Abstract
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.
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Acknowledgements
We thank Zhefeng Gong, John R. Carlson, Junhai Han, the Developmental Studies Hybridoma Bank, the Vienna Drosophila Resource Center, the Kyoto and Bloomington Drosophila stock center for fly stocks and antibodies; Caodi Xu for the initial characterization of miR-210 expression pattern; Feng He for the help with the generation of heatmap. We are grateful to Jun Ma, Ting Gang Chew, Pushpa Sharma, Chao Tong, Feng He, Tao Wang, Zhefeng Gong, Jia Huang, and Nan Liu for their suggestions and help for various experiments. This work was funded by the National Key Research and Development Program of China (2018YFC1003200), and also by a grant (31970668) from the National Natural Science Foundation of China.
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Lyu, J., Chen, Y., Yang, W. et al. The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina. Cell Death Differ 28, 764–779 (2021). https://doi.org/10.1038/s41418-020-00622-w
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DOI: https://doi.org/10.1038/s41418-020-00622-w
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