Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232-2363, USA.
Vanderbilt Institute for Infection, Immunology and Inflammation, Nashville, TN, 37232-2363, USA.
Nat Commun. 2023 Mar 13;14(1):1367. doi: 10.1038/s41467-023-37105-8.
Adenosine-to-inosine RNA editing is a major contributor to transcriptome diversity in animals with far-reaching biological consequences. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of several human malignancies including primary effusion lymphoma (PEL). The extent of RNA editing within the KSHV transcriptome is unclear as is its contribution to the viral lifecycle. Here, we leverage a combination of biochemical and genomic approaches to determine the RNA editing landscape in host- and KSHV transcriptomes during both latent and lytic replication in PEL. Analysis of RNA editomes reveals it is dynamic, with increased editing upon reactivation and the potential to deregulate pathways critical for latency and tumorigenesis. In addition, we identify conserved RNA editing events within a viral microRNA and discover their role in miRNA biogenesis as well as viral infection. Together, these results describe the editome of PEL cells as well as a critical role for A-to-I editing in the KSHV lifecycle.
腺嘌呤到肌苷的 RNA 编辑是动物转录组多样性的主要贡献者，具有深远的生物学后果。卡波济肉瘤相关疱疹病毒 (KSHV) 是几种人类恶性肿瘤的病原体，包括原发性渗出性淋巴瘤 (PEL)。KSHV 转录组中的 RNA 编辑程度尚不清楚，其对病毒生命周期的贡献也不清楚。在这里，我们利用生化和基因组方法的组合，在 PEL 潜伏和裂解复制过程中确定宿主和 KSHV 转录组中的 RNA 编辑景观。RNA 编辑组分析表明，它是动态的，在重新激活时编辑增加，并且有可能使与潜伏期和肿瘤发生相关的途径失活。此外，我们在病毒 microRNA 内鉴定出保守的 RNA 编辑事件，并发现它们在 miRNA 生物发生以及病毒感染中的作用。总之，这些结果描述了 PEL 细胞的编辑组以及 A-to-I 编辑在 KSHV 生命周期中的关键作用。
