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微小 RNA 介导的病毒感染的海洋原甲藻中脂质代谢的调控。

MicroRNA-mediated regulation of lipid metabolism in virus-infected Emiliania huxleyi.

机构信息

College of Ocean Food and Biological Engineering, Jimei University, Xiamen, 361021, China.

出版信息

ISME J. 2022 Nov;16(11):2457-2466. doi: 10.1038/s41396-022-01291-y. Epub 2022 Jul 22.

DOI:10.1038/s41396-022-01291-y
PMID:35869388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9561107/
Abstract

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.

摘要

菱形海线藻（Emiliania huxleyi）与菱形海线藻病毒（EhV）之间的相互作用调控着海洋碳硫生物地球化学循环，对全球气候变化起着重要作用。作为一种大型 DNA 病毒，EhV 已经开发出一种新的“病毒细胞代谢”模型来满足其高代谢需求。尽管已经广泛证明 EhV 感染可以深刻地重新布线脂代谢，但脂代谢的表观遗传调控机制仍不清楚。MicroRNAs（miRNAs）可以通过靶向代谢过程中的枢纽基因来调节生物途径。在这项研究中，应用转录组学、脂质组学和 miRNA 组学来研究 EhV 感染期间菱形海线藻细胞中脂代谢的表观遗传调控。结合转录组学、脂质组学和生理实验，揭示了重新编程的脂代谢，以及线粒体功能障碍和通过细胞膜的钙内流。总共鉴定出 69 个宿主 miRNAs（包括 1 个已知的 miRNA）和 7 个病毒 miRNAs，其中 27 个表现出差异表达。生物信息学预测揭示了 miRNA 参与脂代谢的调节，双荧光素酶报告基因实验表明，磷脂酰肌醇 3-激酶（PI3K）基因可能是 ehx-miR5 的靶基因。进一步的 qPCR 和 Western blot 分析显示，ehx-miR5 的表达与其靶基因 PI3K 呈显著负相关，其下游成分（p-Akt、p-TOR、SREBP）的活性也降低，表明 ehx-miR5 可能通过 PI3K-Akt-TOR 信号通路调节脂代谢。我们的研究结果揭示了病毒操纵宿主脂代谢的几种新策略，并提供了证据表明 ehx-miR5 通过负调控 PI3K 的表达干扰菱形海线藻与 EhV 之间的相互作用中的脂代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b6c/9561107/deabfb33fa22/41396_2022_1291_Fig7_HTML.jpg
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