Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences
Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences
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DOI：
10.1016/j.ygeno.2007.04.006
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发表时间：
2007-08-01
期刊：
影响因子：
4.4
通讯作者：
Escayg, Andrew
中科院分区：
文献类型：
--
作者：
Martin, Melinda S.;Tang, Bin;Escayg, Andrew
染色体2q24上的人类电压门控钠通道基因簇包含三个旁系同源物：SCN1A、SCN2A和SCN3A，它们在中枢神经系统中表达。 SCN1A 和 SCN2A 突变导致特发性癫痫的几种亚型。此外，许多 SCN1A 突变预计会降低蛋白质水平，这强调了精确钠通道基因调控的重要性。为了研究调节 SCN1A、SCN2A 和 SCN3A 表达的遗传因素，我们对每个基因的 5' 非翻译区进行了表征。我们鉴定了多个非编码外显子，并观察了非编码外显子表达水平的大脑区域差异。比较序列分析揭示了直系同源哺乳动物基因之间有 33 个保守的非编码序列 (CNS)，三个人类旁系同源基因之间有 6 个 CNS。七个 CNS 对应于非编码外显子。对 12 个 CNS 改变荧光素酶报告基因转录的能力进行了评估，其中 3 个 CNS 产生了适度但具有统计学意义的变化。 (c) 2007 Elsevier Inc. 保留所有权利。
The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system. Mutations in SCN1A and SCN2A cause several subtypes of idiopathic epilepsy. Furthermore, many SCN1A mutations are predicted to reduce protein levels, emphasizing the importance of precise sodium channel gene regulation. To investigate the genetic factors that regulate the expression of SCN1A, SCN2A, and SCN3A, we characterized the 5' untranslated region of each gene. We identified multiple noncoding exons and observed brain region differences in the expression levels of noncoding exons. Comparative sequence analysis revealed 33 conserved noncoding sequences (CNSs) between the orthologous mammalian genes and 6 CNSs between the three human paralogs. Seven CNSs corresponded to noncoding exons. Twelve CNSs were evaluated for their ability to alter the transcription of a luciferase reporter gene, and 3 resulted in a modest, but statistically significant change. (c) 2007 Elsevier Inc. All rights reserved.