Abstract

RNA plays many important roles in cellular function. In the Central Dogma of Biology, RNA serves as a transient carrier of genetic information and as the adapter molecule that reads the code. RNA catalyzes reactions and serves in post-transcriptional gene regulation, development, and immunity. RNA also plays roles in human disease, including Prader-Willi and myotonic dystrophy. Understanding and harnessing the power of RNA, e.g. with RNAi, antisense technology, or with therapeutic ribozymes, requires an understanding of the structures of these RNA sequences. RNAstructure is a software package for RNA secondary structure prediction and analysis. It is available at: http://rna.urmc.rochester.edu and has been downloaded by a total of over 11,000 users.
The specific aims of this proposal include both development and maintenance for the RNAstructure package: 1) Develop enthalpy nearest neighbor parameters for RNA secondary structure formation to allow structure prediction and analysis at other temperatures. 2) Construct a web server to provide RNA secondary structure nearest neighbor parameters and offer tutorials on their use. 3) Add RNAML support to the existing software to improve interoperability with other software packages. 4) Port RNAstructure to Unix, Linux, and Macintosh OS X using the Java runtime library to build a user-interface. 5) Provide high quality Adobe Acrobat File (pdf) output directly from RNAstructure, so that predicted structures can be edited for publication. 6) Update RNAstructure for 64-bit Microsoft Windows Vista. 7) Provide source code for download under an open license. 8) Construct a web server for the OligoWalk algorithm for predicting equilibrium binding affinities to an RNA target. Web servers are highly popular because of there ease of use. 9) Offer an email reflector for communication by the RNAstructure user community. This work has broad implications for human health. The computer tools contained in RNAstructure are used by others to determine RNA sequences that are good drug targets. RNAstructure is also useful for the design of RNA-based Pharmaceuticals. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076485-03
Application #
7455818
Study Section
Special Emphasis Panel (ZRG1-BST-L (51))
Program Officer
Remington, Karin A
Project Start
2006-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$212,066
Indirect Cost

  Institution

Name
University of Rochester
Department
Pediatrics
Type
Schools of 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

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