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

I Seim; P L Jeffery; P B Thomas; C M Walpole; Michelle Maugham; J N T Fung; P Y Yap; A J O'Keeffe; J Lai; E J Whiteside; A C Herington; L K Chopin

doi:10.1007/s12020-015-0848-7

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

Journal article

Open access

Peer reviewed

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

I Seim, P L Jeffery, P B Thomas, C M Walpole, Michelle Maugham, J N T Fung, P Y Yap, A J O'Keeffe, J Lai, E J Whiteside, …

Endocrine, Vol.52(3), pp.609-617

2016

DOI: https://doi.org/10.1007/s12020-015-0848-7

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Abstract

Clinical Sciences

Paediatrics and Reproductive Medicine

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.

Details

Title: Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide
Authors: I Seim (Author)
P L Jeffery (Author)
P B Thomas (Author)
C M Walpole (Author)
Michelle Maugham (Author) - Queensland University of Technology
J N T Fung (Author)
P Y Yap (Author)
A J O'Keeffe (Author)
J Lai (Author)
E J Whiteside (Author)
A C Herington (Author)
L K Chopin (Author)
Publication details: Endocrine, Vol.52(3), pp.609-617
Publisher: Springer
Date published: 2016
DOI: 10.1007/s12020-015-0848-7
ISSN: 1355-008X
Copyright note: Copyright © The Author(s) 2016. This article is published with open access at Springerlink.com
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450824302621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Endocrinology & Metabolism

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