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The architecture of the SARS-CoV-2 RNA genome inside virion
SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ con...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225788/ https://www.ncbi.nlm.nih.gov/pubmed/34168138 http://dx.doi.org/10.1038/s41467-021-22785-x |
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author | Cao, Changchang Cai, Zhaokui Xiao, Xia Rao, Jian Chen, Juan Hu, Naijing Yang, Minnan Xing, Xiaorui Wang, Yongle Li, Manman Zhou, Bing Wang, Xiangxi Wang, Jianwei Xue, Yuanchao |
author_facet | Cao, Changchang Cai, Zhaokui Xiao, Xia Rao, Jian Chen, Juan Hu, Naijing Yang, Minnan Xing, Xiaorui Wang, Yongle Li, Manman Zhou, Bing Wang, Xiangxi Wang, Jianwei Xue, Yuanchao |
author_sort | Cao, Changchang |
collection | PubMed |
description | SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly. Using vRIC-seq data, we reconstruct the tertiary structure of the SARS-CoV-2 genome and reveal a surprisingly “unentangled globule” conformation. We uncover many long-range duplexes and higher-order junctions, both of which are under purifying selections and contribute to the sequential package of the SARS-CoV-2 genome. Unexpectedly, the D614G and the other two accompanying mutations may remodel duplexes into more stable forms. Lastly, the structure-guided design of potent small interfering RNAs can obliterate the SARS-CoV-2 in Vero cells. Overall, our work provides a framework for studying the genome structure, function, and dynamics of emerging deadly RNA viruses. |
format | Online Article Text |
id | pubmed-8225788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82257882021-07-09 The architecture of the SARS-CoV-2 RNA genome inside virion Cao, Changchang Cai, Zhaokui Xiao, Xia Rao, Jian Chen, Juan Hu, Naijing Yang, Minnan Xing, Xiaorui Wang, Yongle Li, Manman Zhou, Bing Wang, Xiangxi Wang, Jianwei Xue, Yuanchao Nat Commun Article SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly. Using vRIC-seq data, we reconstruct the tertiary structure of the SARS-CoV-2 genome and reveal a surprisingly “unentangled globule” conformation. We uncover many long-range duplexes and higher-order junctions, both of which are under purifying selections and contribute to the sequential package of the SARS-CoV-2 genome. Unexpectedly, the D614G and the other two accompanying mutations may remodel duplexes into more stable forms. Lastly, the structure-guided design of potent small interfering RNAs can obliterate the SARS-CoV-2 in Vero cells. Overall, our work provides a framework for studying the genome structure, function, and dynamics of emerging deadly RNA viruses. Nature Publishing Group UK 2021-06-24 /pmc/articles/PMC8225788/ /pubmed/34168138 http://dx.doi.org/10.1038/s41467-021-22785-x Text en © The Author(s) 2021 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 Cao, Changchang Cai, Zhaokui Xiao, Xia Rao, Jian Chen, Juan Hu, Naijing Yang, Minnan Xing, Xiaorui Wang, Yongle Li, Manman Zhou, Bing Wang, Xiangxi Wang, Jianwei Xue, Yuanchao The architecture of the SARS-CoV-2 RNA genome inside virion |
title | The architecture of the SARS-CoV-2 RNA genome inside virion |
title_full | The architecture of the SARS-CoV-2 RNA genome inside virion |
title_fullStr | The architecture of the SARS-CoV-2 RNA genome inside virion |
title_full_unstemmed | The architecture of the SARS-CoV-2 RNA genome inside virion |
title_short | The architecture of the SARS-CoV-2 RNA genome inside virion |
title_sort | architecture of the sars-cov-2 rna genome inside virion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225788/ https://www.ncbi.nlm.nih.gov/pubmed/34168138 http://dx.doi.org/10.1038/s41467-021-22785-x |
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