Human prodynorphin gene generates several tissue-specific transcripts

Abstract

The present study analyzes the transcription of the human prodynorphin gene. Transfection experiments indicate that promoter activity for the 2.8 kb `brain-type' human prodynorphin mRNA resides in the DNA region 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. Noda, 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 promoter 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 prodynorphin gene, Mol. Endocrinol. 3, 1989, pp. 2070–2078]. Three previously 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 characterized in this study. These mRNAs are generated by alternative splicing of novel 5′-uppermost exons and transcription is probably initiated from other promoters. Human neuroblastoma SH–SY5Y and SK–N–MC cell lines previously used in studies of gene transcription have the 2.8 kb 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 further studies.