mRNA for the three human alcohol dehydrogenase subunits: size heterogeneity and developmental changes

Human alcohol dehydrogenase consists of three types of subunits (alpha, beta, and gamma) which are governed by three separate loci. mRNA components for the three subunits were examined by Northern blot hybridization, using a common cDNA probe and specific oligonucleotide probes. A marked size heterogeneity of beta mRNA, ranging from 1.6 kb to 5.2 kb (of which the 2.4-kb and 3.5-kb were major), was observed in the adult liver. The mRNA for the gamma subunit was homogeneous (about 1.6 kb), and that for the alpha subunit contained a major 1.6-kb and a minor 4.3-kb component. The amount of mRNA was much lower (approximately 10% of adult) and the mRNA was less heterogeneous in the infant liver; i.e., an alpha mRNA (1.6 kb) and two beta mRNAs (a major 1.6 kb and a minor 3.5 kb), and no detectable gamma mRNA. The short beta mRNA, with 1.6 kb, could not be hybridized with a non-coding cDNA fragment that originated from the 3'-end of the 2.6 kb beta cDNA. The observed multiple ADH mRNAs, with a common coding region and different 3'-untranslated regions, are generated by utilization of multiple polyadenylation signals. The selection of polyadenylation signals and the rate of transcription of the three ADH loci are developmentally regulated. The 4.3-kb-long mRNA, which was hybridized with both a- and beta-specific probes, could be related to the previously cloned "fused beta-alpha" cDNA.