Cheng Chin-Hung, Yew David Tai-Wai, Kwan Hiu-Yee, Zhou Qing, Huang Yu, Liu Yong, Chan Wing-Yee, Yao Xiaoqiang
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Mol Biol Cell. 2002 Oct;13(10):3696-705. doi: 10.1091/mbc.e02-03-0127.
CNG channels are cyclic nucleotide-gated Ca(2+)-permeable channels that are suggested to be involved in the activity-dependent alterations of synaptic strength that are thought to underlie information storage in the CNS. In this study, we isolated an endogenous RNA transcript antisense to CNG(alpha)1 mRNA. This transcript was capable of down-regulating the expression of sense CNG(alpha)1 in the Xenopus oocyte expression system. RT-PCR, Northern blot, and in situ hybridization analyses showed that the transcript was coexpressed with CNG(alpha)1 mRNA in many regions of human brain, notably in those regions that were involved in long-term potentiation and long-term depression, such as hippocampal CA1 and CA3, dentate gyrus, and cerebellar Purkinje layer. Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNG(alpha)1. Treatment of human glioma cell T98 with thyroid hormone T(3) caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNG(alpha)1 expression. These data suggest that the suppression of CNG(alpha)1 expression by anti-CNG1 may play an important role in neuronal functions, especially in synaptic plasticity and cortical development. Endogenous antisense RNA-mediated regulation may represent a new mechanism through which the activity of ion channels can be regulated in the human CNS.
环核苷酸门控性钙离子通透通道(CNG通道)被认为参与了突触强度的活动依赖性改变,而这种改变被认为是中枢神经系统信息存储的基础。在本研究中,我们分离出了一种与CNG(α)1 mRNA互补的内源性RNA转录本。该转录本能够在非洲爪蟾卵母细胞表达系统中下调有义CNG(α)1的表达。逆转录聚合酶链反应(RT-PCR)、Northern印迹和原位杂交分析表明,该转录本在人脑的许多区域与CNG(α)1 mRNA共表达,特别是在那些参与长时程增强和长时程抑制的区域,如海马CA1和CA3、齿状回以及小脑浦肯野层。成人和胎儿大脑皮层表达模式的比较显示,抗CNG1和CNG(α)1的表达水平存在同步的发育变化。用甲状腺激素T(3)处理人胶质瘤细胞T98导致抗CNG1表达显著增加,同时有义CNG(α)1表达平行下降。这些数据表明,抗CNG1对CNG(α)1表达的抑制可能在神经元功能中起重要作用,特别是在突触可塑性和皮层发育方面。内源性反义RNA介导的调节可能代表了一种新的机制,通过该机制可以在人类中枢神经系统中调节离子通道的活性。