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

Endocrine
Inge SeimLisa K Chopin

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...Continue Reading

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Citations

Mar 16, 2017·International Journal of Molecular Sciences·Agustina CabralMario Perelló
Aug 31, 2017·Molecular Cancer·Daniel Hormaechea-AgullaRaúl M Luque
Jan 3, 2018·PloS One·David AlfegoAndres Kriete
Oct 8, 2020·Heart Failure Reviews·Shreyasi Gupta, Arkadeep Mitra
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Mar 14, 2021·Cellular Signalling·Karim Nagi, Abdella M Habib
May 30, 2017·General and Comparative Endocrinology·Shayan AbtahiPaul J Currie
Dec 30, 2021·Physiology·Sara L Deschaine, Lorenzo Leggio

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Datasets Mentioned

BETA
AB111891

Methods Mentioned

BETA
PCR
RNA CaptureSeq

Software Mentioned

UCSC multiway tool
GraphPad Prism
BioPerl
BLAST
gmap
custom Perl scripts
R
MUSCLE

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