Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, o...

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Vydáno v:	Nature communications Ročník 12; číslo 1; s. 5113 - 15
Hlavní autoři:	Yang, Siwy Ling, DeFalco, Louis, Anderson, Danielle E., Zhang, Yu, Aw, Jong Ghut Ashley, Lim, Su Ying, Lim, Xin Ni, Tan, Kiat Yee, Zhang, Tong, Chawla, Tanu, Su, Yan, Lezhava, Alexander, Merits, Andres, Wang, Lin-Fa, Huber, Roland G., Wan, Yue
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 25.08.2021 Nature Publishing Group Nature Portfolio
Témata:	45 45/43 49/90 631/326/596/2557 631/326/596/4130 631/61/212/177 COVID-19 COVID-19 - genetics COVID-19 - metabolism COVID-19 - physiopathology COVID-19 - virology DNA Methylation Gene mapping Gene sequencing Genome, Viral Genomes Global health Host Microbial Interactions Humanities and Social Sciences Humans Methylation Mitochondria multidisciplinary Nucleic Acid Conformation Nucleoli Pathogenicity Pathogens Protein structure Public health Ribonucleic acid RNA RNA - chemistry RNA - genetics RNA - metabolism RNA viruses RNA, Viral - chemistry RNA, Viral - genetics RNA, Viral - metabolism SARS-CoV-2 - chemistry SARS-CoV-2 - genetics SARS-CoV-2 - physiology Science Science (multidisciplinary) Secondary structure Severe acute respiratory syndrome coronavirus 2 Structural members Structure-function relationships Viral diseases Viruses
ISSN:	2041-1723, 2041-1723
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Shrnutí:	SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2’-O-methylated. 2’-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy. Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-25357-1