Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22785-x
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Funding
- Strategic Priority Program of CAS [XDB37000000]
- National Key RD Program [2017YFA0504400, 2020YFA0707500, 2018YFA0900801, 2020YFA0707600]
- NSFC [91740201, 91940306, 81921003, 31900465, 31970611]
- National Major Sciences & Technology Project for Control and Prevention of Major Infectious Diseases in China [2018ZX10301401]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [2016-I2M-1-014]
- Strategic Priority Research Program [XDB29010000]
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Researchers have used vRIC-seq technology to reveal the tertiary structure of the SARS-CoV-2 genome in virions, finding an unentangled globule conformation. They also discovered the role of long-range duplexes and higher-order junctions in the sequential packaging of the viral genome, with some mutations potentially contributing to more stable duplex structures.
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. Secondary structures and long-range RNA interactions of the SARS-CoV-2 genome have been investigated by various sequencing methods. Here the authors use an RNA-RNA hybrid sequencing method to predict the secondary and tertiary structure of the SRAS-CoV-2 RNA genome in the virion.
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