The detailed structure of tandem G·A mismatched base-pair motifs in RNA duplexes is context dependent

Heus, Hans A.; Wijmenga, Sybren S.; Hoppe, H. H.; Hilbers, Cornelis W.

doi:10.1006/jmbi.1997.1158

Cited by 56 publications

(87 citation statements)

References 44 publications

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“…8,9 In contrast, the sugar pucker is C2′-endo in the (UGAA) 2 motif, and it has been suggested that the sugar pucker and the base-backbone hydrogen bonding pattern correlate with the stability of the internal loop. 11,60 This is also consistent with the mixed sugar pucker observed here for the (iCGAiG) 2 loop and with observations on tandem GA pairs closed by GU pairs. 15 The current results, however, suggest this is not a strict correlation because the (iGGAiC) 2 internal loop has a favorable free energy increment, but the G has a mixture of C3′ and C2′-endo sugars.…”

Section: Discussionsupporting

confidence: 91%

“…In the minor conformation: (1) the iG6H1′ proton is shifted 1.27 ppm upfield relative to the major conformation ( Figure S1 and Table S4), consistent with the shift induced by the adenine ring of a sheared GA pair, as observed for iC6H1′ in (GCiGGAiCGCA) 2 and other structures; 8,14,64 (2) the G4 imino proton is shifted upfield to 9.8 ppm (Figure 2, 3, and Table S4), consistent with an imino proton not involved in a hydrogen bond; and (3) the G4 ribose ring is observed to exist partially in the C2′-endo conformation ( Figure S4), consistent with the observation that in several structures involving thermodynamically less stable sheared GA pairs, the G ribose is found to be in the C2′-endo conformation. 11,14,15,60,64 It cannot be determined, however, whether the C2′-endo pucker occurs when the GA pair is in the major or minor conformation or both.…”

Section: Discussionmentioning

confidence: 99%

“…The stability [1][2][3][4][5][6][7] and three-dimensional structure [7][8][9][10][11][12][13][14][15] of RNA tandem GA pairs are dependent on sequence context. Tandem sheared GA (trans Hoogsteen/ Sugar edge A-G) pairs ( Figure 1) form with cross-strand base stacking in the symmetric contexts (CGAG) 2 with loop free energy of −0.7 kcal/mol 1,3,8 and (UGAA) 2 with loop free energy of 0.7 kcal/mol.…”

Section: Introductionmentioning

confidence: 99%

“…Tandem sheared GA (trans Hoogsteen/ Sugar edge A-G) pairs ( Figure 1) form with cross-strand base stacking in the symmetric contexts (CGAG) 2 with loop free energy of −0.7 kcal/mol 1,3,8 and (UGAA) 2 with loop free energy of 0.7 kcal/mol. 1,4,11 Tandem imino GA (cis Watson-Crick/Watson-Crick A-G) pairs (Figure 1) form in the symmetric context (GGAC) 2 with loop free energy of −2.5 kcal/ mol. 1,4,9 These results suggest that base stacking interactions (e.g., Coulombic and overlap) determine the hydrogen bonding patterns of RNA tandem GA pairs in these internal loops.…”

Section: Introductionmentioning

confidence: 99%

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Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

et al. 2007

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The Watson-Crick like iGiC pair, with the amino and carbonyl groups transposed relative to the Watson-Crick GC pair, provides an expanded alphabet for understanding interactions that shape nucleic acid structure. Here, thermodynamic stabilities of tandem GA pairs flanked by iGiC pairs are reported along with the NMR structures of the the RNA self-complementary duplexes (GCiGGAiCGCA) 2 and (GGiCGAiGCCA) 2 . A sheared GA pairing forms in (GCiGGAiCGCA) 2 and an imino GA pairing forms in (GGiCGAiGCCA) 2 . The structures contrast with the formation of tandem imino and sheared GA pairs flanked by GC pairs in the RNA self-complementary duplexes (GCGGACGC) 2 and (GGCGAGCC) 2 , respectively. In both iGiC duplexes, WatsonCrick like hydrogen bonds are formed between iG and iC, and iGiC substitutions result in less favorable loop stability. The results provide benchmarks for testing computations of molecular interactions that shape RNA three-dimensional structure.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

et al. 2007

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“…Although less frequent, the C2Ј-endo conformation is highly overrepresented in catalytic active sites and in critical tertiary structures (12,13). At the static structure level, the C2Ј-endo conformation induces greater helical twist in an A-form helix (14,15) and spans a much longer 5Ј-to-3Ј distance (12,16). At the level of local motion, some C2Ј-endo nucleotides exhibit extraordinarily slow conformational dynamics with half-lives on the 10-100-s timescale (17).…”

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confidence: 99%

C2′-endo nucleotides as molecular timers suggested by the folding of an RNA domain

Mortimer

Weeks

2009

Proc. Natl. Acad. Sci. U.S.A.

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A striking and widespread observation is that higher-order folding for many RNAs is very slow, often requiring minutes. In some cases, slow folding reflects the need to disrupt stable, but incorrect, interactions. However, a molecular explanation for slow folding in most RNAs is unknown. The specificity domain of the Bacillus subtilis RNase P ribozyme undergoes a rate-limiting folding step on the minute time-scale. This RNA also contains a C2 -endo nucleotide at A130 that exhibits extremely slow local conformational dynamics. This nucleotide is evolutionarily conserved and essential for tRNA recognition by RNase P. Here we show that deleting this single nucleotide accelerates folding by an order of magnitude even though this mutation does not change the global fold of the RNA. These results demonstrate that formation of a single stacking interaction at a C2 -endo nucleotide comprises the rate-determining step for folding an entire 154 nucleotide RNA. C2 -endo nucleotides exhibit slow local dynamics in structures spanning isolated helices to complex tertiary interactions. Because the motif is both simple and ubiquitous, C2 -endo nucleotides may function as molecular timers in many RNA folding and ligand recognition reactions.RNA folding ͉ RNA SHAPE chemistry T o function properly inside the cell, RNA molecules undergo complex folding transitions to form specific, biologically active, three-dimensional structures (1). These essential structures involve both local base pairing and also complex higherorder tertiary interactions. A persistent and incompletely explained observation is that many RNAs fold very slowly, on timescales requiring minutes or longer. RNAs that fold slowly span all sizes including small riboswitch and catalytic RNAs, medium-sized catalytic introns, and the large RNAs in ribosomes (2-6).Slow folding has important consequences both because correct folding ultimately governs the rate at which an RNA can perform its biological function and because bottlenecks in assembly potentially require cellular mechanisms to overcome slow folding. In some cases, slow folding results from formation of stable, non-native, and kinetically trapped states (7,8). Such misfolding is remedied, in part, by cellular chaperone activities (9-11). In many cases, the molecular basis for slow folding is unknown.The intricate three-dimensional structures formed by RNA molecules ultimately reflect the underlying contributions of individual nucleotides. Most nucleotides in an RNA molecule exist in the C3Ј-endo conformation. Although less frequent, the C2Ј-endo conformation is highly overrepresented in catalytic active sites and in critical tertiary structures (12, 13). At the static structure level, the C2Ј-endo conformation induces greater helical twist in an A-form helix (14, 15) and spans a much longer 5Ј-to-3Ј distance (12,16). At the level of local motion, some C2Ј-endo nucleotides exhibit extraordinarily slow conformational dynamics with half-lives on the 10-100-s timescale (17).Here we show that the slow conformational ...

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The energetics of small internal loops in RNA

Schroeder¹,

Burkard²,

Turner³

1999

Biopolymers

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The energetics of small internal loops are important for prediction of RNA secondary and tertiary structure, selection of drug target sites, and understanding RNA structure–function relationships. Hydrogen bonding, base stacking, electrostatic interactions, backbone distortion, and base‐pair size compatibility all contribute to the energetics of small internal loops. Thus, the sequence dependence of these energetics are idiosyncratic. Current approximations for predicting the free energies of internal loops consider size, asymmetry, closing base pairs, and the potential to form GA, GG, or UU pairs. The database of known three‐dimensional structures allows for comparison with the models used for predicting stability from sequence. © 2001 John Wiley & Sons, Inc. Biopoly (Nucleic Acid Sci) 52: 157–167, 1999/2000

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The detailed structure of tandem G·A mismatched base-pair motifs in RNA duplexes is context dependent

Cited by 56 publications

References 44 publications

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

C2′-endo nucleotides as molecular timers suggested by the folding of an RNA domain

The energetics of small internal loops in RNA

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