translational peptide chain initiation


Summary: A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis.

Top Publications

  1. Powell M, Brown T, Brierley I. Translational termination-re-initiation in viral systems. Biochem Soc Trans. 2008;36:717-22 pubmed publisher
  2. Fernandez Miragall O, Ramos R, Ramajo J, Martinez Salas E. Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation. RNA. 2006;12:223-34 pubmed
    ..Thus, we propose that the central domain of the FMDV IRES contains a structural conformation essential for IRES activity stabilized by a tertiary contact involving residues in the GNRA tetraloop and motif A conserved sequences. ..
  3. Dresios J, Chappell S, Zhou W, Mauro V. An mRNA-rRNA base-pairing mechanism for translation initiation in eukaryotes. Nat Struct Mol Biol. 2006;13:30-4 pubmed
    ..We discuss the possibility that other mRNA elements affect translation by base-pairing to different sites in the 18S rRNA. ..
  4. Ricci E, Soto Rifo R, Herbreteau C, Decimo D, Ohlmann T. Lentiviral RNAs can use different mechanisms for translation initiation. Biochem Soc Trans. 2008;36:690-3 pubmed publisher
    ..Our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism. ..
  5. 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. ..
  6. 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
  7. Dugré Brisson S, Elvira G, Boulay K, Chatel Chaix L, Mouland A, DesGroseillers L. Interaction of Staufen1 with the 5' end of mRNA facilitates translation of these RNAs. Nucleic Acids Res. 2005;33:4797-812 pubmed
    ..Our results support a model in which the expression of Staufen1 and its interaction with the 5' end of RNA and ribosomes facilitate translation initiation. ..
  8. Cornelis S, Tinton S, Schepens B, Bruynooghe Y, Beyaert R. UNR translation can be driven by an IRES element that is negatively regulated by polypyrimidine tract binding protein. Nucleic Acids Res. 2005;33:3095-108 pubmed
    ..In conclusion, our results demonstrate that translation of the ITAF Unr can itself be regulated by an IRES that is downregulated by PTB. ..
  9. Sean P, Nguyen J, Semler B. Altered interactions between stem-loop IV within the 5' noncoding region of coxsackievirus RNA and poly(rC) binding protein 2: effects on IRES-mediated translation and viral infectivity. Virology. 2009;389:45-58 pubmed publisher

More Information


  1. Roy B, Vaughn J, Kim B, Zhou F, Gilchrist M, von Arnim A. The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring upstream open reading frames. RNA. 2010;16:748-61 pubmed publisher
    ..Together, these results attribute a specific molecular function in translation initiation to an individual eIF3 subunit in a multicellular eukaryote. ..
  2. Wang X, Rothnagel J. 5'-untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation. Nucleic Acids Res. 2004;32:1382-91 pubmed
    ..This study shows that for mRNAs containing multiple uORFs/uAUGs, ribosome reinitiation and leaky scanning are efficient mechanisms for initiation at their main AUGs. ..
  3. Hirose T, Sugiura M. Multiple elements required for translation of plastid atpB mRNA lacking the Shine-Dalgarno sequence. Nucleic Acids Res. 2004;32:3503-10 pubmed
    ..We hypothesize for translational initiation of the atpB mRNA that the ribosome enters an upstream region, slides to the start codon and forms an initiation complex with p50 and other components. ..
  4. Jan E, Kinzy T, Sarnow P. Divergent tRNA-like element supports initiation, elongation, and termination of protein biosynthesis. Proc Natl Acad Sci U S A. 2003;100:15410-5 pubmed
    ..Thus, this P-site-occupying IRES directs the assembly of 80S ribosomes, sets the translational reading frame, and mimics the functions of both Met-tRNAi and peptidyl tRNA to support elongation and termination. ..
  5. Kim B, Cai X, Vaughn J, von Arnim A. On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation. Genome Biol. 2007;8:R60 pubmed
    ..The intact eIF3h protein contributes to efficient translation initiation on 5' leader sequences harboring multiple uORFs, although mRNA features independent of uORFs are also implicated. ..
  6. Tats A, Remm M, Tenson T. Highly expressed proteins have an increased frequency of alanine in the second amino acid position. BMC Genomics. 2006;7:28 pubmed
    ..This pattern is well conserved in all three domains of life. ..
  7. Simonetti A, Marzi S, Myasnikov A, Fabbretti A, Yusupov M, Gualerzi C, et al. Structure of the 30S translation initiation complex. Nature. 2008;455:416-20 pubmed publisher
  8. Kieft J. Comparing the three-dimensional structures of Dicistroviridae IGR IRES RNAs with other viral RNA structures. Virus Res. 2009;139:148-56 pubmed publisher
  9. Kozak M. A second look at cellular mRNA sequences said to function as internal ribosome entry sites. Nucleic Acids Res. 2005;33:6593-602 pubmed
    ..The practice of calling even very weak results 'positive' is one of the problems discussed herein. The extremely low efficiency of putative IRESs is inconsistent with their postulated biological roles.' ..
  10. Udagawa T, Shimizu Y, Ueda T. Evidence for the translation initiation of leaderless mRNAs by the intact 70 S ribosome without its dissociation into subunits in eubacteria. J Biol Chem. 2004;279:8539-46 pubmed
    ..These observations strongly suggest that leaderless mRNA translation is initiated by the assembled 70 S ribosome and thereby bypasses the dissociation process. ..
  11. Abdi N, Fredrick K. Contribution of 16S rRNA nucleotides forming the 30S subunit A and P sites to translation in Escherichia coli. RNA. 2005;11:1624-32 pubmed
    ..In addition, we show that G1338A suppresses phenotypes conferred by m(2)G966A and several multiple P-site substitutions, suggesting that adenine at position 1338 can stabilize tRNA interaction in the P site. ..
  12. Spriggs K, Stoneley M, Bushell M, Willis A. Re-programming of translation following cell stress allows IRES-mediated translation to predominate. Biol Cell. 2008;100:27-38 pubmed
    ..Importantly, the genes identified in each of these studies do not show a significant amount of overlap, suggesting that 10-15% of all mRNAs have the capability for their initiation to occur via alternative mechanism(s). ..
  13. Zhang L, Pan X, Hershey J. Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells. J Biol Chem. 2007;282:5790-800 pubmed
    ..Cancer cells appear to require an aberrantly activated translational state to survive, suggesting that the initiation factors may be promising therapeutic targets for treating cancer. ..
  14. Luttermann C, Meyers G. The importance of inter- and intramolecular base pairing for translation reinitiation on a eukaryotic bicistronic mRNA. Genes Dev. 2009;23:331-44 pubmed publisher
    ..Analysis of the essential elements of the TURBS led to a better understanding of the requirements for translation termination/reinitiation in eukaryotes. ..
  15. Srinivasan G, Krebs M, RajBhandary U. Translation initiation with GUC codon in the archaeon Halobacterium salinarum: implications for translation of leaderless mRNA and strict correlation between translation initiation and presence of mRNA. Mol Microbiol. 2006;59:1013-24 pubmed
    ..These results suggest either a strong coupling between translation and mRNA stability or strong transcriptional polarity in H. salinarum...
  16. Laursen B, Sørensen H, Mortensen K, Sperling Petersen H. Initiation of protein synthesis in bacteria. Microbiol Mol Biol Rev. 2005;69:101-23 pubmed
    ..The future challenge is to obtain atomic-resolution structures of complete initiation complexes in order to understand the mechanism of translation initiation in molecular detail. ..
  17. Mauro V, Chappell S, Dresios J. Analysis of ribosomal shunting during translation initiation in eukaryotic mRNAs. Methods Enzymol. 2007;429:323-54 pubmed
  18. Crowe M, Wang X, Rothnagel J. Evidence for conservation and selection of upstream open reading frames suggests probable encoding of bioactive peptides. BMC Genomics. 2006;7:16 pubmed
  19. Spencer A, Spremulli L. Interaction of mitochondrial initiation factor 2 with mitochondrial fMet-tRNA. Nucleic Acids Res. 2004;32:5464-70 pubmed
    ..Finally, the region of IF-2(mt) responsible for the interaction with fMet-tRNA was mapped to the C2 sub-domain of domain VI of this factor. ..
  20. Chappell S, Edelman G, Mauro V. Ribosomal tethering and clustering as mechanisms for translation initiation. Proc Natl Acad Sci U S A. 2006;103:18077-82 pubmed
    ..These observations are consistent with ribosomal tethering at the cap structure and clustering at internal sites. ..
  21. Bornes S, Boulard M, Hieblot C, Zanibellato C, Iacovoni J, Prats H, et al. Control of the vascular endothelial growth factor internal ribosome entry site (IRES) activity and translation initiation by alternatively spliced coding sequences. J Biol Chem. 2004;279:18717-26 pubmed
    ..This is the first report describing the influence of alternatively spliced coding sequences on codon selection by modulating IRES activity. ..
  22. 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
  23. Kapp L, Lorsch J. The molecular mechanics of eukaryotic translation. Annu Rev Biochem. 2004;73:657-704 pubmed
    ..We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway. ..
  24. 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. ..
  25. Pillai R, Bhattacharyya S, Artus C, Zoller T, Cougot N, Basyuk E, et al. Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science. 2005;309:1573-6 pubmed
    ..Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression. ..
  26. Milon P, Konevega A, Gualerzi C, Rodnina M. Kinetic checkpoint at a late step in translation initiation. Mol Cell. 2008;30:712-20 pubmed publisher
  27. Meijer H, Thomas A. Ribosomes stalling on uORF1 in the Xenopus Cx41 5' UTR inhibit downstream translation initiation. Nucleic Acids Res. 2003;31:3174-84 pubmed
    ..Apparently, the block formed by a stalled ribosome on any element in uORF1 prevented the landing of new ribosomal subunits next to the cap and therefore downregulated GFP translation. ..
  28. Heidrich N, Moll I, Brantl S. In vitro analysis of the interaction between the small RNA SR1 and its primary target ahrC mRNA. Nucleic Acids Res. 2007;35:4331-46 pubmed
    ..The intracellular concentrations of SR1 were calculated under different growth conditions. ..
  29. 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. ..
  30. Ryabova L, Pooggin M, Hohn T. Translation reinitiation and leaky scanning in plant viruses. Virus Res. 2006;119:52-62 pubmed
    ..While internal initiation is treated in another section of this issue, we concentrate on leaky scanning, shunt and reinitiation, with emphasis on plant pararetroviruses. ..
  31. Singh C, He H, Ii M, Yamamoto Y, Asano K. Efficient incorporation of eukaryotic initiation factor 1 into the multifactor complex is critical for formation of functional ribosomal preinitiation complexes in vivo. J Biol Chem. 2004;279:31910-20 pubmed
    ..We propose that the coordinated recruitment of eIF1 to the 40 S ribosome in the MFC is critical for the production of functional 40 S preinitiation complex. ..
  32. Liu Z, Dong Z, Han B, Yang Y, Liu Y, Zhang J. Regulation of expression by promoters versus internal ribosome entry site in the 5'-untranslated sequence of the human cyclin-dependent kinase inhibitor p27kip1. Nucleic Acids Res. 2005;33:3763-71 pubmed
    ..The findings in this study also further enforce the importance that more stringent studies, such as promoterless dicistronic and monocistronic DNA and dicistronic RNA tests, are required to safeguard any future claims of cellular IRES. ..
  33. Barría M, Gonzalez A, Vera Otarola J, León U, Vollrath V, Marsac D, et al. Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation. Nucleic Acids Res. 2009;37:957-71 pubmed publisher
    ..These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation. ..
  34. Pacheco A, López de Quinto S, Ramajo J, Fernandez N, Martinez Salas E. A novel role for Gemin5 in mRNA translation. Nucleic Acids Res. 2009;37:582-90 pubmed publisher
    ..Thus, beyond its role in snRNPs biogenesis, Gemin5 also functions as a modulator of translation activity. ..
  35. Rodnina M, Wintermeyer W. Recent mechanistic insights into eukaryotic ribosomes. Curr Opin Cell Biol. 2009;21:435-43 pubmed publisher
    ..Here, we summarize recent progress in deciphering molecular mechanisms of eukaryotic translation. Comparisons with prokaryotic translation are included, emphasizing emerging patterns of common design. ..
  36. Preiss T, W Hentze M. Starting the protein synthesis machine: eukaryotic translation initiation. Bioessays. 2003;25:1201-11 pubmed
    ..This synopsis summarises the current status of the field and identifies intriguing open questions. ..
  37. Fechter P, Chevalier C, Yusupova G, Yusupov M, Romby P, Marzi S. Ribosomal initiation complexes probed by toeprinting and effect of trans-acting translational regulators in bacteria. Methods Mol Biol. 2009;540:247-63 pubmed publisher
    ..Protocols to prepare the ribosome and the subunits are also given for Thermus thermophilus, Staphylococcus aureus, and Escherichia coli. ..
  38. Babitzke P, Baker C, Romeo T. Regulation of translation initiation by RNA binding proteins. Annu Rev Microbiol. 2009;63:27-44 pubmed publisher
    ..Examples also exist in which the bound protein traps the ribosome in a complex that is incapable of initiating translation. ..
  39. Saeys Y, Abeel T, Degroeve S, Van de Peer Y. Translation initiation site prediction on a genomic scale: beauty in simplicity. Bioinformatics. 2007;23:i418-23 pubmed
    ..Detailed analyses show that the model is useful, both on its own and in a simple gene prediction setting. Datafiles and a web interface for the StartScan program are available at ..
  40. Schwab S, Shugart J, Horng T, Malarkannan S, Shastri N. Unanticipated antigens: translation initiation at CUG with leucine. PLoS Biol. 2004;2:e366 pubmed
    ..This initiation mechanism could also be used at non-AUG initiation codons often found in viral transcripts as well as in a growing list of cellular genes. ..
  41. Steiner Mosonyi M, Creuzenet C, Keates R, Strub B, Mangroo D. The Pseudomonas aeruginosa initiation factor IF-2 is responsible for formylation-independent protein initiation in P. aeruginosa. J Biol Chem. 2004;279:52262-9 pubmed publisher
    ..Furthermore these findings give important clues to the basis for discriminating the initiator Met-tRNA by IF-2 and for the evolution of alternative mechanisms for discrimination...
  42. Wang B, Yanez A, Novina C. MicroRNA-repressed mRNAs contain 40S but not 60S components. Proc Natl Acad Sci U S A. 2008;105:5343-8 pubmed publisher
    ..Our results suggest that miRNAs repress translation initiation by preventing 60S subunit joining to miRNA-targeted mRNAs. ..
  43. 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
  44. Belsham G. Divergent picornavirus IRES elements. Virus Res. 2009;139:183-92 pubmed publisher
    ..The selection of the initiation codon by these distinct IRES elements is also discussed. ..
  45. Standart N, Jackson R. MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. Genes Dev. 2007;21:1975-82 pubmed
  46. Sonenberg N, Hinnebusch A. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136:731-45 pubmed publisher
  47. Nakamoto T. A unified view of the initiation of protein synthesis. Biochem Biophys Res Commun. 2006;341:675-8 pubmed
    ..An analysis and a recapitulation of the initiation process and ribosomal specificity are presented. The apparent conflicts with the SD hypothesis are resolved in a unified mechanism where accessibility is the dominant factor. ..
  48. Reigadas S, Pacheco A, Ramajo J, López de Quinto S, Martinez Salas E. Specific interference between two unrelated internal ribosome entry site elements impairs translation efficiency. FEBS Lett. 2005;579:6803-8 pubmed
    ..The interference effect of FMDV IRES was observed in cis and trans, in support of competition for common transacting factors different than those used in cap- and HCV-dependent initiation. ..
  49. Rivas Aravena A, Ramdohr P, Vallejos M, Valiente Echeverría F, Dormoy Raclet V, Rodríguez F, et al. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites. Virology. 2009;392:178-85 pubmed publisher
    ..Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression. ..
  50. Tinton S, Schepens B, Bruynooghe Y, Beyaert R, Cornelis S. Regulation of the cell-cycle-dependent internal ribosome entry site of the PITSLRE protein kinase: roles of Unr (upstream of N-ras) protein and phosphorylated translation initiation factor eIF-2alpha. Biochem J. 2005;385:155-63 pubmed
  51. 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 ..
  52. 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. ..
  53. de Breyne S, Yu Y, Unbehaun A, Pestova T, Hellen C. Direct functional interaction of initiation factor eIF4G with type 1 internal ribosomal entry sites. Proc Natl Acad Sci U S A. 2009;106:9197-202 pubmed publisher
    ..These data suggest that fundamental aspects of the mechanisms of initiation on these unrelated classes of IRESs are similar. ..