G-U 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. 

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...

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. " ... 

In RNA, the original set consisting of the Watson-Crick base pairs is complemented by the G-U wobble pair, which is admissible in RNA double helices. Other admissible bps include U-U in internal loops as well as A-A, G-A or G-G (purine-purine closing pairs) at the ends of double helical regions or in multiloops. The secondary structures, which can be drawn in two dimensions without knots or pseudoknots, are indispensable for the... 

Strand (57). Other problems such as the formation of G-quadruplexes by G-rich template strands, and non-Watson-Crick base pairings (e.g., G-U wobble pairing) further inhibit high-fidelity sequence transfer in template-directed synthesis. These problems would greatly restrict the sequence space for evolving ribozymes and proto-ribozymes as newly mutated sequences that possess new catalytic properties may not be replicable (i.e., heritable). 

Fig. 8. Non-Watson-Crick base pairs occurring in double-stranded RNA where — represents the site of attachment to the sugar (a) A—U reverse-Watson-Crick (b) G—C reverse-Watson-Crick (c) A—U Hoogsteen (d) A—U reverse-Hoogsteen (e) G—U wobble and (f) G—U reverse-wobble.

I I I I I Watson-Crick pairs G-U wobble base pair /WWW exon... 

Fig. 16.14. The wobble G-U base pair GU22 formed by guanine and uracil is of importance in the codon-anticodon interaction between messenger RNA and transfer RNA...

G U wobble base pairs at the donor/acceptor junction are important for the reaction. When replaced by G C pairs, the value of kcat decreased 14-fold, while the template-only directed reaction is optimal with a completely Watson-Crick base paired duplex. The described ribozyme is also capable of forming amide bonds which was demonstrated by replacing the attacking 5 -hydroxyl group by an amino group. 

The U U pair is polymorphic. What are called cis U U wobble pairs have been observed in two RNA dodecamer structures (46,47). The U U pairs, each held together with two hydrogen bonds are formed (Fig. 6a) and although an ordered solvent is not observed in both crystal structures, this pair has what appears to be an attractive site to bring in a water molecule in both major and minor groove sides. This would be similar to the G T mismatch discussed above. The nonameric... 

G frequently pairs across from U, forming a G U wobble, which means that information is often lost. Some level of mutation is necessary for evolution to occur, but too many mutations will result in an error catastrophe, the loss of all information (see Sect. 9.3). Still, it is important to note the potential for information transfer in the complete absence of enzymes, and the importance of chemical reactions based on proximity and positioning. 

This application exemplifies how theoretical methods were used to extend the MC-SYM database. The symmetrical tandem of G U mismatches is a motif that was identified in ribosomal RNAs. The secondary structure and a selected spanning tree of the motif are shown in Figure 11. The list of possible G U base pairing patterns that involve two hydrogen bonds are shown in Table 5. Two of these patterns, XXVII (reverse Wobble) and XXVIII (Wobble), were described in Saenger and both were found in RNA and DNA X-ray crystallography and NMR spectroscopy three-dimensional structures. 

Figure 11 Symmetrical tandem of G U mismatches, (a) Secondary structure. The arrows indicate the selected edges in the spanning tree, (b) MC-SYM script corresponding to the spanning tree in (a). The ANY-ANY list corresponds to combinations of C3 -, C2 -endo, anti, and syn nucleotide conformations. The XXVII relational list corresponds to the reverse Wobble G U base pairing pattern (see Table 5). The indicates that all examples of a given list are tested by MC-SYM...

Using the new database, MC-SYM produced consistent three-dimensional structures that contained the reverse Wobble, the Wobble, and the XXXI G U base pairing patterns. The three MC-SYM three-dimensional structures of symmetrical tandem of G U mismatches, refined using AMBER 4.1, are shown in Figure 12. In the case of class structures that include the reverse Wobble base pairing pattern, the guanosines were... 

The number of mammalian mitochondrial tRNA molecules is 22, which is less than the minimum number (32) needed to translate the universal code. This is possible because in each of the fourfold redundant sets—e.g., the four alanine codons GCU, GCC, GCA, and GCG—only one tRNA molecule (rather than two, as explained above) is used. In each set of four tRNA molecules, the base in the wobble position of the anticodon is U or a modified U (not I). It is not yet known whether this U is base-paired in the codon-anticodon interaction or manages to pair weakly with each of the four possible bases. For those codon sets that are doubly redundant—e.g., the two histidine codons CAU and CAC—the wobble base always forms, a G-U pair, as in the universal code. The structure of the human mitrochondrial tRNA molecule is also different from that of the standard tRNA molecule (except for mitochondrial tRNA UUX). (X = any nucleotide.) The most notable differences are the following ... 

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. ... 

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