The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in theDrosophilaretina
The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in theDrosophilaretina
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DOI：
10.1038/s41418-020-00622-w
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发表时间：
2020-09-10
影响因子：
12.4
通讯作者：
Ge, Wanzhong
中科院分区：
文献类型：
--
作者：
Lyu, Jialan;Chen, Yuchen;Ge, Wanzhong
越来越多的证据表明，miRNAs在神经系统中发挥着重要的调节作用。然而，特定的miRNAs如何影响神经元发育和功能的分子机制仍然不太清楚。在本研究中，我们提供了证据表明，保守的microRNA miR-210调节果蝇的脂代谢，防止神经退行性变。MIR-210在光感受器神经元和其他感觉器官中特异表达。MiR-210基因缺失会导致视网膜内脂滴堆积和感光器退化。这些效应与果蝇甾醇调节元件结合蛋白信号的异常激活有关。在此背景下，我们进一步确定乙酰辅酶A合成酶(ACS)是miR-210的一个重要功能靶点。MiR-210突变背景中ACS的减少抑制了神经变性缺陷，表明miR-210通过调控ACS转录本发挥作用。综上所述，这些结果揭示了miR-210在控制脂代谢和神经功能方面出人意料的作用。
Increasing evidence suggests that miRNAs play important regulatory roles in the nervous system. However, the molecular mechanisms of how specific miRNAs affect neuronal development and functions remain less well understood. In the present study, we provide evidence that the conserved microRNA miR-210 regulates lipid metabolism and prevents neurodegeneration in theDrosophilaretina. miR-210 is specifically expressed in the photoreceptor neurons and other sensory organs. Genetic deletion of miR-210 leads to lipid droplet accumulation and photoreceptor degeneration in the retina. These effects are associated with abnormal activation of theDrosophilasterol regulatory element-binding protein signaling. We further identify the acetyl-coenzyme A synthetase (ACS) as one functionally important target of miR-210 in this context. Reduction of ACS in the miR-210 mutant background suppresses the neurodegeneration defects, suggesting that miR-210 acts through regulation of the ACS transcript. Together, these results reveal an unexpected role of miR-210 in controlling lipid metabolism and neuronal functions.