Classification, Characterization and Database Searching of RNA Motifs

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DESCRIPTION (provided by applicant): This project is designed to carry out specific research tasks relevant to and supportive of the development of the RNA Ontology (RNAO), a core, orthogonal ontology of the Open Biomedical Ontologies (OBO) Consortium and companion to the Sequence Ontology (SO). The P.I. is the convener of the RNA Ontology Consortium (ROC), which is developing RNAO under the auspices of the RNA Society. The first version of the ontology (RNAO.owl) is being presented at the RNA Society annual meeting, May 2009. By integrating diverse databases pertaining to RNA 3D structures, RNA sequences, and RNA functions, the RNAO will serve multiple RNA research agendas, including prediction of RNA 3D structures from sequence, multiple alignment of homologous RNA sequence, genome searching for non-coding RNAs, and the design of RNA-based nanostructures for diverse applications, such as biosensing and drug delivery. The proposed research applies bioinformatic, computational, and biophysical tools to obtain fundamental data on RNA interactions and recurrent 3D motifs. The specific aims of this project include: A.1. Base Stacking: To carry out bioinformatic statistical studies and targeted experimental studies to explore the base specificity of stacking interactions in RNA motifs. A.2. Base Triples: To extract, classify and cluster all base triples in 3D structures and to identify isosteric base triples that substitute at corresponding positions in homologous RNA molecules. To carry out QM calculations on selected base triples that are highly over- or under-represented in the 3D database, optimize their structures, compare their energetics and assess their structural stabilities. A.3. Multi-helix junctions and tertiary interactions: To develop algorithms and write software that will extract from RNA 3D structures all multi-helix junctions and all tertiary interactions, including pseudoknots. To cluster and classify all motifs based on geometric criteria and to extend the on-line RNA 3D Motif Library to include multi-helix junction and tertiary interaction motifs. A.4. Collaborative Environment: To create an on-line collaborative environment for members of the RNA Ontology Consortium (ROC) to compare and evaluate proposed RNA 3D Motif classes and definitions. A.5. SCFG/MRF models which incorporate stacking and base-phosphate interactions. Incorporate scoring terms for base stacking and base-phosphate interactions into the SCFG/MRF models developed previously to test their ability to enhance the identification of motif 3D structure from sequence alone. A.6. Experimental Studies. To perform thermodynamic studies to assess the contributions of base-stacking, base-pairing, and base-phosphate interactions to the stabilities of recurrent RNA 3D motifs. PUBLIC HEALTH RELEVANCE: RNA molecules play essential roles in all stages of gene expression in human cells and have been implicated in many diseases including heart disease, diabetes, and various forms of cancer. Many RNA molecules form unique 3D structures to carry out their functions. This proposal supports the development of the RNA Ontology (RNAO), a core ontology of the Open Biomedical Ontologies (OBO) Consortium and companion to the Sequence Ontology (SO), to facilitate integration of databases pertaining to RNA 3D structure, homologous sequences, and RNA functions to enable intelligent data-mining of diverse RNA data and their rapid translation into useful knowledge.