Control of human potassium channel inactivation by editing of a small mRNA hairpin
Control of human potassium channel inactivation by editing of a small mRNA hairpin
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DOI：
10.1038/nsmb825
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发表时间：
2004-10-01
影响因子：
16.8
通讯作者：
Reenan, R
中科院分区：
文献类型：
--
作者：
Bhalla, T;Rosenthal, JJC;Reenan, R
通过A-->I RNA编辑的基因组重编码在使参与电兴奋性的蛋白质多样化方面起着重要作用。在这里，我们描述了一个无内含子钾通道基因的编辑。人K（V）1.1 mRNA序列的一个小区域指导作用于RNA 2的人腺苷脱氨酶（hADAR 2）对一个腺苷的有效修饰。突变分析表明，该区域采用发夹结构。电生理特性表明，编辑事件（I/V）深刻地影响通道失活所赋予的辅助β亚基。果蝇Shaker通道通过突变模仿这种编辑事件，表现出类似的效果。此外，我们证明了旁系同源D.黑腹鼠Shab钾通道在同一位置被果蝇ADAR编辑-腺苷脱氨驱动的趋同进化的一个明显例子。这些结果表明，一个古老的和关键的调节作用，这个残基在K-V通道。
Genomic recoding by A-->I RNA editing plays an important role in diversifying the proteins involved in electrical excitability. Here, we describe editing of an intronless potassium channel gene. A small region of human K(V)1.1 mRNA sequence directs efficient modification of one adenosine by human adenosine deaminase acting on RNA 2 (hADAR2). Mutational analysis shows that this region adopts a hairpin structure. Electrophysiological characterization reveals that the editing event (I/V) profoundly affects channel inactivation conferred by accessory beta subunits. Drosophila melanogaster Shaker channels, mimicking this editing event through mutation, exhibit a similar effect. In addition, we demonstrate that mRNAs for the paralogous D. melanogaster Shab potassium channel are edited at the same position by fly ADAR-a clear example of convergent evolution driven by adenosine deamination. These results suggest an ancient and key regulatory role for this residue in K-V channels.