Cloning, sequence analysis, and processing of the rat and human atrial natriuretic peptide precursors

Complementary DNA sequences and structural genes encoding the atrial natriuretic peptide precursor (prepro-ANP) have been cloned. Analysis of DNA sequences, complementary to rat atrial prepro-ANP mRNA, has revealed that the various natriuretic peptides isolated from rat atrium reside at the carboxy terminus of a 152-amino-acid precursor protein. The human gene, comprised of three exons and two intervening sequences, encodes a protein of 151 amino acids highly homologous to the rat precursor. Although putative proteolytic processing sites can be identified throughout the prepro-ANP amino acid sequence, the natural form of the mature ANP has not been identified. Therefore, the sites and mechanisms of prepro-ANP processing to mature peptides forms are unknown. However, the successful cloning of the prepro-ANP gene and corresponding cDNAs provide the necessary molecular tools to address these fundamental questions relating to the regulation of ANP synthesis and processing in atrial and extraatrial tissues.