Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide

Seim, Inge and Jeffrey, Penny L. and Thomas, Patrick B. and Walpole, Carina M. and Maugham, Michelle and Fung, Jenny N. T. and Yap, Pei-Yi and O'Keeffe, Angela and Lai, John and Whiteside, Eliza J. and Herington, Adrian C. and Chopin, Lisa K. (2016) Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide. Endocrine, 52 (3). pp. 609-617. ISSN 1355-008X

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © copyright The Author(s) 2016. Files associated with this item cannot be displayed due to copyright restrictions.
Faculty / Department / School: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing
Date Deposited: 08 Jul 2016 06:02
Last Modified: 24 Jan 2018 01:49
Uncontrolled Keywords: ghrelin; peptide hormone; evolution; comparative endocrinology; alternative splicing
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110306 Endocrinology
11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
06 Biological Sciences > 0604 Genetics > 060409 Molecular Evolution
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Funding Details:
Identification Number or DOI: 10.1007/s12020-015-0848-7
URI: http://eprints.usq.edu.au/id/eprint/28710

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