We are analyzing, annotating, organizing, and integrating nucleic acid 3D structural data with sequence and functional data and delivering it to biomedical researchers. The significance of the proposal lies in the prominent roles of nucleic acids in a host of cellular and physiological processes, mediated by interaction with specific DNA- and RNA-binding proteins. DNA encodes genetic information and takes part in replication, recombination, transcription, and repair. RNA transmits genetic information and takes part in all aspects of gene regulation. RNA is also the key component of the ribosome, the universal protein-making nano-machine and an important target for drug design. RNA/DNA hybrids occur in many biological contexts, including transcription complexes, origins of replication, and the widely heralded CRISPR-CAS systems for precision editing of genes (Wright 2016). They form unique structures different from double helical RNA or DNA. High throughput methods have catalogued many new non-coding RNAs (ncRNAs) and RNA-binding proteins lacking previously known RNA-binding domains.
The Specific Aims of this proposal are: 1) Create more complete annotations for all nucleic acid 3D structures, 2) create new annotations for nucleic acid-protein complexes, and 3) create a Nucleic Acid Knowledge Base (NAKB) that allows for both deep and wide searching of information about nucleic acid sequences and structures. Under these aims, we will analyze and annotate all types of nucleic acid 3D structures, including DNA, RNA, and DNA/RNA hybrids, and improve our ability to predict 3D structures from sequence. The NAKB resource will provide new search capabilities, enhanced reports, and link-outs to external data, features and tools. The proposed enhancements will greatly improve our abilities to search and visualize existing data on nucleic acid sequence and structural features and will further enrich the user experience and enable data discovery. The innovation of the proposal is the creation of a unified resource for all nucleic acid 3D structures.
Nucleic acids (DNA, RNA, and RNA/DNA hybrids) play vitally important roles in the human body, from storing and transmitting genetic information to regulating which genes are active, carrying messages between cells, responding to environmental signals, and catalyzing important processes such as making proteins. We are studying the shapes of nucleic acids and how they interact with proteins and disseminating this information through the Nucleic Acid Knowledge Base (NAKB).
| Roll, James; Zirbel, Craig L; Sweeney, Blake et al. (2016) JAR3D Webserver: Scoring and aligning RNA loop sequences to known 3D motifs. Nucleic Acids Res 44:W320-7 |
| Parlea, Lorena G; Sweeney, Blake A; Hosseini-Asanjan, Maryam et al. (2016) The RNA 3D Motif Atlas: Computational methods for extraction, organization and evaluation of RNA motifs. Methods 103:99-119 |
| Zirbel, Craig L; Roll, James; Sweeney, Blake A et al. (2015) Identifying novel sequence variants of RNA 3D motifs. Nucleic Acids Res 43:7504-20 |
| Sweeney, Blake A; Roy, Poorna; Leontis, Neocles B (2015) An introduction to recurrent nucleotide interactions in RNA. Wiley Interdiscip Rev RNA 6:17-45 |
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| Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I et al. (2015) R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server. Nucleic Acids Res 43:W15-23 |
| Coimbatore Narayanan, Buvaneswari; Westbrook, John; Ghosh, Saheli et al. (2014) The Nucleic Acid Database: new features and capabilities. Nucleic Acids Res 42:D114-22 |
| Akkuratov, Evgeny E; Walters, Lorraine; Saha-Mandal, Arnab et al. (2014) Bioinformatics analysis of plant orthologous introns: identification of an intronic tRNA-like sequence. Gene 548:81-90 |
| Rahrig, Ryan R; Petrov, Anton I; Leontis, Neocles B et al. (2013) R3D Align web server for global nucleotide to nucleotide alignments of RNA 3D structures. Nucleic Acids Res 41:W15-21 |
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