Post-transcriptional RNA modifications in the anticodon of transfer RNAs frequently contribute to the high fidelity of protein synthesis. In eubacteria, two genome-encoded transfer RNA (tRNA) species bear the same CAU sequence as the anticodons, which are differentiated by modified cytidines at the wobble positions. The elongator tRNA Met accepts an acetyl moiety at the wobble base to form N 4 -acetylcytidine (ac 4 C): an inherent modification ensures precise decoding of the AUG codon by strengthening CÀG base-pair interaction and concurrently preventing misreading of the near cognate AUA codon. We have determined the crystal structure of tRNA Met cytidine acetyltransferase (TmcA) from Escherichia coli complexed with two natural ligands, acetyl-CoA and ADP, at 2.35 Å resolution. The structure unexpectedly reveals an idiosyncratic RNA helicase module fused with a GCN5-related N-acetyltransferase (GNAT) fold, which intimately crossinteract. Taken together with the biochemical evidence, we further unravelled the function of acetyl-CoA as an enzyme-activating switch, and propose that an RNA helicase motor driven by ATP hydrolysis is used to deliver the wobble base to the active centre of the GNAT domain.

Pesttranseriptional modrfications ut the first base of tRNA anticedon (wobbte IH)sition) conier the decodillg property ef tRNAs in the genetic translation. A single posttranscriptional medification, lysidine {k2C), at the wobble position of bactcrial minor tRNA[ie bearing CAU anticodon converse both cedon and amine acid specificities from AUG tu AUA and rnethiolline tu isoleucine, respectively. Interestingly, in somc bacteria. tRNAsMe' having the saine CAU anticoden, are altemativcly modified to 4-acetylcytidinc (ac ℃) at the wobble pesition. This modificatioo hus heen reported to stabilizc thc C3'-endo forrn and strellgthcn ap the C-G hasepair interaction; thereforc, ensllring the decoding ot' AUG cedon as methiolline.

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