Here is a sampling for some of the work that the Znosko lab has been a part of.
Brief overviews and recent publications are provided in each section.
Thermodynamic characterization of RNA secondary structure motifs
Most of the research in the Znosko lab has focused on thermodynamic characterization of RNA secondary structure motifs, an area of little prior study. We have collected experimental thermodynamic parameters for a variety of motifs in nature (internal loops, bulge loops, and hairpin loops) and used this data to derive better predictive models for motifs with no experimental values. We hope to soon incorporate the experimental values and predictive models into secondary structure prediction software. This work will likely impact the more than 25,000 users of RNAstructure alone and anyone who uses RNA secondary structure prediction from sequence to guide nucleic acid experiments. A sampling of our publications in this area is shown below.
Saon, Md. S., and Znosko, B. M. (2022) "Thermodynamic characterization of naturally occurring RNA pentaloops," RNA 28, 832-841.
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Tomcho, J. C., Tillman, M. R., and Znosko, B. M. (2015) "Improved model for predicting the free energy contribution of dinucleotide bulges to RNA duplex stability," Biochemistry 54, 5290-5296
DOI: 10.1021/acs.biochem.5b00474
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Murray, M. H., Hard, J. A., and Znosko, B. M. (2014) "Improved model to predict the free energy contribution of trinucleotide bulges to RNA duplex stability," Biochemistry 53, 3502-3508.
DOI: 10.1021/bi500204e
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Sheehy, J. P., Davis, A. R., and Znosko, B. M. (2010) "Thermodynamic characterization of naturally occurring RNA tetraloops," RNA 16, 417-429.
DOI: 10.1261/rna.1773110
RNA thermodynamics in buffers that better mimic biological conditions
Realizing that buffers used for most RNA thermodynamic studies are not very relevant to biological systems or biochemical experiments, the Znosko lab has studied RNA thermodynamics in buffers that better mimic biological conditions. This work will likely impact the more than 25,000 users of RNAstructure alone and anyone who uses RNA secondary structure prediction from sequence to guide nucleic acid experiments. A sampling of our publications in this area is shown below.
Arteaga, S. J., Dolenz, B. J., and Znosko, B. M. (2024) "Competitive influence of alkali metals in the ion atmosphere on nucleic acid duplex stability," ACS Omega 9, 1287-1297.
DOI: doi.org/10.1021/acsomega.3c07563
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Arteaga, S. J., Adams, M. S., Meyer, N. L., Richardson, K. E., Hoener, S., and Znosko, B. M. (2023) "Thermodynamic determination of RNA duplex stability in magnesium solutions," Biophys. J. 122, 565-576.
DOI: 10.1016/j.bpj.2022.12.025
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Adams, M. S. and Znosko, B. M. (2019) "Thermodynamic characterization and nearest neighbor parameters for RNA duplexes under molecular crowding conditions," Nucleic Acids Res. 47, 3658-3666.
DOI: 10.1093/nar/gkz019
Thermodynamic characterization of short RNA oligonucleotides containing common non-standard nucleotide
Due to the prevalence of non-standard nucleotides in natural RNA, the Znosko lab has thermodynamically characterized short RNA oligonucleotides containing common non-standard nucleotides. Currently, software used to predict RNA stability and secondary structure from sequence cannot directly accommodate non-standard nucleotides. When our experimental data is added, this work will likely impact anyone who wants to do RNA secondary structure prediction from a sequence containing a non-standard nucleotide. A sampling of our publications in this area is shown below.
Hopfinger, M. C., Kirkpatrick, C. C., and Znosko, B. M. (2020) "Predictions and analyses of RNA nearest neighbor parameters for modified nucleotides," Nucleic Acids Res. 48, 8901-8913.
DOI: 10.1093/nar/gkaa654
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Wright, D. J., Force, C. R., and Znosko, B. M. (2018) "Stability of RNA duplexes containing inosine-cytoside pairs," Nucleic Acids Res. 46, 12099-12108.
DOI: 10.1093/nar/gky907
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Jolley, E. A. and Znosko, B. M. (2016) "The loss of a hydrogen bond: Thermodynamic contributions of a non-standard nucleotide," Nucleic Acids Res. 45, 1479-1487.
DOI: 10.1093/nar/gkw830
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Richardson, K. E. and Znosko, B. M. (2016) "Nearest-neighbor parameters for 7-deaza-adenosine-uridine base pairs in RNA duplexes," RNA 22, 934-942.
Structural characterization of short RNA oligonucleotides by NMR
Much of PI Znosko’s early work focused on structural characterization of short, RNA oligonucleotides by NMR. These oligonucleotides contained a biologically relevant secondary structure motif or base modification. These studies led to the deposit of 10 NMR-derived three-dimensional structures in the Protein Data Bank. A sampling of our publications in this area is shown below.
Levengood, J. D., Rollins, C., Mishler, C. H., Johnson, C. A., Miner, G., Rajan, P., Znosko, B. M., and Tolbert, B. S. (2012) "Solution structure of the HIV-1 exon splicing silencer 3," J. Mol. Biol. 415, 680-698.
DOI: 10.1016/j.jmb.2011.11.034
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Chen, G., Znosko, B. M., Kennedy, S. D., Krugh, T. R., and Turner, D. H. (2005) "Solution structure of an RNA internal loop with three consecutive sheared GA pairs," Biochemistry 44, 2845-2856.
DOI: 10.1021/bi048079y
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Znosko, B. M., Kennedy, S. D., Wille, P. C., Krugh, T. R., and Turner, D. H. (2004) "Structural features and thermodynamics of the J4/5 loop from the Candida albicans and Candida dubliniensis group I introns," Biochemistry 43, 15822-15837.
DOI: 10.1021/bi049256y
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Znosko, B. M., Barnes T. W., Krugh T. R., and Turner, D. H. (2003) "NMR studies of DNA single strands and DNA:RNA hybrids with and without 1-propynylation at C5 of oligopyrimidines," J. Am. Chem. Soc. 125, 6090-6097.
DOI: 10.1021/ja021285d
Identifying, annotating, and comparing RNA secondary structure motifs in 3D structures
Recent projects in the Znosko lab have focused on identifying, annotating, and comparing RNA secondary structure motifs in three-dimensional structures. Identifying sequence families that adopt similar structural features can predict structural features of sequences that have yet to be solved by NMR or X-ray crystallography. The information learned here could improve RNA tertiary structure prediction from sequence. A sampling of our publications in this area is shown below.
Saon, Md. S., Kirkpatrick, C. C., and Znosko, B. M. (2023) "Identification and characterization of RNA pentaloop sequence families," NAR Genom. Bioinform. 5, lqac102.
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Richardson, K. E., Kirkpatrick, C. C., and Znosko, B. M. (2020) "RNA CoSSMos 2.0: An improved searchable database of secondary structure motifs in RNA three-dimensional structures," Database 2020, baz153.
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Richardson, K. E., Adams, M. S., Kirkpatrick, C. C., Gohara, D. W., and Znosko, B. M. (2019) "Identification and characterization of new RNA tetraloop sequence families," Biochemistry 58, 4809-4820.
DOI: 10.1021/acs.biochem.9b00535
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Vanegas, P. L., Hudson, G. A., Davis, A. R., Kelly, S. C., Kirkpatrick, C. C., and Znosko, B. M. (2012) "RNA CoSSMos: Characterization of secondary structure motifs - A searchable database of secondary structure motifs in RNA three-dimensional structures," Nucleic Acids Res. 40, D439-D444.
DOI: 10.1093/nar/gkr943