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

Abstract

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.

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

“…1) because base-pair identity and orientation can affect the structure of a loop (Chen et al 2007;Hammond et al 2010). Additional base pairs and 39 dangling end nucleotides were chosen to provide melting temperatures near 37°C with approximately equal stabilities for the Lerman et al…”

“…There are relatively few benchmarks available, however, for testing and optimizing these methods, especially all atom methods. NMR structures of small RNA internal loops in solution (SantaLucia and Turner 1993;Wu and Turner 1996;Heus et al 1997;Butcher et al 1999;Schmitz et al 1999a,b;Znosko et al 2002;Chen et al 2005Chen et al , 2007Shankar et al 2006Shankar et al , 2007Tolbert et al 2007) provide benchmarks for the full range of methods. Comparisons with predictions are straightforward because the structures depend only on interactions within the RNA and between the RNA and solvent.…”

Nuclear Magnetic Resonance Structure of an 8 × 8 Nucleotide RNA Internal Loop Flanked on Each Side by Three Watson–Crick Pairs and Comparison to Three-Dimensional Predictions

“…25, 26 Moreover, two GA pairs in tandem can be in slow exchange between imino and sheared conformations when flanked by iGiC pairs. 21 Clearly, the energetics of stacking and hydrogen bonding are closely balanced as also suggested for CA pairs. The different types of potential GA pairs (Figure 1) provide different availability of functional groups and dramatically different backbone conformations.…”

“…Noncanonical pairs, 20 especially GA 21–26 and AC 27, 28 (Figure 1), have conformations that are very sensitive to sequence and structural environment. GA pairs can be involved in a two hydrogen bond imino pair (cis Watson-Crick/Watson-Crick), two hydrogen bond sheared pair (trans Hoogsteen/sugar edge), and base triples.…”

Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides

“…Base–base stacking interactions are sequence environment dependent (42,43,59,60), which may explain one extra 2-thio U modification in 1-Rs 2 U3, which is flanked by C and U (Table 1), increases T m1 by only ∼3°C relative to 1-Rs 2 U2 (Figure 4C). In contrast, the 2-thio U modifications present in 1-Rs 2 U1, 1-Rs 2 U2 and 3-Rs 2 U2 are all flanked by two C’s, with each modification increasing T m1 by ∼10°C (Figure 4C and D).…”