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MicroRNA-mediated regulation of lipid metabolism in virus-infected Emiliania huxleyi
The ISME Journal ( IF 11.0 ) Pub Date : 2022-07-22 , DOI: 10.1038/s41396-022-01291-y
Enquan Zhang 1 , Jingjing Gao 1 , Zehua Wei 1 , Jun Zeng 1 , Jian Li 1 , Guiling Li 1 , Jingwen Liu 1
Affiliation  

The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycles and play a prominent role in global climate change. As a large DNA virus, EhV has developed a novel “virocell metabolism” model to meet its high metabolic needs. Although it has been widely demonstrated that EhV infection can profoundly rewire lipid metabolism, the epigenetic regulatory mechanisms of lipid metabolism are still obscure. MicroRNAs (miRNAs) can regulate biological pathways by targeting hub genes in the metabolic processes. In this study, the transcriptome, lipidome, and miRNAome were applied to investigate the epigenetic regulation of lipid metabolism in E. huxleyi cells during a detailed time course of viral infection. Combined transcriptomic, lipidomic, and physiological experiments revealed reprogrammed lipid metabolism, along with mitochondrial dysfunction and calcium influx through the cell membrane. A total of 69 host miRNAs (including 1 known miRNA) and 7 viral miRNAs were identified, 27 of which were differentially expressed. Bioinformatic prediction revealed that miRNAs involved in the regulation of lipid metabolism and a dual-luciferase reporter assay suggested that phosphatidylinositol 3-kinase (PI3K) gene might be a target of ehx-miR5. Further qPCR and western blot analysis showed a significant negative correlation between the expression of ehx-miR5 and its target gene PI3K, along with the lower activity of its downstream components (p-Akt, p-TOR, SREBP), indicating that lipid metabolism might be regulated by ehx-miR5 through the PI3K-Akt-TOR signaling pathway. Our findings reveal several novel mechanisms of viral strategies to manipulate host lipid metabolism and provide evidence that ehx-miR5 negatively modulates the expression of PI3K and disturbs lipid metabolism in the interactions between E. huxleyi and EhV.



中文翻译:

MicroRNA介导的病毒感染艾米利亚胡胥黎脂质代谢的调节

Emiliania huxleyiE. huxleyi病毒 (EhV)之间的相互作用调节海洋碳和硫的生物地球化学循环,在全球气候变化中发挥着重要作用。作为一种大型 DNA 病毒,EhV 开发了一种新的“病毒细胞代谢”模型,以满足其高代谢需求。尽管已广泛证明 EhV 感染可以深刻地重新连接脂质代谢,但脂质代谢的表观遗传调控机制仍然不清楚。MicroRNAs (miRNAs) 可以通过靶向代谢过程中的枢纽基因来调节生物通路。在这项研究中,转录组、脂质组和 miRNA 组被用于研究E. huxleyi脂质代谢的表观遗传调控。细胞在病毒感染的详细时间过程中。结合转录组学、脂质组学和生理学实验揭示了重新编程的脂质代谢,以及线粒体功能障碍和钙通过细胞膜的流入。共鉴定出69个宿主miRNA(包括1个已知miRNA)和7个病毒miRNA,其中27个差异表达。生物信息学预测显示,参与脂质代谢调节的 miRNA 和双荧光素酶报告基因分析表明,磷脂酰肌醇 3-激酶 (PI3K) 基因可能是 ehx-miR5 的靶标。进一步的 qPCR 和蛋白质印迹分析显示 ehx-miR5 的表达与其靶基因PI3K呈显着负相关,以及其下游成分(p-Akt、p-TOR、SREBP)的较低活性,表明 ehx-miR5 可能通过 PI3K-Akt-TOR 信号通路调节脂质代谢。我们的研究结果揭示了操纵宿主脂质代谢的病毒策略的几种新机制,并提供了 ehx-miR5 负调节 PI3K 表达并扰乱E. huxleyi和 EhV 之间相互作用中的脂质代谢的证据。

更新日期:2022-07-22
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