Evolution of Translational Initiation: From Archaea to Eukarya

  • Dario Benelli
  • Anna La Teana
  • Paola LondeiEmail author


Because of its obvious importance for cell survival, translation is perhaps the most conserved of cellular mechanisms in evolution.


Translation Initiation Ribosomal Subunit Large Ribosomal Subunit Small Ribosomal Subunit Initiator tRNA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Arkhipova V, Stolboushkina E, Kravchenko O, Kljashtorny V, Gabdulkhakov A, Garber M, Nikonov S, Märtens B, Bläsi U, Nikonov O. Binding of the 5′-Triphosphate end of mRNA to the γ-subunit of translation initiation factor 2 of the Crenarchaeon Sulfolobus solfataricus. J Mol Biol. 2015 Sep 25;427(19):3086–95.Google Scholar
  2. 2.
    Barthelme D, Dinkelaker S, Albers SV, Londei P, Ermler U, Tampé R. Ribosome recycling depends on a mechanistic link between the FeS cluster domain and a conformational switch of the twin-ATPase ABCE1. Proc Natl Acad Sci USA. 2011 Feb 22;108(8):3228–33.Google Scholar
  3. 3.
    Benelli D, Londei P. Translation initiation in Archaea: conserved and domain-specific features. Biochem Soc Trans. 2011;39(1):89–93.CrossRefPubMedGoogle Scholar
  4. 4.
    Benelli D, Maone E, Londei P. Two different mechanisms for ribosome/mRNA interaction in archaeal translation initiation. Mol Microbiol. 2003;50:635–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Benelli D, Marzi S, Mancone C, Alonzi T, La Teana A, Londei P. Function and ribosomal localization of aIF6, a translational regulator shared by archaea and eukarya. Nucleic Acids Res. 2009 Jan;37(1):256–67.Google Scholar
  6. 6.
    Boelens R, Gualerzi CO. Structure and function of bacterial initiation factors. Curr Protein Pept Sci. 2002 Feb;3(1):107–19.Google Scholar
  7. 7.
    Carter AP, Clemons WM Jr, Brodersen DE, Morgan-Warren RJ, Hartsch T, Wimberly BT, Ramakrishnan V. Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science. 2001;291:498–501.CrossRefPubMedGoogle Scholar
  8. 8.
    Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhauser N, Marchisio PC, Biffo S. Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature. 2003;426:579–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Chaudhuri J, Si K, Maitra U. Function of eukaryotic translation initiation factor 1A (eIF1A) in initiation of protein synthesis. J Biol Chem. 1997;272:7883–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Choi SK, Lee JH, Zoll WL, Merrick WC, Dever TE. Promotion of met-tRNAi Met binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast. Science. 1998;280:1757–60.CrossRefPubMedGoogle Scholar
  11. 11.
    Condò I, Ciammaruconi A, Benelli D, Ruggero D, Londei P. Cis-acting signals controlling translational initiation in the thermophilic archaeon Sulfolobus solfataricus. Mol Microbiol. 1999;19:5233–40.Google Scholar
  12. 12.
    De Marco N, Iannone L, Carotenuto R, Biffo S, Vitale A, Campanella C. p27(BBP)/eIF6 acts as an anti-apoptotic factor upstream of Bcl-2 during Xenopus laevis development. Cell Death Differ. 2010 Feb;17(2):360–72.Google Scholar
  13. 13.
    De Marco N, Tussellino M, Vitale A, Campanella C. Eukaryotic initiation factor 6 (eif6) overexpression affects eye development in Xenopus laevis. DifferentiationSep. 2011;82(2):108–15.CrossRefGoogle Scholar
  14. 14.
    Dev K, Santangelo TJ, Rothenburg S, Neculai D, Dey M, Sicheri F, Dever TE, Reeve JN, Hinnebusch AG. Archaeal aIF2B interacts with eukaryotic translation initiation factors eIF2alpha and eIF2Balpha: implications for aIF2B function and eIF2B regulation. J Mol Biol. 2009 Sep 25;392(3):701–22.Google Scholar
  15. 15.
    Donnelly N, Gorman AM, Gupta S, Samali A. The eIF2α kinases: their structures and functions. Cell Mol Life Sci. 2013 Oct;70(19):3493–511.Google Scholar
  16. 16.
    Gandin V, Miluzio A, Barbieri AM, Beugnet A, Kiyokawa H, Marchisio PC, Biffo S. Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation. Nature. 2008;455:684–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Giliberti J, O’Donnell S, Etten WJ, Janssen GR. A 5′-terminal phosphate is required for stable ternary complex formation and translation of leaderless mRNA in Escherichia coli. RNA. 2012 Mar;18(3):508–18.Google Scholar
  18. 18.
    Greber BJ, Boehringer D, Godinic-Mikulcic V, Crnkovic A, Ibba M, Weygand-Durasevic I, Ban N. Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolution. J Mol Biol. 2012 May 4;418(3–4):145–60.Google Scholar
  19. 19.
    Grill S, Gualerzi CO, Londei P, Bläsi U. Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation. EMBO J. 2000 Aug 1;19(15):4101–10.Google Scholar
  20. 20.
    Groft CM, Beckmann R, Sali A, Burley SK. Crystal structures of ribosome anti-association factor IF6. Nat Struct Biol. 2000 Dec;7(12):1156–64.Google Scholar
  21. 21.
    Gualerzi CO, Pon CL. Initiation of mRNA translation in prokaryotes. Biochemistry. 1990 Jun 26;29(25):5881–9.Google Scholar
  22. 22.
    Guenneugues M, Caserta E, Brandi L, Spurio R, Meunier S, Pon CL, Boelens R, Gualerzi CO. Mapping the fMet-tRNA f-met binding site of initiation factor IF2. EMBO J. 2000.Google Scholar
  23. 23.
    Guillon L, Schmitt E, Blanquet S, Mechulam Y. Initiator tRNA binding by e/aIF5B, the eukaryotic/archaeal homologue of bacterial initiation factor IF2. Biochemistry. 2005 Nov 29;44(47):15594–601.Google Scholar
  24. 24.
    Hasenöhrl D, Lombo T, Kaberdin V, Londei P, Bläsi U. Translation initiation factor a/eIF2(-gamma) counteracts 5′ to 3′ mRNA decay in the archaeon Sulfolobus solfataricus. Proc Natl Acad Sci USA. 2008 Feb 12;105(6):2146–50.Google Scholar
  25. 25.
    Hinnebusch AG. The scanning mechanism of eukaryotic translation initiation. Annu Rev Biochem. 2014;83:779–812.CrossRefPubMedGoogle Scholar
  26. 26.
    Hinnebusch AG, Lorsch JR. The mechanism of eukaryotic translation initiation: new insights and challenges. Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10).Google Scholar
  27. 27.
    Klinge S, Voigts-Hoffmann F, Leibundgut M, Arpagaus S, Ban N. Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6. Science. 2011 Nov 18;334(6058):941–8.Google Scholar
  28. 28.
    Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–41.Google Scholar
  29. 29.
    Kramer P, Gäbel K, Pfeiffer F, Soppa J. Haloferax volcanii, a prokaryotic species that does not use the Shine Dalgarno mechanism for translation initiation at 5′-UTRs. PLoS One. 2014 Apr 14;9(4):e94979. doi: 10.1371/journal.pone.0094979.Google Scholar
  30. 30.
    Le Quesne JP, Spriggs KA, Bushell M, Willis AE. Dysregulation of protein synthesis and disease. J Pathol. 2010 Jan;220(2):140–51.Google Scholar
  31. 31.
    Londei P. Evolution of translational initiation: new insights from the archaea. FEMS Microbiol Rev. 2005 Apr;29(2):185–200.Google Scholar
  32. 32.
    Maone E, Di Stefano M, Berardi A, Benelli D, Marzi S, La Teana A, Londei P. Functional analysis of the translation factor aIF2/5B in the thermophilic archaeon Sulfolobus solfataricus. Mol Microbiol. 2007 Aug;65(3):700–13.Google Scholar
  33. 33.
    Märtens B, Manoharadas S, Hasenöhrl D, Zeichen L, Bläsi U. Back to translation: removal of aIF2 from the 5′-end of mRNAs by translation recovery factor in the crenarchaeon Sulfolobus solfataricus. Nucleic Acids Res. 2014 Feb;42(4):2505–11.Google Scholar
  34. 34.
    Moll I, Hirokawa G, Kiel MC, Kaji A, Blasi U. Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs. Nucleic Acids Res. 2004;32:3354–63.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Pedullà N, Palermo R, Hasenöhrl D, Bläsi U, Cammarano P, Londei P. The archaeal eIF2 homologue: functional properties of an ancient translation initiation factor. Nucleic Acids Res. 2005 Mar 23;33(6):1804–12.Google Scholar
  36. 36.
    Pestova TV, Lomakin IB, Lee JH, Choi SK, Dever TE, Hellen CU. The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature. 2000;403:332–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Pinzaglia M, Montaldo C, Polinari D, Simone M, La Teana A, Tripodi M, Mancone C, Londei P, Benelli D. EIF6 over-expression increases the motility and invasiveness of cancer cells by modulating the expression of a critical subset of membrane-bound proteins. BMC Cancer. 2015 Mar 15;15:131.Google Scholar
  38. 38.
    Roll-Mecak A, Cao C, Dever TE, Burley SK. X-ray structures of the universal translation initiation factor IF2/eIF5B: conformational changes on GDP and GTP binding. Cell. 2000 Nov 22;103(5):781–92.Google Scholar
  39. 39.
    Ruggero D. Translational control in cancer etiology. Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2).Google Scholar
  40. 40.
    Sartorius-Neef S, Pfeifer F. In vivo studies on putative Shine-Dalgarno sequences of the halophilic archaeon Halobacterium salinarum. Mol Microbiol. 2004 Jan;51(2):579–88.Google Scholar
  41. 41.
    Schmitt E, Blanquet S, Mechulam Y. The large subunit of initiation factor aIF2 is a close structural homologue of elongation factor Tu. EMBO J. 2002;21:1821–32.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Schmitt E, Naveau M, Mechulam Y. Eukaryotic and archaeal translation initiation factor 2: a heterotrimeric tRNA carrier. FEBS Lett. 2010 Jan 21;584(2):405–12.Google Scholar
  43. 43.
    Shi Z, Barna M. Translating the genome in time and space: specialized ribosomes, RNA regulons, and RNA-binding proteins. Annu Rev Cell Dev Biol. 2015;31:31–54.Google Scholar
  44. 44.
    Si K, Maitra U. The Saccharomyces cerevisiae homologue of mammalian translation initiation factor 6 does not function as a translation initiation factor. Mol Cell Biol. 1999;19:1416–26.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Siddiqui N, Sonenberg N. Signalling to eIF4E in cancer. Biochem Soc Trans. 2015 Oct;43(5):763–72.Google Scholar
  46. 46.
    Slupska MM, King AG, Fitz-Gibbon S, Besemer J, Borodovsky M, Miller JH. Leaderless transcripts of the crenarchaeal hyperthermophile Pyrobaculum aerophilum. J Mol Biol. 2001 Jun 1;309(2):347–60.Google Scholar
  47. 47.
    Spriggs KA, Bushell M, Willis AE. Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010 Oct 22;40(2):228–37.Google Scholar
  48. 48.
    Stolboushkina E, Nikonov S, Nikulin A, Bläsi U, Manstein DJ, Fedorov R, Garber M, Nikonov O. Crystal structure of the intact archaeal translation initiation factor 2 demonstrates very high conformational flexibility in the alpha- and beta-subunits. J Mol Biol. 2008 Oct 10;382(3):680–91.Google Scholar
  49. 49.
    Stumpf CR, Ruggero D. The cancerous translation apparatus. Curr Opin Genet Dev. 2011 Aug;21(4):474–83.Google Scholar
  50. 50.
    Tahara M, Ohsawa A, Saito S, Kimura M. In vitro phosphorylation of initiation factor 2 alpha (aIF2 alpha) from hyperthermophilic archaeon Pyrococcus horikoshii OT3. J Biochem (Tokyo). 2004;135:479–85.CrossRefGoogle Scholar
  51. 51.
    Tolstrup N, Sensen CW, Garrett RA, Clausen IG. Two different and highly organized mechanisms of translation initiation in the archaeon Sulfolobus solfataricus. Extremophiles. 2000 Jun;4(3):175–9.Google Scholar
  52. 52.
    Valenzuela DM, Chaudhuri A, Maitra U. Eukaryotic ribosomal subunit anti-association activity of calf liver is contained in a single polypeptide chain protein of Mr = 25,500 (eukaryotic initiation factor 6). J Biol Chem. 1982;257:7712–9.PubMedGoogle Scholar
  53. 53.
    Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, Traynor D, Kay RR, Warren AJ. Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol. 2015 Nov;22(11):914–9.Google Scholar
  54. 54.
    Xue S, Barna M. Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat Rev Mol Cell Biol. 2012 May 23;13(6):355–69.Google Scholar
  55. 55.
    Yatime L, Mechulam Y, Blanquet S, Schmitt E. Structural switch of the gamma subunit in an archaeal aIF2 alpha gamma heterodimer. Structure. 2006 Jan;14(1):119–28.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Istituto Pasteur-Fondazione Cenci- Bolognetti and Dpt. Biotecnologie Cellulari ed Ematologia, Policlinico Umberto IUniversity of Rome SapienzaRomeItaly
  2. 2.Dpt. Scienze Della Vita e dell’AmbienteUniversità Politecnica delle MarcheAnconaItaly

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