Transfer RNA in Decoding and the Wobble Hypothesis

The translation of the genetic code stored in messenger RNA requires significantly fewer tranfer RNAs than there are codons. This is achieved through an increased flexibility in the allowable base-pair interactions between the mRNA and tRNA involving the third position of the codon. The rules governing the allowable base-pair interactions were originally summarized in Crick's ‘wobble hypothesis’.

Keywords: wobble hypothesis; tRNA; mRNA decoding; codon recognition

Figure 1. mRNAtRNA interactions involve base pairing between the anticodon of the transfer RNA (tRNA) and the messenger RNA (mRNA) codon. (a) Standard depiction of the two dimensional ‘clover-leaf’ structure of a tRNA molecule. (b) An Arg-inserting tRNA with a UCU anticodon can translate both the AGA codon by standard base-pair interactions at all three positions, and the AGG codon by a non-Watson and Crick pairing in the third ‘wobble’ position of the codon.
Figure 2. The three dimensional structure of a transfer RNA (tRNA) molecule. tRNA molecules take up an L-shaped structure due to a variety of intramolecular base interactions. The anticodon is present in a large unpaired region of the molecule with the three bases of the anticodon all pointing approximately in the same direction. The ‘U turn’ base (U33) immediately adjacent to the anticodon is indicated.
Figure 3. Wobble base-pair interactions that occur between the first base of the anticodon (left) and the third base of the codon (right).
Figure 4. Translation of the UGA codon in Escherichia coli by a Trp-inserting tRNA. The relative, approximate efficiencies of UGG/UGA decoding by (a) the wild-type transfer RNA (tRNA), (b) a nonsense suppressor mutant of the tRNA in which C34 has been replaced by U34; and (c) a novel suppressor variant of the tRNA with G24 replaced by A24.
close
 References
    Andachi Y, Yamao F, Muto A and Osawa S (1989) Codon recognition patterns as deduced from sequences of the complete set of transfer RNA species in Mycoplasma capricolum: resemblance to mitochondria. Journal of Molecular Biology 209: 37–54.
    Crick FHC (1966) Codon–anticodon pairing: the wobble hypothesis. Journal of Molecular Biology 19: 548–555.
    Hirsh D and Gold L (1971) Translation of the UGA triplet in vitro by tryptophan transfer RNA. Journal of Molecular Biology 58: 459–468.
    Lagerkvist U (1978) ‘Two out of three’: an alternative method for codon reading. Proceedings of the National Academy of Sciences of the USA 75: 1759–1762.
    Low SC and Berry MJ (1996) Knowing when not to stop: selenocysteine incorporation in eukaryotes. Trends in Biochemical Sciences 21: 203–208.
    Muramatsu T, Nishikawa K, Nemoto F et al. (1988) Codon and amino-acid specificities of a transfer RNA are both converted by a single post-transcriptional modification. Nature 336: 179–181.
    Osawa S, Jukes TH, Watanabe K and Muto A (1992) Recent evidence for evolution of the genetic code. Microbiological Reviews 56: 229–264.
    book Parker J (1992) "Variations in reading the genetic code". In: Hatfield DL, Lee BJ and Pirtle RM (eds) Transfer RNA in Protein Synthesis, pp. 191–267. Boca Raton, FL: CRC Press.
    Sibler AP, Dirheimer G and Martin RP (1986) Codon reading patterns in Saccharomyces cerevisiae mitochondria based on sequences of mitochondrial tRNAs. FEBS Letters 194: 131–138.
    Sprinzl M, Horn C, Brown M, Loudovitch A and Steinberg S (1998) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Research 26: 148–153.
    Thompson RC, Dix DB, Gerson RB and Karim AM (1981) A GTPase reaction accompanying the rejection of Leu-tRNA2 by UUU-programmed ribosomes. Journal of Biological Chemistry 256: 81–89.
 Further Reading
    Eggertsson G and Soll D (1988) Transfer ribonucleic acid-mediated suppression of termination codons in Escherichia coli. Microbiological Reviews 52: 354–374.
    book Osawa S (1995) Evolution of the Genetic Code. Oxford: Oxford Science Publications.
    book Soll D and RajBhandary UL (1995) tRNA Structure, Biosynthesis and Function. Washington DC: ASM Press
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Tuite, Mick F(Apr 2001) Transfer RNA in Decoding and the Wobble Hypothesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001497]