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.
Summary
Alkali-treated proteins were prepared by digestion of bovine serum with 1 N sodium hydroxide solution at room temperature for various periods of time up to 24 hours. The alkali-treated ...proteins were recovered from the digests by isoelectric precipitation. These proteins differed in the ease with which they could be dissolved in slightly alkaline solution. Bovine serum protein exposed to alkali for 5 minutes was rendered insoluble under these conditions. Serological and toxicological studies with these derived proteins revealed that, with increased exposure to the alkali, the protein first lost its capacity to produce specific antibodies; then lost its antigenic capacity but retained its power to act as a hapten; and finally lost its haptenic capacity, thus becoming non-antigenic but simultaneously becoming toxic.
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