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. 2020 Jun 17;6(25):eabb5813.
doi: 10.1126/sciadv.abb5813. eCollection 2020 Jun.

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

Salvatore Di Giorgio  1   2 , Filippo Martignano  1   2 , Maria Gabriella Torcia  3 , Giorgio Mattiuz  1   3 , Silvestro G Conticello  1   4
Affiliations

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

Salvatore Di Giorgio et al. Sci Adv. .

Abstract

The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.

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Figures

Fig. 1
Fig. 1. SNVs identified in SARS-CoV-2 transcriptomes.
The bar charts show the number of SNVs identified in each SARS-CoV-2 transcriptome for each SNV type (e.g., A>C, AC). The sequencing depth for each sample is indicated.
Fig. 2
Fig. 2. SNV identified in SARS-CoV-2 transcriptomes.
(A) Allelic fraction and (B) number of SNVs for each nucleotide change in the entire dataset and (C) for SNVs recurring in at least two samples. (D) Distribution of SNVs across the SARS-CoV-2 genome. A-to-G (blue) and C-to-U (red) SNVs are grouped in 400-nucleotide (nt) bins and plotted above (AG and CT) or below the line (TC and GA) based on the edited strand. Dots (white/black) indicate recurring SNVs. Genetic organization of SARS-CoV-2 (top). The dark/white shading indicates the viral coding sequences; coverage distribution of all analyzed samples (bottom).
Fig. 3
Fig. 3. Sequence contexts for SARS-CoV-2 RNA edited sites.
(A) Local sequence context for A-to-I and C-to-U edited sites in the viral transcriptome and (B) for recurring sites.
Fig. 4
Fig. 4. Nucleotide changes across Coronaviridae strains.
(A to C) Number of SNVs for each nucleotide change and (D to F) local sequence context for C-to-U edited sites in genome alignments from SARS-CoV-2 (A and D), human-hosted MERS-CoV (B and E), and human-hosted SARS-CoV (C and F).
Fig. 5
Fig. 5. Model of APOBEC RNA editing on SARS-CoV-2 transcriptome.
The four panels model the editing frequencies and the C>U/G/A ratios expected from four different scenarios: (A) C-to-U editing on the negative-sense transcripts, (B) “early” editing on the viral genomes before viral replication, (C) “late” editing after viral replication, and (D) “late” editing after viral replication with loss of negative-sense transcripts. Red dots indicate editing on the positive-sense transcript; orange dots indicate editing on the positive-sense transcript. Green and blue segments indicate positive- and negative-sense viral transcripts, respectively.
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