CLONING AND CHARACTERIZATION OF THE CDNA-ENCODING THE HUMAN NEUROMEDIN U (NMU) PRECURSOR - NMU EXPRESSION IN THE HUMAN GASTROINTESTINAL-TRACT

Many peptide precursors encode more than one bioactive peptide. Recent cloning of the rat neuromedin U (NmU) precursor revealed potential pr oteolytic processing sites which may generate three associated peptide s in addition to the NmU peptide, which is known to have potent uterin e contractile effects. To assess the degree of evolutionary conservati on, which often suggests conserved biological function and hence physi ological importance, we have cloned and sequenced the cDNA encoding th e human NmU precursor. Sequence analysis revealed a 174 amino acid hum an precursor containing the 25 residue NmU peptide near the C terminus of the precursor. The human message sequence was 74% homologous with that of the rat, indicating evolutionary conservation of the precursor between these two species. Four out of five of the putative proteolyt ic processing sites, first revealed in the rat precursor, were conserv ed in the human precursor, indicating a similar processing mechanism i n both species. Two such processing sites flank a 33 residue peptide s equence which differed in only two amino acids compared with the rat h omologue. This conservation suggests a possible biological role for th is putative peptide. Northern blot analysis of human gastrointestinal tissues revealed a similar level of mRNA throughout the gastrointestin al tract. RIA using a porcine specific assay showed the highest levels of peptide in the jejunum samples.