Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076485-12
Application #
9338248
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sammak, Paul J
Project Start
2006-07-01
Project End
2018-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
12
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Biochemistry
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Spasic, Aleksandar; Kennedy, Scott D; Needham, Laura et al. (2018) Molecular dynamics correctly models the unusual major conformation of the GAGU RNA internal loop and with NMR reveals an unusual minor conformation. RNA 24:656-672
Berger, Kyle D; Kennedy, Scott D; Schroeder, Susan J et al. (2018) Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops. Biochemistry 57:2121-2131
Spasic, Aleksandar; Berger, Kyle D; Chen, Jonathan L et al. (2018) Improving RNA nearest neighbor parameters for helices by going beyond the two-state model. Nucleic Acids Res 46:4883-4892
Lai, Wan-Jung C; Kayedkhordeh, Mohammad; Cornell, Erica V et al. (2018) mRNAs and lncRNAs intrinsically form secondary structures with short end-to-end distances. Nat Commun 9:4328
Payea, Matthew J; Sloma, Michael F; Kon, Yoshiko et al. (2018) Widespread temperature sensitivity and tRNA decay due to mutations in a yeast tRNA. RNA 24:410-422
Bellaousov, Stanislav; Kayedkhordeh, Mohammad; Peterson, Raymond J et al. (2018) Accelerated RNA secondary structure design using preselected sequences for helices and loops. RNA 24:1555-1567
Belashov, Ivan A; Crawford, David W; Cavender, Chapin E et al. (2018) Structure of HIV TAR in complex with a Lab-Evolved RRM provides insight into duplex RNA recognition and synthesis of a constrained peptide that impairs transcription. Nucleic Acids Res 46:6401-6415
Aytenfisu, Asaminew H; Spasic, Aleksandar; Grossfield, Alan et al. (2017) Revised RNA Dihedral Parameters for the Amber Force Field Improve RNA Molecular Dynamics. J Chem Theory Comput 13:900-915
Gamache, Eric R; Doh, Jung H; Ritz, Justin et al. (2017) Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA. Viruses 9:
Zuber, Jeffrey; Sun, Hongying; Zhang, Xiaoju et al. (2017) A sensitivity analysis of RNA folding nearest neighbor parameters identifies a subset of free energy parameters with the greatest impact on RNA secondary structure prediction. Nucleic Acids Res 45:6168-6176

Showing the most recent 10 out of 58 publications