As noted earlier, the AUG codon for methionine functions as the start codon in the vast majority of mRNAs. A critical aspect of translation initiation is to begin protein synthesis at the start codon, thereby establishing the correct reading frame for the entire mRNA. Both bacteria and eukaryotes contain two different methionine tRNAs: tRNA_i^Met can initiate protein synthesis, and tRNA^Met can incorporate methionine only into a growing protein chain. The same aminoacyl-tRNA synthetase (MetRS) charges both tRNAs with methionine. But only Met-tRNA_i^Met (i.e., activated methionine attached to tRNA_i^Met) can bind at the appropriate site on the small ribosomal subunit, the P site, to begin synthesis of a polypeptide chain. The regular Met-tRNA^Met, and all other charged tRNAs, bind only to the A site, as described later. tRNAs enter the exit or E site after transferring their covalently bound amino acids to the growing polypeptide chain.

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