Role of Unsatisfied Hydrogen Bond Acceptors in RNA Energetics and Specificity
Abstract
RNA plays essential roles in much of biology. These functions are dictated by structures mediated by hydrogen bonding, stacking, electrostatics, and steric interactions. Roles of unsatisfied hydrogen bond functionalities in these structures are less well understood. Herein, we evaluated the energetic contributions of unsatisfied hydrogen bonding groups by placing chemically modified substituents in select internal positions in RNA helices and conducting thermodynamic studies. We find that unsatisfied carbonyl groups make exceptional contributions to structure formation (approximately 3 kcal/mol in free energy), most likely due to a combination of strain and dehydration effects. Thus, unsatisfied hydrogen bonding groups are likely key determinants in the folding energetics and specificity of many RNA and DNA molecules and may be especially important in tertiary structure interactions.
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The G:2-thio-C base-pair is only 0.6 kcal/mol less stable than a standard G:C base-pair at an internal position in an RNA duplex, and replacement of G with inosine to generate an I:2-thio-C base-pair has almost no effect.
“Interestingly, the G:2-thio-C base-pair is only 0.6 kcal/mol less stable than a standard G:C base-pair at an internal position in a RNA duplex, and replacement of G with inosine (I) to generate an I:2-thio-C base-pair has almost no effect [38], suggesting that RNA templates that include either G or I residues should also be examined.”
From The eightfold path to non-enzymatic RNA replication (2012) · cites this paper as [38]
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The eightfold path to non-enzymatic RNA replication
Szostak, J. W. (2012) · Journal of Systems Chemistry · doi:10.1186/1759-2208-3-2 · Cited by 359 · see citing works
Rios, A. C., & Tor, Y. (2013) · Israel Journal of Chemistry · doi:10.1002/ijch.201300009 · Cited by 98 · see citing works
- Authors
- Siegfried, N. A., Kierzek, R., & Bevilacqua, P. C.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Siegfried, Nathan A.
- Bevilacqua, Philip C.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-03-26
- Volume
- 132
- Issue
- 15
- Pages
- 5342-5344
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2065160396
- Cited by
- 36
- References
- 43
- Citations by year
- 2025: 3 · 2024: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- chemically modified nucleotides, carbonyl compounds, thermodynamic contribution, dehydration effects, RNA tertiary structure, RNA-DNA interactions
- MeSH terms
- Hydrogen Bonding, RNA, Thermodynamics, Base Pairing
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