FoldAtlas: a repository for genome-wide RNA structure probing data

SummarySARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome of ∼30 kb, whose outbreak caused the still ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle. Despite this, only a handful of functionally conserved structural elements within coronavirus RNA genomes have been identified to date.Here, we performed RNA structure probing by SHAPE-MaP to obtain a single-base resolution secondary structure map of the full SARS-CoV-2 coronavirus genome. The SHAPE-MaP probing data recapitulate the previously described coronavirus RNA elements (5′ UTR, ribosomal frameshifting element, and 3′ UTR), and reveal new structures. Secondary structure-restrained 3D modeling of highly-structured regions across the SARS-CoV-2 genome allowed for the identification of several putative druggable pockets. Furthermore, ∼8% of the identified structure elements show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. In addition, we identify a set of persistently single-stranded regions having high sequence conservation, suitable for the development of antisense oligonucleotide therapeutics.Collectively, our work lays the foundation for the development of innovative RNA-targeted therapeutic strategies to fight SARS-related infections.

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Genome-Wide Approaches for RNA Structure Probing

Advances in Experimental Medicine and Biology - RNA Processing ◽

10.1007/978-3-319-29073-7_2 ◽

2016 ◽

pp. 29-59 ◽

Cited By ~ 13

Author(s):

Ian M. Silverman ◽

Nathan D. Berkowitz ◽

Sager J. Gosai ◽

Brian D. Gregory

Keyword(s):

Rna Structure ◽

Structure Probing ◽

Genome Wide

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A map of the SARS-CoV-2 RNA structurome

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqab043 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Ryan J Andrews ◽

Collin A O’Leary ◽

Van S Tompkins ◽

Jake M Peterson ◽

Hafeez S Haniff ◽

...

Keyword(s):

Experimental Data ◽

Rna Structure ◽

Drug Targets ◽

Rna Binding ◽

Large Reservoir ◽

Model Comparisons ◽

Functional Regions ◽

Structure Probing ◽

Genome Wide ◽

Potential Drug Targets

Abstract SARS-CoV-2 has exploded throughout the human population. To facilitate efforts to gain insights into SARS-CoV-2 biology and to target the virus therapeutically, it is essential to have a roadmap of likely functional regions embedded in its RNA genome. In this report, we used a bioinformatics approach, ScanFold, to deduce the local RNA structural landscape of the SARS-CoV-2 genome with the highest likelihood of being functional. We recapitulate previously-known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a large reservoir of potential drug targets for RNA-binding small molecules. Results are enhanced via the re-analyses of publicly-available genome-wide biochemical structure probing datasets that are broadly in agreement with our models. Additionally, ScanFold was updated to incorporate experimental data as constraints in the analysis to facilitate comparisons between ScanFold and other RNA modelling approaches. Ultimately, ScanFold was able to identify eight highly structured/conserved motifs in SARS-CoV-2 that agree with experimental data, without explicitly using these data. All results are made available via a public database (the RNAStructuromeDB: https://structurome.bb.iastate.edu/sars-cov-2) and model comparisons are readily viewable at https://structurome.bb.iastate.edu/sars-cov-2-global-model-comparisons.

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