Abstract
The peptide hormones ACTH, β-endorphin, α- and β-melanotropin(MSH) and possibly γ-MSH are synthesized in the pituitary gland by the processing of a 32,000-molecuIar weight (MW) polypeptide called proopiomelanocortin (POMC)1–5. The existence of a further precursor (pre form) to POMC containing an additional N-terminal ‘leader’ peptide has been suggested by analysis of the in vitro translation products of poly(A)-containing RNA from AtT-20 cells, a mouse ACTH-producing cell line of pituitary origin6. Nakanishi et al.7 cloned and sequenced a cDNA copy of the bovine prePOMC mRNA. This sequence confirmed the known structure of the carboxyl half of POMC and revealed the presence of a new MSH-like moiety, γ-MSH, within the 16,000-MW amino half of the precursor (16K fragment). Recent experiments have suggested that this peptide may act in synergy with ACTH to increase corticosterone and aldosterone production in vivo and in vitro8,9. We have now isolated from a rat genomic DNA library10 a segment of a DNA encoding most of POMC, using as probe a mouse 144-base pair cloned cDNA fragment encoding β-MSH and β-endorphin11. The cloned rat gene is one of two (or more) closely related POMC genes. The DNA sequence obtained shows that the cloned POMC gene is not interrupted by any intervening sequence (IVS) between the codon for amino acid 19 and the presumptive poly(A) addition site. This region of POMC encodes all the biologically active peptides mentioned above. The DNA sequence encoding the putative γ-MSH and the coding sequence that precedes it are highly conserved between rat and cow. This may indicate an as yet unrecognized biological function(s) for the NH2-terminal portion of the 16K fragment.
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Drouin, J., Goodman, H. Most of the coding region of rat ACTHβ–LPH precursor gene lacks intervening sequences. Nature 288, 610–613 (1980). https://doi.org/10.1038/288610a0
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DOI: https://doi.org/10.1038/288610a0
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