RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers in
            <i>Betacoronavirus</i>

Rojas-Cruz, Alexis Felipe; Gallego-Gómez, Juan Carlos; Bermúdez-Santana, Clara Isabel

doi:10.1080/15476286.2022.2115750

Cited by 3 publications

(5 citation statements)

References 106 publications

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“…For example, there are still many structured subregions on the viral genome that could be the target of positive selection to generate new regions that could become precursors of ncRNAs. Some examples have been found by our group for ZIKV and some betacoronaviruses [186][187][188]. However, it will take several more years to carefully integrate and validate these RNAs and their potential function as RNA mediators in silencing.…”

Section: Discussionmentioning

confidence: 99%

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

Bermudez-Santana,

Gallego-Gómez

2024

Viruses

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In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA–RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA–host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV–host-cell interactions.

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Section: Discussionmentioning

confidence: 99%

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

Bermudez-Santana,

Gallego-Gómez

2024

Viruses

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“…We retrieved conserved RNA structures under negative selection ( s ≤ 2.99) in Beta-CoV genomes that were found in bats, intermediate animals, and humans from a recent study [ 39 ]. Briefly, the prediction of structured regions across the whole viral genome was scanned in windows of length 120 nucleotides sliding by 40 nucleotides with RNAz (v2.1) [ 40 ].…”

Section: Methodsmentioning

confidence: 99%

“…The following supporting information can be downloaded at https: //www.mdpi.com/article/10.3390/v15081647/s1, Figure S1: Flowchart showing approach to data collection, curation process, and range of sequence lengths for the three Beta-CoVs used in the study by [39], Figure S2 S1: DEGs of Beta-CoVs using a |log 2 FC| > 1.5 and FDR < 0.05, Table S2: Full list of hsa-miRNAs targeting Beta-CoVs highly supported by either computational or experimental studies [35,[66][67][68][69], Table S3: Number of hsa-miRNA:3 UTR interactions resulting…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…Whether Beta-CoVs produce functional v-miRNAs has been controversial for several years [ 38 ]. Here, conserved RNA structures with strong negative selection signals ( s ≤ 2.99), recently identified in a wide range of Beta-CoVs circulating in bats, a variety of animal species, and humans [ 39 ], are proposed as model RNA structures to unravel potential RNA–RNA interactions with the capacity to function as vsRNAs in host gene regulation. Additionally, putative vsRNAs are validated using bulk RNA sequencing (RNA-seq) of the epithelial lung cancer cell line Calu-3 infected with SARS-CoV, MERS-CoV, and SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

“…The following supporting information can be downloaded at , Figure S1: Flowchart showing approach to data collection, curation process, and range of sequence lengths for the three Beta-CoVs used in the study by [ 39 ], Figure S2: Volcano plots showing the differential expression profiling of mock cultures of Calu-3 cells infected with Beta-CoVs between the final and initial time (MM), Figure S3: Potential common miRNA:virusRNA pairings predicted by RNAhybrid, miRanda, and mirTarP in Beta-CoVs , Figure S4: Comparison of vsRNAs encoded by Beta-CoVs across hosts of bats, intermediate animals, and humans, Figure S5: Number of predicted targets in the human genome for each vsRNA candidate in the three Beta-CoVs , Table S1: DEGs of Beta-CoVs using a |log 2 FC| > 1.5 and FDR < 0.05, Table S2: Full list of hsa-miRNAs targeting Beta-CoVs highly supported by either computational or experimental studies [ 35 , 66 , 67 , 68 , 69 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ], Table S3: Number of hsa-miRNA:3′UTR interactions resulting from RNAhybrid, miRanda, and mirTarP overlaps, Table S4: Number of hsa-miRNA:viralRNA interactions resulting from RNAhybrid, miRanda, and mirTarP overlaps, Table S5: Repertoire of identified vsRNAs in Beta-CoV genomes using RNA–RNA interactions, Table S6: Number of targets identified for SARS-CoV by vsRNAs, Table S7: Number of targets identified for MERS-CoV by vsRNAs, Table S8: Number of targets identified for SARS-CoV-2 by vsRNAs, Table S9: Functional enrichment of DEGs that are possibly silenced by vsRNAs identified in ...…”

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confidence: 99%

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Computational Prediction of RNA–RNA Interactions between Small RNA Tracks from Betacoronavirus Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA

Rojas-Cruz

Bermúdez-Santana

2023

Viruses

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Whether RNA–RNA interactions of cytoplasmic RNA viruses, such as Betacoronavirus, might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been controversial. Even more, whether RNA–RNA interactions of wild animal viruses may act as virus-derived small RNAs is unknown. Here, we address these issues in four ways. First, we use conserved RNA structures undergoing negative selection in the genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating in different bat species, intermediate animals, and human hosts. Second, a systematic literature review was conducted to identify Betacoronavirus-targeting hsa-miRNAs involved in lung cell infection. Third, we employed sophisticated long-range RNA–RNA interactions to refine the seed sequence homology of hsa-miRNAs with conserved RNA structures. Fourth, we used high-throughput RNA sequencing of a Betacoronavirus-infected epithelial lung cancer cell line (Calu-3) to validate the results. We proposed nine potential virus-derived small RNAs: two vsRNAs in SARS-CoV (Bats: SB-vsRNA-ORF1a-3p; SB-vsRNA-S-5p), one vsRNA in MERS-CoV (Bats: MB-vsRNA-ORF1b-3p), and six vsRNAs in SARS-CoV-2 (Bats: S2B-vsRNA-ORF1a-5p; intermediate animals: S2I-vsRNA-ORF1a-5p; and humans: S2H-vsRNA-ORF1a-5p, S2H-vsRNA-ORF1a-3p, S2H-vsRNA-ORF1b-3p, S2H-vsRNA-ORF3a-3p), mainly encoded by nonstructural protein 3. Notably, Betacoronavirus-derived small RNAs targeted 74 differentially expressed genes in infected human cells, of which 55 upregulate the molecular mechanisms underlying acute respiratory distress syndrome (ARDS), and the 19 downregulated genes might be implicated in neurotrophin signaling impairment. These results reveal a novel small RNA-based regulatory mechanism involved in neuropathogenesis that must be further studied to validate its therapeutic use.

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Computational methods in the analysis of SARS-CoV-2 in mammals: A systematic review of the literature

Silva,

Nobre

2024

Computers in Biology and Medicine

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RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers in Betacoronavirus

Cited by 3 publications

References 106 publications

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

Computational Prediction of RNA–RNA Interactions between Small RNA Tracks from Betacoronavirus Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA

Computational methods in the analysis of SARS-CoV-2 in mammals: A systematic review of the literature

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