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RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection.

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收录情况： ◇ 自然指数

作者：
Liu Geng[1] ; Du Wenya[1] ; Sang Xiongbo[1] ; Tong Qiyu[1] ; Wang Ye[2] ; Chen Guoqing[3] ; Yuan Yi[4] ; Jiang Lili[5] ; Cheng Wei[3] ; Liu Dan[2] ; Tian Yan[1] ; Fu Xianghui[1] ;
机构： [1]Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041 Sichuan, China. [2]Division of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China. [3]Division of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China. [4]Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041 Sichuan, China [5]Lab of Pathology, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China.
出处：
DOI： 10.1038/s41467-022-29135-5

摘要：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.© 2022. The Author(s).

基金：
This work was supported by National Natural Science Foundation of China (92157205 and 81970561 to X.F.; 82172986 to Y.T.; 82173182 to D.L.; 82000547 to G.L.); Ministry of Science and Technology (2018ZX09201018-005 to X.F.); the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC18049 to X.F.); National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z20191005 to X.F.); the Fellowship of China Postdoctoral Science Foundation (2020TQ0215, 2021M690112 to G.L.) and Sichuan University Postdoctoral Interdisciplinary Innovation Fund to G.L.
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外文
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出版当年[2022]版：
大类 | 1 区 综合性期刊
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最新[2023]版：
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小类 | 1 区 综合性期刊
第一作者：
第一作者机构： [1]Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041 Sichuan, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Geng,Du Wenya,Sang Xiongbo,et al.RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection.[J].Nature communications.2022,13(1):1444.doi:10.1038/s41467-022-29135-5.
APA：
Liu Geng,Du Wenya,Sang Xiongbo,Tong Qiyu,Wang Ye...&Fu Xianghui.(2022).RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection..Nature communications,13,(1)
MLA：
Liu Geng,et al."RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection.".Nature communications 13..1(2022):1444

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