Effects of 3' dangling end stacking on the stability of GGCC and CCGG double helixes

Freier, Susan M.; Burger, Barbara J.; Alkema, Dirk; Neilson, Thomas; Turner, Douglas H.

doi:10.1021/bi00295a025

Cited by 126 publications

(161 citation statements)

References 69 publications

(73 reference statements)

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“…(3) Perhaps the most important obserVation is that the nature of the closing basepair plays a central role (29)(30)(31)(32)(33)(34). The same dangling nucleobase stacking on a G-C closing basepair with three hydrogen bonds always provides more stabilization than the A-U closing basepair with two hydrogen bonds.…”

Section: Resultsmentioning

confidence: 99%

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

Isaksson

Chattopadhyaya

2005

Biochemistry

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The geometry of the dangling base in 105 published structures (from X-ray/NMR) containing single-stranded overhangs has been analyzed and correlated to the thermodynamic stabilization found (UV) for the corresponding dangling base/closing basepair combination in short oligonucleotides. The study considers most combinations of closing basepairs, sequence and dangling base residue type, attached in both the 3′-and 5′-ends of both DNA and RNA. Linear regression analysis showed a straightforward correlation (R ) 0.873) between the degree of screening for the hydrogen bonds of the closing basepair provided by the dangling base and the resulting thermodynamic stabilization in both DNA and RNA series with dangling ends either at the 3′-or at the 5′-terminus. Regression analysis of only the datasets from RNA gives an improved correlation, R ) 0.934, showing that dangling ends on RNA are more ordered than the dangling ends on DNA, R ) 0.376. This study highlights the gain in the free energy of stabilization owing to the favorable stacking between the dangling nucleobase and the neighboring basepair and the resulting strengthening of the hydrogen bond of the closing basepair. By acting as a hydrophobic cap on the terminal of the DNA or RNA duplex, the dangling-end residue restricts the bulk water access to the terminal basepair, thereby providing it with a microenvironment devoid of water, which consequently enhances its thermodynamic stability, making it energetically comparable to the corresponding internal basepair. Thus, one single structural model consisting of the interplay of the above electrostatic interactions can be used to explain the molecular basis of the observed thermodynamic effects for dangling-end attachment to the 3′-and 5′-ends of both DNA and RNA duplexes, which is a key step toward accurate dangling-end effect prediction.Unpaired terminal nucleotides naturally occur in various biologically important RNA structures: The acceptor stem in tRNA (1-3) has a characteristic 3′-NCCA nucleobase overhang that determines its structure, stability, and function. The dangling ends neighboring the codon-anticodon pair have also been found to stabilize the interaction between tRNA and mRNA (4, 5) for protein synthesis in the ribosomal machinery. The efficiency of down regulation of gene expression by RNA interference (RNAi) has been shown to be dependent on a two to three nucleotide overhang (6-9). Similarly, the structures of pseudoknots (10) are stabilized by a complicated interplay between single-stranded and double-stranded motifs. A multitude of literature on the stabilizing interactions of native single-stranded oligonucleotides is available (9,(11)(12)(13)(14).Accurate prediction of nucleic acid secondary structure and stability from its primary sequence is a key interest for probe binding optimization in biotechnological applications such as microarrays (15) and molecular beacons (16). To develop an accurate algorithm (14,(17)(18)(19)(20)(21)(22)(23)(24) for predicting the thermodynamics of hybridi...

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Section: Resultsmentioning

confidence: 99%

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

Isaksson

Chattopadhyaya

2005

Biochemistry

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“…The GGCC core duplex was chosen because the stability of all the single 3Ј terminal overhangs have been previously determined (Freier et al 1983). The measured thermodynamic parameters for all 16 3Ј double terminal overhangs are presented in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Single 3Ј dangling nucleotides have been shown to significantly increase the stability of an RNA duplex (Freier et al 1983(Freier et al , 1986Petersheim and Turner 1983;Sugimoto et al 1987). The geometry of the RNA helix allows for the 3Ј dangling nucleotide to form stacking interactions with neighboring bases in the helix.…”

Section: Introductionmentioning

confidence: 99%

Stability of 3′ double nucleotide overhangs that model the 3′ ends of siRNA

O’Toole¹,

Miller²,

Serra³

2005

RNA

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Thermodynamic parameters are reported for duplex formation in 1 M NaCl for 16 RNA sequences, each containing a core tetramer duplex, GGCC, and a 3 overhang consisting of two bases. The results indicate additional double-helical stability is conferred by the double 3 terminal overhang relative to the single 3 terminal overhang. A nearest-neighbor analysis of the data indicates that the free energy contribution at 37°C of the second base in the double 3 terminal overhang varies from 0 to 0.7 kcal/mol. The second base in the 3 double overhang can contribute nearly the same stability to a duplex as a base pair or a 3 dangling overhang. Stability contribution of a dangling base, two nucleotides removed from the 3 end of a duplex, is dependent upon both the identity of the base as well as that of the dangling base that it neighbors. A second dangling base only increases the stability of the duplex when it is neighboring a 3 purine dangling nucleotide. Furthermore, a second dangling pyrimidine provides a greater contribution to duplex stability than a purine. A nearest-neighbor model was developed to predict the influence of 3 double overhang on the stability of duplex formation. The model improves the prediction of free energy and melting temperature when tested against six sequences with different core duplexes.

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“…has yielded an extremely useful database of thermodynamic parameters from which the stabilities of conformational states of larger nucleic acid sequences can be estimated. The estimation of the thermodynamic parameters is based on the nearest-neighbor approximation for inter-residue interactions of the closest along the sequence nucleotide residues (9,19).…”

Section: Hybridizationmentioning

confidence: 99%

New Method for Sequence Alignment Based on Probabilities of Nucleotide Correspondences

Dimitrov

Gouliamova

2012

Biotechnology & Biotechnological Equipment

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Effects of 3' dangling end stacking on the stability of GGCC and CCGG double helixes

Cited by 126 publications

References 69 publications

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

A Uniform Mechanism Correlating Dangling-End Stabilization and Stacking Geometry

Stability of 3′ double nucleotide overhangs that model the 3′ ends of siRNA

New Method for Sequence Alignment Based on Probabilities of Nucleotide Correspondences

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