实验验证候选精神分裂症基因 ZNF804A 是 hsa-miR-137 的作用靶点。
Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137.
机构信息
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA, USA.
Department of Molecular Human Genetics, Virginia Commonwealth University, Richmond, VA, USA.
出版信息
Schizophr Res. 2012 Oct;141(1):60-64. doi: 10.1016/j.schres.2012.06.038. Epub 2012 Aug 9.
MicroRNAs (miRNAs) are small non-coding RNAs that mainly function as negative regulators of gene expression (Lai, 2002) and have been shown to be involved in schizophrenia etiology through genetic and expression studies (Burmistrova et al., 2007; Hansen et al., 2007a; Perkins et al., 2007; Beveridge et al., 2010; Kim et al., 2010). In a mega analysis of genome-wide association study (GWAS) of schizophrenia (SZ) and bipolar disorders (BP), a polymorphism (rs1625579) located in the primary transcript of a miRNA gene, hsa-miR-137, was reported to be strongly associated with SZ. Four SZ loci (CACNA1C, TCF4, CSMD1, C10orf26) achieving genome-wide significance in the same study were predicted and later experimentally validated (Kwon et al., 2011) as hsa-miR-137 targets. Here, using in silico, cellular and luciferase based approaches we also provide evidence that another well replicated candidate schizophrenia gene, ZNF804A, is also target for hsa-miR-137.
微小 RNA（miRNAs）是一类主要作为基因表达负调控因子的小非编码 RNA（Lai，2002），通过遗传和表达研究表明其与精神分裂症的病因有关（Burmistrova 等人，2007；Hansen 等人，2007a；Perkins 等人，2007；Beveridge 等人，2010；Kim 等人，2010）。在一项对精神分裂症（SZ）和双相情感障碍（BP）的全基因组关联研究（GWAS）的大型分析中，报道了位于 miRNA 基因 hsa-miR-137 初级转录物中的一个多态性（rs1625579）与 SZ 强烈相关。在同一研究中，四个达到全基因组显著水平的 SZ 基因座（CACNA1C、TCF4、CSMD1、C10orf26）被预测为 hsa-miR-137 的靶基因，后来通过实验验证（Kwon 等人，2011）。在这里，我们通过计算机模拟、细胞和荧光素酶报告基因方法，也提供了证据表明另一个具有高度可重复性的候选精神分裂症基因 ZNF804A 也是 hsa-miR-137 的靶基因。
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