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.
【저자키워드】 SARS-CoV-2, epigenomics, Virus-host interactions, 【초록키워드】 Sequencing, Genome, virus, RNAs, global health, RNA, Health, Viral, cells, SARS-CoV-2 genome, subgenomic RNA, RNA sequencing, mutant, virus infection, molecular, pathogenicity, targeted therapy, RNA-RNA interaction, Illumina, platform, interactions, Methylation, cellular, Interaction, structures, secondary structure, viral genome, mitochondrial, untranslated regions, small nucleolar RNA, Δ382, wildtype, subgenomic RNAs, report, element, virus genome, RNA-RNA interactions, Host, regions, Cell, host mRNA, bind, SARS-CoV-2 viral, observé, identify, approach, functional, in viral, the SARS-CoV-2 genome, 【제목키워드】 Virus-host interaction, in vivo, Interaction, Comprehensive, functional, reveal,