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 alternative 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 90% 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. Two more recent studies have independently shown that 17 or more non-AUG start codons may initiate translation in E. coli.[13][14]

Standard genetic code

Amino acids biochemical properties nonpolar polar basic acidic Termination: 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) [B] UGA Stop (Opal) [B] A
UUG 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
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.[15]
B ^ ^ ^ The historical basis for designating the stop codons as amber, ochre and opal is described in an autobiography by Sydney Brenner[16] and in a historical article by Bob Edgar.[17]

See also

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 3311535. 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 3105428. 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 553041. 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 204563. 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. ↑ Hecht, Ariel; Glasgow, Jeff; Jaschke, Paul R.; Bawazer, Lukmaan A.; Munson, Matthew S.; Cochran, Jennifer R.; Endy, Drew; Salit, Marc (2017). "Measurements of translation initiation from all 64 codons in E. coli". Nucleic Acids Research. doi:10.1093/nar/gkx070.
  14. ↑ Firnberg, Elad; Labonte, Jason; Gray, Jeffrey; Ostermeir, Marc A. (2014). "A comprehensive, high-resolution map of a gene's fitness landscape". Molecular Biology & Evolution. doi:10.1093/molbev/msu081. PMC 4839222.
  15. ↑ 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.
  16. ↑ Brenner S. A Life in Science (2001) Published by Biomed Central Limited ISBN 0-9540278-0-9 see pages 101-104
  17. ↑ Edgar B (2004). "The genome of bacteriophage T4: an archeological dig". Genetics. 168 (2): 575–82. PMC 1448817. PMID 15514035. see pages 580-581
  • The Genetic Codes. Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell, National Center for Biotechnology Information (NCBI), Bethesda, Maryland, US
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