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RNA. Oct 1999; 5(10): 1374–1383.
PMCID: PMC1369859

Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES).


Internal initiation of translation is promoted by internal ribosome entry site (IRES) cis-acting elements. Using transcripts that correspond to the structural domains of the foot-and-mouth disease virus (FMDV) IRES, we have identified RNA-RNA interactions between separated domains (1-2, 3, 4-5, or HH) of the IRES structure. All the assayed domains were able to interact with the full-length IRES as well as with domain 3, although to a different extent, with the most efficient interactions being those occurring between domains 3 and 4-5, and domains 3 and 1-2. RNA-RNA complexes were stable over 1 h of incubation at 37 degrees C, and depended on Mg2+ and RNA concentration. Neither the antisense domain 1-2 nor tRNA interacted with domain 3, providing experimental evidence of the specificity for the sense strand of the IRES sequence. Additionally, domain 1-2 did not interact with 4-5, leading to the suggestion that domain 3 acts as a scaffold structure where the other domains bind. The thermal disassociation profile of these complexes indicated different strength in these interactions. Whereas 50% of the complexes between domains 3 and 4-5 were destabilized at 45 degrees C, those formed by domain 1-2 and 3 required temperatures higher than 51 degrees C. Efficient self-dimerization of domains 3 and 4-5 was found in the absence of other transcripts. Formation of domain 3 homodimer competed with formation of heterocomplexes with other domains, and conversely, domain 3 homodimers were competed out by the presence of the other domains. RNA interactions were also observed at physiological concentrations of Mg2+ and K1+. The identification of the RNA-RNA complexes reported here provide direct experimental evidence of tertiary interactions within IRES elements.

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Selected References

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  • Bolten R, Egger D, Gosert R, Schaub G, Landmann L, Bienz K. Intracellular localization of poliovirus plus- and minus-strand RNA visualized by strand-specific fluorescent In situ hybridization. J Virol. 1998 Nov;72(11):8578–8585. [PMC free article] [PubMed]
  • Carrasco L. Modification of membrane permeability by animal viruses. Adv Virus Res. 1995;45:61–112. [PubMed]
  • Cate JH, Gooding AR, Podell E, Zhou K, Golden BL, Szewczak AA, Kundrot CE, Cech TR, Doudna JA. RNA tertiary structure mediation by adenosine platforms. Science. 1996 Sep 20;273(5282):1696–1699. [PubMed]
  • Conn GL, Draper DE. RNA structure. Curr Opin Struct Biol. 1998 Jun;8(3):278–285. [PubMed]
  • Costa M, Michel F. Frequent use of the same tertiary motif by self-folding RNAs. EMBO J. 1995 Mar 15;14(6):1276–1285. [PMC free article] [PubMed]
  • Costa M, Michel F. Rules for RNA recognition of GNRA tetraloops deduced by in vitro selection: comparison with in vivo evolution. EMBO J. 1997 Jun 2;16(11):3289–3302. [PMC free article] [PubMed]
  • Drew J, Belsham GJ. trans complementation by RNA of defective foot-and-mouth disease virus internal ribosome entry site elements. J Virol. 1994 Feb;68(2):697–703. [PMC free article] [PubMed]
  • Egberts E, Hackett PB, Traub P. Alteration of the intracellular energetic and ionic conditions by mengovirus infection of Ehrlich ascites tumor cells and its influence on protein synthesis in the midphase of infection. J Virol. 1977 Jun;22(3):591–597. [PMC free article] [PubMed]
  • Ferrandon D, Koch I, Westhof E, Nüsslein-Volhard C. RNA-RNA interaction is required for the formation of specific bicoid mRNA 3' UTR-STAUFEN ribonucleoprotein particles. EMBO J. 1997 Apr 1;16(7):1751–1758. [PMC free article] [PubMed]
  • Hellen CU, Wimmer E. Translation of encephalomyocarditis virus RNA by internal ribosomal entry. Curr Top Microbiol Immunol. 1995;203:31–63. [PubMed]
  • Jackson RJ, Kaminski A. Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond. RNA. 1995 Dec;1(10):985–1000. [PMC free article] [PubMed]
  • Jaeger L, Michel F, Westhof E. Involvement of a GNRA tetraloop in long-range RNA tertiary interactions. J Mol Biol. 1994 Mar 11;236(5):1271–1276. [PubMed]
  • Kaminski A, Jackson RJ. The polypyrimidine tract binding protein (PTB) requirement for internal initiation of translation of cardiovirus RNAs is conditional rather than absolute. RNA. 1998 Jun;4(6):626–638. [PMC free article] [PubMed]
  • Kolupaeva VG, Pestova TV, Hellen CU, Shatsky IN. Translation eukaryotic initiation factor 4G recognizes a specific structural element within the internal ribosome entry site of encephalomyocarditis virus RNA. J Biol Chem. 1998 Jul 17;273(29):18599–18604. [PubMed]
  • Kolupaeva VG, Hellen CU, Shatsky IN. 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 Dec;2(12):1199–1212. [PMC free article] [PubMed]
  • Le SY, Siddiqui A, Maizel JV., Jr A common structural core in the internal ribosome entry sites of picornavirus, hepatitis C virus, and pestivirus. Virus Genes. 1996;12(2):135–147. [PubMed]
  • López de Quinto S, Martínez-Salas E. Conserved structural motifs located in distal loops of aphthovirus internal ribosome entry site domain 3 are required for internal initiation of translation. J Virol. 1997 May;71(5):4171–4175. [PMC free article] [PubMed]
  • Malmgren C, Wagner EG, Ehresmann C, Ehresmann B, Romby P. Antisense RNA control of plasmid R1 replication. The dominant product of the antisense rna-mrna binding is not a full RNA duplex. J Biol Chem. 1997 May 9;272(19):12508–12512. [PubMed]
  • Marquet R, Baudin F, Gabus C, Darlix JL, Mougel M, Ehresmann C, Ehresmann B. Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism. Nucleic Acids Res. 1991 May 11;19(9):2349–2357. [PMC free article] [PubMed]
  • Martínez-Salas E, Regalado MP, Domingo E. Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution. J Virol. 1996 Feb;70(2):992–998. [PMC free article] [PubMed]
  • Martínez-Salas E, Sáiz JC, Dávila M, Belsham GJ, Domingo E. A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo. J Virol. 1993 Jul;67(7):3748–3755. [PMC free article] [PubMed]
  • Meyer K, Petersen A, Niepmann M, Beck E. Interaction of eukaryotic initiation factor eIF-4B with a picornavirus internal translation initiation site. J Virol. 1995 May;69(5):2819–2824. [PMC free article] [PubMed]
  • Michel F, Westhof E. Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. J Mol Biol. 1990 Dec 5;216(3):585–610. [PubMed]
  • Niepmann M, Petersen A, Meyer K, Beck E. Functional involvement of polypyrimidine tract-binding protein in translation initiation complexes with the internal ribosome entry site of foot-and-mouth disease virus. J Virol. 1997 Nov;71(11):8330–8339. [PMC free article] [PubMed]
  • Novak JE, Kirkegaard K. Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells. J Virol. 1991 Jun;65(6):3384–3387. [PMC free article] [PubMed]
  • Paillart JC, Skripkin E, Ehresmann B, Ehresmann C, Marquet R. A loop-loop "kissing" complex is the essential part of the dimer linkage of genomic HIV-1 RNA. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5572–5577. [PMC free article] [PubMed]
  • Pilipenko EV, Blinov VM, Romanova LI, Sinyakov AN, Maslova SV, Agol VI. Conserved structural domains in the 5'-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology. 1989 Feb;168(2):201–209. [PubMed]
  • Roberts LO, Belsham GJ. Complementation of defective picornavirus internal ribosome entry site (IRES) elements by the coexpression of fragments of the IRES. Virology. 1997 Jan 6;227(1):53–62. [PubMed]
  • Wang C, Le SY, Ali N, Siddiqui A. An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5' noncoding region. RNA. 1995 Jul;1(5):526–537. [PMC free article] [PubMed]
  • Weeks KM. Protein-facilitated RNA folding. Curr Opin Struct Biol. 1997 Jun;7(3):336–342. [PubMed]

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