Computational Pipeline for Reference-Free Comparative Analysis of RNA 3D Structures Applied to SARS-CoV-2 UTR Models

Gumna, Julita; Antczak, Maciej; Adamiak, Ryszard W.; Bujnicki, Janusz; Chen, Shijie; Ding, Feng; Ghosh, Pritha; Li, Jun; Mukherjee, Sunandan; Nithin, Chandran; Pachulska-Wieczorek, Katarzyna; Ponce-Salvatierra, Almudena; Popenda, Mariusz; Sarzyñska, Joanna; Wirecki, Tomasz; Zhang, Dong; Zhang, Sicheng; Żok, Tomasz; Westhof, Éric; Miao, Zhichao; Szachniuk, Marta; Rybarczyk, Agnieszka

doi:10.3390/ijms23179630

Cited by 17 publications

(13 citation statements)

References 73 publications

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“…Only the region containing the s2m element was significantly different between the two viruses. These data suggests that the s2m hairpin structure does not interact with any other elements in the 3’UTR region of SARS-CoV-2 as predicted previously by computational analysis 29 . Taken together, our RNA structural analysis suggests that there is no impact on the overall 3’ UTR RNA structure upon deletion of the s2m element, as found in the majority of the SARS-CoV-2 virus isolated since March 2022.…”

Section: Discussionsupporting

confidence: 81%

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2

Jiang

Joshi

Gan

et al. 2023

Preprint

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The stem-loop II motif (s2m) is a RNA structural element that is found in the 3′ untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro, or growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3′ UTR of wild type and s2m deletion viruses using SHAPE-MaP and DMS-MaPseq. These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3′UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2.

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Section: Discussionsupporting

confidence: 81%

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2

Jiang

Joshi

Gan

et al. 2023

Preprint

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“…Targets R1149 (SL5 SARS‐CoV‐2 human) and R1156 (SL5 SARS‐CoV‐2 bat) were predicted based on the consensus secondary structure of stem‐loop 5 (SL5) in 5′ untranslated region (UTR) of SARS‐CoV‐2 8,47 . SL5 is a well‐established domain that, in SARS‐related viruses, has a long stem (SL5‐stem) supplemented with a four‐way junction branching into three additional stems (SL5A, SL5B, and SL5C).…”

Section: Resultsmentioning

confidence: 99%

“…It is fast and convenient to use, which has translated into its high popularity in the community—from launch, its two instances have recorded over 13 million computing sessions by users from 150 countries worldwide in total. Our team, consisting of the system's authors and developers, tests it regularly in RNA‐Puzzles by participating in the human and web server modeling categories 5–8 . Most recently, we challenged the prediction of all RNA targets in CASP15.…”

Section: Introductionmentioning

confidence: 99%

“…Our team, consisting of the system's authors and developers, tests it regularly in RNA-Puzzles by participating in the human and web server modeling categories. [5][6][7][8] Most recently, we challenged the prediction of all RNA targets in CASP15. The experience gained in these competitions is translated into improvements and new functionalities that we have introduced to the system.…”

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confidence: 99%

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RNA tertiary structure prediction using RNAComposer in CASP15

Sarzynska,

Popenda,

Antczak

et al. 2023

Proteins

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As CASP15 participants, in the new category of 3D RNA structure prediction, we applied expert modeling with the support of our proprietary system RNAComposer. Although RNAComposer is primarily known as an automated web server, its features allow it to be used interactively, for example, for homology‐based modeling or assembling models from user‐provided structural elements. In the paper, we present various scenarios of applying the system to predict the 3D RNA structures that we employed. Their combination with expert input, comparative analysis of models, and routines to select representative resultant structures form a ready‐for‐reuse workflow. With selected examples, we demonstrate its application for the in silico modeling of natural and synthetic RNA molecules targeted in CASP15.

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“…These targets were the SL5 elements of the Betacoronavirus 5 0 UTRs, and were very similar to the sequence, for which we and other groups have previously generated models. 37,38 Already before the start of the CASP15 contest, our models of the SL5 element of the human SARS-CoV-2 virus were validated and refined using chemical probing data and low-resolution cryo-EM maps (8-10 Å) built from experimental data generated in-house. For targets R1149 and R1156, we adjusted the sequences of these pre-existing models and used them as starting points for the optimization with SimRNA.…”

Section: R1149 and R1156mentioning

confidence: 99%

RNA tertiary structure prediction in CASP15 by the GeneSilico group: Folding simulations based on statistical potentials and spatial restraints

Baulin,

Mukherjee,

Moafinejad

et al. 2023

Proteins

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Ribonucleic acid (RNA) molecules serve as master regulators of cells by encoding their biological function in the ribonucleotide sequence, particularly their ability to interact with other molecules. To understand how RNA molecules perform their biological tasks and to design new sequences with specific functions, it is of great benefit to be able to computationally predict how RNA folds and interacts in the cellular environment. Our workflow for computational modeling of the 3D structures of RNA and its interactions with other molecules uses a set of methods developed in our laboratory, including MeSSPredRNA for predicting canonical and non‐canonical base pairs, PARNASSUS for detecting remote homology based on comparisons of sequences and secondary structures, ModeRNA for comparative modeling, the SimRNA family of programs for modeling RNA 3D structure and its complexes with other molecules, and QRNAS for model refinement. In this study, we present the results of testing this workflow in predicting RNA 3D structures in the CASP15 experiment. The overall high score of the computational models predicted by our group demonstrates the robustness of our workflow and its individual components in terms of predicting RNA 3D structures of acceptable quality that are close to the target structures. However, the variance in prediction quality is still quite high, and the results are still too far from the level of protein 3D structure predictions. This exercise led us to consider several improvements, especially to better predict and enforce stacking interactions and non‐canonical base pairs.

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Computational Pipeline for Reference-Free Comparative Analysis of RNA 3D Structures Applied to SARS-CoV-2 UTR Models

Cited by 17 publications

References 73 publications

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2

RNA tertiary structure prediction using RNAComposer in CASP15

RNA tertiary structure prediction in CASP15 by the GeneSilico group: Folding simulations based on statistical potentials and spatial restraints

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