MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration
MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration
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DOI：
10.1101/gad.209619.112
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发表时间：
2013-07-01
影响因子：
10.5
通讯作者：
Zhou, Feng-Quan
中科院分区：
文献类型：
--
作者：
Liu, Chang-Mei;Wang, Rui-Ying;Zhou, Feng-Quan
受调控的基因表达决定了神经元延伸轴突的内在能力，而这种能力的丧失是导致成熟哺乳动物中枢神经系统轴突再生失败的主要原因。microrna和组蛋白修饰是基因表达的关键表观遗传调控因子，但它们在哺乳动物轴突再生中的作用尚未得到很好的探讨。在这里，我们报道了microRNA-138 （miR-138）是轴突再生的一种新的抑制因子，并表明SIRT1， nad依赖性组蛋白去乙酰化酶，是miR-138的功能靶点。重要的是，我们提供了miR-138和SIRT1在体内调节哺乳动物轴突再生的第一个证据。此外，我们发现SIRT1还作为转录抑制因子抑制miR-138在成人感觉神经元中对周围神经损伤的表达。因此，miR-138和SIRT1形成了一个相互负反馈的调节回路，这为控制轴突固有再生能力提供了一种新的机制。
Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.