Evaluating RNA Structural Flexibility: Viruses Lead the Way

Fairman, Connor W; Lever, Andrew; Kenyon, Julia C.

doi:10.3390/v13112130

Cited by 3 publications

(2 citation statements)

References 80 publications

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“…Nonetheless, information about the connectivity of long RNA molecules can provide important clues about their biological function. For example, the RNA genomes of certain viruses form connections that are thought to direct a range of functions, including the production of viral proteins 54 and the replication of new viral RNA strands 55 , and there is growing evidence that these connections can rearrange in response to changing conditions [56][57][58][59] , possibly triggering changes in functionality. Quantifying the prevalence of connections is therefore an important step in understanding how RNA virus genomes orchestrate infections, and could inform strategies for blocking infections by pathogenic viruses.…”

Section: Discussionmentioning

confidence: 99%

Measuring intramolecular connectivity in long RNA molecules using two-dimensional DNA patch-probe arrays

Chiang

Kimchi

Dhaliwal

et al. 2023

Preprint

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We describe a simple method to infer intramolecular connections in a population of long RNA molecules in vitro. First we add DNA oligonucleotide 'patches' that perturb the RNA connections, then we use a microarray containing a complete set of DNA oligonucleotide 'probes' to record where perturbations occur. The pattern of perturbations reveals couplings between different regions of the RNA sequence, from which we infer connections as well as their prevalences in the population. We validate this patch-probe method using the 1,058-nucleotide RNA genome of satellite tobacco mosaic virus (STMV), which has previously been shown to have multiple long-range connections. Our results not only indicate long duplexes that agree with previous structures but also reveal the prevalence of competing connections. Together, these results suggest that globally-folded and locally-folded structures coexist in solution. We show that the prevalence of connections changes when pseudouridine, an important component of natural and synthetic RNA molecules, is substituted for uridine in STMV RNA.

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Section: Discussionmentioning

confidence: 99%

Measuring intramolecular connectivity in long RNA molecules using two-dimensional DNA patch-probe arrays

Chiang

Kimchi

Dhaliwal

et al. 2023

Preprint

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“…Such new treatment modalities include small molecules targeting ribonucleic acids (RNA), e. g ., aiming to modify RNA splicing [2,4–6] . RNA molecules exhibit substantial structural diversity, high flexibility, and a large propensity for nonspecific intercalation with small‐molecule ligands, rendering the identification of druggable RNA binding sites challenging [3,7] . Deep learning may help address some of these challenges and facilitate the discovery of druggable RNA targets.…”

Section: Figurementioning

confidence: 99%

Translating from Proteins to Ribonucleic Acids for Ligand‐binding Site Detection

Möller

Guerci

Isert

et al. 2022

Molecular Informatics

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Identifying druggable ligand‐binding sites on the surface of the macromolecular targets is an important process in structure‐based drug discovery. Deep‐learning models have been shown to successfully predict ligand‐binding sites of proteins. As a step toward predicting binding sites in RNA and RNA‐protein complexes, we employ three‐dimensional convolutional neural networks. We introduce a dataset splitting approach to minimize structure‐related bias in training data, and investigate the influence of protein‐based neural network pre‐training before fine‐tuning on RNA structures. Models that were pre‐trained on proteins considerably outperformed the models that were trained exclusively on RNA structures. Overall, 71 % of the known RNA binding sites were correctly located within 4 Å of their true centres.

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Human Antibodies for Viral Infections

Crowe

2022

Annu. Rev. Immunol.

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Antibodies have been used to prevent or treat viral infections since the nineteenth century, but the full potential to use passive immunization for infectious diseases has yet to be realized. The advent of efficient methods for isolating broad and potently neutralizing human monoclonal antibodies is enabling us to develop antibodies with unprecedented activities. The discovery of IgG Fc region modifications that extend antibody half-life in humans to three months or more suggests that antibodies could become the principal tool with which we manage future viral epidemics. Antibodies for members of most virus families that cause severe disease in humans have been isolated, and many of them are in clinical development, an area that has accelerated during the effort to prevent or treat COVID-19 (coronavirus disease 2019). Broad and potently neutralizing antibodies are also important research reagents for identification of protective epitopes that can be engineered into active vaccines through structure-based reverse vaccinology. Expected final online publication date for the Annual Review of Immunology, Volume 40 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Evaluating RNA Structural Flexibility: Viruses Lead the Way

Cited by 3 publications

References 80 publications

Measuring intramolecular connectivity in long RNA molecules using two-dimensional DNA patch-probe arrays

Measuring intramolecular connectivity in long RNA molecules using two-dimensional DNA patch-probe arrays

Translating from Proteins to Ribonucleic Acids for Ligand‐binding Site Detection

Human Antibodies for Viral Infections

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