Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea

A modified base at the first (wobble) position of some tRNA anticodons is critical for deciphering the genetic code. In eukaryotes and eubacteria, AUA codons are decoded by tRNAsIle with modified bases pseudouridine (and/or inosine) and lysidine, respectively. The mechanism by which archaeal species translate AUA codons is unclear. We describe a polyamine-conjugated modified base, 2-agmatinylcytidine (agm 2 C or agmatidine), at the wobble position of archaeal tRNA Ile that decodes AUA codons specifically. We demonstrate that archaeal cells use agmatine to synthesize agm 2 C of tRNA Ile. We also identified a new enzyme, tRNA Ile -agm 2 C synthetase (TiaS), that catalyzes agm 2 C formation in the presence of agmatine and ATP. Although agm 2 C is chemically similar to lysidine, TiaS constitutes a distinct class of enzyme from tRNA Ile -lysidine synthetase (TilS), suggesting that the decoding systems evolved convergently across domains. © 2010 Nature America, Inc. All rights reserved.