3′ Terminal Nucleotides Determine Thermodynamic Stabilities of Mismatches at the Ends of RNA Helices

Clanton-Arrowood, Koree; McGurk, John; Schroeder, Susan J.

doi:10.1021/bi801594k

Cited by 28 publications

(49 citation statements)

References 77 publications

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“…A GU pair stacked on a GC or CG pair is more favorable than one stacked on an AU or UA pair, respectively. If (45) and thermodynamic stabilities of 3 0 dangling ends (8). The predicted values are consistent with prior similar measurements on duplexes with slightly different stem duplexes (46).…”

Section: Resultssupporting

confidence: 89%

Consecutive Terminal GU Pairs Stabilize RNA Helices

Nguyen

Schroeder

2010

Biochemistry

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Consecutive GU pairs at the ends of RNA helices provide significant thermodynamic stability between -1.0 and -3.8 kcal/mol at 37 °C, which is equivalent to approximately 2 orders of magnitude in the value of a binding constant. The thermodynamic stabilities of GU pairs depend on the sequence, stacking orientation, and position in the helix. In contrast to GU pairs in the middle of a helix that may be destabilizing, all consecutive terminal GU pairs contribute favorable thermodynamic stability. This work presents measured thermodynamic stabilities for 30 duplexes containing two, three, or four consecutive GU pairs at the ends of RNA helices and a model to predict the thermodynamic stabilities of terminal GU pairs. Imino proton NMR spectra show that the terminal GU nucleotides form hydrogen-bonded pairs. Different orientations of terminal GU pairs can have different conformations with equivalent thermodynamic stabilities. These new data and prediction model will help improve RNA secondary structure prediction, identification of miRNA target sequences with GU pairs, and efforts to understand the fundamental physical forces directing RNA structure and energetics.

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Section: Resultssupporting

confidence: 89%

Consecutive Terminal GU Pairs Stabilize RNA Helices

Nguyen

Schroeder

2010

Biochemistry

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“…Further breakthroughs in prediction accuracy will require innovation in the underlying stability models by discovery of features that affect stability that are currently unknown. These innovations will derive from new computational analyses (Parisien and Major 2008) and continued experimental determination of motif stabilities (Chen et al 2005;Blose et al 2007;Clanton-Arrowood et al 2008;Davis and Znosko 2008).…”

Section: Discussionmentioning

confidence: 99%

Improved RNA secondary structure prediction by maximizing expected pair accuracy

Lü

Gloor²,

Mathews³

2009

RNA

210

238

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Free energy minimization has been the most popular method for RNA secondary structure prediction for decades. It is based on a set of empirical free energy change parameters derived from experiments using a nearest-neighbor model. In this study, a program, MaxExpect, that predicts RNA secondary structure by maximizing the expected base-pair accuracy, is reported. This approach was first pioneered in the program CONTRAfold, using pair probabilities predicted with a statistical learning method. Here, a partition function calculation that utilizes the free energy change nearest-neighbor parameters is used to predict basepair probabilities as well as probabilities of nucleotides being single-stranded. MaxExpect predicts both the optimal structure (having highest expected pair accuracy) and suboptimal structures to serve as alternative hypotheses for the structure. Tested on a large database of different types of RNA, the maximum expected accuracy structures are, on average, of higher accuracy than minimum free energy structures. Accuracy is measured by sensitivity, the percentage of known base pairs correctly predicted, and positive predictive value (PPV), the percentage of predicted pairs that are in the known structure. By favoring doublestrandedness or single-strandedness, a higher sensitivity or PPV of prediction can be favored, respectively. Using MaxExpect, the average PPV of optimal structure is improved from 66% to 68% at the same sensitivity level (73%) compared with free energy minimization.

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“…If the 3'-terminal A of the target strand further stacks onto the 5'-terminal A of the probe strand, a zipperlike stacking arrangement could result that reduces the likelihood of duplex dissociation, further adding to what 3'-dangling residues contribute to stability. [32] Independent of the cause of the poor mismatch discrimination, the lack of selectivity in base pairing for duplexes with a purine at the 5'-terminus of the probe motivates a search for caps as fidelity-enhancing elements more than other constellations in the sequence space of nucleic acids. The cap to be identified should be large enough to provide additional enthalpic gains upon duplex formation.…”

Section: Resultsmentioning

confidence: 99%

A 5′‐Cap for DNA Probes Binding RNA Target Strands

Egetenmeyer

Richert

2011

Chemistry A European J

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Detecting short RNA strands with high fidelity at any of the bases of their sequence, including the termini, can be challenging, since fraying, wobbling, and refolding all compete with canonical base pairing. We performed a search for 5'-substituents of oligodeoxynucleotides that increase base pairing fidelity at the terminus of duplexes with RNA target strands. From a total of over 70 caps, differing in stacking moiety and linker, a phosphodiester-linked sequence of the residues of L-prolinol, glycine, and oxolinic acid, dubbed ogOA, was identified as a 5'-cap that stabilizes any of the four canonical base pairs, with ΔT(m) values of up to +13.1 °C for an octamer. At the same time, the cap increases discrimination against any of the 12 possible terminal mismatches, including mismatches that are more stable than their perfectly matched counterparts in the control duplex, such as A:A. A probe with the cap also showed increased selectivity in the detection of two closely related microRNAs, let7c and let7a, with a ΔT(m) value of 9.2 °C. Melting curves also yielded thermodynamic data that shed light on the uniformity of molecular recognition in the sequence space of DNA:DNA and DNA:RNA duplexes. Hybridization probes with fidelity-enhancing caps should find applications in the individual and parallel detection of biologically active RNA species.

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3′ Terminal Nucleotides Determine Thermodynamic Stabilities of Mismatches at the Ends of RNA Helices

Cited by 28 publications

References 77 publications

Consecutive Terminal GU Pairs Stabilize RNA Helices

Consecutive Terminal GU Pairs Stabilize RNA Helices

Improved RNA secondary structure prediction by maximizing expected pair accuracy

A 5′‐Cap for DNA Probes Binding RNA Target Strands

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