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Organization of the Mouse Ghrelin Gene and Promoter: Occurrence of a Short Noncoding First Exon

Department of Biochemistry, Faculty of Medicine (M.T., T.I., N.Nak., N.Nao., K.N.), Department of Animal Science Faculty of Bioresources (Y.H.), Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan

Address all correspondence and requests for reprints to: Minoru Tanaka, Mie University Faculty of Medicine, Department of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

Ghrelin is a growth hormone-releasing peptide recently discovered in the stomach of rat and human as an endogenous ligand for growth hormone-secretagogue receptor. In the present study, a full-length cDNA for mouse ghrelin has been cloned from the stomach using the oligo-capping and rapid amplification methods, and the organization of its gene and promoter has been analyzed. The mouse ghrelin cDNA was 521 bp long, consisting of 44 bp 5’-noncoding region, 354 bp coding region encoding a pre-proghrelin composed of 117 amino acid residues and 123 bp 3’-noncoding region. The genomic sequence analysis has revealed that the mouse ghrelin gene consists of 5 exons and 4 introns. The first exon was revealed to be only 19 bp long presented at the noncoding region of cDNA. The identical 19 bp sequence was also found as the first exon at the 5’-end of full-length rat ghrelin cDNA obtained from the stomach. A TATA box-like sequence, TATATAA was localized 24 bp upstream of the transcription start site of the mouse ghrelin gene. The sequence of the 5’-promoter region of mouse ghrelin gene including the TATA-like sequence and short exon 1 was highly homologous to that of reported human ghrelin gene. These findings suggest that the structure of the promoter region including the short noncoding first exon and its transcriptional regulation are conserved among the mammalian ghrelin genes.