Rapid sequencing methods have identified functional RNA sequences across all domains of life. Determining the roles of these RNA sequences and their mechanisms of action is central to biology and human health. RNA secondary structure prediction is one of the tools that is commonly used to aid in understanding RNA function, and we have addressed the need for RNA secondary structure prediction by developing RNAstructure. RNAstructure is a user-friendly software package for RNA secondary structure prediction, display, and analysis. It includes methods for structure prediction of a single sequence, including pseudoknots, structure prediction for bimolecular interactions, and prediction of the conserved structure for multiple homologous sequences. Thermodynamic parameters are provided for both RNA and DNA sequences, which extends the structure predictions to DNA. The programs are available with a graphical user interface (for Windows, Mac OS X, or Linux), command line interfaces, and also as web servers. The algorithms are also available for use in other programs as a set of well-documented C++ classes. The package is fully open source, under the GNU Public License. This proposal is for continued development and maintenance of the software. For the next period of support, we are proposing high-impact aims that will keep RNAstructure cutting-edge and user-friendly. We will develop a new interface for facilitating comparative sequence analysis to determine a conserved RNA structure, continue to support and extend the existing programs and interfaces, and develop a new method for structure prediction for pseudoknotted sequences.

Public Health Relevance

RNA structure is important in both human health and disease, including genetic diseases and infectious diseases. Here we are developing a software tool that predicts and analyzes RNA structure. This provides important information that can be used to understand disease mechanisms, target RNA with pharmaceuticals, and develop RNA as a pharmaceutical.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01GM076485-09
Application #
8784766
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Swain, Amy L
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Rochester
Department
Biochemistry
Type
School of Medicine & Dentistry
DUNS #
City
Rochester
State
NY
Country
United States
Zip Code
14627
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) Using the RNAstructure Software Package to Predict Conserved RNA Structures. Curr Protoc Bioinformatics 46:12.4.1-12.4.22
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
Hajdin, Christine E; Bellaousov, Stanislav; Huggins, Wayne et al. (2013) Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots. Proc Natl Acad Sci U S A 110:5498-503
Shen, Manli; Bellaousov, Stanislav; Hiller, Michael et al. (2013) Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure. Nucleic Acids Res 41:3819-32
Bellaousov, Stanislav; Reuter, Jessica S; Seetin, Matthew G et al. (2013) RNAstructure: Web servers for RNA secondary structure prediction and analysis. Nucleic Acids Res 41:W471-4
Leonard, Christopher W; Hajdin, Christine E; Karabiber, Fethullah et al. (2013) Principles for understanding the accuracy of SHAPE-directed RNA structure modeling. Biochemistry 52:588-95
Liu, Biao; Diamond, Joshua M; Mathews, David H et al. (2011) Fluorescence competition and optical melting measurements of RNA three-way multibranch loops provide a revised model for thermodynamic parameters. Biochemistry 50:640-53
Nasrallah, Chris A; Mathews, David H; Huelsenbeck, John P (2011) Quantifying the impact of dependent evolution among sites in phylogenetic inference. Syst Biol 60:60-73
Mathews, David H (2010) Using OligoWalk to identify efficient siRNA sequences. Methods Mol Biol 629:109-21

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