Abstract

The ultimate goal of this research is to characterize the interactions directing RNA folding, and to use this knowledge to reliably predict structures of RNA molecules from their sequences. Since most diseases are mediated through RNA, and some viruses, including HIV, have RNA genomes, the results can lead to rational design of therapeutics. The results should also further the interpretation of sequences determined by the Human Genome Project and other sequencing efforts. The foundation for structure prediction will be provided by studies of the thermodynamic and structural properties of oligonucleotides. Particular emphasis will be placed on the sequence dependence of stability and structure for internal loops and multibranch loops. Secondary structure prediction by free energy minimization will be augmented with constraints from structure mapping and sequence comparison to partially compensate for incomplete knowledge of the factors affecting folding. The power of the method will be tested by attempting to determine the secondary structure of a messenger RNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM022939-25
Application #
6046041
Study Section
Special Emphasis Panel (ZRG1-BMT (03))
Program Officer
Lewis, Catherine D
Project Start
1979-03-01
Project End
2004-02-29
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
25
Fiscal Year
2000
Total Cost
$420,995
Indirect Cost

  Institution

Name
University of Rochester
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

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
Smith, Louis G; Zhao, Jianbo; Mathews, David H et al. (2017) Physics-based all-atom modeling of RNA energetics and structure. Wiley Interdiscip Rev RNA 8:
Pinamonti, Giovanni; Zhao, Jianbo; Condon, David E et al. (2017) Predicting the Kinetics of RNA Oligonucleotides Using Markov State Models. J Chem Theory Comput 13:926-934
Kauffmann, Andrew D; Kennedy, Scott D; Zhao, Jianbo et al. (2017) Nuclear Magnetic Resonance Structure of an 8 × 8 Nucleotide RNA Internal Loop Flanked on Each Side by Three Watson-Crick Pairs and Comparison to Three-Dimensional Predictions. Biochemistry 56:3733-3744
Lenartowicz, Elzbieta; Nogales, Aitor; Kierzek, Elzbieta et al. (2016) Antisense Oligonucleotides Targeting Influenza A Segment 8 Genomic RNA Inhibit Viral Replication. Nucleic Acid Ther 26:277-285
Lenartowicz, Elzbieta; Kesy, Julita; Ruszkowska, Agnieszka et al. (2016) Self-Folding of Naked Segment 8 Genomic RNA of Influenza A Virus. PLoS One 11:e0148281
Gleghorn, Michael L; Zhao, Jianbo; Turner, Douglas H et al. (2016) Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation. Nucleic Acids Res 44:8417-24
Jiang, Tian; Nogales, Aitor; Baker, Steven F et al. (2016) Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture. PLoS One 11:e0156906
Condon, David E; Kennedy, Scott D; Mort, Brendan C et al. (2015) Stacking in RNA: NMR of Four Tetramers Benchmark Molecular Dynamics. J Chem Theory Comput 11:2729-2742
Chen, Jonathan L; Kennedy, Scott D; Turner, Douglas H (2015) Structural features of a 3' splice site in influenza a. Biochemistry 54:3269-85

Showing the most recent 10 out of 162 publications