Characterizing Light-Regulated Retinal MicroRNAs Reveals Rapid Turnover as a Common Property of Neuronal MicroRNAs
Characterizing Light-Regulated Retinal MicroRNAs Reveals Rapid Turnover as a Common Property of Neuronal MicroRNAs
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DOI：
10.1016/j.cell.2010.03.039
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发表时间：
2010-05-14
期刊：
影响因子：
64.5
通讯作者：
Filipowicz, Witold
中科院分区：
文献类型：
--
作者：
Krol, Jacek;Busskamp, Volker;Filipowicz, Witold
对不同照明水平的适应是视网膜功能的核心。在这里，我们证明了miR-183/96/182簇，miR-204和miR-211的水平受小鼠视网膜中不同光水平的调节。这些microRNA的浓度在暗适应过程中下调，在光适应视网膜中上调，快速衰减和转录增加是导致相应变化的原因。我们确定电压依赖性谷氨酸转运蛋白Slc 1a 1是感光细胞中miR-183/96/182的靶点之一。我们发现视网膜神经元中的microRNA比非神经元细胞中的microRNA衰减得快得多。高周转也是海马和皮层神经元以及体外从ES细胞分化的神经元中microRNA的特征。阻断活性降低了神经元细胞中microRNA的周转，而谷氨酸的刺激加速了它。我们的研究结果表明，神经元中microRNA的代谢高于大多数其他细胞类型，并与神经元的活动有关。
Adaptation to different levels of illumination is central to the function of the retina. Here, we demonstrate that levels of the miR-183/96/182 cluster, miR-204, and miR-211 are regulated by different light levels in the mouse retina. Concentrations of these microRNAs were downregulated during dark adaptation and upregulated in light-adapted retinas, with rapid decay and increased transcription being responsible for the respective changes. We identified the voltage-dependent glutamate transporter Slc1a1 as one of the miR-183/96/182 targets in photoreceptor cells. We found that microRNAs in retinal neurons decay much faster than microRNAs in nonneuronal cells. The high turnover is also characteristic of microRNAs in hippocampal and cortical neurons, and neurons differentiated from ES cells in vitro. Blocking activity reduced turnover of microRNAs in neuronal cells while stimulation with glutamate accelerated it. Our results demonstrate that microRNA metabolism in neurons is higher than in most other cells types and linked to neuronal activity.