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 a modified Met (fMet) in prokaryotes. The most common start codon is AUG.

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

Alternative start codons are different from the standard AUG codon and are found in both prokaryotes (bacteria) 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 transfer RNA (tRNA) is used for initiation.

Bioinformatics programs usually allow for alternate start codons when searching for protein coding genes.

Alternate start codons (non AUG) are very rare in eukaryotic genomes. 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 were functional as translation start sites in mammalian cells. In addition to the canonical Met-tRNA Met and AUG codon pathway, mammalian cells can initiate translation with leucine using a specific leucyl-tRNA that decodes the codon CUG.

Mitochondrial genomes (and prokaryotes) use alternate start codons more significantly (AUA and AUU in humans and mainly GUG and UUG in prokaryotes).

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).

Well-known coding regions that do not have AUG initiation codons are those of lacI (GUG) and lacA (UUG) in the E. coli lac operon. Two more recent studies have independently shown that 17 or more non-AUG start codons may initiate translation in E. coli .

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