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 the Drosophila retina. 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 the Drosophila sterol 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.

越来越多的证据表明，miRNA 在神经系统中发挥着重要的调节作用。然而，特定 miRNA 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，我们提供证据表明保守的 microRNA miR-210 调节脂质代谢并防止果蝇视网膜中的神经变性。miR-210 在感光神经元和其他感觉器官中特异性表达。miR-210 的遗传缺失导致视网膜中的脂滴积累和光感受器退化。这些影响与果蝇的异常激活有关甾醇调节元件结合蛋白信号。我们进一步将乙酰辅酶 A 合成酶 (ACS) 确定为 miR-210 在此背景下的一个重要功能靶标。miR-210 突变背景中 ACS 的减少抑制了神经变性缺陷，表明 miR-210 通过调节 ACS 转录物起作用。总之，这些结果揭示了 miR-210 在控制脂质代谢和神经元功能方面的意外作用。