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

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.[1]

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

Eukaryotes

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.[2] 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.[3] 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.[4][5]

Mitochondrial genomes (and prokaryotes) use alternate start codons more significantly (AUA and AUU in humans and mainly GUG and UUG in prokaryotes).[6]

Prokaryotes

E. coli uses 83% AUG (3542/4284), 14% (612) GUG, 3% (103) UUG [7] and one or two others (e.g., an AUU and possibly a CUG).[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.

Standard genetic code

nonpolar polar basic acidic (stop codon)
Standard genetic code
1st
base		 2nd base 3rd
base
U C A G
U UUU (Phe/F) Phenylalanine UCU (Ser/S) Serine UAU (Tyr/Y) Tyrosine UGU (Cys/C) Cysteine U
UUC UCC UAC UGC C
UUA (Leu/L) Leucine UCA UAA Stop (Ochre) UGA Stop (Opal) A
UUG UCG UAG Stop (Amber) UGG (Trp/W) Tryptophan     G
C CUU CCU (Pro/P) Proline CAU (His/H) Histidine CGU (Arg/R) Arginine U
CUC CCC CAC CGC C
CUA CCA CAA (Gln/Q) Glutamine CGA A
CUG CCG CAG CGG G
A AUU (Ile/I) Isoleucine ACU (Thr/T) Threonine         AAU (Asn/N) Asparagine AGU (Ser/S) Serine U
AUC ACC AAC AGC C
AUA ACA AAA (Lys/K) Lysine AGA (Arg/R) Arginine A
AUG[A] (Met/M) Methionine ACG AAG AGG G
G GUU (Val/V) Valine GCU (Ala/A) Alanine GAU (Asp/D) Aspartic acid GGU (Gly/G) Glycine U
GUC GCC GAC GGC C
GUA GCA GAA (Glu/E) Glutamic acid GGA A
GUG GCG GAG GGG G
A The codon AUG both codes for methionine and serves as an initiation site: the first AUG in an mRNA's coding region is where translation into protein begins.[13]

See also

External links

References

  1. ↑ Lobanov, A. V.; Turanov, A. A.; Hatfield, D. L.; Gladyshev, V. N. (2010). "Dual functions of codons in the genetic code". Critical Reviews in Biochemistry and Molecular Biology. 45 (4): 257–65. doi:10.3109/10409231003786094. PMC 3311535Freely accessible. PMID 20446809.
  2. ↑ Ivanov IP, Firth AE, Michel AM, Atkins JF, Baranov PV (2011). "Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences". Nucleic Acids Research. 39 (10): 4220–4234. doi:10.1093/nar/gkr007. PMC 3105428Freely accessible. PMID 21266472.
  3. ↑ Peabody, D. S. (1989). "Translation initiation at non-AUG triplets in mammalian cells". The Journal of Biological Chemistry. 264 (9): 5031–5. PMID 2538469.
  4. ↑ Starck, S. R.; Jiang, V; Pavon-Eternod, M; Prasad, S; McCarthy, B; Pan, T; Shastri, N (2012). "Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I". Science. 336 (6089): 1719–23. doi:10.1126/science.1220270. PMID 22745432.
  5. ↑ Dever, T. E. (2012). "Molecular biology. A new start for protein synthesis". Science. 336 (6089): 1645–6. doi:10.1126/science.1224439. PMID 22745408.
  6. ↑ Watanabe, Kimitsuna; Suzuki, Tsutomu (2001). "Genetic Code and its Variants". doi:10.1038/npg.els.0000810.
  7. ↑ Blattner, F. R.; Plunkett g, G.; Bloch, C. A.; Perna, N. T.; Burland, V.; Riley, M.; Collado-Vides, J.; Glasner, J. D.; Rode, C. K.; Mayhew, G. F.; Gregor, J.; Davis, N. W.; Kirkpatrick, H. A.; Goeden, M. A.; Rose, D. J.; Mau, B.; Shao, Y. (1997). "The Complete Genome Sequence of Escherichia coli K-12". Science. 277 (5331): 1453–1462. doi:10.1126/science.277.5331.1453. PMID 9278503.
  8. ↑ Sacerdot, C.; Fayat, G.; Dessen, P.; Springer, M.; Plumbridge, J. A.; Grunberg-Manago, M.; Blanquet, S. (1982). "Sequence of a 1.26-kb DNA fragment containing the structural gene for E.coli initiation factor IF3: Presence of an AUU initiator codon". The EMBO Journal. 1 (3): 311–315. PMC 553041Freely accessible. PMID 6325158.
  9. ↑ Missiakas, D.; Georgopoulos, C.; Raina, S. (1993). "The Escherichia coli heat shock gene htpY: Mutational analysis, cloning, sequencing, and transcriptional regulation". Journal of Bacteriology. 175 (9): 2613–2624. PMC 204563Freely accessible. PMID 8478327.
  10. ↑ E.coli lactose operon with lacI, lacZ, lacY and lacA genes GenBank: J01636.1
  11. ↑ Farabaugh, P. J. (1978). "Sequence of the lacI gene". Nature. 274 (5673): 765–769. doi:10.1038/274765a0. PMID 355891.
  12. ↑ NCBI Sequence Viewer v2.0
  13. ↑ Nakamoto T (March 2009). "Evolution and the universality of the mechanism of initiation of protein synthesis". Gene. 432 (1–2): 1–6. doi:10.1016/j.gene.2008.11.001. PMID 19056476.
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