Start codon

The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids.

The start codon is often preceded by a 5' untranslated region (5' UTR). In prokaryotes this includes the ribosome binding site.

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. In bacteria and organelles, an acceptor stem C1:A72 mismatch guide formylation, which directs recruitment by the 30S ribosome into the P site; so-called "3GC" base pairs allow assembly into the 70S ribosome. 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.

In any case, the natural initiating tRNA only codes for methionine. Knowledge of the key recognizing features has allowed researchers to construct alternative initiating tRNAs that code for different amino acids; see below.

Alternative start codons are different from the standard AUG codon and are found in both prokaryotes (bacteria and archaea) and eukaryotes. Alternate start codons are still translated as Met when they are at the start of a protein (even if the codon encodes a different amino acid otherwise). This is because a separate tRNA is used for initiation.

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. However, naturally occurring non-AUG start codons have been reported for some cellular mRNAs. Seven out of the nine possible single-nucleotide substitutions at the AUG start codon of dihydrofolate reductase are functional as translation start sites in mammalian cells.

Bacteria do not generally have the wide range of translation factors monitoring start codon fidelity. GUG and UUG are the main, even "canonical", alternate start codons. GUG in particular is important to controlling the replication of plasmids.

E. coli uses 83% AUG (3542/4284), 14% (612) GUG, 3% (103) UUG and one or two others (e.g., an AUU and possibly a CUG).