IIIT Hyderabad Publications |
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Magnesium Motifs in RNA (MagMotiRNA) A suite of tools for investigating magnesium-RNA interaction patternsAuthor: Rohit Roy Date: 2020-08-21 Report no: IIIT/TH/2020/77 Advisor:Abhijit Mitra AbstractPositive counterions, such as metal cations, are necessary for the electrostatic neutralization of the polyanionic ribonucleic acids (RNA) as the negatively charged RNA backbone folds onto itself to adopt a 3D structure. Magnesium ions are the most frequently observed metal ion in experimentally determined RNA structures, and have been noted for their influence on the stability, dynamics and function of RNA molecules. Identifying motifs at magnesium-RNA sites is necessary to better characterize the role played by the ions in RNA molecules. Previously available tools to detect magnesium-RNA motifs are either based on manual annotation or rigidly defined ion-RNA binding characteristics that cannot be used to describe many recently identified motifs. In this work, a set of methods have been developed to help detect, characterize and discover magnesium-RNA motifs that overcome the limitations of previously available tools. A graph-based querying system “MagMotiRNA” has been developed to query for welldefined motifs in literature as well as user-defined patterns at magnesium-RNA sites. In keeping with the evidence regarding variability in magnesium-RNA binding patterns and the role played by magnesium in stabilizing certain inter-nucleotide contacts, the tool allows for defining queries with fuzzy ion-RNA binding descriptions and queries involving the local RNA structure at the site. The results from MagMotiRNA were benchmarked against MgRNA tool, the prevalent magnesium motif detection tool, and the discrepancies in the results could be largely attributed to the higher sensitivity in the hydrogen bond detection method used in MagMotiRNA. The occurrences of five distinct base-coordinated magnesium-RNA motifs in a redundant dataset were analyzed and the distinct structural contexts in which they occur were studied. The case study revealed that the ion-RNA binding patterns at these contexts are often variable, and hence it may not be appropriate to define magnesium-RNA motifs solely based on ion-RNA binding details. Instead, a bottom-up approach is proposed for defining motifs based on the invariant features in the local RNA structure at these sites that are indicative of the putative role played by magnesium ions. A set of heuristics has been developed as part of this work whereby conserved magnesiumRNA sites can be detected in an RNA molecule by analyzing multiple structures of the molecule. Building upon these heuristics, a metal-RNA binding profile was created for 19 RNA molecules by transposing all metal-RNA sites associated with these molecules in a redundant dataset onto a representative structure. The rather complex problem of studying magnesium-RNA sites given the sparsity of reliable experimental data would benefit from these profiles of frequently conserved metal-RNA sites provided by the MagMotiRNA-Atlas database. The Atlas equips users to perform top-down exploration of magnesium-RNA motifs, and can act as a complementary tool to the bottom-up analysis of magnesium-RNA sites developed in the other MagMotiRNA tools. Full thesis: pdf Centre for Computational Natural Sciences and Bioinformatics |
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