A NOVEL MEPRIN BETA' MESSENGER-RNA IN MOUSE EMBRYONAL AND HUMAN COLON-CARCINOMA CELLS

Meprins, metalloendopeptidases of the astacin family, are composed of alpha and/or beta subunits and are expressed at high levels in mammali an renal and intestinal brush-border membranes. Only one mRNA has been identified previously for each of the subunits in adult human and rod ent tissues; a 3,6-kilobase message for the alpha subunit and a 2.5-ki lobase message for the beta subunit. The present study reports that a larger beta subunit message (2.7 kilobases, referred to as beta'), and no alpha subunit message, is expressed in embryonal carcinoma cell li nes, F9 and Nulli-SSC1, and in human colon adenocarcinoma cells, HT-28 -18-C-1. Furthermore, in Nulli-SSC1 cells, the beta' isoform is induce d by the morphogen retinoic acid. The beta' isoform differs from beta only in a portion of the 5'-coding (corresponding to the signal and pr osequence domains of the protein) and noncoding region. Only one gene was found for the beta subunit in the mouse and human genome. The dedu ced amino acid sequence of beta' has no homology with beta in the firs t 35 NH2-terminal residues, but the two sequences are identical after that. In vitro translation experiments indicated that the size of the protein product of beta' cDNA was similar to that of the beta cDNA pro tein product, and, in the presence of microsomal membranes, both were glycosylated. These studies indicate that the messages for the meprin beta and beta' subunit result from differential promoter usage and alt ernate splicing. Expression of the two isoforms may be regulated diffe rentially depending on cell type and/or differentiation state of the c ell.