TY - JOUR
AU - Zhang, Yan
AU - Huang, Kun
AU - Xie, Dejian
AU - Lau, Jian You
AU - Shen, Wenlong
AU - Li, Ping
AU - Wang, Dong
AU - Zou, Zhong
AU - Shi, Shu
AU - Ren, Hongguang
AU - Wang, Youliang
AU - Mao, Youzhi
AU - Jin, Meilin
AU - Kudla, Grzegorz
AU - Zhao, Zhihu
PY - 2021
DA - September
TI - In vivo structure and dynamics of the SARS-CoV-2 RNA genome
JO - Nature Communications
VL - 12
IS - 1
DO - https://doi.org/10.1038/s41467-021-25999-1
AB - The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5′-UTR and 3′-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies.
PB - Springer Nature
UR - https://www.research.ed.ac.uk/en/publications/517e8c48-3eaa-45b7-9311-4b3c8d7b66d9
KW - Coronavirus (COVID-19)
ER