Start codon


The start codon is the first codon of a messenger RNA transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a modified Met in bacteria, mitochondria and plastids. The most common start codon is AUG.
The start codon is often preceded by a 5' untranslated region. In prokaryotes this includes the ribosome binding site.

Alternative start codons

Alternative start codons are different from the standard AUG codon and are found in both prokaryotes and eukaryotes. Alternate start codons are still translated as Met when they are at the start of a protein. This is because a separate transfer RNA is used for initiation.

Eukaryotes

Alternate start codons 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.
Candida albicans uses a CAG start codon.

Prokaryotes

Prokaryotes use alternate start codons significantly, mainly GUG and UUG.
E. coli uses 83% AUG, 14% GUG, 3% UUG and one or two others.
Well-known coding regions that do not have AUG initiation codons are those of lacI and lacA 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.

Mitochondria

s use alternate start codons more significantly. Many such examples, with codons, systematic range, and citations, are given in the NCBI list of translation tables.

Standard genetic code

Engineered start codons

Engineered initiator tRNAs have been used to initiate translation at the amber stop codon UAG. This type of engineered tRNA is called a nonsense suppressor tRNA because it suppresses the translation stop signal that normally occurs at UAG codons. One study has shown that the amber initiator tRNA does not initiate translation to any measurable degree from genomically-encoded UAG codons, only plasmid-borne reporters with strong upstream Shine-Dalgarno sites.