miR-980 是一种记忆抑制 microRNA，可调节自闭症易感基因 A2bp1。
MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1.
机构信息
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
出版信息
Cell Rep. 2016 Feb 23;14(7):1698-1709. doi: 10.1016/j.celrep.2016.01.040. Epub 2016 Feb 11.
MicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement.
微小 RNA 与许多不同的生物学功能有关，但它们在条件行为中的作用知之甚少。我们证明，果蝇 miR-980 是一种记忆抑制基因，在成年大脑的多个区域发挥作用。miR-980 的抑制作用可增加记忆的获得和稳定性。全细胞记录和功能成像实验表明，miR-980 调节神经元兴奋性。我们确定了自闭症易感性基因 A2bp1 作为 miR-980 的 mRNA 靶标。A2bp1 水平与 miR-980 表达呈负相关；记忆表现与 A2bp1 水平直接相关。此外，A2bp1 的敲低逆转了 miR-980 抑制产生的记忆增益，这与 A2bp1 是 miR-980 负责记忆表型的下游靶标一致。我们的研究结果表明，miR-980 抑制 A2bp1 的表达来调节神经元的兴奋状态，而兴奋状态的总体情况会导致记忆损伤或改善。
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