ALTERNATIVE SPLICE-SITE SELECTION IN THE HUMAN GROWTH-HORMONE GENE TRANSCRIPT AND SYNTHESIS OF THE 20 KDA ISOFORM - ROLE OF HIGHER-ORDER TRANSCRIPT STRUCTURE

Expression of the human growth hormone (hGH) gene in somatotrophs of t he anterior pituitary gland results in the synthesis and secretion of a major 22 kDa and a minor 20 kDa GH isohormone. The expression of the se two proteins reflects the alternative utilization of a major (B) an d a minor (B') splice acceptor site in exon 3 of the hGH-N transcript. By comparing the structure and splicing patterns of the hGH-N gene tr anscript with that of the structurally related, placentally expressed, hGH-V gene transcript, which uses only the major (B) exon 3 splice ac ceptor, it has been possible to define the cis-acting elements in exon 3 that are critical for activation of the B' splice acceptor. The pre sent paper demonstrates that, in addition to the importance of sequenc es in the immediate proximity of the two alternative splice acceptor s ites, additional more remote sequences in the transcript also contribu te to this alternative splice site selection. The data further suggest that these more distal sequences do not act individually, but interac t so that the net level of alternative splicing in exon 3 is dictated by the overall higher order structure of the hGH-N transcript.