Codon anticodon pairing

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.

Figure 10 Alteration of the genetic code for incorporation of non-natural amino acids, (a) In nonsense suppression, the stop codon UAG is decoded by a non-natural tRNA with the anticodon CUA. In vivo decoding of the UAG codon by this tRNA is in competition with termination of protein synthesis by release factor 1 (RFl). Purified in vitro translation systems allow omission of RF1 from the reaction mixture, (b) A new codon-anticodon pair can be created using four-base codons such as GGGU. Crystal structures of these codon-anticodon complexes in the ribosomal decoding center revealed that the C in the third anticodon position interacts with both the third and fourth codon position (purple line) while the extra A in the anticodon loop does not contact the codon.(c) Non-natural base pairs also allow creation of new codon-anticodon pairs. Shown here is the interaction of the base Y with either base X or (hydrogen bonds are indicated by red dashes).

These experiments make it clear that removing competition with release factors leads to more efficient incorporation of the desired amino acid. Unfortunately, the technology to incorporate nonstandard nucleotides into mRNAs coding for full-length proteins is not yet available. Alternatives that have been tested include using (i) a 4-nucleotide codon-anticodon pair, dubbed frame-shift suppression (Sect. 6.1), (ii) a rare codon, and (iii) cell-free extracts from organisms that are either deficient in a release factor (Sect. 5.1) or unable to translate one or more codons (Sect. 6.2). 

In an effort to reduce the competition encountered with naturally occurring tRNAs, even when rare codons are used, Hardesty and co-workers have devised a strategy based on 4-nucleotide codon-anticodon pairs [48]. An extra thymidine was inserted either 5 or 3 to the rare arginine codon AGG to yield TAGG... 

Examination of these and other codon-anticodon pairings led Crick to conclude that the third base of most codons pairs rather loosely with the corresponding base of its anticodon to use his picturesque word, the third base of such codons (and the first base of their corre-... 

The Code Is Not Quite Universal The Rules Regarding Codon-Anticodon Pairing Are Species-Specific The Steps in Translation... 

The Rules Regarding Codon-Anticodon Pairing Are Species-Specific... 

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

Cochella, L., and Green, R. (2005). An active role for tRNA in decoding beyond codon anticodon pairing. Science 308, 1178—1180. 

Several hypotheses have been developed in order to interpret the paradox of a degenerate code and the specific synthesis of proteins. The wobble theory of Crick (1966 a) postulates the possibility of alternate ways of pairing between the bases of the w-RNA and -RNA. Within the framework of this theory it is assumed that the pairing for the two first positions of each codon-anticodon pair is normal, A <—>TJ, C <—>G. But in order to explain the multiple correspondence it is necessary to assume other possibilities of pairing for the third position. The postulated rela-... 

For a confirmation of these assumptions extensive calculations should be carried on the hydrogen-bonded codon-anticodon pairs. In addition, the importance of the van der Waals forces should be investigated17. 

Transfer RNA (Mr s= 25,000) functions as an adapter in polypeptide chain synthesis. It comprises 10-20 percent of the total RNA in a cell, and there is at least one type of tRNA for each type of amino acid. Transfer RNAs are unique in that they contain a relatively high proportion of nucleosides of unusual structure (e.g., pseudouridine, inosine, and 2 -0-methylnucleosides) and many types of modified bases (e.g., methylated or acetylated adenine, cytosine, guanine, and uracil). As examples, the structures of pseudouridine and inosine are shown below. Inosine has an important role in codon-anticodon pairing (Chap. 17). 

Grundy FJ, Winkler WC, Henkin TM. tRNA-mediated transcription antitermination in vitro codon-anticodon pairing independent of the ribosome. Proc. Natl. Acad. Sci. U.S.A. 2002 99 11121-11126. 

Each anticodon of a tRNA can base pair with a complementary codon oh the tRNA. For example, Arginine is specified by two codons, AGA and AGG but there is only one tRNA anticodon for Arg, 3 UCU 5. The tRNA recognizes and base pairs with either of the two Arg codons. Base pairing occurs between the first two bases of the codon and the anticodon, the third base of the codon does not match. Thus, base pairing is not strict for the last nucleotide of the codon anticodon pair, this phenomenon is called wobble. 

Correct codon-anticodon pairing. The former results from the specificity of interaction of the enzyme, the amino acid, and the tRNA molecule. The latter is assured by base pairing. 

R H. C. Crick. Codon-anticodon pairing the wobble hypothesis. Journal of Molecular Biology, 19 (1966), 548-55. 

To study the codon-anticodon pairing properties, a model system has been prepared in which the codon and anticodon nucleotides are synthesised in a... 

Kinetic proofreading is a mechanism that ensures that the correct codon-anticodon pairing occurs in the A site of ribosomes. In eukaryotes eEF-la mediates the binding of aminoacyl-tRNAs to the A site. When the correct pairing occurs eEF-1 a hydrolyses its bound GTP and subsequently exits the ribosome. 

Rodin, S., Rodin, A. and Ohno, S. (1996) The presence of codon-anticodon pairs in the acceptor stem of tRNAs. Proc. Natl. Acad. Sci. USA 93 4537. 

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