Start codon

The start codon always codes for methionine in eukaryotes and archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids.

In all three domains of life, the start codon is decoded by a special "initiation" transfer RNA different from the tRNAs used for elongation.

There are important structural differences between an initiating tRNA and an elongating one, with distinguish features serving to satisfy the constraints of the translation system.

[1] In eukaryotes and archaea, the T stem prevents the elongation factors from binding, while eIF2 specifically recognizes the attached methionine and a A1:U72 basepair.

[3] Knowledge of the key recognizing features has allowed researchers to construct alternative initiating tRNAs that code for different amino acids; see below.

[3] Alternate start codons (non-AUG) are very rare in eukaryotic genomes: a wide range of mechanisms work to guarantee the relative fidelity of AUG initiation.

[8][9] Well-known coding regions that do not have AUG initiation codons are those of lacI (GUG)[10][11] and lacA (UUG)[12] in the E. coli lac operon.

[16] Archaea, which are prokaryotes with a translation machinery similar to but simpler than that of eukaryotes, allow initiation at UUG and GUG.

Start codon (blue circle) of the human mitochondrial DNA MT-ATP6 gene. For each nucleotide triplet (square brackets), the corresponding amino acid is given (one-letter code), either in the +1 reading frame for MT-ATP8 (in red) or in the +3 frame for MT-ATP6 (in blue). In this genomic region, the two genes overlap .