1. DNA polymorphisms of the KiSS1 3' untranslated region interfere with the folding of a G-rich sequence into G-quadruplex.
- Author
-
Huijbregts L, Roze C, Bonafe G, Houang M, Le Bouc Y, Carel JC, Leger J, Alberti P, and de Roux N
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Circular Dichroism, DNA chemistry, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Nucleic Acid Conformation, Puberty genetics, Young Adult, 3' Untranslated Regions, DNA genetics, G-Quadruplexes, Kisspeptins genetics, Polymorphism, Single Nucleotide
- Abstract
KISS1R and its ligand, the kisspeptins, are key hypothalamic factors that regulate GnRH hypothalamic secretion and therefore the pubertal timing. During studies analysing KiSS1 as a candidate gene in pubertal onset disorders, two SNP and one nucleotide insertion were observed in a 23 nucleotides G-rich sequence located 65 nucleotides downstream of the stop codon. The polymorphisms formed four haplotypes. Biophysical experiments revealed the ability of this G-rich sequence to fold into G-quadruplex structures and demonstrated that the three DNA polymorphisms did not perturb the folding into G-quadruplex but affected G-quadruplex conformation. A functional luciferase reporter-based assay revealed functional differences between 3'UTR haplotypes. These data show that polymorphisms in a G-rich sequence of the 3'UTR of KISS1, able to fold into G-quadruplex structures, can modulate gene expression. They highlight the potential role of this G-quadruplex in the regulation of KISS1 expression and in the timing of pubertal onset., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF