Nonstandard Base Pairing Often Occurs Between Codons and Anticodons
If perfect Watson-Crick base pairing between codons and anticodons were required, cells would have to contain at least 61 different types of tRNAs, one for each codon that specifies an amino acid. As noted above, however, many cells contain fewer than 61 tRNAs. The explanation for the smaller number lies in the capability of a single tRNA anticodon to recognize more than one, but not necessarily every, codon corresponding to a given amino acid. This broader recognition can occur because of nonstandard pairing between bases in the so-called wobble position: that is, the third (3′) base in an mRNA codon and the corresponding first (5′) base in its tRNA anticodon.
The first and second bases of a codon almost always form standard Watson-Crick base pairs with the third and second bases, respectively, of the corresponding anticodon, but four nonstandard interactions can occur between bases in the wobble position. Particularly important is the G·U base pair, which fits into the short, 3-bp RNA-RNA double-stranded region formed between the codon and the anticodon almost as well as the standard G·C pair. Thus a tRNA anticodon with G in the first (wobble) position can base-pair with the two corresponding codons that have either pyrimidine (C or U) in the third position (Figure 5-21). For example, the phenylalanine codons UUU and UUC (5′→3′) are both recognized by the tRNA that has GAA (5′→3′) as its anticodon. In fact, any two codons of the type NNPyr (N = any base; Pyr = pyrimidine) encode a single amino acid and are decoded by a single tRNA with G in the first (wobble) position of the anticodon.
FIGURE 5-21 Nonstandard base pairing at the wobble position. The base in the third (or wobble) position of an mRNA codon often forms a nonstandard base pair with the base in the first (or wobble) position of a tRNA anticodon. Wobble pairing allows a tRNA to recognize more than one mRNA codon (top); conversely, it allows a codon to be recognized by more than one kind of tRNA (bottom), although each of those tRNAs will bear the same amino acid. Note that a tRNA with I (inosine) in the wobble position can “read” (become paired with) three different codons, and a tRNA with G or U in the wobble position can read two codons. Although A is theoretically possible in the wobble position of the anticodon, it is almost never found in nature. (Note that this is a simplified diagram of a tRNA. The actual structure of a tRNA is shown in Figure 5-20b.)
Although adenine is rarely found in the anticodon wobble position, many tRNAs in plants and animals contain inosine (I), a deaminated product of adenine, at this position. Inosine can form nonstandard base pairs with A, C, and U. A tRNA with inosine in the wobble position thus can recognize the corresponding mRNA codons with A, C, or U in the third (wobble) position (see Figure 5-21). For this reason, inosine-containing tRNAs are heavily employed in translation of the synonymous codons that specify a single amino acid. For example, four of the six codons for leucine (CUA, CUC, CUU, and UUA) are all recognized by the same tRNA with the anticodon 3′-GAI-5′; the inosine in the wobble position forms nonstandard base pairs with the third base in each of these four codons. In the case of the UUA codon, a nonstandard G·U pair also forms between position 3 of the anticodon and position 1 of the codon.