Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Joint Primate Research Center for Chronic Diseases, Institute of Zoology of Guangdong Academy of Science, Jiangnan University, Wuxi, Jiangsu, China.
BMC Genomics. 2024 May 1;25(1):431. doi: 10.1186/s12864-024-10324-z.
Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.
眼科表现已在由 SARS-CoV-2 感染引起的 COVID-19 的急性和后期并发症中被观察到。我们的宝贵研究表明，宿主 RNA 编辑与 RNA 病毒感染有关，但 COVID-19 中，SARS-CoV-2 感染期间眼部腺苷到肌苷（A-to-I）RNA 编辑尚未被研究。在此，我们使用一个转录后组学分析流程，分析了 37 个样本，研究了五种眼部组织类型（包括结膜、角膜缘、角膜、巩膜和视网膜类器官）中与 SARS-CoV-2 感染相关的 A-to-I 编辑。我们的结果揭示了五个眼部组织中 A-to-I RNA 编辑的显著改变。值得注意的是，角膜中 RNA 编辑的全转录组平均水平增加，但其他四个眼部组织中一般降低。功能富集分析表明，差异 RNA 编辑（DRE）主要在与泛素依赖性蛋白分解代谢过程、转录调控和 RNA 剪接相关的基因中。除了每个组织中发现的组织特异性 RNA 编辑外，还观察到不同组织中存在共同的 RNA 编辑，特别是在先天抗病毒免疫基因 MAVS 和 E3 泛素蛋白连接酶 MDM2 中。在视网膜类器官中的分析进一步揭示了 SARS-CoV-2 感染期间时间依赖性的高度动态 RNA 编辑改变。因此，我们的研究表明 RNA 编辑在 COVID-19 的眼部表现中可能发挥作用，并强调了其对先天免疫的潜在转录组影响。
