DNA polymorphisms of the KiSS1 3′ Untranslated region interfere with the folding of a G-rich sequence into G-quadruplex
DNA polymorphisms of the KiSS1 3′ Untranslated region interfere with the folding of a G-rich sequence into G-quadruplex
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DOI：
10.1016/j.mce.2011.12.014
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发表时间：
2012-04-04
影响因子：
4.1
通讯作者：
de Roux, Nicolas
中科院分区：
文献类型：
--
作者：
Huijbregts, Lukas;Roze, Catherine;de Roux, Nicolas
KISS 1 R及其配体kisspeptins是调节下丘脑GnRH分泌从而调节青春期时间的关键下丘脑因子。在分析KiSS 1作为青春期发病疾病的候选基因的研究期间，在位于终止密码子下游65个核苷酸的23个核苷酸的富含G的序列中观察到两个SNP和一个核苷酸插入。这些多态性形成了4种单倍型。生物物理实验揭示了这种富含G的序列折叠成G-四链体结构的能力，并证明了三种DNA多态性不会干扰折叠成G-四链体，但会影响G-四链体构象。基于功能性荧光素酶的测定揭示了3 'UTR单倍型之间的功能差异。这些数据表明，KISS 1的3 'UTR的富含G的序列中的多态性，能够折叠成G-四链体结构，可以调节基因表达。他们强调了这种G-四链体在调节KISS 1表达和青春期开始时间方面的潜在作用。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.