Transfer RNA in Decoding and the Wobble Hypothesis
Mick F Tuite, University of Kent, Canterbury, Kent, UK
Tobias von der Haar, University of Kent, Canterbury, Kent, UK
Published online: November 2016
DOI: 10.1002/9780470015902.a0001497.pub2
Abstract
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
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