Gene encoding parathyroid hormone. Nucleotide sequence of the rat gene and deduced amino acid sequence of rat preproparathyroid hormone.

The nucleotide sequence of the rat parathyroid hormone (PTH) gene was established from a 14.5-kilobase pair fragment of rat liver DNA cloned in bacteriophage Charon 4A. The transcriptional unit of the gene of 2.5 kilobase pairs is interrupted by two introns (1600 and 111 base pairs). Blot hybridization of restriction enzyme digests of rat spleen DNA using 32P-labeled fragments of the cloned PTH gene suggests that the gene is unique and present in a single copy in the genome. A promoter sequence (Goldberg-Hogness or TATA box) is situated 28 base pairs upstream from the point of initiation of transcription which was found by S1 nuclease mapping and by oligonucleotide-primed reverse transcription of rat PTH mRNA. The gene is flanked on its 5' side by repetitive DNA and contains a different, more abundant repetitive DNA on its 3' side. The mRNA encoded by the parathyroid hormone gene consists of 800 +/- 50 nucleotides as determined by electrophoresis on agarose gels. The 5' untranslated region of the mRNA contains three AUG triplets. Only one AUG triplet initiates biosynthesis of preproparathyroid hormone (prepro-PTH). The 3' untranslated segment of the mRNA contains two AATAAA sequences characteristic of polyadenylation signals. The mRNA encodes prepro-PTH, a precursor of PTH of 115 amino acids. When the amino acid sequence of the rat precursor is compared with the analagous bovine and human precursors, it becomes evident that the hormone sequences are highly conserved in two regions of known function near the NH2 terminus and in a third region near the carboxyl terminus whose biologic function, if any, has not yet been defined.