Detection of A-to-I RNA Editing in SARS-COV-2

Figures

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  Figure 1. RNA editing and expression of key genes in total RNAseq data from Calu-3 infected cells at three time points post-infection (4 h, 12 h, and 24 h). (A) Distribution of hyper-edited reads identified in infected Calu-3 cells in which A-to-G and T-to-C events appear prominent. (B) Nucleotide context one nucleotide upstream and downstream the detected hyper-edited sites. (C) Gene expression of type-I interferon (IFNB1) and key sensor genes, DDX58 (RIG-I) and IFIH1 (MDA5), in infected Calu-3 cells. Here, we report only IFNB1 as main interferon gene modulated upon infection. As expected, DDX58 and IFIH1 increase their expression during the infection. Gene expression of type-I interferons, RIG-I and TLR receptors, and APOBECs are reported in the Supplementary Figure S1A. (D) Expression of ADAR1 (ADAR) and ADAR2 (ADARB1) genes in infected Calu-3 cells. While ADAR2 is expressed at extremely low levels and does not change during the infection, ADAR1 is positively modulated and its expression increases significantly (DESeq2 adjusted p-value < 0.05) from 4 to 12 h post-infection. (E) Enrichment of unique hyper editing positions in infected Calu-3 cells. (F) Alu editing index (AEI) in infected…

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  Figure 2. RNA editing and expression of key genes in RNAseq data from infected (inf) and uninfected (ctrl) Vero cells. (A) Gene expression of type-I interferon (IFNB1) and key sensor genes, DDX58 (RIG-I) and IFIH1 (MDA5) in Vero cells. Here, we report the expression of IFNB1 as representative gene of type-I interferons. Although IFIH1 were up-regulated, type-I interferons are not modulated. (B) Expression of ADAR1 (ADAR) and ADAR2 (ADARB1) genes in Vero cells. Although ADAR1 is downregulated in infected cells (DESeq2 adjusted p-value < 0.05), it is expressed in all samples. ADAR2 is also expressed in all samples but at very low levels. (C) Enrichment of unique hyper editing positions in Vero cells. (D) Distribution of hyper-edited reads identified in infected Vero cells. A-to-G and T-to-C events outnumber other substitution types. (E) Nucleotide context one base upstream and downstream the detected hyper-edited sites.

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  Figure 3. Genomic context of A-to-I RNA editing clusters detected in total RNAseq data from infected Calu-3 cells and Vero cells. We report also known SARS-COV-2 transcripts and putative RNA secondary structures from Rangan et al. [44]. A-to-I clusters in forward orientation are marked in blue, while clusters in reverse orientation are in red.