initiator codon


Summary: A codon that directs initiation of protein translation (TRANSLATION, GENETIC) by stimulating the binding of initiator tRNA (RNA, TRANSFER, MET). In prokaryotes, the codons AUG or GUG can act as initiators while in eukaryotes, AUG is the only initiator codon.

Top Publications

  1. Gallien S, Perrodou E, Carapito C, Deshayes C, Reyrat J, Van Dorsselaer A, et al. Ortho-proteogenomics: multiple proteomes investigation through orthology and a new MS-based protocol. Genome Res. 2009;19:128-35 pubmed publisher
  2. Shabalina S, Ogurtsov A, Spiridonov N. A periodic pattern of mRNA secondary structure created by the genetic code. Nucleic Acids Res. 2006;34:2428-37 pubmed
  3. Ventoso I, Sanz M, Molina S, Berlanga J, Carrasco L, Esteban M. Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR. Genes Dev. 2006;20:87-100 pubmed
    ..Genetic and biochemical data showed a highly stable RNA hairpin loop located downstream of the AUG initiator codon that is necessary to provide translational resistance to eIF2alpha phosphorylation...
  4. Stamm S, Riethoven J, Le Texier V, Gopalakrishnan C, Kumanduri V, Tang Y, et al. ASD: a bioinformatics resource on alternative splicing. Nucleic Acids Res. 2006;34:D46-55 pubmed
    ..ASD data has been integrated with Ensembl genome annotation project as a Distributed Annotation System (DAS) resource and can be viewed on Ensembl genome browser. The ASD resource is presented at ( ..
  5. Meyer I, Miklós I. Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs. Nucleic Acids Res. 2005;33:6338-48 pubmed
  6. Chen S, Lin G, Chang K, Yeh L, Wang C. Translational efficiency of a non-AUG initiation codon is significantly affected by its sequence context in yeast. J Biol Chem. 2008;283:3173-80 pubmed
    ..these results suggest that sequence context is more important for translation initiation in yeast than previously appreciated. ..
  7. Kozak M. Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene. 2005;361:13-37 pubmed
    ..Examples are described. Some mistaken ideas about regulation of translation that have found their way into textbooks are pointed out and corrected. ..
  8. Churbanov A, Rogozin I, Babenko V, Ali H, Koonin E. Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes. Nucleic Acids Res. 2005;33:5512-20 pubmed
  9. Krzywinski J, Grushko O, Besansky N. Analysis of the complete mitochondrial DNA from Anopheles funestus: an improved dipteran mitochondrial genome annotation and a temporal dimension of mosquito evolution. Mol Phylogenet Evol. 2006;39:417-23 pubmed
    ..Although existing evidence does not unequivocally favor one of the alternatives, fossil-based predictions of the age of the family Culicidae are in better agreement with dates inferred from protein-coding genes. ..

Scientific Experts

More Information


  1. Algire M, Lorsch J. Where to begin? The mechanism of translation initiation codon selection in eukaryotes. Curr Opin Chem Biol. 2006;10:480-6 pubmed
  2. Kochetov A, Sarai A, Rogozin I, Shumny V, Kolchanov N. The role of alternative translation start sites in the generation of human protein diversity. Mol Genet Genomics. 2005;273:491-6 pubmed
    ..These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties. ..
  3. Brock J, Paz R, Cottle P, Janssen G. Naturally occurring adenines within mRNA coding sequences affect ribosome binding and expression in Escherichia coli. J Bacteriol. 2007;189:501-10 pubmed
    ..This work provides evidence that adenine-rich sequence motifs might serve as a general enhancer of E. coli translation. ..
  4. Rentero C, Puigdomenech P. Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene. BMC Mol Biol. 2006;7:39 pubmed
    ..Our data suggest the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants. ..
  5. Zhou W, Song W. Leaky scanning and reinitiation regulate BACE1 gene expression. Mol Cell Biol. 2006;26:3353-64 pubmed
    ..Such leaky scanning and reinitiation resulted in weak expression of BACE1 under normal conditions. Alterations of the leaky scanning and reinitiation in BACE1 gene expression could play an important role in AD pathogenesis. ..
  6. Tech M, Meinicke P. An unsupervised classification scheme for improving predictions of prokaryotic TIS. BMC Bioinformatics. 2006;7:121 pubmed
    ..These features are particularly useful on genomes with high G+C content. The algorithm has been implemented in the tool "TICO" (TIs COrrector) which is publicly available from our web site. ..
  7. Walter M, Witt T, Weigel B, Reilich P, Richard P, Pongratz D, et al. Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2005;15:40-4 pubmed
    ..the LMNA gene -3del15, resulting in the loss of 15 nucleotides from -3 to +12, including the translation ATG initiator codon. The mutation segregates in a previously described family with a clinical phenotype that shared features of ..
  8. Sabariegos R, Nadal A, Beguiristain N, Piron M, Gomez J. Catalytic RNase P RNA from Synechocystis sp. cleaves the hepatitis C virus RNA near the AUG start codon. FEBS Lett. 2004;577:517-22 pubmed
    ..This provides additional support for the presence of an RNA structure similar to tRNA near the AUG start codon and suggests that Synechocystis P RNA may be an active agent for HCV antigenomic interventions. ..
  9. Jin H, Zhao Q, Gonzalez de Valdivia E, Ardell D, Stenström M, Isaksson L. Influences on gene expression in vivo by a Shine-Dalgarno sequence. Mol Microbiol. 2006;60:480-92 pubmed
    ..Analysis of the E. coli K12 genome suggests that the SD+ or SD-like sequences are systematically avoided in the early coding region suggesting an evolutionary significance. ..
  10. Studer S, Joseph S. Unfolding of mRNA secondary structure by the bacterial translation initiation complex. Mol Cell. 2006;22:105-15 pubmed
    ..We show that unfolding of structured mRNAs requires a SD sequence, the start codon, fMet-tRNA(fMet), and the GTP bound form of initiation factor 2 bound to the 30S subunit. ..
  11. Kochetov A. AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context. Bioinformatics. 2005;21:837-40 pubmed
  12. Pöyry T, Kaminski A, Connell E, Fraser C, Jackson R. The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation. Genes Dev. 2007;21:3149-62 pubmed
  13. Spevak C, Park E, Geballe A, Pelletier J, Sachs M. her-2 upstream open reading frame effects on the use of downstream initiation codons. Biochem Biophys Res Commun. 2006;350:834-41 pubmed
    ..Primer extension inhibition (toeprint) assays of ribosomes loaded at initiation codons in reticulocyte lysates indicated that the uORF affected the interaction of ribosomes with the primary her-2 AUG codon. ..
  14. Hu G, Zheng X, Yang Y, Ortet P, She Z, Zhu H. ProTISA: a comprehensive resource for translation initiation site annotation in prokaryotic genomes. Nucleic Acids Res. 2008;36:D114-9 pubmed
    ..As of July 2007, ProTISA includes 440 microbial genomes with more than 390 000 confirmed TISs. The database is available at ..
  15. Bornes S, Prado Lourenco L, Bastide A, Zanibellato C, Iacovoni J, Lacazette E, et al. Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress. Circ Res. 2007;100:305-8 pubmed
    ..These results demonstrate the in vivo efficacy of the VEGF IRESs in response to a local environmental stress such as hypoxia. ..
  16. Meyers G. Characterization of the sequence element directing translation reinitiation in RNA of the calicivirus rabbit hemorrhagic disease virus. J Virol. 2007;81:9623-32 pubmed
    ..The sequence mapping resulted in a refined model of the reinitiation mechanism leading to VP2 expression. ..
  17. Oyama M, Kozuka Hata H, Suzuki Y, Semba K, Yamamoto T, Sugano S. Diversity of translation start sites may define increased complexity of the human short ORFeome. Mol Cell Proteomics. 2007;6:1000-6 pubmed
  18. Huang H, Tang H, Chao H, Yeh L, Wang C. An unusual pattern of protein expression and localization of yeast alanyl-tRNA synthetase isoforms. Mol Microbiol. 2006;60:189-98 pubmed
    ..Thus, the sequence upstream of the first in-frame AUG initiator not only carries an unusual initiation site, but also contributes to a novel pattern of protein expression and localization. ..
  19. Chang K, Lin G, Men L, Wang C. Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of translation in yeast. J Biol Chem. 2006;281:7775-83 pubmed
    ..Cumulatively, the results suggest that this feature of redundancy of non-AUG initiators in a single mRNA per se may represent a novel paradigm for improving the efficiency of a poor or otherwise nonproductive initiation event. ..
  20. Li H, Jiang T. A class of edit kernels for SVMs to predict translation initiation sites in eukaryotic mRNAs. J Comput Biol. 2005;12:702-18 pubmed
  21. Qin D, Fredrick K. Control of translation initiation involves a factor-induced rearrangement of helix 44 of 16S ribosomal RNA. Mol Microbiol. 2009;71:1239-49 pubmed publisher
    ..These data provide evidence that the interaction between the initiator tRNA and the 30S P site is tuned to balance efficiency and accuracy during initiation. ..
  22. Tech M, Pfeifer N, Morgenstern B, Meinicke P. TICO: a tool for improving predictions of prokaryotic translation initiation sites. Bioinformatics. 2005;21:3568-9 pubmed
    ..Our program is based on a clustering algorithm for completely unsupervised scoring of potential TIS locations. Our tool can be freely accessed through a web interface at ..
  23. Kim I, Cha S, Yoon M, Hwang J, Lee S, Sohn H, et al. The complete nucleotide sequence and gene organization of the mitochondrial genome of the oriental mole cricket, Gryllotalpa orientalis (Orthoptera: Gryllotalpidae). Gene. 2005;353:155-68 pubmed publisher
    ..However, the relationships of ancient insect orders were unstable, indicating the limited use of mitogenome information at deeper phylogenetic depth...
  24. Zivanovic Y, Armengaud J, Lagorce A, Leplat C, Guerin P, Dutertre M, et al. Genome analysis and genome-wide proteomics of Thermococcus gammatolerans, the most radioresistant organism known amongst the Archaea. Genome Biol. 2009;10:R70 pubmed publisher
    ..This proteogenomic study also indicates that the high radiotolerance of T. gammatolerans is probably due to proteins that remain to be characterized rather than a larger arsenal of known DNA repair enzymes. ..
  25. Hasenöhrl D, Fabbretti A, Londei P, Gualerzi C, Blasi U. Translation initiation complex formation in the crenarchaeon Sulfolobus solfataricus. RNA. 2009;15:2288-98 pubmed publisher
    ..Thus, despite the resemblance of eIF2 and a/eIF2, recruitment of initiator tRNA to the ribosome is mechanistically different in Pro- and Eukaryotes. ..
  26. Torarinsson E, Klenk H, Garrett R. Divergent transcriptional and translational signals in Archaea. Environ Microbiol. 2005;7:47-54 pubmed
    ..High levels of leaderless transcripts are found in the longer branched Archaea. ..
  27. Cheung Y, Maag D, Mitchell S, Fekete C, Algire M, Takacs J, et al. Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo. Genes Dev. 2007;21:1217-30 pubmed
  28. Boore J. The complete sequence of the mitochondrial genome of Nautilus macromphalus (Mollusca: Cephalopoda). BMC Genomics. 2006;7:182 pubmed publisher
    ..tunicata implies that mutational bias during replication also plays a role. This appears to be yet another case where polyadenylation of mitochondrial tRNAs restores what would otherwise be an incomplete structure...
  29. Araud T, Genolet R, Jaquier Gubler P, Curran J. Alternatively spliced isoforms of the human elk-1 mRNA within the 5' UTR: implications for ELK-1 expression. Nucleic Acids Res. 2007;35:4649-63 pubmed
  30. Slamovits C, Saldarriaga J, Larocque A, Keeling P. The highly reduced and fragmented mitochondrial genome of the early-branching dinoflagellate Oxyrrhis marina shares characteristics with both apicomplexan and dinoflagellate mitochondrial genomes. J Mol Biol. 2007;372:356-68 pubmed
    ..Overall, the combination of characteristics found in the Oxyrrhis genome allows us to plot the sequence of many events that led to the extreme organisation of apicomplexan and dinoflalgellate mitochondrial genomes. ..
  31. Saini A, Nanda J, Lorsch J, Hinnebusch A. Regulatory elements in eIF1A control the fidelity of start codon selection by modulating tRNA(i)(Met) binding to the ribosome. Genes Dev. 2010;24:97-110 pubmed publisher
  32. Chen S, Ko C, Yen C, Wang C. Translational efficiency of redundant ACG initiator codons is enhanced by a favorable sequence context and remedial initiation. J Biol Chem. 2009;284:818-27 pubmed publisher
    ..5-fold). Thus, the sequence context plays a much more important role than remedial initiation in modulating the efficiency of translational initiation from redundant non-AUG codons. ..
  33. Powell M, Napthine S, Jackson R, Brierley I, Brown T. Characterization of the termination-reinitiation strategy employed in the expression of influenza B virus BM2 protein. RNA. 2008;14:2394-406 pubmed publisher
    ..This suggests that the full complement of initiation factors is not required for the reinitiation process. ..
  34. Ivanov I, Loughran G, Atkins J. uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs. Proc Natl Acad Sci U S A. 2008;105:10079-84 pubmed publisher
    ..This repression is part of an autoregulatory circuit, and one of its sensors is the AUU codon, which suggests that translation initiation codon identity is likely used for regulation in eukaryotes. ..
  35. Choi M, Kim D, Lee D, Lee J, Koh K, Paik S, et al. Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection. J Viral Hepat. 2007;14:161-8 pubmed
    ..These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication. ..
  36. Song K, Hwang C, Kim C, Choi H, Law P, Wei L, et al. Translational repression of mouse mu opioid receptor expression via leaky scanning. Nucleic Acids Res. 2007;35:1501-13 pubmed
    ..These results support the hypothesis that uORFs in mouse MOR mRNA act as negative regulators through a ribosome leaky scanning mechanism. Such leaky scanning resulted in the suppression of mouse MOR under normal conditions. ..
  37. Rison S, Mattow J, Jungblut P, Stoker N. Experimental determination of translational starts using peptide mass mapping and tandem mass spectrometry within the proteome of Mycobacterium tuberculosis. Microbiology. 2007;153:521-8 pubmed
    ..This method can be performed with little or no additional experimental work during proteomics investigations. ..
  38. Fernandez J, Yaman I, Huang C, Liu H, Lopez A, Komar A, et al. Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation. Mol Cell. 2005;17:405-16 pubmed
    ..This control is reminiscent of translation attenuation in prokaryotic operons, where inhibition of translation elongation can regulate both mRNA translation and gene transcription by altering mRNA structure. ..
  39. Starmer J, Stomp A, Vouk M, Bitzer D. Predicting Shine-Dalgarno sequence locations exposes genome annotation errors. PLoS Comput Biol. 2006;2:e57 pubmed
    ..Thus, our RS metric provides a new way to explore the role of rRNA-mRNA nucleotide hybridization in translation initiation. ..
  40. Terenin I, Dmitriev S, Andreev D, Royall E, Belsham G, Roberts L, et al. A cross-kingdom internal ribosome entry site reveals a simplified mode of internal ribosome entry. Mol Cell Biol. 2005;25:7879-88 pubmed
    ..We suggest that the single-stranded nature of the RhPV IRES accounts for its strong but less selective potential to bind key mRNA recruiting components of the translation initiation apparatus from diverse origins. ..
  41. Algire M, Maag D, Lorsch J. Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation. Mol Cell. 2005;20:251-62 pubmed
    ..Release of P(i), which makes GTP hydrolysis irreversible, appears to be controlled by the AUG-dependent dissociation of eIF1 from the preinitiation complex. ..
  42. Pisarev A, Kolupaeva V, Pisareva V, Merrick W, Hellen C, Pestova T. Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex. Genes Dev. 2006;20:624-36 pubmed
  43. Clyde K, Harris E. RNA secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication. J Virol. 2006;80:2170-82 pubmed publisher
    ..While numerous regulatory elements have been identified in the untranslated regions of RNA viral genomes, we show that the cHP is a coding-region RNA element that directs start codon selection and is required for viral replication...
  44. Dmitriev S, Bykova N, Andreev D, Terenin I. [Adequate system for investigation of translation initiation of the human retrotransposon L1 mRNA in vitro]. Mol Biol (Mosk). 2006;40:25-30 pubmed
    ..These and other experiments allowed us to clearly demonstrate that the new combined cell-free system is much more adequate to study mechanisms of translation initiation than a regular RRL. ..
  45. Watanabe R, Murai M, Singh C, Fox S, Ii M, Asano K. The eukaryotic initiation factor (eIF) 4G HEAT domain promotes translation re-initiation in yeast both dependent on and independent of eIF4A mRNA helicase. J Biol Chem. 2010;285:21922-33 pubmed publisher
    ..Based on the RNA-binding activities identified within the unstructured segments flanking the eIF4G2 HEAT domain, we discuss the role of the HEAT domain in scanning beyond loading eIF4A onto the pre-initiation complex. ..
  46. Kawaguchi R, Bailey Serres J. mRNA sequence features that contribute to translational regulation in Arabidopsis. Nucleic Acids Res. 2005;33:955-65 pubmed
    ..Notably, the mRNA features that contribute to translational regulation could not fully explain the variation in ribosome loading, indicating that additional factors contribute to translational regulation in Arabidopsis. ..
  47. Londei P. Evolution of translational initiation: new insights from the archaea. FEMS Microbiol Rev. 2005;29:185-200 pubmed
    ..A model of the initiation step of translation in the Last Universal Common Ancestor of extant cells is presented and discussed. ..
  48. Dong J, Nanda J, Rahman H, Pruitt M, Shin B, Wong C, et al. Genetic identification of yeast 18S rRNA residues required for efficient recruitment of initiator tRNA(Met) and AUG selection. Genes Dev. 2008;22:2242-55 pubmed publisher
    ..Hence, the nonconserved 928:1389 base pair in h28, plus conserved 18S rRNA residues corresponding to P-site contacts in bacterial ribosomes, are critical for efficient Met-tRNA(i)(Met) binding and AUG selection in eukaryotes. ..
  49. Dmitriev S, Andreev D, Terenin I, Olovnikov I, Prassolov V, Merrick W, et al. Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5' untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated. Mol Cell Biol. 2007;27:4685-97 pubmed
    ..Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event. ..
  50. Meinicke P, Tech M, Morgenstern B, Merkl R. Oligo kernels for datamining on biological sequences: a case study on prokaryotic translation initiation sites. BMC Bioinformatics. 2004;5:169 pubmed
    ..Attractive features of our approach are its flexibility with respect to oligomer length and position conservation. By means of these two parameters oligo kernels can easily be adapted to different biological problems. ..
  51. Thomas J, Ughy B, Lagoutte B, Ajlani G. A second isoform of the ferredoxin:NADP oxidoreductase generated by an in-frame initiation of translation. Proc Natl Acad Sci U S A. 2006;103:18368-73 pubmed
    ..Our results strongly suggest that FNR(L) is an NADP(+) reductase, whereas FNR(S) is an NADPH oxidase. ..
  52. Zamora Romo E, Cruz Vera L, Vivanco Domínguez S, Magos Castro M, Guarneros G. Efficient expression of gene variants that harbour AGA codons next to the initiation codon. Nucleic Acids Res. 2007;35:5966-74 pubmed
    ..However, the induction of lacZ AGA AGA gene in pth cells accumulated peptidyl-tRNA(Arg4) as well as a short 5'-proximal lacZ mRNA fragment suggesting ribosome stalling due to depletion of aminoacylated-tRNA(Arg4). ..
  53. Asano K, Sachs M. Translation factor control of ribosome conformation during start codon selection. Genes Dev. 2007;21:1280-7 pubmed