An Operational RNA Code for Faithful Assignment of AUG Triplets to Methionine

SummaryThe assignment of AUG codons to methionine remains a central question of the evolution of the genetic code. We have unveiled a strategy for the discrimination among tRNAs containing CAU (AUG-decoding) anticodons. Mycoplasma penetrans methionyl-tRNA synthetase can directly differentiate between tRNAIleCAU and tRNAMetCAU transcripts (a recognition normally achieved through the modification of anticodon bases). This discrimination mechanism is based only on interactions with the acceptor stems of tRNAIleCAU and tRNAMetCAU. Thus, in certain species, the fidelity of translation of methionine codons requires a discrimination mechanism that is independent of the information contained in the anticodon.