Gene-encoding parathyroid hormone-like peptide: nucleotide sequence of the rat gene and comparison with the human...

The single-copy gene coding for rat PTH-like peptide was isolated from a rat liver genomic DNA library. The gene spans 12 kilobases and contains four exons. Exon I encodes the 5'-noncoding region, exon II encodes the prepro region, exon III encodes the mature peptide sequence up to amino acid 139 and exon IV encodes the carboxyl-terminal two amino acids, a stop codon, and the 3'-noncoding region. Splicing of these exons yields the 1.4 kilobase mRNA which is the predominant transcript observed in the hypercalcemic rat Leydig cell tumor and several normal rat tissues. The overall exon/intron organization of the rat parathyroid hormone-like peptide (PLP) gene is similar to that of the PTH gene and emphasizes the likelihood that PLP and PTH arose from a common ancestral gene. A comparison of the single promoter region of the rat with the second promoter of the human gene indicates conserved TATA and CAAT box homologies, GC box regions (SP-1 binding sites), putative AP-2 binding sites, and a vitamin D responsive element. When compared to the seven exon human PLP gene, which uses multiple promoters and encodes three peptide isoforms, the simpler organization of the rat gene predicts, in mammals, the predominant use of a single promoter and generation of a 141-amino acid peptide as the major molecular form.