Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.
Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, 700-8525, Japan.
Sci Rep. 2023 Jun 27;13(1):10413. doi: 10.1038/s41598-023-36680-6.
We herein elucidate the function of SARS-CoV-2derived 5'UTR in the human cells. 5'UTR bound host cellular RNAs were immunoprecipitated by gRNA-dCas13 (targeting luciferase RNA fused to SARS-CoV-2 5'UTR) in HEK293T and A549 cells. The 5'UTR bound RNA extractions were predominantly enriched for regulating lipid metabolism. Overexpression of SARS-CoV-2 5'UTR RNA altered the expression of factors involved in the process of the human Mevalonate pathway. In addition, we found that HMG-CoA reductase inhibitors were shown to suppress SARS-CoV-2 5'UTR-mediated translation activities. In conclusion, we deduce the array of host RNAs interacting with SARS-CoV-2 5'UTR that drives SARS-CoV-2 translation and influences host metabolic pathways.
我们在此阐明了 SARS-CoV-2 5'UTR 在人体细胞中的功能。在 HEK293T 和 A549 细胞中,gRNA-dCas13(靶向与 SARS-CoV-2 5'UTR 融合的荧光素酶 RNA)将 5'UTR 结合的宿主细胞 RNA 进行免疫沉淀。5'UTR 结合的 RNA 提取物主要富集了调节脂质代谢的物质。SARS-CoV-2 5'UTR RNA 的过表达改变了参与人类甲羟戊酸途径的因子的表达。此外,我们发现 HMG-CoA 还原酶抑制剂可抑制 SARS-CoV-2 5'UTR 介导的翻译活性。总之,我们推断出与 SARS-CoV-2 5'UTR 相互作用的一系列宿主 RNA,这些 RNA 驱动 SARS-CoV-2 的翻译并影响宿主代谢途径。