A Novel Meprin ‘ mRNA in Mouse Embryonal and Human Colon Carcinoma Cells

Meprins, metalloendopeptidases of the astacin family, are composed of α and/or β subunits and are expressed at high levels in mammalian renal and intestinal brush-border membranes. Only one mRNA has been identified previously for each of the subunits in adult human and rodent tissues; a 3.6-kilobase message for the α subunit and a 2.5-kilobase message for the β subunit. The present study reports that a larger β subunit message (2.7 kilobases, referred to as β‘), and no α subunit message, is expressed in embryonal carcinoma cell lines, F9 and Nulli-SSC1, and in human colon adenocarcinoma cells, HT-28-18-C 1 . Furthermore, in Nulli-SSC1 cells, the β‘ isoform is induced by the morphogen retinoic acid. The β‘ isoform differs from β only in a portion of the 5‘-coding (corresponding to the signal and prosequence domains of the protein) and noncoding region. Only one gene was found for the β subunit in the mouse and human genome. The deduced amino acid sequence of β‘ has no homology with β in the first 35 NH 2 -terminal residues, but the two sequences are identical after that. In vitro translation experiments indicated that the size of the protein product of β‘ cDNA was similar to that of the β cDNA protein product, and, in the presence of microsomal membranes, both were glycosylated. These studies indicate that the messages for the meprin β and β‘ subunit result from differential promoter usage and alternate splicing. Expression of the two isoforms may be regulated differentially depending on cell type and/or differentiation state of the cell.