CALCITONIN CALCITONIN GENE-RELATED PEPTIDE TRANSCRIPTION UNIT - TISSUE-SPECIFIC EXPRESSION INVOLVES SELECTIVE USE OF ALTERNATIVE POLYADENYLATION SITES

Different 3'' coding exons in the rat calcitonin gene are used to generate distinct mRNA encoding the hormone calcitonin in thyroidal C-cells or a new neuropeptide referred to as calcitonin gene-related peptide in neuronal tissue; this indicates that the RNA processing regulation is one strategy used in tissue-specific regulation of gene expression in the brain. Although the 2 mRNA use the same transcriptional initiation site and have identical 5'' terminal sequences, their 3'' termini are distinct. The polyadenylation sites for calcitonin and calcitonin gene-related peptide mRNA are located at the end of the exons 4 and 6, respectively. Termination of transcription after the calcitonin exon does not dictate the production of calcitonin mRNA because transcription proceeds through both calcitonin and calcitonin gene-related peptide exons irrespective of which mRNA is ultimately produced. In isolated nuclei, both polyadenylation sites appear to be utilized; the proximal (calcitonin) site is preferentially used in nuclei from tissues producing calcitonin mRNA. The mechanism dictating production of each mRNA apparently involves the selective use of alternative polyadenylation sites.