tRNAiMet

tRNAiMet, the initiator methionyl-tRNA, is a specialized transfer RNA that delivers the first amino acid to the ribosome at the start of protein synthesis. Its anticodon, typically CAU, pairs with the start codon AUG, helping to establish the reading frame and recruit the ribosome for initiation. Across domains, tRNAiMet carries methionine and possesses identity elements that distinguish it from tRNA used during elongation. It is charged with methionine by methionyl-tRNA synthetase (MetRS) and then targeted to the initiation machinery.

In bacteria, initiation often uses formylated methionine. Met-tRNAiMet is converted to formylmethionyl-tRNAiMet (fMet-tRNAiMet) by methionyl-tRNA transformylase. This formyl group assists recognition by the initiation factor IF2 and the 30S ribosomal subunit during start codon selection. After the first peptide bond is formed, deformylase removes the formyl group, and the tRNA participates in elongation with methionine. Initiation factors IF1, IF2, and IF3 collaborate to ensure correct placement of fMet-tRNAiMet at the start codon and to prevent premature entry of tRNA into elongation.

In archaea and eukaryotes, tRNAiMet is not formylated. Initiation uses eukaryotic or archaeal initiation factors (eIF2 or aIF2) to deliver the initiator tRNAiMet to the ribosome, typically after scanning for AUG in many organisms. The initiator tRNA in these lineages has features that promote specific recognition by initiation factors and the ribosome, while elongation uses different tRNAMet species. Organisms also possess organellar equivalents of tRNAiMet in mitochondria and chloroplasts, reflecting variation in translation initiation systems.