BRIO: a web server for RNA sequence and structure motif scan

Pepe, Gerardo; Ballesio, Francesco; Adinolfi, Marta; Pietrosanto, Marco; Sangiovanni, Elisa; Vitale, Ilio; Ausiello, Gabriele; Helmer‐Citterich, Manuela

doi:10.1093/nar/gkab400

Cited by 12 publications

(11 citation statements)

References 16 publications

(22 reference statements)

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“…To explore whether predicted nsORFs contain binding motifs for human proteins, further bioinformatic analysis using the Beam RNA Interaction motif search tool [ 27 ] was conducted ( Supplementary Table S3 ). This RNA interaction motif analysis revealed many interesting hits: nsORF9 (and its overlapping nsORF8) contains a motif that is significantly similar to the PUM1 binding sequence ( P -value = 0.012).…”

Section: Resultsmentioning

confidence: 99%

“…A combination of four tools was used to discover ORFs and Kozak sequences on the negative-sense strand: TISRover prediction tool for predicting translation initiation sites in human by convolutional neural networks [ 21 ]; ATGpr tool ( https://atgpr.dbcls.jp/ ) that uses linear discriminant analysis for identifying the initiation codons [ 22 ]; NCBI ORFfinder ( https://www.ncbi.nlm.nih.gov/orffinder/ ) to predict all potential ORFs; and StarORF ( http://star.mit.edu/orf/index.html ) to cross examine ORFfinder results. The Beam RNA Interaction motif search tool (BRIO) [ 27 ] was used for the transcription factor binding site analysis with default parameters and all resulting hits are enclosed in the Supplementary Table S2 . Interaction network analysis of proteins predicted by BRIO was done using STRING tool [ 38 ] with default parameters ( https://string-db.org/cgi/input?sessionId=bVBUeCTKWYuE&input_page_show_search=on ).…”

Section: Methodsmentioning

confidence: 99%

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Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

Bartas

Volná

Beaudoin

et al. 2022

Briefings in Bioinformatics

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SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

Bartas

Volná

Beaudoin

et al. 2022

Briefings in Bioinformatics

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“…Moreover, the experimentally verified and predicted RNA–protein and RNA–RNA binding sites were acquired from ENCORI ( 44 ), POSTAR2 ( 45 ) and NPinter 4.0 ( 29 ). Besides, we identified known sequence and secondary structure protein binding motifs in RNAs from humans and mice via BRIO web server ( 46 ). As another LLPS-associated property, RNA modification can also potentially contribute to the features of native condensate.…”

Section: Methodsmentioning

confidence: 99%

RPS: a comprehensive database of RNAs involved in liquid–liquid phase separation

Liu

Luo

et al. 2021

Nucleic Acids Research

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Liquid–liquid phase separation (LLPS) is critical for assembling membraneless organelles (MLOs) such as nucleoli, P-bodies, and stress granules, which are involved in various physiological processes and pathological conditions. While the critical role of RNA in the formation and the maintenance of MLOs is increasingly appreciated, there is still a lack of specific resources for LLPS-related RNAs. Here, we presented RPS (http://rps.renlab.org), a comprehensive database of LLPS-related RNAs in 20 distinct biomolecular condensates from eukaryotes and viruses. Currently, RPS contains 21,613 LLPS-related RNAs with three different evidence types, including ‘Reviewed’, ‘High-throughput’ and ‘Predicted’. RPS provides extensive annotations of LLPS-associated RNA properties, including sequence features, RNA structures, RNA–protein/RNA–RNA interactions, and RNA modifications. Moreover, RPS also provides comprehensive disease annotations to help users to explore the relationship between LLPS and disease. The user-friendly web interface of RPS allows users to access the data efficiently. In summary, we believe that RPS will serve as a valuable platform to study the role of RNA in LLPS and further improve our understanding of the biological functions of LLPS.

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“…The search for sequence and structure motifs in the putative LIN28B binding module was performed using the BRIO (BEAM RNA Interaction mOtifs) web server [65]. This tool enables the identification of RNA sequence and structure motifs involved in protein binding in one or more input RNA molecules, by measuring, through a Fisher's exact test, their enrichment compared to a background of RNAs from Rfam with similar length and structure content, defined as the fraction of paired nucleotides in the RNA secondary structure.…”

Section: Author Summarymentioning

confidence: 99%

Human lncRNAs harbor conserved modules embedded in different sequence contexts

Ballesio,

Pepe,

Ausiello

et al. 2023

Preprint

Self Cite

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We analyzed the structure of human long non-coding RNA (lncRNAs) genes to investigate whether the non-coding transcriptome is organized in modular domains, as is the case for protein-coding genes. To this aim, we compared all known human lncRNA exons and identified 340 pairs of exons with high sequence and/or secondary structure similarity but embedded in a dissimilar sequence context. We grouped these pairs in 106 clusters based on their reciprocal similarities. These shared modules are highly conserved between humans and the four great ape species, display evidence of purifying selection and likely arose as a result of recent segmental duplications. Our analysis contributes to the understanding of the mechanisms driving the evolution of the non-coding genome and suggests additional strategies towards deciphering the functional complexity of this class of molecules.Author summaryThe Human genome includes more than 18,000 genes coding for RNAs that are not translated into proteins, called long non-coding RNAs (lncRNA). Mounting evolutionary and experimental evidence shows that a large amount of these RNAs have a specific function, mainly as regulators of a diverse set of biological processes. Here we set out to investigate whether these genes have a modular organization similar to that of protein-coding genes. Accordingly, we compared the sequence of all the exonic regions of human lncRNAs and identified 106 clusters of non-repetitive exonic modules shared between this class of genes. These modules display evidence of purifying selection, are highly conserved between humans and the four great ape species, and may represent distinct functional units that have been shuffled among multiple lncRNA genes, in a manner similar to the exon-shuffling process that is observed in the coding genome.

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BRIO: a web server for RNA sequence and structure motif scan

Cited by 12 publications

References 16 publications

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

RPS: a comprehensive database of RNAs involved in liquid–liquid phase separation

Human lncRNAs harbor conserved modules embedded in different sequence contexts

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