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通过 CRISPR/dCas13 的 RNA 免疫沉淀揭示了 SARS-CoV-2 5'UTR RNA 与人类脂质代谢过程之间的相互作用。

An RNA-immunoprecipitation via CRISPR/dCas13 reveals an interaction between the SARS-CoV-2 5'UTR RNA and the process of human lipid metabolism.

机构信息

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.

出版信息

Sci Rep. 2023 Jun 27;13(1):10413. doi: 10.1038/s41598-023-36680-6.

DOI:10.1038/s41598-023-36680-6
PMID:37369697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10300121/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/8ae99950e379/41598_2023_36680_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/37f00df6d840/41598_2023_36680_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/e321d8801d37/41598_2023_36680_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/5abb06902bb9/41598_2023_36680_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/c3b0d4181b83/41598_2023_36680_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/8ae99950e379/41598_2023_36680_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/37f00df6d840/41598_2023_36680_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/e321d8801d37/41598_2023_36680_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/5abb06902bb9/41598_2023_36680_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/c3b0d4181b83/41598_2023_36680_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d1/10300121/8ae99950e379/41598_2023_36680_Fig5_HTML.jpg

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