Role of Unsatisfied Hydrogen Bond Acceptors in RNA Energetics and Specificity

Siegfried, Nathan A.; Kierzek, Ryszard; Bevilacqua, Philip C.

doi:10.1021/ja9107726

Cited by 31 publications

(45 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interaction of G6 carbonyl oxygen with the crossstrand 29-OH proton in the R2 loop, 59AAG/39AGG, is replaced by interaction of the adenine amino proton with the cross-strand 29-OH oxygen in 59GAA/39AGG. The hydrogen bond to the G6 carbonyl avoids an ''unsatisfied hydrogen bond acceptor,'' which is expected to be energetically very unfavorable (Siegfried et al 2010). Hydrogen bonds with 29-OH groups in tertiary interactions have been shown to add z1 kcal/mol favorable free energy for folding (Sugimoto et al 1989;Bevilacqua and Turner 1991;Pyle and Cech 1991).…”

Section: Discussionmentioning

confidence: 99%

NMR structure of a 4 × 4 nucleotide RNA internal loop from an R2 retrotransposon: Identification of a three purine–purine sheared pair motif and comparison to MC-SYM predictions

Lerman

Kennedy²,

Shankar³

et al. 2011

RNA

View full text Add to dashboard Cite

The NMR solution structure is reported of a duplex, 59GUGAAGCCCGU/39UCACAGGAGGC, containing a 4 @ 4 nucleotide internal loop from an R2 retrotransposon RNA. The loop contains three sheared purine-purine pairs and reveals a structural element found in other RNAs, which we refer to as the 3RRs motif. Optical melting measurements of the thermodynamics of the duplex indicate that the internal loop is 1.6 kcal/mol more stable at 37°C than predicted. The results identify the 3RRs motif as a common structural element that can facilitate prediction of 3D structure. Known examples include internal loops having the pairings: 59GAA/39AGG, 59GAG/39AGG, 59GAA/39AAG, and 59AAG/39AGG. The structural information is compared with predictions made with the MC-Sym program.

show abstract

Section: Discussionmentioning

confidence: 99%

NMR structure of a 4 × 4 nucleotide RNA internal loop from an R2 retrotransposon: Identification of a three purine–purine sheared pair motif and comparison to MC-SYM predictions

Lerman

Kennedy²,

Shankar³

et al. 2011

RNA

View full text Add to dashboard Cite

show abstract

“…Since any prebiotic chemistry leading to 2-thio-U is also likely to generate 2-thio-C, it will be important to assess the effect of this modification on the rate and fidelity of copying of RNA templates. 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.…”

Section: Fidelity Of Template Copying Chemistrymentioning

confidence: 99%

The eightfold path to non-enzymatic RNA replication

2012

View full text Add to dashboard Cite

The first RNA World models were based on the concept of an RNA replicase -a ribozyme that was a good enough RNA polymerase that it could catalyze its own replication. Although several RNA polymerase ribozymes have been evolved in vitro, the creation of a true replicase remains a great experimental challenge. At first glance the alternative, in which RNA replication is driven purely by chemical and physical processes, seems even more challenging, given that so many unsolved problems appear to stand in the way of repeated cycles of nonenzymatic RNA replication. Nevertheless the idea of non-enzymatic RNA replication is attractive, because it implies that the first heritable functional RNA need not have improved replication, but could have been a metabolic ribozyme or structural RNA that conferred any function that enhanced protocell reproduction or survival. In this review, I discuss recent findings that suggest that chemically driven RNA replication may not be completely impossible.

show abstract

“…Base–base hydrogen bonding interaction (between the imino proton H3 in 2-thio U and N7 in A) is also enhanced with decreased p K a of N3 (from 9.3 to 8.8) on thiolation of U (49,57). In addition, 2-thio U modification enhances TFO binding by reduced thermodynamic cost of dehydration and improved van der Waals contact between sulfur atom in 2-thio U and H8 hydrogen in A (Figures 1A and 5) (37,58). …”

Section: Resultsmentioning

confidence: 99%

Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides

Zhou

Kierzek

Loo

et al. 2013

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

Triplex is emerging as an important RNA tertiary structure motif, in which consecutive non-canonical base pairs form between a duplex and a third strand. RNA duplex region is also often functionally important site for protein binding. Thus, triplex-forming oligonucleotides (TFOs) may be developed to regulate various biological functions involving RNA, such as viral ribosomal frameshifting and reverse transcription. How chemical modification in TFOs affects RNA triplex stability, however, is not well understood. Here, we incorporated locked nucleic acid, 2-thio U- and 2′-O methyl-modified residues in a series of all pyrimidine RNA TFOs, and we studied the binding to two RNA hairpin structures. The 12-base-triple major-groove pyrimidine–purine–pyrimidine triplex structures form between the duplex regions of RNA/DNA hairpins and the complementary RNA TFOs. Ultraviolet-absorbance-detected thermal melting studies reveal that the locked nucleic acid and 2-thio U modifications in TFOs strongly enhance triplex formation with both parental RNA and DNA duplex regions. In addition, we found that incorporation of 2′-O methyl-modified residues in a TFO destabilizes and stabilizes triplex formation with RNA and DNA duplex regions, respectively. The (de)stabilization of RNA triplex formation may be facilitated through modulation of van der Waals contact, base stacking, hydrogen bonding, backbone pre-organization, geometric compatibility and/or dehydration energy. Better understanding of the molecular determinants of RNA triplex structure stability lays the foundation for designing and discovering novel sequence-specific duplex-binding ligands as diagnostic and therapeutic agents targeting RNA.

show abstract

Role of Unsatisfied Hydrogen Bond Acceptors in RNA Energetics and Specificity

Cited by 31 publications

References 44 publications

NMR structure of a 4 × 4 nucleotide RNA internal loop from an R2 retrotransposon: Identification of a three purine–purine sheared pair motif and comparison to MC-SYM predictions

NMR structure of a 4 × 4 nucleotide RNA internal loop from an R2 retrotransposon: Identification of a three purine–purine sheared pair motif and comparison to MC-SYM predictions

The eightfold path to non-enzymatic RNA replication

Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides

Contact Info

Product

Resources

About