A huge number of G-rich sequences forming quadruplexes are found in the human genome, especially in telomeric regions, UTRs, and the promoter regions of a number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl-D-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia, a genetic disorder characterized by hallucinations, delusions, and psychosis. Involvement of the GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed. Recent reports have demonstrated that polymorphism in the promoter region of GRIN1 at position −855 (G/C) has a possible association with schizophrenia. The binding site for the NF-κB transcription factor gets altered due to this mutation, resulting in reduced gene expression as well as NMDA activity. By combining gel electrophoresis (PAGE), circular dichroism (CD) and CD melting techniques, the G → C single nucleotide polymorphism (SNP) at the G-rich sequence (d-CTTAGCCCGAGGAGGGGGTCCCAAGT; GRIN1) was investigated. We report that the GRIN1 sequence can form an octameric/multistranded quadruplex structure with parallel conformation in the presence of K⁺ as well as Na⁺. CD and gel studies are in good correlation in order to detect molecularity and strand conformation. The parallel G-quadruplex species was hypothesized to be octameric in K⁺/Na⁺ salts. The mutated sequence (d-CTTAGCCCGAGGAGGGGGTCCCAAGT; GRIN1M) remained single stranded under physiological conditions. CD melting studies support the formation of an interstranded G-quadruplex structure by the GRIN1 sequence. Two structural models are propounded for a multistranded parallel G-quadruplex conformation which might be responsible for regulating the gene expression normally underlying memory and learning.

中文翻译：

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人类GRIN1基因启动子中的点突变导致结构从多链G-四链体转换为单链

在人类基因组中，尤其是在端粒区域，UTR和许多基因的启动子区域中，发现了形成四链体的大量富含G的序列。一种这样的基因是编码N-甲基-D-天冬氨酸受体（NMDA）的NR1亚基的GRIN1。几篇报道暗示，NMDA的功能减弱会导致精神分裂症，这是一种以幻觉，妄想和精神病为特征的遗传性疾病。已经广泛分析了GRIN1基因参与精神分裂症的发病机理。最近的报道表明，GRIN1的启动子区域具有多态性。在-855（G / C）位置可能与精神分裂症有关。NF-κB转录因子的结合位点由于这种突变而改变，从而导致基因表达降低以及NMDA活性降低。通过结合凝胶电泳（PAGE），圆二色性（CD）和CD熔解技术，研究了富G序列（d-CTTAGCCCGAGGA GGGGGTCCCAAGT; GRIN1）的G→C单核苷酸多态性（SNP）。我们报告说，GRIN1序列可以在存在K ⁺以及Na ⁺的情况下形成具有平行构象的八聚体/多链四链体结构。CD和凝胶研究密切相关，以检测分子和链构象。假设平行的G-四链体物质在K ⁺ / Na ⁺盐中为八聚体。突变序列（d-CTTAGCCCGAGGA GGGGGTCCCAAGT； GRIN1M）在生理条件下保持单链。CD熔解研究支持通过GRIN1序列形成链间G-四链体结构。提出了两种结构模型用于多链平行G-四链构象，其可能负责调节通常在记忆和学习基础上的基因表达。