ADAR mediated A-to-I RNA editing affects SARS-CoV-2 characteristics and fuels its evolution
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Abstract
Upon SARS-CoV-2 infection, viral intermediates activate the Type I interferon (IFN) response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, and on average, approximately 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans. Collectively, our data suggest that SARS-CoV-2 hijacks components of the host antiviral machinery to edit its genome and fuel its evolution.
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SciScore for 10.1101/2021.07.22.453345: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Gene expression level quantification: TPM (Transcripts Per Million) was used to represent ADAR1 and MDA5 (IFIH1 gene) expression. MDA5suggested: NoneSoftware and Algorithms Sentences Resources The cleaned reads were mapped to the reference sequence using BWA (36) aln (bwa aln -t 20) and mem (bwa mem -M -t 20 -k 50). BWAsuggested: (BWA, RRID:SCR_010910)Next, we inspected all editing positions using samtools for editing level quantification. samtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Reads were mapped to the human reference genome GRCh38 using Hisat2 (Version 2.0.4) (38) with default … SciScore for 10.1101/2021.07.22.453345: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Gene expression level quantification: TPM (Transcripts Per Million) was used to represent ADAR1 and MDA5 (IFIH1 gene) expression. MDA5suggested: NoneSoftware and Algorithms Sentences Resources The cleaned reads were mapped to the reference sequence using BWA (36) aln (bwa aln -t 20) and mem (bwa mem -M -t 20 -k 50). BWAsuggested: (BWA, RRID:SCR_010910)Next, we inspected all editing positions using samtools for editing level quantification. samtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Reads were mapped to the human reference genome GRCh38 using Hisat2 (Version 2.0.4) (38) with default parameters. Hisat2suggested: (HISAT2, RRID:SCR_015530)Then, StringTie (Version v1.3.0) (39) was used to calculate the TPM values with default parameters. StringTiesuggested: (StringTie , RRID:SCR_016323)To evaluate the effects of RNA editing on spike protein, spike-ACE2, and spike-mAbs stability, all recoding sites in spike protein were used as the input mutation list, and impacts of single mutations on protein or protein complex stability were calculated by MAESTRO (40). MAESTROsuggested: (Maestro, RRID:SCR_016748)Structure visualization and variant annotation were performed with PyMOL (http://www.pymol.org/). PyMOLsuggested: (PyMOL, RRID:SCR_000305)Motif logos were plotted with WebLogo v. WebLogosuggested: (WEBLOGO, RRID:SCR_010236)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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