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40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs

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Chamond, Nathalie, Deforges, Jules, Ulryck, Nathalie, Sargueil, Bruno·2014·Nucleic Acids Research
DOI 10.1093/nar/gku720PMC PMC4176346
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Abstract

Initiation of translation on Type II IRESs, such as those of EMCV and FMDV viruses, has been well documented in the recent years. For EMCV, the current model argues for a mechanism in which the key interaction necessary for the pre-initiation complex recruitment is eIF4G binding to the central J-K domains of EMCV-IRES. Here we demonstrate that, in contrast with the current model, the molecular mechanism of EMCV-IRES involves direct recruitment of the 40S subunit. Importantly, we identified a specific structural element that prevents the correct positioning of the initiation codon in the close vicinity of the ribosomal P site. This work clarifies how this interaction could not be anticipated by earlier studies and allows us to propose a new model for initiation complex assembly on EMCV-IRES. The role attributed to eIF4G/4A can thus be refined as stabilizing/promoting the conformational changes that are necessary for IRES function, thus resembling the role conventionally assigned to ITAFs. This raises the interesting possibility that IRESs are primarily ribosome binders, some of which having partly lost the ability to fold into the active structure without the help of proteins.

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  1. [1]Aitken C.E. Lorsch J.R. A mechanistic overview of translation initiation in eukaryotes Nat. Struct. Mol. Biol. 2012 19 568 576 22664984
  2. [2]Jackson R.J. Hellen C.U. Pestova T.V. The mechanism of eukaryotic translation initiation and principles of its regulation Nat. Rev. Mol. Cell Biol. 2010 11 113 127 20094052 PMC4461372
  3. [3]Jang S.K. Krausslich H.G. Nicklin M.J. Duke G.M. Palmenberg A.C. Wimmer E. A segment of the 5′ nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation J. Virol. 1988 62 2636 2643 2839690 PMC253694
  4. [4]Pelletier J. Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA Nature 1988 334 320 325 2839775
  5. [5]Balvay L. Soto Rifo R. Ricci E.P. Decimo D. Ohlmann T. Structural and functional diversity of viral IRESes Biochim. Biophys. Acta. 2009 1789 542 557 19632368
  6. [6]Semler B.L. Waterman M.L. IRES-mediated pathways to polysomes: nuclear versus cytoplasmic routes Trends Microbiol. 2008 16 1 5 18083033
  7. [7]Pestova T.V. Hellen C.U. Shatsky I.N. Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry Mol. Cell. Biol. 1996 16 6859 6869 8943341 PMC231689
  8. [8]Kaminski A. Jackson R.J. The polypyrimidine tract binding protein (PTB) requirement for internal initiation of translation of cardiovirus RNAs is conditional rather than absolute RNA 1998 4 626 638 9622122 PMC1369645
  9. [9]Kolupaeva V.G. Pestova T.V. Hellen C.U. Shatsky I.N. Translation eukaryotic initiation factor 4G recognizes a specific structural element within the internal ribosome entry site of encephalomyocarditis virus RNA J. Biol. Chem. 1998 273 18599 18604 9660832
  10. [10]Evstafieva A.G. Ugarova T.Y. Chernov B.K. Shatsky I.N. A complex RNA sequence determines the internal initiation of encephalomyocarditis virus RNA translation Nucleic Acids Res. 1991 19 665 671 1849266 PMC333663
  11. [11]Kolupaeva V.G. Lomakin I.B. Pestova T.V. Hellen C.U. Eukaryotic initiation factors 4G and 4A mediate conformational changes downstream of the initiation codon of the encephalomyocarditis virus internal ribosomal entry site Mol. Cell. Biol. 2003 23 687 698 12509466 PMC151537
  12. [12]Lomakin I.B. Hellen C.U. Pestova T.V. Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A strongly enhances binding of eIF4G to the internal ribosomal entry site of encephalomyocarditis virus and is required for internal initiation of translation Mol. Cell. Biol. 2000 20 6019 6029 10913184 PMC86078
  13. [13]Jang S.K. Wimmer E. Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein Genes Dev. 1990 4 1560 1572 2174810
  14. [14]Yu Y. Sweeney T.R. Kafasla P. Jackson R.J. Pestova T.V. Hellen C.U. The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES EMBO J. 2011 30 4423 4436 21873976 PMC3230369
  15. [15]Locker N. Chamond N. Sargueil B. A conserved structure within the HIV gag open reading frame that controls translation initiation directly recruits the 40S subunit and eIF3 Nucleic Acids Res. 2011 39 2367 2377 21071421 PMC3064776
  16. [16]Pisarev A.V. Unbehaun A. Hellen C.U. Pestova T.V. Assembly and analysis of eukaryotic translation initiation complexes Methods Enzymol. 2007 430 147 177 17913638
  17. [17]Ali I.K. McKendrick L. Morley S.J. Jackson R.J. Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation EMBO J. 2001 20 4233 4242 11483526 PMC149147
  18. [18]Kieft J.S. Zhou K. Jubin R. Doudna J.A. Mechanism of ribosome recruitment by hepatitis C IRES RNA RNA 2001 7 194 206 11233977 PMC1370078
  19. [19]Mortimer S.A. Weeks K.M. A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry J. Am. Chem. Soc. 2007 129 4144 4145 17367143
  20. [20]Mortimer S.A. Weeks K.M. Time-resolved RNA SHAPE chemistry: quantitative RNA structure analysis in one-second snapshots and at single-nucleotide resolution Nat. Protoc. 2009 4 1413 1421 19745823 PMC4950915
  21. [21]Darty K. Denise A. Ponty Y. VARNA: Interactive drawing and editing of the RNA secondary structure Bioinformatics 2009 25 1974 1975 19398448 PMC2712331
  22. [23]Kafasla P. Morgner N. Poyry T.A. Curry S. Robinson C.V. Jackson R.J. Polypyrimidine tract binding protein stabilizes the encephalomyocarditis virus IRES structure via binding multiple sites in a unique orientation Mol. Cell 2009 34 556 568 19524536
  23. [24]Kolupaeva V.G. Hellen C.U. Shatsky I.N. Structural analysis of the interaction of the pyrimidine tract-binding protein with the internal ribosomal entry site of encephalomyocarditis virus and foot-and-mouth disease virus RNAs RNA 1996 2 1199 1212 8972770 PMC1369448
  24. [25]McGinnis J.L. Dunkle J.A. Cate J.H. Weeks K.M. The mechanisms of RNA SHAPE chemistry J. Am. Chem. Soc. 2012 134 6617 6624 22475022 PMC4337229
  25. [26]Pilipenko E.V. Blinov V.M. Chernov B.K. Dmitrieva T.M. Agol V.I. Conservation of the secondary structure elements of the 5′-untranslated region of cardio- and aphthovirus RNAs Nucleic Acids Res. 1989 17 5701 5711 2548167 PMC318190
  26. [27]Hoffman M.A. Palmenberg A.C. Revertant analysis of J-K mutations in the encephalomyocarditis virus internal ribosomal entry site detects an altered leader protein J Virol. 1996 70 6425 6430 8709275 PMC190673
  27. [28]Gould P.S. Bird H. Easton A.J. Translation toeprinting assays using fluorescently labeled primers and capillary electrophoresis Biotechniques 2005 38 397 400 15786806
  28. [29]Shirokikh N.E. Alkalaeva E.Z. Vassilenko K.S. Afonina Z.A. Alekhina O.M. Kisselev L.L. Spirin A.S. Quantitative analysis of ribosome-mRNA complexes at different translation stages Nucleic Acids Res. 2009 38 e15 19910372 PMC2817456
  29. [30]Pestova T.V. Shatsky I.N. Fletcher S.P. Jackson R.J. Hellen C.U. A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs Genes Dev. 1998 12 67 83 9420332 PMC316404
  30. [31]Wilson J.E. Pestova T.V. Hellen C.U. Sarnow P. Initiation of protein synthesis from the A site of the ribosome Cell 2000 102 511 520 10966112
  31. [32]Pestova T.V. Shatsky I.N. Hellen C.U. Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes Mol. Cell. Biol. 1996 16 6870 6878 8943342 PMC231690
  32. [33]Yu Y. Abaeva I.S. Marintchev A. Pestova T.V. Hellen C.U. Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors Nucleic Acids Res. 2011 39 4851 4865 21306989 PMC3113573
  33. [34]Shih D.S. Park I.W. Evans C.L. Jaynes J.M. Palmenberg A.C. Effects of cDNA hybridization on translation of encephalomyocarditis virus RNA J. Virol. 1987 61 2033 2037 3033330 PMC254214
  34. [35]Spahn C.M. Jan E. Mulder A. Grassucci R.A. Sarnow P. Frank J. Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: the IRES functions as an RNA-based translation factor Cell 2004 118 465 475 15315759
  35. [36]Filbin M.E. Vollmar B.S. Shi D. Gonen T. Kieft J.S. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation Nat. Struct. Mol. Biol. 2013 20 150 158 23262488 PMC3864654
  36. [37]Abaeva I.S. Marintchev A. Pisareva V.P. Hellen C.U. Pestova T.V. Bypassing of stems versus linear base-by-base inspection of mammalian mRNAs during ribosomal scanning EMBO J. 2011 30 115 129 21113134 PMC3020121
  37. [38]Kafasla P. Lin H. Curry S. Jackson R.J. Activation of picornaviral IRESs by PTB shows differential dependence on each PTB RNA-binding domain RNA 2011 17 1120 1131 21518806 PMC3096044
  38. [39]Hellen C.U. Witherell G.W. Schmid M. Shin S.H. Pestova T.V. Gil A. Wimmer E. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein Proc. Natl Acad. Sci. U.S.A. 1993 90 7642 7646 8395052 PMC47198
  39. [40]Pilipenko E.V. Pestova T.V. Kolupaeva V.G. Khitrina E.V. Poperechnaya A.N. Agol V.I. Hellen C.U. A cell cycle-dependent protein serves as a template-specific translation initiation factor Genes Dev. 2000 14 2028 2045 10950867 PMC316860
  40. [41]Cech T.R. Crawling out of the RNA world Cell 2009 136 599 602 19239881
  41. [42]Lehman N. RNA in evolution Wiley Interdiscip. Rev. RNA 2010 1 202 213 21935885
  42. [43]Malygin A.A. Kossinova O.A. Shatsky I.N. Karpova G.G. HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation Nucleic Acids Res. 2013 41 8706 8714 23873958 PMC3794592

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Authors
Chamond, N., Deforges, J., Ulryck, N., & Sargueil, B.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Sargueil, Bruno
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2014-08-26
Volume
42
Issue
16
Pages
10373-10384
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gku720
PMC
PMC4176346
OpenAlex
W2123186931
Cited by
53
References
1
Citations by year
2026: 7 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 1
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Styrelsen för Internationellt Utvecklingssamarbete
  • Agence Nationale de la Recherche
  • Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
EMCV IRES, eIF4G, eIF4A, translation initiation, ribosomal P site, viral protein synthesis
MeSH terms
Encephalomyocarditis virus, Models, Genetic, Nucleic Acid Conformation, Peptide Chain Initiation, Translational, RNA, Viral, Open Reading Frames, 5' Untranslated Regions, Eukaryotic Initiation Factor-4A, Eukaryotic Initiation Factor-4G, Ribosome Subunits, Small, Eukaryotic

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