Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites.

Abstract

Different 3' coding exons in the rat calcitonin gene are used to generate distinct mRNAs encoding either the hormone calcitonin in thyroidal C-cells or a new neuropeptide referred to as calcitonin gene-related peptide in neuronal tissue, indicating the RNA processing regulation is one strategy used in tissue-specific regulation of gene expression in the brain. Although the two mRNAs use t-he 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 mRNAs 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 c4lcitonin and calcitonin gene-related peptide exons irrespective of which mRNA is ultimately produced. In isolated nuclei, both polyadenylation sites appear to be utilized; however, the proximal (calcitonin) site is preferentially used in nuclei from tissues producing calcitonin mRNA. These data suggest that the mechanism dictating production of each mRNA involves the selective use of alternative polyadenylation sites.

A specific DNA sequence controls termination of transcription in the gastrin gene.

“…The gastrin gene transcripts derived from plasmids pSG24 and pSG12 were analyzed by Si nuclease mapping (1,3). Total RNA extracted from CV-1 cells 24 h after transfection was used in the Si nuclease analysis.…”

Expression of v-Ha-ras driven by the calcitonin/calcitonin gene-related peptide promoter: a novel transgenic murine model for medullary thyroid carcinoma

“…The rascal transgene, shown schematically in Figure 1, consists of three components; 2041 base pairs of the calcitonin/CGRP gene from 71934 to +107 bases around the transcriptional start site (at +1), 1013 bases of v-Ha-ras containing the coding sequence of p21, and 847 bases containing the early mRNA polyadenylation signals of the SV40 T antigen (Amara et al, 1984;Kimura et al, 1995;Berk and Sharp, 1978;Dhar et al, 1982). Five independent lineages have been derived.…”

The action of CGRP and SP on cultured skin fibroblasts

“…CGRP is a 37-amino acid peptide expressed by neurons and endocrine cells in different tissues [11]. Two isoforms of the CGRP peptide have been described: alpha-CGRP, which is formed by the alternative mRNA splicing of the calcitonin gene located on chromosome 11; and beta-CGRP, which is encoded by a different, but closely related gene [11][12][13][14][15][16][17]. Alpha-CGRP and beta-CGRP differ from each other by three amino acids in humans and by one amino acid in rats [13,15], and exhibit overlapping biological actions [16].…”