To Knot or Not to Knot: Multiple Conformations of the SARS-CoV-2 Frameshifting RNA Element

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Abstract

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  1. SciScore for 10.1101/2021.03.31.437955: (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
    MD simulations were performed using Gromacs 2020.4, 58 with the Amber OL3 forcefield.
    Gromacs
    suggested: (GROMACS, RRID:SCR_014565)

    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: We detected the following sentences addressing limitations in the study:
    While our predictions using 2D folding programs and chemical reactivity data do not identify other conformations besides the two pseudoknots and the 3-way junction, other possibilities cannot be excluded due to limitations in both the folding programs and reactivity experiments. Results for other works suggest other possible conformations, including two 3_8 pseudoknots, a different 3_3 pseudoknot (with Stem 2 formed by Stem 3 loop and 3′ end), a two-stem 2_1, and a two-stem-with-internal-loop 2_2 (Table S1 and Fig. S13). The length-dependent and context-specific conformations for the FSE emphasized in our work could be exploited biologically by the insidious virus in mechanisms of interactions with the ribosome. The bulky pseudo-knot may block and encourage ribosome pausing as the ribosome rolls over the FSE region, and any structural transitions may similarly interfere with this template-directed process. In the 2.3–7 Å-resolution Cryo-EM study by Bhatt et al., 21 the researchers observe the 3_6 pseudoknot wedged between the head and body of the small ribosomal subunit. Specifically, the residues before Stem 1 are found to be located at the mRNA entry tunnel so that, as translation proceeds, the GC-rich Stem 1 residues are unwound upon entering the mRNA tunnel. Stem 2 of the pseudoknot is found to be shorter by two base pairs than that predicted by computational 2D structure methods. To confirm these inferred structural interactions, the researchers mutated single residues i...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.

    About SciScore

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