The ultimate goals of this research are to characterize the forces directing RNA folding, and to use this knowledge to reliably predict RNA structure from sequence and to suggest lead compounds for therapeutics targeting RNA. Insights into the role of electrostatic interactions in directing RNA folding will be provided by thermodynamic and NMR structural studies of duplexes containing isoC-isoG base pairs. A hypothesis for providing selective formation of AU and GU base pairs by antisense agents will be tested with oligonucleotides containing 2- thiouridine and 4-thiouridine. Binding will be measured to short oligonucleotides and to a group I ribozyme derived from mouse Pneumocystis carinii. The results will lay a foundation for facilitating discovery of therapeutics based on RNA sequence information.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Small Research Grants (R03)
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International and Cooperative Projects 1 Study Section (ICP)
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Katz, Flora N
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University of Rochester
Schools of Arts and Sciences
United States
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Kierzek, Elzbieta; Kierzek, Ryszard; Moss, Walter N et al. (2008) Isoenergetic penta- and hexanucleotide microarray probing and chemical mapping provide a secondary structure model for an RNA element orchestrating R2 retrotransposon protein function. Nucleic Acids Res 36:1770-82
Yajima, Rieko; Proctor, David J; Kierzek, Ryszard et al. (2007) A conformationally restricted guanosine analog reveals the catalytic relevance of three structures of an RNA enzyme. Chem Biol 14:23-30
Chen, Gang; Kierzek, Ryszard; Yildirim, Ilyas et al. (2007) Stacking effects on local structure in RNA: changes in the structure of tandem GA pairs when flanking GC pairs are replaced by isoG-isoC pairs. J Phys Chem B 111:6718-27
Pasternak, Anna; Kierzek, Elzbieta; Pasternak, Karol et al. (2007) A chemical synthesis of LNA-2,6-diaminopurine riboside, and the influence of 2'-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes. Nucleic Acids Res 35:4055-63
Kierzek, Elzbieta; Kierzek, Ryszard; Turner, Douglas H et al. (2006) Facilitating RNA structure prediction with microarrays. Biochemistry 45:581-93
Ma, Hairong; Proctor, David J; Kierzek, Elzbieta et al. (2006) Exploring the energy landscape of a small RNA hairpin. J Am Chem Soc 128:1523-30
Kierzek, Elzbieta; Mathews, David H; Ciesielska, Anna et al. (2006) Nearest neighbor parameters for Watson-Crick complementary heteroduplexes formed between 2'-O-methyl RNA and RNA oligonucleotides. Nucleic Acids Res 34:3609-14
Broda, Magdalena; Kierzek, Elzbieta; Gdaniec, Zofia et al. (2005) Thermodynamic stability of RNA structures formed by CNG trinucleotide repeats. Implication for prediction of RNA structure. Biochemistry 44:10873-82
Kierzek, Elzbieta; Ciesielska, Anna; Pasternak, Karol et al. (2005) The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes. Nucleic Acids Res 33:5082-93
Proctor, David J; Ma, Hairong; Kierzek, Elzbieta et al. (2004) Folding thermodynamics and kinetics of YNMG RNA hairpins: specific incorporation of 8-bromoguanosine leads to stabilization by enhancement of the folding rate. Biochemistry 43:14004-14

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