Background
The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including a role in energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene (GHRL) splice variants have been described. In this manuscript, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons.
Results
We have identified a novel human exon 2-deleted preproghrelin variant and provide preliminary evidence that this splice variant and the in1-ghrelin preproghrelin variant encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These preproghrelin variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to canonical ghrelin, as treatment with exogenous minighrelin peptide stimulates appetite and feeding in mice. Forced expression of the exon 2-deleted preproghrelin variant mirrors the effect of the canonical preproghrelin, stimulating cell proliferation and migration in the PC3 prostate cancer cell line.
Conclusions
This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of preproghrelin splice variants that encode a truncated ghrelin peptide. This adds further impetus for studies into the alternative splicing of the ghrelin gene and the function of novel ghrelin peptides in vertebrates.