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.