The calcitonin/CGRP-I (calcitonin gene-related peptide) gene consists of six exons that give rise to two different products by alternative RNA processing: 1)calcitonin produced by C cells of the thyroid and 2) CGRP-I produced in many neuronal cell types. The generation of these involves alternative exon usage. Calcitonin is produced when exon 4 is used with polyadenylation occurring at this exon. cGRP-I is produced by excluding exon 4 and splicing of exon 3 to exon 5 and use of the polyadenylation signal in exon 6. Thus, the difference in 3' splice site choice, either using the 3' splice site at exon 4 or exon 5 generates calcitonin or cGRP-I, respectively. The transacting factor(s) controlling this 3' splice site choice will be identified. The corresponding cDNA will be subcloned into a bacterial expression vector and the protein purified to apparent homogeneity for detailed molecular analysis of this splice site switch.
