Abstract
Insulin consists of two polypeptide chains, A (21 amino acids) and B (30 amino acids), linked by disulphide bonds. Both chains are derived from one precursor, proinsulin, which includes a connecting peptide (C) between the A and B chains, and which is excised before the secretion of insulin from the pancreatic B cells1. The observation that the C-peptide varies between species, in contrast to the highly conserved A and B sequences1–3, is consistent with the theory that it serves a purely structural function in insulin synthesis. During in vitro translation of insulin mRNA, a larger peptide containing about 25 additional residues at the N-terminal end (preproinsulin) is the primary product4–7. The prepeptide is cleaved to leave proinsulin during transport into the endoplasmic reticulum and is thought to direct this process specifically8. Using automated amino acid sequence analysis, the partial amino acid sequences of the prepeptide regions of bovine, rat, sea raven and anglerfish preproinsulin have been established4,5,7. The nucleotide sequences of the cloned cDNA and gene coding for rat insulin I have confirmed the amino acid sequence of rat proinsulin I, and have also predicted the sequence of the prepeptide9–11. Like the prepeptides of other secreted proteins, this prepeptide has a prominent hydrophobic region12. We report here the cloning of a cDNA prepared from human insulin mRNA and an analysis of the nucleotide sequence of the cloned molecule including the region coding for the prepeptide and portions of the 5′- and the 3′-untranslated regions of the molecule. We also compare the structure of the human molecule with the previously reported rat mRNA9–11.
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Bell, G., Swain, W., Pictet, R. et al. Nucleotide sequence of a cDNA clone encoding human preproinsulin. Nature 282, 525–527 (1979). https://doi.org/10.1038/282525a0
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DOI: https://doi.org/10.1038/282525a0
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