Abstract
Kisspeptin receptors are G-Protein-Coupled Receptors that regulate GnRH synthesis and release in vertebrates. Here, we report the gene structure of two kisspeptin receptors (kissr2 and kissr3) in pejerrey fish. Genomic analysis exposed a gene structure with 5 exons and 4 introns for kissr2 and 6 exons and 5 introns for kissr3. Two alternative variants for both genes, named kissr2_v1 and _v2, and kissr3_v1 and v2, were revealed by gene expression analyses of several tissues. For both receptors, these variants were originated by alternative splicing retaining intron 3 and intron 4 for kissr2_v2 and kissr3_v2, respectively. In the case of kissr2, the intron retention introduced two stop codons leading to a putatively truncated protein whereas for kissr3, the intron retention produced a reading shift leading to a stop codon in exon 5. Modeling and structural analysis of Kissr2 and Kissr3 spliced variants revealed that truncation of the proteins may lead to non-functional proteins, as the structural elements missing are critical for receptor function. To understand the functional significance of splicing variants, the expression pattern for kissr2 was characterized on fish subjected to different diets. Fasting induced an up-regulation of kissr2_v1 in the hypothalamus, a brain region implicated in control of reproduction and food intake, with no expression of kissr2_v2. On the other hand, fasting did not elicit differential expression in testes and habenula. These results suggest that alternative splicing may play a role in regulating Kissr2 function in pejerrey.
Highlights
G-protein-coupled receptors (GPCRs) play key roles in many physiological processes and have been associated with multiple human diseases [1]
A few years later, kisspeptin and its receptor were regarded as essential regulators of the reproductive axis, since hypogonadotropic hypogonadism in both humans and mice was shown to be associated with mutations of KISS1R [9, 10]
We report the predicted structure of two kissr genes, kissr2 and kissr3 in pejerrey fish (Odontesthes bonariensis)
Summary
G-protein-coupled receptors (GPCRs) play key roles in many physiological processes and have been associated with multiple human diseases [1]. The superfamily of GPCRs is characterized by having seven-transmembrane (7TM) α-helices connected by three extracellular loops (ECLs) and three intracellular loops (ICLs), an extracellular amino-terminal segment, and an intracellular carboxy-terminal tail [4] According to their amino acid sequence, GPCRs are classified into five major classes (families): (i) A or Rhodopsin-like Two kissr transcripts were identified in this species, a short one named kissr2_v1 corresponding to the normally-spliced messenger, and a long kissr2_v2 (putatively non-functional) transcript characterized by retaining the entire intron 3 [20]. The first report supporting such a role was a study on Senegalese sole that showed up-regulation of hypothalamic kiss and kissr expression during starvation, in concert with an increase of transcript levels of gonadotropins in the pituitary [26]. Our findings suggest a novel kissr gene regulatory mechanism in the hypothalamus involving expression of alternatively spliced variants with intron retention that produce potentially non-functional proteins
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