SARS-CoV-2 Helicase might interfere with cellular nonsense-mediated RNA decay, insights from a bioinformatics study

  1. Behnia Akbari
  2. Ehsan Ahmadi
  3. Mina Roshan Zamir
  4. Mina Sadeghi Shaker
  5. Farshid Noorbakhsh

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Abstract

Unraveling molecular interactions between viral proteins and host cells is key to understanding the pathogenesis of viral diseases. We hypothesized that potential sequence and structural similarities between SARS-CoV2 proteins and proteins of infected cells might influence host cell biology and antiviral defense. Comparing the proteins of SARS-CoV-2 with human and mammalian proteins revealed sequence and structural similarities between viral helicase with human UPF1. The latter is a protein that is involved in nonsense mediated RNA decay (NMD), an mRNA surveillance pathway which also acts as a cellular defense mechanism against viruses. Protein sequence similarities were also observed between viral nsp3 and human Poly ADP-ribose polymerase (PARP) family of proteins. Gene set enrichment analysis on transcriptomic data derived from SARS-CoV-2 positive samples illustrated the enrichment of genes belonging to the NMD pathway compared with control samples. Moreover, comparing transcriptomic data from SARS-CoV2-infected samples with transcriptomic data derived from UPF1 knockout cells demonstrated a significant overlap between datasets. These findings suggest that helicase/UPF1 sequence and structural similarity might have the ability to interfere with the NMD pathway with pathogenic and immunological implications.

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    SciScore for 10.1101/2022.05.30.494036: (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

    Software and Algorithms
    SentencesResources
    PDB: https://www.rcsb.org/).
    https://www.rcsb.org/
    suggested: (Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, RRID:SCR_012820)
    RNA sequencing datasets were obtained from NCBI Gene Expression Omnibus (
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    (Domain Enhanced Lookup Time Accelerated BLAST: https://blast.ncbi.nlm.nih.gov/Blast.cgi).
    https://blast.ncbi.nlm.nih.gov/Blast.cgi
    suggested: (TBLASTX, RRID:SCR_011823)
    Gene Ontology analysis: Functional enrichment analysis was performed using the Gene Ontology (GO) database (http://geneontology.org) and ClusterProfiler R package.
    ClusterProfiler
    suggested: (clusterProfiler, RRID:SCR_016884)
    Digital gene expression lists were generated using edgeR package and “DEGList” function.
    edgeR
    suggested: (edgeR, RRID:SCR_012802)
    The biomaRt package were further used to match Ensembl gene IDs to official gene names extracted from hgu133plus2.db.
    biomaRt
    suggested: (biomaRt, RRID:SCR_019214)
    GSEA results were visualized with “gseaplot2” function of R software’s enrichplot package.
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2022.05.30.494036v1 on bioRxiv