Virus Genes

, Volume 12, Issue 2, pp 135–147 | Cite as

A common structural core in the internal ribosome entry sites of picornavirus, hepatitis C virus, and pestivirus

  • Shu-Yun Le
  • Aleem Siddiqui
  • Jacob V. MaizelJr.


Cap-independent translations of viral RNAs of enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, hepatitis A and C viruses (HAV and HCV), and pestivirus are initiated by the direct binding of 40S ribosomal subunits to acis-acting genetic element termed theinternal ribosome entry site (IRES) orribosome landing pad (RLP) in the 5′ noncoding region (5′NCR). RNA higher ordered structure models for these IRES elements were derived by a combined approach using thermodynamic RNA folding, Monte Carlo simulation, and phylogenetic comparative analysis. The structural differences among the three groups of picornaviruses arise not only from point mutations, but also from the addition or deletion of structural domains. However, a common core can be identified in the proposed structural models of these IRES elements from enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, and HAV. The common structural core identified within the picornavirus IRES is also conserved in the 5′NCR of the divergent viruses, HCV, and pestiviruses. Furthermore, the proposed structural motif shares a structural feature similar to that observed in the catalytic core of the group I intron. The conserved structural motif from these divergent sequences that looks like the common core region of group I introns is probably a crucial element involved in the IRES-dependent translation.

Key words

translation control internal ribosome entry site phylogenetic comparative analysis RNA folding and common structure 


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  1. 1.
    PelletierJ. and SonenbergN., Nature334, 320–325, 1988.Google Scholar
  2. 2.
    JangS.K., KrausslichH.-G., NicklinM.J.H., DukeG.M., PalmenbergA.C., and WimmerE., J Virol62, 2636–2643, 1988.Google Scholar
  3. 3.
    WimmerE., HellenC.U.T., and CaoX., Annu Rev Genet27, 353–436, 1993.Google Scholar
  4. 4.
    BandyopadhyayP.K., WangC., and LiptonH.L., J Virol66, 6249–6256, 1992.Google Scholar
  5. 5.
    BormanA. and JacksonR.J., Virology188, 685–696, 1992.Google Scholar
  6. 6.
    NicholsonR., PelletierJ., LeS.-Y., and SonenbergN., J Virol65, 5886–5894, 1991.Google Scholar
  7. 7.
    JangS.K., DaviesM.V., KaufmanR.J., and WimmerE., J Virol63, 1651–1660, 1989.Google Scholar
  8. 8.
    PilipenkoE.V., GmylA.P., MaslovaS.V., SvitkinY.V., SinyakovA.N., and AgolV.I., Cell68, 119–131, 1992.Google Scholar
  9. 9.
    Tsukiyama-KoharaK., IizukaN., KoharaM., and NomotoA., J Virol66, 1476–1483, 1992.Google Scholar
  10. 10.
    WangC., SarnowP., and SiddiquiA., J Virol67, 3338–3344, 1993Google Scholar
  11. 11.
    WangC. and SiddiquiA. in SarnowP. (ed.)Current Topics in Microbiology and Immunology. Springer-Verlag, Berlin, 1995, pp. 99–116.Google Scholar
  12. 12.
    PooleT.L., WangC., PopR.A., PotgieterL.N.D., SiddiquiA., and CollettM.S., Virology206, 750–754, 1995.Google Scholar
  13. 13.
    GebhardJ.R. and EhrenfeldE., J Virol66, 3101–3109, 1992.Google Scholar
  14. 14.
    MeerovitchK., PelletierJ., and SonenbergN., Genes Dev3, 1026–1034, 1989.Google Scholar
  15. 15.
    PestovaT.V., HellenC.U.T., and WimmerE., J Virol65, 6194–6204, 1991.Google Scholar
  16. 16.
    DelAngelR.M., PapavassilouA.G., Fernandez-ThomasC., SilversteinS.J., and RacanielloV.R., Proc Natl Acad Sci USA86, 8299–8303, 1989.Google Scholar
  17. 17.
    HallerA.A., NguyenJ.H., and SemlerB.L., J Virol67, 7461–7471, 1993.Google Scholar
  18. 18.
    BormanA., HowellM.T., PattonJ.G., and JacksonR.J., J Gen Virol74, 1775–1788, 1993.Google Scholar
  19. 19.
    JangS.K. and WimmerE., Genes Dev4, 1560–1572, 1990.Google Scholar
  20. 20.
    LuzN. and BeckE., J Virol65, 6486–6494, 1991.Google Scholar
  21. 21.
    SkinnerM.A., RacanielloV.R., DunnG., CooperJ., MinorP.D., and AlmondJ.W., J Mol Biol207, 379–392, 1989.Google Scholar
  22. 22.
    LeS.-Y., ChenJ.-H., SonenbergN., and MaizelJ.V.Jr, Virology191, 858–866, 1992; Nucleic Acids Res21, 2445–2451, 1993.Google Scholar
  23. 23.
    WangC., SarnowP., and SiddiquiA., J Virol68, 7301–7307, 1994.Google Scholar
  24. 24.
    LeS.-Y., SonenbergN., and MaizelJ.V.Jr., Gene154, 137–143, 1995.Google Scholar
  25. 25.
    PilipenkoE.V., BlinovM., ChernovB.K., DmitrievaT.M., and AgolV.I., Nucleic Acids Res17, 5701–5710, 1989.Google Scholar
  26. 26.
    PilipenkoE.V., BlinovM., RomanovaL.I., SinyakovA.N., MaslovaS.V., and AgolV.I., Virology168, 201–209, 1989.Google Scholar
  27. 27.
    BrownE.A., DayS.P., JansenR.W., and LemonS.M., J Virol65, 5828–5838, 1991.Google Scholar
  28. 28.
    BrownE.A., ZhangH., PingL.-H., and LemonS.M., Nucleic Acids Res20, 5041–5045, 1992.Google Scholar
  29. 29.
    DukeG.M., HoffmanM.A., and PalmenbergA.C., J Virol66, 1602–1609, 1992.Google Scholar
  30. 30.
    WangC., LeS.-Y., AliN., and SiddiquiA., RNA1, 526–537, 1995.Google Scholar
  31. 31.
    DengR. and BrockK.V., Nucleic Acids Res21, 1949–1957, 1993.Google Scholar
  32. 32.
    RiveraV.M., WelshJ.D., and MaizelJ.V.Jr., Virology165, 42–50, 1988.Google Scholar
  33. 33.
    LeS.-Y. and MaizelJ.V.Jr., J Theor Biol216, 729–741, 1989.Google Scholar
  34. 34.
    LeS.-Y., ChenJ.-H., and MaizelJ.V.Jr. in SarmaR.H. and SarmaM.H. (eds).Structure and Methods: Human Genome Initiative and DNA Recombination, Vol. 1. Adenine Press, New York, 1990, pp. 127–136.Google Scholar
  35. 35.
    LeS.-Y. and ZukerM., J Mol Biol216, 729–741, 1990.Google Scholar
  36. 36.
    ChenJ.-H., LeS.-Y., and MaizelJ.V.Jr., Comput Appl Biosci8, 243–248, 1992.Google Scholar
  37. 37.
    FreierS.M., KierzekR., JaegerJ.A., SugimotoN., CaruthersM.H., NeilsonT., and TurnerD.H., Proc Natl Acad Sci USA83, 9373–9377, 1986.Google Scholar
  38. 38.
    CechT.R., Gene73, 259–271, 1988.Google Scholar
  39. 39.
    MichelF. and WesthofE., J Mol Biol216, 585–610, 1990.Google Scholar
  40. 40.
    LeS.-Y., ChenJ.-H., and MaizelJ.V.Jr., Nucleic Acids Res21, 2173–2178, 1993.Google Scholar
  41. 41.
    YanofskyC. and KolterR., Ann Rev Genetics16, 113–134, 1982.Google Scholar
  42. 42.
    JamesB.D., OlsenG.J., LiuJ., and PaceN.R., Cell52, 19–26, 1988.Google Scholar
  43. 43.
    MurphyF.L., WangY.-H., GriffithJ.D., and CechT.D., Science265, 1709–1712, 1994.Google Scholar
  44. 44.
    ReynoldsJ.E., KaminskiA., KettinenH.J., GraceK., ClarkeB.E., CarrolA.R., RowlandsD.J., and JacksonR.J., EMBO J14, 6010–6020, 1995.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Shu-Yun Le
    • 1
  • Aleem Siddiqui
    • 2
    • 3
    • 4
  • Jacob V. MaizelJr.
    • 1
  1. 1.Laboratory of Mathematical Biology, Division of Cancer Biology Diagnosis and Centers, National Cancer InstituteNIHFrederickUSA
  2. 2.Department of MicrobiologyUniversity of Colorado Medical SchoolDenverUSA
  3. 3.Department of Biochemistry, Biophysics and GeneticsUniversity of Colorado Medical SchoolDenverUSA
  4. 4.Program in Molecular BiologyUniversity of Colorado Medical SchoolDenverUSA

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