The start codon is the first codon of a transfer RNA (tRNA) 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 most common start codon is AUG (i.e., ATG in the corresponding DNA sequence).
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 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 transfer RNA (tRNA) is used for initiation.
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.
Candida albicans uses a CAG start codon.
Prokaryotes use alternate start codons significantly, mainly GUG and UUG. These alternate start codons and the frequency of their use compared to eukaryotes has been studied and shown to refute the common ancestor theory.
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.
Mitochondrial genomes use alternate start codons more significantly (AUA and AUU in humans). Many such examples, with codons, systematic range, and citations, are given in the NCBI list of translation tables.
|Amino-acid biochemical properties||Nonpolar||Polar||Basic||Acidic||Termination: stop codon|
|U||UUU||(Phe/F) Phenylalanine||UCU||(Ser/S) Serine||UAU||(Tyr/Y) Tyrosine||UGU||(Cys/C) Cysteine||U|
|UUA||(Leu/L) Leucine||UCA||UAA||Stop (Ochre)[B]||UGA||Stop (Opal)[B]||A|
|UUG[A]||UCG||UAG||Stop (Amber)[B]||UGG||(Trp/W) Tryptophan||G|
|C||CUU||CCU||(Pro/P) Proline||CAU||(His/H) Histidine||CGU||(Arg/R) Arginine||U|
|A||AUU||(Ile/I) Isoleucine||ACU||(Thr/T) Threonine||AAU||(Asn/N) Asparagine||AGU||(Ser/S) Serine||U|
|AUA||ACA||AAA||(Lys/K) Lysine||AGA||(Arg/R) Arginine||A|
|G||GUU||(Val/V) Valine||GCU||(Ala/A) Alanine||GAU||(Asp/D) Aspartic acid||GGU||(Gly/G) Glycine||U|
|GUA||GCA||GAA||(Glu/E) Glutamic acid||GGA||A|
Engineered initiator tRNAs (tRNAfMet2 with CUA anticodon) 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.