title: Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide.
abstract: The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described. Here, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons. We identified a novel human exon 2-deleted variant and provide preliminary evidence that this splice variant and in1-ghrelin encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to full-length 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. This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of ghrelin gene-derived 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.
authors.affiliation: Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia. i.seim@qut.edu.au.|Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia. i.seim@qut.edu.au.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia. i.seim@qut.edu.au.
authors.forename: Inge
authors.initials: I
authors.lastname: Seim
authors.affiliation: Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Penny L
authors.initials: PL
authors.lastname: Jeffery
authors.affiliation: Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Thomas
authors.affiliation: Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Carina M
authors.initials: CM
authors.lastname: Walpole
authors.affiliation: Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Maugham
authors.affiliation: Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
authors.forename: Jenny N T
authors.initials: JN
authors.lastname: Fung
authors.affiliation: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Yap
authors.affiliation: Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: O'Keeffe
authors.affiliation: Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Lai
authors.affiliation: Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Eliza J
authors.initials: EJ
authors.lastname: Whiteside
authors.affiliation: Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Herington
authors.affiliation: Comparative and Endocrine Biology Laboratory, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Ghrelin Research Group, Translational Research Institute-Institute of Health and Biomedical Innovation (TRI-IHBI), Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Research Centre, Queensland, Princess Alexandra Hospital, Queensland University of Technology, Woolloongabba, QLD, 4102, Australia.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Chopin
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017124:Conserved Sequence; D054439:Ghrelin / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D054439:Ghrelin; D020033:Protein Isoforms
keywords: Alternative splicing; Comparative endocrinology; Evolution; Ghrelin; Peptide hormone