THE EXPRESSION OF MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-ASYNTHASE IN NEONATAL RAT INTESTINE AND LIVER IS UNDER TRANSCRIPTIONALCONTROL

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HOMeGlt-CoA) synthase re gulates 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 ge ne in intestine and liver of suckling rats a quantitative PCR amplific ation of the pre-mRNA (heteronuclear RNA), composed of part of the fir st exon and of the first intron, was carried out. Results show that th e intestinal pre-mRNA for mitochondrial HOMeGlt-CoA synthase from suck ling 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. Mito chondrial HOMeGlt-CoA synthase protein follows a pattern that is ident ical to the pre-mRNA and mature mRNA, suggesting no translational regu lation. The changes in transcriptional activity are not produced by th e presence of an alternative promoter, since the transcription-initiat ion 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 c ytosol, which coincides with what is found in liver. By using analogou s techniques we conclude that hepatic pre-mRNA of mitochondrial HOMeGl t-CoA synthase from suckling rats follows a pattern of expression iden tical to that of mature hepatic mRNA, which also suggests a transcript ional modulation of this gene in the liver of neonatal rats.