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Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions.
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.
  • Yang SL; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • DeFalco L; Biomolecular Function Discovery, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Matrix #07-01, Singapore, Singapore.
  • Anderson DE; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
  • Zhang Y; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Aw JGA; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Lim SY; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Lim XN; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Tan KY; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Zhang T; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Chawla T; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
  • Su Y; Laboratory of translational diagnostics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Lezhava A; Laboratory of translational diagnostics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Merits A; Institute of Technology, University of Tartu, Tartu, Estonia.
  • Wang LF; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. linfa.wang@duke-nus.edu.sg.
  • Huber RG; Biomolecular Function Discovery, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Matrix #07-01, Singapore, Singapore. rghuber@bii.a-star.edu.sg.
  • Wan Y; Epigenetic and Epitranscriptomic Regulation, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. wany@gis.a-star.edu.sg.
Nat Commun ; 12(1): 5113, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1373413
Preprint
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ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA / RNA, Viral / Host Microbial Interactions / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25357-1

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA / RNA, Viral / Host Microbial Interactions / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25357-1