase from suckling rats follows a pattern that is nearly identical to that of mature mRNA, with maximum levels on the ninth postnatal day then decreasing smoothly so that at weaning there is no transcriptional activity. Mitochondrial HOMeGlt-CoA synthase protein follows a pattern that is identical to the pre-mRNA and mature mRNA, suggesting no translational regulation. The changes in transcriptional activity are not produced by the presence of an alternative promoter, since the transcription-initiation site is identical in several tissues assayed, including intestine and liver. Enterocytes are the only intestinal cells that express this ketogenic enzyme, as deduced from immunolocalization experiments. The mature intestinal protein is located in mitochondria and not in the cytosol, which coin cides with what is found in liver. By using analogous techniques we conclude that hepatic pre-mRNA of mitochondrial HOMeGlt-CoA synthase from suckling rats follows a pattern of expression identical to that of mature hepatic mRNA, which also suggests a transcriptional modulation of this gene in the liver of neonatal rats.