Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia.
Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia.
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DOI：
10.1371/journal.pone.0128830
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Cox JJ
中科院分区：
文献类型：
--
作者：
Koenig J;Werdehausen R;Linley JE;Habib AM;Vernon J;Lolignier S;Eijkelkamp N;Zhao J;Okorokov AL;Woods CG;Wood JN;Cox JJ
由SCN 9A编码的Nav1.7电压门控钠通道对人类疼痛感知至关重要，但调控该基因的转录和转录后机制仍不完全清楚。在这里，我们描述了一种新的天然反义转录本（NAT）的SCN 9A是保守的人类和小鼠。NAT具有与正义基因相似的组织表达模式，并且在背根神经节内选择性剪接。人和小鼠NAT与有义基因以尾对尾的方向顺式存在，并且两者共享与SCN 9A/Scn 9a的末端外显子互补的序列。人NAT在人胚肾（HEK 293 A）和人神经母细胞瘤（SH-SY 5 Y）细胞系中的过表达分析表明，它可以下调Nav1.7 mRNA、蛋白水平和电流。NAT可能在调节人类疼痛阈值中起重要作用，并且是患有慢性疼痛疾病的个体的潜在候选基因，所述慢性疼痛疾病映射到SCN 9A位点，例如遗传性原发性红斑性肢痛症、阵发性极端疼痛障碍和疼痛性小纤维神经病，但在有义基因中不包含突变。我们的研究结果强烈表明，SCN 9A NAT是基于增强现有反义RNA治疗人类慢性疼痛病症的新疗法的主要候选者。
The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a. Overexpression analyses of the human NAT in human embryonic kidney (HEK293A) and human neuroblastoma (SH-SY5Y) cell lines show that it can function to downregulate Nav1.7 mRNA, protein levels and currents. The NAT may play an important role in regulating human pain thresholds and is a potential candidate gene for individuals with chronic pain disorders that map to the SCN9A locus, such as Inherited Primary Erythromelalgia, Paroxysmal Extreme Pain Disorder and Painful Small Fibre Neuropathy, but who do not contain mutations in the sense gene. Our results strongly suggest the SCN9A NAT as a prime candidate for new therapies based upon augmentation of existing antisense RNAs in the treatment of chronic pain conditions in man.
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长的非编码RNA通过在原发性传入神经元中沉默的KCNA2导致神经性疼痛。
影响因子：
25
作者：
Zhao, Xiuli;Tang, Zongxiang;Zhang, Hongkang;Atianjoh, Fidelis E.;Zhao, Jian-Yuan;Liang, Lingli;Wang, Wei;Guan, Xiaowei;Kao, Sheng-Chin;Tiwari, Vinod;Gao, Yong-Jing;Hoffman, Paul N.;Cui, Hengmi;Li, Min;Dong, Xinzhong;Tao, Yuan-Xiang
通讯作者：
Tao, Yuan-Xiang
先天性对疼痛和红细胞毛的不敏感性中的SCN9A突变很少发生。
DOI：
10.1136/jnnp-2012-303719
发表时间：
2013-04
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Klein CJ;Wu Y;Kilfoyle DH;Sandroni P;Davis MD;Gavrilova RH;Low PA;Dyck PJ
通讯作者：
Dyck PJ
影响因子：
11.2
作者：
Faber, Catharina G.;Hoeijmakers, Janneke G. J.;Merkies, Ingemar S. J.
通讯作者：
Merkies, Ingemar S. J.
影响因子：
25
作者：
Usoskin, Dmitry;Furlan, Alessandro;Ernfors, Patrik
通讯作者：
Ernfors, Patrik
影响因子：
5.8
作者：
Vetter, Irina;Mozar, Christine A.;Lewis, Richard J.
通讯作者：
Lewis, Richard J.