Anticodon, wobbling

Y4. Yasukawa, T., Suzuki, T., Ueda, T., Ohta, S., and Watanabe, K., Modification defect at anticodon wobble nucleotide of mitochondrial tRNALeu(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. J. Biol. Chem. 275, 4251-4257 (2000). 

Although adenine rarely is found in the anticodon wobble position, many tRNAs in plants and animals contain inosine... 

Queuosine and archaeosine are known to occur only in tRNA, with queuosine in the anticodon wobble position of tRNAs with anticodons of G-U-N in eukarya and eubacteria. Archaeosine occurs in position 15 of the D loop of the majority of archaeal tRNAs. Both these bases (or their precursors) are incorporated into tRNA via the action of TGT, which is found in all three kingdoms. PseudoU is generated by a family of pseudoU synthases and is found in various positions in tRNAs as well as rRNAs, and snRNAs (small nuclear RNAs). ... 

There are 64 different three-letter codons, but we don t have to have 64 different tRNA molecules. Some of the anticodon loops of some of the tRNAs can recognize (bind to) more than one condon in the mRNA. The anticodon loops of the various tRNAs may also contain modified bases that can read (pair with) multiple normal bases in the RNA. This turns out to be the reason for the wobble hypothesis, in which the first two letters of a codon are more significant than the last letter. Look in a codon table and you ll see that changing the last base in a codon often doesn t change the identity of the amino acid. A tRNA that could recognize any base in codon position 3 would translate all four codons as the same amino acid. If you ve actually bothered to look over a codon table, you realize that it s not quite so simple. Some amino acids have single codons (such as AUG for Met), some amino acids have only two codons, and some have four. 

Figure 3 Cognate and near-cognate codon-anticodon interactions. The anticodon ioop of tRNA is shown as an example interacting with various codons on the mRNA. In correct, cognate codon-anticodon pairings, two Watson-Crick base pairs can be formed in the first two positions while the third position contains either a Watson-Crick or a wobble base pair.

The third position of the codon does not always need to be paired with the anticodon (e.g., it is allowed to wobble in some cases). 

Figure 12-1. Codon-anticodon base pairing. Special wobble base-pairing rules apply to the third (3 ) position of the codon. The first (S ) position of the tRNA anticodon is frequently inosine (I) to provide this flexibility in hydrogen bonding.

The wobble (or third) base of the codon contributes to specificity, but, because it pairs only loosely with its corresponding base in the anticodon, it permits rapid dissociation of the tRNA from its codon during protein synthesis. If all three bases of a codon engaged in strong Watson-Crick pairing with the three... 

TABLE 27-4 How the Wobble Base of the Anticodon Determines the Number of Codons a tRNA Can Recognize... 

Note X and Y denote bases complementary to and capable of strong Watson-Crick base pairing with X andY respectively, Wobble bases—in the 3 position of codons and 5 position of anticodons—are shaded in pink. 

Terms in bold are defined aminoacyl-tRNA 1035 aminoacyl-tRNA synthetases 1035 translation 1035 codon 1035 reading frame 1036 initiation codon 1038 termination codons 1038 open reading frame (ORF) 1039 anticodon 1039 wobble 1041... 

Wobble Nontraditional base-pairing between the 5-nucleotide (first nucleotide) of the anticodon with the 3 -nucleotide (last nucleotide) of the codon. I = inosine. 

The "wobble" hypothesis states that the first (5 ) base of the anticodon is not as spatially defined as the other two bases. Movement of that first base allows nontraditional base-pairing with the last (31) base of the codon, thus allowing a single tRNA to recognize more than one codon for a specific amino acid. 

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... 

Selenium is found to a minor extent wherever sulfur exists in nature. This includes the sulfur-containing modified bases of tRNA molecules. In addition to a small amount of nonspecific incorporation of Se into all S-containing bases there are, at least in bacteria, specific Se-containing tRNAs. In E. coli one of these is specific for lysine and one for glutamate. One of the modified bases has been identified as 5-methyl-amino-methyl-2-selenouridine.570 It is present at the first position of the anticodon, the "wobble" position.571... 

The Code Was Deciphered with the Help of Synthetic Messengers The Code Is Highly Degenerate Wobble Introduces Ambiguity into Codon-Anticodon Interactions... 

Wobble Introduces Ambiguity into Codon-Anticodon Interactions... 

The 3 terminal redundancy of the genetic code and its mechanistic basis were first appreciated by Francis Crick in 1966. He proposed that codons and anticodons interact in an antiparallel manner on the ribosome in such a way as to require strict Watson-Crick pairing (that is, A-U and G-C) in the first two positions of the codon but to allow other pairings in its 3 terminal position. Nonstandard base pairing between the 3 terminal position of the codon and the 5 terminal position of the anticodon alters the geometry between the paired bases Crick s proposal, labeled the wobble hypothesis, is now viewed as correctly describing the codon-anticodon interactions that underlie the translation of the genetic code. 

Examples of standard (a) and wobble (b and c) base pairs formed between the first base in the anticodon and the third base in the codon. 

Crick, F. H. C., Codon-anticodon pairing The wobble hypothesis. J. Mol. Biol. 19 548-555, 1966. A classic paper. 

Wobble. A proposed explanation for base-pairing that is not of the Watson-Crick type and that often occurs between the 3 base in the codon and the 5 base in the anticodon. 

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