TROUT AND CHICKEN PROGLUCAGON - ALTERNATIVE SPLICING GENERATES MESSENGER-RNA TRANSCRIPTS ENCODING GLUCAGON-LIKE PEPTIDE-2

In mammals, the proglucagon gene is transcribed into a single identica l mRNA in pancreas, intestine, and brain. The proglucagon mRNA encodes glucagon and two glucagon-like peptides (GLP 1 and GLP 2), whose prod uction is regulated by tissue-specific proteolytic processing. Previou sly characterized pancreatic proglucagon cDNAs from birds and fish enc ode glucagon and only one glucagonlike peptide, GLP 1. The isolation o f intestinal proglucagon cDNAs from the rainbow trout, Oncorhynchus my kiss, and chicken, Gallus gallus, shows that the proglucagon gene of f ish and birds also contains the sequence of a second glucagonlike pept ide, GLP 2. In contrast to the proglucagon mRNAs from mammals, fish an d bird proglucagon mRNAs from pancreas and intestine have different 3' -ends that are due to alternative mRNA splicing. The intestinal mRNA w as found to be spliced to one or more exons, which encode GLP 2, while the pancreatic mRNA terminates within the intron between the exons en coding GLP 1 and GLP 2. These results show that proglucagon gene expre ssion is regulated at the level of mRNA splicing and serve to reemphas ize the potential biological importance of GLP 2.