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      ElTetrado: a tool for identification and classification of tetrads and quadruplexes

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          Abstract

          Background

          Quadruplexes are specific structure motifs occurring, e.g., in telomeres and transcriptional regulatory regions. Recent discoveries confirmed their importance in biomedicine and led to an intensified examination of their properties. So far, the study of these motifs has focused mainly on the sequence and the tertiary structure, and concerned canonical structures only. Whereas, more and more non-canonical quadruplex motifs are being discovered.

          Results

          Here, we present ElTetrado, a software that identifies quadruplexes (composed of guanine- and other nucleobase-containing tetrads) in nucleic acid structures and classifies them according to the recently introduced ONZ taxonomy. The categorization is based on the secondary structure topology of quadruplexes and their component tetrads. It supports the analysis of canonical and non-canonical motifs. Besides the class recognition, ElTetrado prepares a dot-bracket and graphical representations of the secondary structure, which reflect the specificity of the quadruplex’s structure topology. It is implemented as a freely available, standalone application, available at https://github.com/tzok/eltetrado.

          Conclusions

          The proposed software tool allows to identify and classify tetrads and quadruplexes based on the topology of their secondary structures. It complements existing approaches focusing on the sequence and 3D structure.

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          Most cited references18

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          Geometric nomenclature and classification of RNA base pairs

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            DSSR: an integrated software tool for dissecting the spatial structure of RNA

            Insight into the three-dimensional architecture of RNA is essential for understanding its cellular functions. However, even the classic transfer RNA structure contains features that are overlooked by existing bioinformatics tools. Here we present DSSR (Dissecting the Spatial Structure of RNA), an integrated and automated tool for analyzing and annotating RNA tertiary structures. The software identifies canonical and noncanonical base pairs, including those with modified nucleotides, in any tautomeric or protonation state. DSSR detects higher-order coplanar base associations, termed multiplets. It finds arrays of stacked pairs, classifies them by base-pair identity and backbone connectivity, and distinguishes a stem of covalently connected canonical pairs from a helix of stacked pairs of arbitrary type/linkage. DSSR identifies coaxial stacking of multiple stems within a single helix and lists isolated canonical pairs that lie outside of a stem. The program characterizes ‘closed’ loops of various types (hairpin, bulge, internal, and junction loops) and pseudoknots of arbitrary complexity. Notably, DSSR employs isolated pairs and the ends of stems, whether pseudoknotted or not, to define junction loops. This new, inclusive definition provides a novel perspective on the spatial organization of RNA. Tests on all nucleic acid structures in the Protein Data Bank confirm the efficiency and robustness of the software, and applications to representative RNA molecules illustrate its unique features. DSSR and related materials are freely available at http://x3dna.org/.
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              RNA G-quadruplexes: emerging mechanisms in disease

              Abstract RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health. Here, we review the different molecular mechanisms underlying the link between RNA G4s and human diseases by proposing several overlapping models of deregulation emerging from recent research, including (i) sequestration of RNA-binding proteins, (ii) aberrant expression or localization of RNA G4-binding proteins, (iii) repeat associated non-AUG (RAN) translation, (iv) mRNA translational blockade and (v) disabling of protein–RNA G4 complexes. This review also provides a comprehensive survey of the functional RNA G4 and their mechanisms of action. Finally, we highlight future directions for research aimed at improving our understanding on RNA G4-mediated regulatory mechanisms linked to diseases.
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                Author and article information

                Contributors
                mszachniuk@cs.put.poznan.pl
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                31 January 2020
                31 January 2020
                2020
                : 21
                : 40
                Affiliations
                [1 ]ISNI 0000 0001 0729 6922, GRID grid.6963.a, Institute of Computing Science and European Centre for Bioinformatics and Genomics, Poznan University of Technology, ; Piotrowo 2, Poznan, 60-965 Poland
                [2 ]ISNI 0000 0004 0631 2857, GRID grid.418855.5, Poznan Supercomputing and Networking Center, ; Jana Pawla II 10, Poznan, 61-139 Poland
                [3 ]ISNI 0000 0004 0631 2857, GRID grid.418855.5, Institute of Bioorganic Chemistry, Polish Academy of Sciences, ; Noskowskiego 12/14, Poznan, 61-704 Poland
                Author information
                http://orcid.org/0000-0002-8724-7908
                Article
                3385
                10.1186/s12859-020-3385-1
                6995151
                32005130
                5a3398a3-84f3-45a9-8b25-09191c1eeb09
                © The Author(s) 2020

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 June 2019
                : 24 January 2020
                Categories
                Software
                Custom metadata
                © The Author(s) 2020

                Bioinformatics & Computational biology
                quadruplexes,classification,secondary structure topology,dot-bracket notation,arc diagram

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