Transfer RNA in Decoding and the Wobble Hypothesis


Translation of the genetic code stored in messenger ribonucleic acid (RNA) requires significantly fewer transfer RNAs (35–45) than there are codons (61, amino acid specifying). This is achieved through an increased flexibility in the allowable base‐pair interactions between the messenger RNA and the transfer RNA involving the third position of the codon and the first position of the corresponding anticodon. The rules governing this RNA:RNA interaction were originally summarised in Crick's ‘wobble hypothesis’. Covalent modification of the first base of an anticodon of a transfer RNA can profoundly affect the degree of flexibility in its base‐pairing potential by either extending or restricting such interactions. Recent studies suggest that the rate at which a codon is processed by the ribosome is influenced by whether or not decoding of that codon is via wobble base interactions. Yet, in spite of this flexibility and different rates of processing, decoding by transfer RNAs is achieved with considerable accuracy.

Key Concepts

  • The genetic code is decoded via transient interactions between messenger RNA (mRNA) and a series of ‘adaptor’ RNA molecules called transfer RNAs (tRNAs).
  • The mRNA–tRNA interaction occurs on the ribosome via the complementary base pairing between the three‐base anticodon of the tRNA and the three‐base codon in the mRNA.
  • A greater degree of flexibility of allowable base‐pair interactions between mRNA and tRNA allows most organisms to have far fewer tRNA species than there are codons.
  • Specific non‐Watson–Crick base‐pair interactions occur between the third base of a codon and the first base of the anticodon of a tRNA during decoding, the so‐called wobble.
  • Wobble base pairing enables the decoding of two or more codons by the same tRNA.
  • Certain modified bases, for example inosine (I) can extend or restrict the degree of flexibility in the range of mRNA:tRNA interactions.
  • Codons that are decoded by wobble base interactions are processed at a slower rate in the ribosome.
  • Certain antibiotics, for example streptomycin can promote misreading at the wobble third position of a codon.
  • The genetic code assignments are not universally conserved particularly in organellar genes, for example mitochondrial genes.

Keywords: wobble hypothesis; tRNA; anticodon; codon; mRNA decoding; codon recognition; base modification

Figure 1. mRNA–tRNA 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 because of 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.


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Further Reading

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Osawa S (1995) Evolution of the Genetic Code. Oxford: Oxford Science Publications.

Soll D and RajBhandary UL (1995) tRNA Structure, Biosynthesis and Function. Washington, DC: ASM Press.

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Tuite, Mick F, and von der Haar, Tobias(Nov 2016) Transfer RNA in Decoding and the Wobble Hypothesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001497.pub2]