AN INTRONIC PROMOTER CONTROLS THE EXPRESSION OF TRUNCATED HUMAN GAMMA-GLUTAMYL-TRANSFERASE MESSENGER-RNAS

We have identified and characterized a genomic DNA fragment containing the coding sequences corresponding to the human gamma-glutamyltransfe rase type 1 mRNA. The coding part of the gene spans over 16 kb and com prises 12 exons and 11 introns exhibiting a similar organization as fo r the mouse and rat GGT genes. The exons 1-7 encode the heavy subunit whereas exons 8-12 which encode the carboxy-terminal part of the heavy subunit (exon 8) and the light subunit are clustered in a 1.6-kb BglI I fragment. Exons 7 and 8 are separated by a 3.9-kb intron containing in its 3' part the sequences corresponding to the 5'-UTRs of the trunc ated GGT mRNAs described for human lung. Sequence analysis upstream th is transcribed region exhibited putative promoter sequences and after transient transfection significant promoter activities were measured i n V79 lung fibroblasts and KYN-2 hepatoma cells but not in A2780 ovari an cells. This specificity disappeared when only 550 bp upstream the t ranscription start site were used as promoter. These results argue for a promoter of truncated GGT mRNAs in intron 7, specifically regulated in human tissues. (C) 1998 Federation of European Biochemical Societi es.