miR-149 reduces while let-7 elevates ASIC1a expression in vitro.
miR-149 reduces while let-7 elevates ASIC1a expression in vitro.
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发表时间：
2017-11
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通讯作者：
Yu-Qing Jiang;Xiang-ming Zha
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作者：
Yu-Qing Jiang;Xiang-ming Zha
酸敏感离子通道1a（ASIC 1a）是决定神经元酸激活电流的关键亚基。ASIC 1a对神经可塑性、学习和多种神经系统疾病（包括中风、多发性硬化和创伤性损伤）都很重要。这些发现强调了更好地定义调节ASIC 1a表达的机制的重要性。在过去的十年中，microRNA已经成为控制蛋白质表达的一组重要的调控分子。然而，关于microRNA是否调控ASIC 1a的研究却知之甚少。在这里，我们评估了几种在小鼠ASIC 1a的3'非翻译区（UTR）中预测靶向序列的microRNA。我们的研究结果表明，miR-144和-149降低ASIC 1a表达，而Let-7增加ASIC 1a蛋白水平。miR-30 c、-98、-125、-182* 无显著影响。由于ASIC 1a表达的减少可能在治疗神经元损伤中具有翻译潜力，我们进一步询问了miR-144和miR-149的作用是否通过特异性靶向ASIC 1a上的预测位点来降低ASIC 1a表达。我们突变了miR-144和miR-149在ASIC 1a UTR中的靶向序列。miR-149的作用在相应的突变中被消除。相比之下，当其预测的靶序列发生突变时，miR-144仍然降低ASIC 1a水平。该结果表明miR-149靶向ASIC 1a的3 'UTR并降低其表达。
Acid-sensing ion channel 1a (ASIC1a) is the key subunit that determines acid-activated currents in neurons. ASIC1a is important for neural plasticity, learning, and for multiple neurological diseases, including stroke, multiple sclerosis, and traumatic injuries. These findings underline the importance for better defining mechanisms that regulate ASIC1a expression. During the past decade, microRNA has emerged as one important group of regulatory molecules in controlling protein expression. However, little is known about whether microRNA regulates ASIC1a. Here, we assessed several microRNAs that have predicted targeting sequences in the 3' untranslated region (UTR) of mouse ASIC1a. Our results indicated that miR-144 and -149 reduced ASIC1a expression while Let-7 increased ASIC1a protein levels. miR-30c, -98, -125, -182* had no significant effect. Since a reduction in ASIC1a expression may have translational potentials in treating neuronal injury, we further asked whether the effect of miR-144 and miR-149, both reduced ASIC1a expression, was through specific targeting of the predicted sites on ASIC1a. We mutated the targeting sequence of miR-144 and miR-149 in ASIC1a UTR. The effect of miR-149 was abolished in the corresponding mutation. In contrast, miR-144 still reduced ASIC1a level when its predicted target sequence was mutated. This result indicates that miR-149 targets the 3'UTR of ASIC1a and reduces its expression.