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

Article


Seim, Inge, Jeffrey, Penny L., Thomas, Patrick B., Walpole, Carina M., Maugham, Michelle, Fung, Jenny N. T., Yap, Pei-Yi, O'Keeffe, Angela, Lai, John, Whiteside, Eliza J., 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. https://doi.org/10.1007/s12020-015-0848-7
Article Title

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

ERA Journal ID16050
Article CategoryArticle
AuthorsSeim, Inge (Author), Jeffrey, Penny L. (Author), Thomas, Patrick B. (Author), Walpole, Carina M. (Author), Maugham, Michelle (Author), Fung, Jenny N. T. (Author), Yap, Pei-Yi (Author), O'Keeffe, Angela (Author), Lai, John (Author), Whiteside, Eliza J. (Author), Herington, Adrian C. (Author) and Chopin, Lisa K. (Author)
Journal TitleEndocrine
Journal Citation52 (3), pp. 609-617
Number of Pages9
Year2016
Place of PublicationUnited States
ISSN1355-008X
1559-0100
Digital Object Identifier (DOI)https://doi.org/10.1007/s12020-015-0848-7
Web Address (URL)http://link.springer.com/article/10.1007/s12020-015-0848-7
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.

Keywordsghrelin; peptide hormone; evolution; comparative endocrinology; alternative splicing
ANZSRC Field of Research 2020320208. Endocrinology
321101. Cancer cell biology
310510. Molecular evolution
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Byline AffiliationsQueensland University of Technology
Queensland Institute of Medical Research, Australia
Institution of OriginUniversity of Southern Queensland
Funding source
NHMRC
Grant ID
1059021
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