Evidence for a long-range RNA-RNA interaction between ORF8 and Spike of SARS-CoV-2

  1. Okiemute B. Omoru
  2. Filipe Pereira
  3. Sarath Chandra Janga
  4. Amirhossein Manzourolajdad

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Abstract

SARS-CoV-2 has affected people worldwide as the causative agent of COVID-19. The virus is related to the highly lethal SARS-CoV responsible for the 2002-2003 SARS outbreak in Asia. Research is ongoing to understand why both viruses have different spreading capacities and mortality rates. Like other beta coronaviruses, RNA-RNA interactions occur between different parts of the viral genomic RNA, resulting in discontinuous transcription and production of various sub-genomic RNAs. These sub-genomic RNAs are then translated into other viral proteins. In this work, we performed a comparative analysis for novel long-range RNA-RNA interactions that may involve the Spike region. Comparing predictions between reference sequences of SARS-CoV-1 and SARS-CoV-2 revealed several predictions amongst which a thermodynamically stable long-range RNA-RNA interaction between (23660-23703 Spike ) and (28025-28060 ORF8 ) unique to SARS-CoV-2 was observed. Using data gathered worldwide, sequence variation patterns observed in the population support the in-silico RNA-RNA base-pairing predictions within these regions, suggesting further evidence for the interaction. The predicted interactions can potentially be related to the regulation of sub-genomic RNA production rates in SARS-CoV-2 and their subsequent accessibility to the host transcriptome.

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  1. Version published to 10.1101/2021.11.09.467911v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.11.09.467911: (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
    RNA structural analyses: Different components of the RNAstructure software package (Reuter and Mathews 2010) along with other tools were used for secondary structure predictions.
    RNAstructure
    suggested: (RNAstructure, RRID:SCR_017216)
    The structure of the shortened main sequence was then predicted using ProbKnot.
    ProbKnot
    suggested: None
    Compensatory Mutations Analysis of Long-range RNA-RNA interactions: Compensatory mutations within the multiple sequence alignments were investigated using the R-scape software package (Rivas, Clements et al. 2017, Rivas 2020, Rivas, Clements et al. 2020, Rivas and Eddy 2020), which analyzes covariation in nucleotide pairs in the population to infer possible compensatory mutations in an RNA base pair.
    R-scape
    suggested: None

    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.

    About SciScore

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  3. Version published to 10.1101/2021.11.09.467911v1 on bioRxiv