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.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Swain, Amy L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
School of Medicine & Dentistry
United States
Zip Code
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

Showing the most recent 10 out of 38 publications