One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors
One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors
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DOI：
10.14800/rd.1560
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发表时间：
2017-06
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影响因子：
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通讯作者：
William J. Jaremko;Zhen-Hua Huang;Wei Wen;Andrew Wu;Nicholas Karl;L. Niu
中科院分区：
文献类型：
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作者：
William J. Jaremko;Zhen-Hua Huang;Wei Wen;Andrew Wu;Nicholas Karl;L. Niu
AMPA和kainate受体以及NMDA受体是谷氨酸离子通道的不同亚型。AMPA和盐酸盐受体的过度活性与神经系统疾病有关，如癫痫和神经性疼痛。因此，阻断其活性的拮抗剂是潜在的候选药物。在Jaremko等人2017年发表在《生物化学杂志》上的一篇文章中，我们报道了一种具有双重功能的RNA适配体的发现和分子表征：全长RNA（101核苷酸）抑制AMPA受体，而截断或缩短的RNA（55核苷酸）抑制AMPA和kainate受体。全长RNA适配体通过特别设计的系统进化配体通过指数富集（SELEX）分离，仅使用HEK-293细胞中表达的单一类型的AMPA受体。本文强调了我们最近文章的设计特点和结果，因为它们证明了SELEX方法的实用性，以及使用单一AMPA受体类型开发针对多个亚基和具有长度依赖功能的AMPA/kainate受体亚型的有效的新型RNA适体的潜力。
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.