MiR-210 Regulates Lipid Metabolism And Maintains The Structure And Function Of Photoreceptors In Drosophila

Micro RNAs?miRNAs?are non-coding small RNAs with a length of about 22nucleotides that are abundant in organisms and inhibit gene expression through transcription and post-transcriptional regulation.In recent years,several studies have shown that miRNAs play an important role in maintaining the structure and function of the nervous system.Dysregulation of miRNAs is associated with many neurodegenerative diseases.Discovering novel nervous system-specific miRNAs and identifying their mechanisms in various types of neurons are essential to understanding basic neurodevelopmental processes and neuronal degeneration mechanisms.miR-210belongs to a family of miRNAs that is highly conserved among different species.Earlier studies found that miR-210 was highly expressed under hypoxic condition and regulated a variety of biological processes.Multiple studies have also shown that miR-210 is highly expressed in a variety of cancer tissues including breast cancer,osteosarcoma and lung cancer and plays an important role in the development of cancer.Nevertheless,the physiological functions of miR-210 are not entirely clear.Here the experiments'results show that miR-210 could regulate lipid metabolism and maintain the structure and function of Drosophila eyes,preventing the degeneration of photoreceptor neurons.miR-210 was specifically expressed in a variety of Drosophila sensory organs,including the eye.Using the CRISPR-Cas9 technology,we constructed a miR-210 deletion mutant—miR-210^?130,and found that the mutant had a defect in the eye structure,and the photoreceptors R1-R7 degenerated in advance,arranged irregularly.In addition,the microvilli had a loose arrangement in rhabdomere.Rh1,INAD,and PLC are necessary for eye function maintenance.Western Blot results all showed a significant reduction in the amount of these proteins.At the same time,we also found the accumulation of lipid droplets in miR-210^?130 mutant.Lipid metabolomics analysis showed that triglyceride levels were elevated in miR-210 mutant.Further research found that the level of mature SREBP protein in miR-210^?130 mutant increased significantly.Knocking down the expression of SREBP could rescue the phenotype of lipid droplets accumulation in the eyes of miR-210^?130 mutant,and partially rescue the degeneration of photoreceptors.RNA-Seq and bioinformatics analysis showed that acetyl-Co A synthetase?ACS?may be a target gene of miR-210 and confirmed by Dual-Luciferase Reporter assay.Further genetic experiments had also shown that reducing ACS's expression in the miR-210^?130mutant background could partially inhibit the degeneration phenotype of photoreceptors.In summary,miR-210 affects lipid metabolism and maintains the structure and function of photoreceptors by regulating the SREBP signaling pathway and ACS.This research will help us understand the function and mechanism of miR-210 in the nervous system,and reveals the correlation between lipid metabolism and neurodegenerative diseases.