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

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....

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Autores principales: Liu, Geng, Du, Wenya, Sang, Xiongbo, Tong, Qiyu, Wang, Ye, Chen, Guoqing, Yuan, Yi, Jiang, Lili, Cheng, Wei, Liu, Dan, Tian, Yan, Fu, Xianghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931161/
https://www.ncbi.nlm.nih.gov/pubmed/35301316
http://dx.doi.org/10.1038/s41467-022-29135-5
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author Liu, Geng
Du, Wenya
Sang, Xiongbo
Tong, Qiyu
Wang, Ye
Chen, Guoqing
Yuan, Yi
Jiang, Lili
Cheng, Wei
Liu, Dan
Tian, Yan
Fu, Xianghui
author_facet Liu, Geng
Du, Wenya
Sang, Xiongbo
Tong, Qiyu
Wang, Ye
Chen, Guoqing
Yuan, Yi
Jiang, Lili
Cheng, Wei
Liu, Dan
Tian, Yan
Fu, Xianghui
author_sort Liu, Geng
collection PubMed
description 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.
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spelling pubmed-89311612022-04-01 RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection Liu, Geng Du, Wenya Sang, Xiongbo Tong, Qiyu Wang, Ye Chen, Guoqing Yuan, Yi Jiang, Lili Cheng, Wei Liu, Dan Tian, Yan Fu, Xianghui Nat Commun Article 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. Nature Publishing Group UK 2022-03-17 /pmc/articles/PMC8931161/ /pubmed/35301316 http://dx.doi.org/10.1038/s41467-022-29135-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Geng
Du, Wenya
Sang, Xiongbo
Tong, Qiyu
Wang, Ye
Chen, Guoqing
Yuan, Yi
Jiang, Lili
Cheng, Wei
Liu, Dan
Tian, Yan
Fu, Xianghui
RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title_full RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title_fullStr RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title_full_unstemmed RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title_short RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
title_sort rna g-quadruplex in tmprss2 reduces sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931161/
https://www.ncbi.nlm.nih.gov/pubmed/35301316
http://dx.doi.org/10.1038/s41467-022-29135-5
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