HUMAN PRODYNORPHIN GENE GENERATES SEVERAL TISSUE-SPECIFIC TRANSCRIPTS

The present study analyzes the transcription of the human prodynorphin gene. Transfection experiments indicate that promoter activity for th e 2.8 kb 'brain-type' human prodynorphin mRNA resides in the DNA regio n located 140-180 b upstream of the exon 1/intron A boundary and not 1 .2 kb further upstream, as proposed by others [S. Horikawa, T. Takai, M. Toyosato, H. Takahashi, M. Nods, H. Kakidani, T. Kubo, T. Hirose, S . Tanayama, H. Hayashida, T. Miyata, S. Numa, Isolation and structural organization of the human preproenkephalin B gene, Nature 306, 1983, pp. 611-614]. The new data locates the human prodynorphin gene promote r for the brain-type mRNA in a position corresponding to the position of the rat prodynorphin gene promoter [J. Douglass, C.T. McMurray, J.E . Garett, J.P. Adelman, L. Calavetta, Characterization of the rat prod ynorphin gene, Mel. Endocrinol. 3, 1989, pp. 2070-2078]. Three previou sly not described types of human prodynorphin mRNA of the same size, 2 .8 kb, one expressed in fetal brain and two others in testis, were cha racterized in this study. These mRNAs are generated by alternative spl icing of novel 5'-uppermost exons and transcription is probably initia ted from other promoters. Human neuroblastoma SH-SY5Y and SK-N-MC cell lines previously used in studies of gene transcription have the 2.8 k b prodynorphin mRNA of adult brain alongside a more abundant, shorter 2.3 kb transcript. The latter transcript was also found in testis and in fetal brain. It lacked the 5'-part of the 2.8 kb mRNA including the signal peptide encoding sequence. The complex pattern of prodynorphin gene expression and its functional consequences are issues for furthe r studies. (C) 1998 Published by Elsevier Science B.V. All rights rese rved.