RNA plays important roles in many areas of Biology. Functional RNA sequences that work at the level of RNA, i.e. not as an mRNA coding region, are called non-coding RNA (ncRNA). ncRNA sequences serve diverse roles from sequence recognition, such as hybridization in RNA interference, to catalyzing reactions, such as peptide bond formation by ribosomal RNA. To understand RNA function and to harness the power of RNA, with RNA interference, therapeutic RNA enzymes, or RNA nanostructures, an understanding of RNA structure is required. RNAstructure is a software package for RNA secondary structure prediction and analysis. It has been downloaded by over 17,000 different users and is available at the Mathews lab website http://rna.urmc.rochester.edu. It provides state-of-the-art algorithms for RNA structure prediction using the most current understanding of RNA folding thermodynamics. It also provides algorithms for finding the optimal secondary structure shared by two sequences, which is, on average, much more accurate than predicting a structure for a single sequence. Furthermore, it provides methods to predict the affinity of structured oligonucleotides (DNA or RNA) annealing to a structured RNA target. These predictions are important for the selection of effective small interfering RNA (siRNA) for gene silencing. RNAstructure is provided with user-friendly graphical user interfaces in C++ for Microsoft Windows and in JAVA for Linux or Mac OS-X. Text interfaces are provided for scripting or command line use. These can be compiled on Unix/Linux/Mac OS-X and executables are provided for Windows. Finally, a shared C++ class library is available for programmers to include algorithms in new programs. The proposal is to extend and maintain RNAstructure. Four formal aims are proposed for the next period of support.
Aim 1 is to provide a new wizard mode for RNAstructure to guide users through the analysis of their sequence(s).
Aim 2 is to update the nearest neighbor parameters for predicting conformational stability using the most recent experimental data.
Aim 3 is to provide all the RNAstructure components via web interfaces.
Aim 4 is to provide fast and accurate prediction of secondary structures that include pseudoknots, which are currently not predicted by most algorithms.

Public Health Relevance

This proposal has direct public health relevance. We provide software tools for predicting, understanding, and targeting RNA structure. These can be applied to understanding the biology of infectious diseases because some viruses, including influenza and HIV, are RNA viruses. Furthermore, they can be used to design novel therapeutics, such as antisense oligonucleotides or small interfering RNA that both target RNA. This RNA-targeting therapeutics could be used for diseases such as cancer or inherited diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biodata Management and Analysis Study Section (BDMA)
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Swain, Amy L
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University of Rochester
Schools of Dentistry
United States
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DiChiacchio, Laura; Sloma, Michael F; Mathews, David H (2016) AccessFold: predicting RNA-RNA interactions with consideration for competing self-structure. Bioinformatics 32:1033-9
Sloma, Michael F; Mathews, David H (2016) Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures. RNA 22:1808-1818
Liberman, Joseph A; Suddala, Krishna C; Aytenfisu, Asaminew et al. (2015) Structural analysis of a class III preQ1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics. Proc Natl Acad Sci U S A 112:E3485-94
Aytenfisu, Asaminew H; Liberman, Joseph A; Wedekind, Joseph E et al. (2015) Molecular mechanism for preQ1-II riboswitch function revealed by molecular dynamics. RNA 21:1898-907
Fu, Yinghan; Xu, Zhenjiang Zech; Lu, Zhi J et al. (2015) Discovery of Novel ncRNA Sequences in Multiple Genome Alignments on the Basis of Conserved and Stable Secondary Structures. PLoS One 10:e0130200
Sloma, Michael F; Mathews, David H (2015) Improving RNA secondary structure prediction with structure mapping data. Methods Enzymol 553:91-114
Chen, Jonathan L; Bellaousov, Stanislav; Tubbs, Jason D et al. (2015) Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints. Biochemistry 54:6769-82
Guy, Michael P; Young, David L; Payea, Matthew J et al. (2014) Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis. Genes Dev 28:1721-32
Andronescu, Mirela; Condon, Anne; Turner, Douglas H et al. (2014) The determination of RNA folding nearest neighbor parameters. Methods Mol Biol 1097:45-70
Mathews, David H (2014) RNA Secondary Structure Analysis Using RNAstructure. Curr Protoc Bioinformatics 46:12.6.1-25

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