Uracil wobble

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

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. 

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... 

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...

The base hypoxanthine is found in the anticodon of tRNA molecules (it is formed by the deamination of an adenine base). Hypoxanthine s role in tRNA is to allow wobble base-pairs to form, as the base hypoxanthine can base pair with adenine, cytosine, or uracil. The wobbling allows one tRNA molecule to potentially form base pairs with three different codons. 

When the wobble base of the anticodon is uracil, it can base-pair not only with adenine, as expected, but also with guanine, the other purine base. When the wobble base is guanine, it can base-pair with cytosine, as expected, and also with uracil, the other pyrimidine base. The purine base hypoxanthine frequently occurs in the wobble position in many tRNAs, and it can base-pair with adenine, cytosine, and uracil in the codon (Figure 12.5). Adenine and cytosine do not form any base pairs other than the expected ones with uracil and guanine, respectively (Table 12.2). To summarize, when the wobble position is occupied by I (from inosine, the nucleoside made up of ribose and hypoxanthine), G, or U, variations in hydrogen bonding are allowed when the wobble position is occupied by A or C, these variations do not occur. 

Hypoxanthine is the most versatile of the wobble bases it can base pair with adenine, cytosine, or uracil. 

Thiolation of uracil residues, especially in RNA wobble positions, affect the conformation of the nucleic acid in solution [99] and has implications for recognition processes. Furthermore, 4-thiouridine is found in bacterial and archaeal tRNA [100,101]. Therefore, we shall have a short look on 2-thiouridine (U2S) and 4-thiouridine (U4S) (see Figure 8, bottom part) and their complexes formed with Cd and Cu [102,103]. The exchange of an O atom by a S atom in uridine (see Figure 1) is expected, of course, to alter not only the acid-base but also the metal ion-binding properties [15,17,104]. Indeed, the acidity of (N3)H is increased by about one pXunit as follows from column 3 in Table 6 [105]. However, despite the reduced basicity of (N3) in (U2S - H) and (U4S - H)" the stabilities of their complexes with Cd " and Cu " are by about 1 and 1.8 log units higher than those of Cd(Urd - H)-" and Cu(Urd - H)-" (Table 6, column 5). 

---