Wobble pairs

Nucleic acids which contain only adenosine, guanosine and uridine are able to form A-U Watson-Crick pairs and G-U wobble pairs. They should be able to build up complex secondary and tertiary structures. 

Another pairing that occurs in tRNAs allows guanine to pair with uracil, e.g., G4 with U69. This was originally proposed to account for codon-anticodon interactions betweentRNA molecules and messenger RNA (Chapter 29). It is commonly called wobble pairing because the uracil must wobble away from its orientation in the normal Watson-Crick pair.27 37... 

While tRNAs consist largely of loops and stems containing Watson-Crick base pairs, they also contain Hoogsteen pairs, wobble pairs, and triplets such as the following. 

Wobble pairing 209 Wood-Ljundahl pathway 881 Work 282... 

Figure 29-8 Pairing of inosine with cytosine (a Watson-Crick pair) and of inosine with adenine and uracil (wobble pairs).

By inspecting the geometry that would result from different wobble pairings (fig. 29.8) and recognizing that ino-sine, the deaminated form of adenine, frequently occurs in... 

Figure 13.1 (A) Structure of 2-aminopurine and its base pairing partners. For reference, a G U wobble pair is shown. (B) Jablonski diagrams...

For the purine-purine combination hypoxanthine-adenine, there are six possible base pairs with two hydrogen bonds. Of these, only two can occur in the nucleic acids, XA12 and XA22, with XA12 representing a wobble pair which is of some biological importance in transfer RNA, and comparable to the guanine-uracil wobble illustrated in Fig. 16.14. 

Barsky, D. Colvin, M. E. Guanine-cytosine base pairs in parallel-stranded DNA An ab initio study of the keto-amino wobble pair versus the enol-imino minor tautomer pair, J. Phys. Ghent. A 2000,104, 8570-8576. 

The positioning of the N3/02 acceptor atoms provides a simple and reliable mechanism to distinguish the Watson-Crick pairs from the wobble pair and other mismatches. As suggested initially by Bruskov and Poltev (34), the fidelity of... 

Perrotta AT, Been MD. Core sequences and a cleavage site wobble pair required for HDV antigenomic ribozyme self-cleavage. Nucleic Acids Res. 1996 24 1314-1321. 

One problem for targeting RNA is that the A U and G U base pairs have similar stability, and G U wobble pairs account for almost half of known non-Watson-Crick pairs. 2-Thiouridine will increase the specificity for pairing with adenosine by a factor of 10. It has been reported that the complete substitution of pyrimidines by C5-propynyl pyrimidines enhances this specificity 100-fold without altering base pairing specificity. " ... 

An RNA-HNA (hexitol) hybrid duplex structure has been studied by NMR. " The P-P distances across the minor groove are a determinant for cleavage by RNase H. In the structure, the duplex is in an A-form, and the P-P bond distance similar to that for an RNA-RNA duplex, which may explain the resistance of HNA duplexes to RNase H. A self-complementary HNA duplex h(GCGCTTTTGCGC) containing a central T-tract has been studied by NMR. " The duplex exists in the A-form in the stem regions, with minor distortions in the T-tract causing a 9 A displacement of the helical axes. The T-tract is stabilised by wobble pairs enhancing the overall stability of the duplex. 

Sequence covariations are a direct consequence of RNA basepairing rules. RNA helices normally contain only 6 out of the 16 possible combinations the Watson-Crick pairs GC, CG, AU, UA, and the somewhat weaker wobble pairs GU and UG. Mutations in helical regions therefore have to be correlated. In particular, we often find compensatory mutations where a mutation on one side of the helix is compensated by a second mutation on the other side, e.g., a C G pair changes into a U A pair. Mutations where only one pairing partner changes (such as C G to U G) are termed consistent mutations. ... 

Eoff, R.L., Irimia, A., Egli, M., and Guengerich, F.P. (2007) Sulfolobus solfataricus DNA polymerase Dpo4is partially inhibited by wobble pairing between O6-methylguanine and cytosine, but accurate bypass is preferred. J. Biol. Chem., 282,1456-1467. 

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