The Role of RNA-Binding Proteins in IRES-Dependent Translation

  • Sung Key Jang
  • Eckard Wimmer
Part of the Endocrine Updates book series (ENDO, volume 16)


Picornaviridae are a large family of human and animal RNA viruses whose best known members are poliovirus (PV) belonging to genus Enterovirus, human rhinovirus (HRV) of Rhinovirus, encephalomyocarditis virus (EMCV) of Cardiovirus, hepatitis A virus (HA V) of Hepatovirus, and foot-and-mouth disease virus (FMDV) of Aphthovirus. It has been estimated that the incidence of human infections by picornaviruses exceeds 6 billion per year. Fortunately, the vast majority of these infections are self limiting, with no serious sequelae. However, the diseases range from the very serious (poliomyelitis, meningitis, heart disease, hepatitis) to the benign (common cold) and together, they cause enormous hardship in the human population. The genome of picornaviruses is single stranded and of plus strand polarity. That is, it functions as mRNA after the virus has entered the host cell. Molecular biologic studies of these viruses have revealed numerous important mechanisms, including the internal ribosomal entry site (IRES) (1,2). The description of picornaviral IRES elements broke the dogma that all eukaryotic translation begins with a mechanism of cap-dependent ribosome “scanning” from the 5’ end of mRNA. This chapter will discuss the role of RNA binding proteins in IRES-dependent translation of picornaviruses. The existence of viral IRESs has led to the discovery of IRES elements in numerous cellular mRNAs. These concepts regarding IRESs have revolutionized the general perception of the control of gene expression by translation in eukaryotic cells.


Internal Ribosomal Entry Site Classical Swine Fever Virus Internal Ribosomal Entry Site Element Internal Initiation Internal Ribosomal Entry Site Activity 
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  1. 1.
    Jang, S. K., Krausslich, H. G., Nicklin, M. J., Duke, G. M., Palmenberg, A. C., and Wimmer, E. (1988). A segment of the 5’ nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol 62, 2636–43.PubMedGoogle Scholar
  2. 2.
    Pelletier, J., and Sonenberg, N. (1988). Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334, 320–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Tsukiyama-Kohara, K., Iizuka, N., Kohara, M., and Nomoto, A. (1992). Internal ribosome entry site within hepatitis C virus RNA. J Virol 66, 1476–83.PubMedGoogle Scholar
  4. 4.
    Poole, T. L., C. Wang, R. A. Popp, L. N. Potgieter, A. Siddiqui, and M. S. Collett. (1995). Pestivirus translation initiation occurs by internal ribosome entry. Virology. 206, 750–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Sasaki, J., and Nakashima, N. (1999). Translation initiation at the CUU codon is mediated by the internal ribosome entry site of an insect picorna-like virus in vitro. J Virol 73, 1219–26.PubMedGoogle Scholar
  6. 6.
    Wilson, J. E., Powell, M. J., Hoover, S. E., and Sarnow, P. (2000b). Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites. Mol Cell Bio120, 4990–9.Google Scholar
  7. 7.
    Molla, A., Jang, S. K., Paul, A. V., Reuer, Q., and Wimmer, E. (1992). Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus. Nature 356, 255–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Sasaki, J., and Nakashima, N. 2000. Methionine-independent initiation of translation in the capsid protein of an insect virus. Proc. Natl Acad. Sci. USA 97, 1512–1515.PubMedCrossRefGoogle Scholar
  9. 9.
    Wilson, J. E., Pestova, T. V., Hellen, C. U., and Sarnow, P. (2000a). Initiation of protein synthesis from the A site of the ribosome. Cell 102, 511–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Muthukrishnan, S., Both, G. W., Furuichi, Y., and Shatkin, A. J. (1975). 5’-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Nature 255, 33–7.Google Scholar
  11. 11.
    Furuichi, Y., and Shatkin, A. J. (2000). Viral and cellular mRNA capping: past and prospects. Adv Virus Res 55, 135–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Gale, M., Tan, S-L., and Katze, M.G. 2000. Translational control of viral gene expression in eukaryotes. Microb. Mol. Biol. Rev. 64, 239–280.CrossRefGoogle Scholar
  13. 13.
    Kozak, M. (1986). Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44, 283–92.PubMedCrossRefGoogle Scholar
  14. 14.
    Sachs, A. B., and Buratowski, S. (1997). Common themes in translational and transcriptional regulation. Trends Biochem Sci 22, 189–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Pelham, H. R. B., and Jackson, R. J. 1976. An efficient mRNA-dependent translation system from rabbit reticulocyte lysates. Eur. J. Biochem. 67, 247–256Google Scholar
  16. 16.
    Wimmer, E., and Reichmann, M. E. (1968). Pyrophosphate in the 5’ terminal position of a viral ribonucleic acid. Science 160, 1452–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Nomoto, A., Kitamura, N., Golini, F., and Wimmer, E. 1977. The 5’-terminal structures of poliovirion RNA and poliovirus mRNA differ only in the genome-linked protein. Proc. Natl. Acad. Sci. USA 74, 5345–5349.PubMedCrossRefGoogle Scholar
  18. 18.
    Semler, B. L., Anderson, C. W., Hanecak, R., Dorner, L. F., and Wimmer, E. (1982). A membrane-associated precursor to poliovirus VPg identified by immunoprecipitation with antibodies directed against a synthetic heptapeptide. Cell 28, 405–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Wimmer, E. 1982. Genome-linked proteins of viruses. Cell 28, 199–201.PubMedCrossRefGoogle Scholar
  20. 20.
    Pilipenko, E. V., Blinov, V. M., Chernov, B. K., Dmitrieva, T. M., and Agol, V. I. (1989a). Conservation of the secondary structure elements of the 5’-untranslated region of cardio-and aphthovirus RNAs. Nucleic Acids Res 1 7, 5701–11.CrossRefGoogle Scholar
  21. 21.
    Pilipenko, E. V., Blinov, V. M., Romanova, L. I., Sinyakov, A. N., Maslova, S. V., and Agol, V. I. (1989b). Conserved structural domains in the 5’-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology 168, 201–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Jang, S. K., and Wimmer, E. (1990). 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 4, 1560–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Wimmer, E., Hellen, C. U., and Cao, X. (1993). Genetics of poliovirus. Annu Rev Genet 27, 353–436.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen, C. Y., and Sarnow, P. (1995). Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268, 415–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Etchison, D., Milburn, S. C., Edery, I., Sonenberg, N., and Hershey, J. W. (1982). Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J Biol Chem 257, 14806–10.PubMedGoogle Scholar
  26. 26.
    Bernstein, H. D., Sonenberg, N., and Baltimore, D. (1985). Poliovirus mutant that does not selectively inhibit host cell protein synthesis. Mol Cell Biol 5, 2913–23.PubMedGoogle Scholar
  27. 27.
    Krausslich, H. G., Nicklin, M. J., Toyoda, H., Etchison, D., and Wimmer, E. (1987). Poliovirus proteinase 2A induces cleavage of eucaryotic initiation factor 4F polypeptide p220. J Virol 61, 2711–8.PubMedGoogle Scholar
  28. 28.
    Lamphear, B. J., Yan, R., Yang, F., Waters, D., Liebig, H. D., Klump, H., Kuechler, E., Skern, T., and Rhoads, R. E. (1993). Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. J Biol Chem 268, 19200–3.PubMedGoogle Scholar
  29. 29.
    Devaney, M. A., Vakharia, V. N., Lloyd, R. E., Ehrenfeld, E., and Grubman, M. J. (1988). Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. J Virol 62, 4407–9.PubMedGoogle Scholar
  30. 30.
    Gingras, A. C., Svitkin, Y., Belsham, G. J., Pause, A., and Sonenberg, N. (1996). Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus. Proc Natl Acad Sci U S A 93, 5578–83.PubMedCrossRefGoogle Scholar
  31. 31.
    Sarnow, P. (1989). Translation of glucose-regulated protein 78/immunoglobulin heavy-chain binding protein mRNA is increased in poliovirus-infected cells at a time when cap-dependent translation of cellular mRNAs is inhibited. Proc Natl Acad Sci U S A 86, 5795–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Macejak, D. G., and Sarnow, P. (1991). Internal initiation of translation mediated by the 5’ leader of a cellular mRNA [see comments]. Nature 353, 90–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Gingras, A. C., Raught, B., and Sonenberg, N. (1999). eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 68, 913–63.Google Scholar
  34. 34.
    Witherell, G. W., Gil, A., and Wimmer, E. (1993). Interaction of polypyrimidine tract binding protein with the encephalomyocarditis virus mRNA internal ribosomal entry site. Biochemistry 32, 8268–75.PubMedCrossRefGoogle Scholar
  35. 35.
    Alexander, L., Lu, H. H., and Wimmer, E. (1994). Polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal entry site elements: genetic hybrids and the expression of a foreign gene. Proc Natl Acad Sci U S A 91, 1406–10.PubMedCrossRefGoogle Scholar
  36. 36.
    Lu, H. H., and Wimmer, E. (1996). Poliovirus chimeras replicating under the translational control of genetic elements of hepatitis C virus reveal unusual properties of the internal ribosomal entry site of hepatitis C virus. Proc Natl Acad Sci U S A 93, 1412–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Gromeier, M., Alexander, L., and Wimmer, E. (1996). Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Nati Acad Sci U S A 93, 2370–5.CrossRefGoogle Scholar
  38. 38.
    Meerovitch, K., Nicholson, R., and Sonenberg, N. (1991). In vitro mutational analysis of cis-acting RNA translational elements within the poliovirus type 2 5’ untranslated region. J Virol 65, 5895–901.PubMedGoogle Scholar
  39. 39.
    Skinner, M. A., Racaniello, V. R., Dunn, G., Cooper, J., Minor, P. D., and Almond, J. W. (1989). New model for the secondary structure of the 5’ non-coding RNA of poliovirus is supported by biochemical and genetic data that also show that RNA secondary structure is important in neurovirulence. J Mol Biol 207, 379–92.PubMedCrossRefGoogle Scholar
  40. 40.
    Stewart, S. R., and Semler, B. L. (1998). RNA structure adjacent to the attenuation determinant in the 5’-non-coding region influences poliovirus viability. Nucleic Acids Res 26, 5318–26.PubMedCrossRefGoogle Scholar
  41. 41.
    Stone, D. M., Almond, J. W., Brangwyn, J. K., and Belsham, G. J. (1993). trans complementation of cap-independent translation directed by poliovirus 5’ noncoding region deletion mutants: evidence for RNA-RNA interactions. J Virol 67, 6215–23.Google Scholar
  42. 42.
    Drew, J., and Belsham, G. J. (1994). trans complementation by RNA of defective foot-and-mouth disease virus internal ribosome entry site elements. J Virol 68, 697–703.Google Scholar
  43. 43.
    Van Der Velden, A., Kaminski, A., Jackson, R. J., and Belsham, G. J. (1995). Defective point mutants of the encephalomyocarditis virus internal ribosome entry site can be complemented in trans. Virology 214, 82–90.CrossRefGoogle Scholar
  44. 44.
    Jang, S. K., Pestova, T. V., Hellen, C. U., Witherell, G. W., and Wimmer, E. (1990). Cap-independent translation of picornavirus RNAs: structure and function of the internal ribosomal entry site. Enzyme 44, 292–309.PubMedGoogle Scholar
  45. 45.
    Nicholson, R., Pelletier, J., Le, S. Y., and Sonenberg, N. (1991). Structural and functional analysis of the ribosome landing pad of poliovirus type 2: in vivo translation studies. J Virol 65, 5886–94.PubMedGoogle Scholar
  46. 46.
    Pilipenko, E. V., Gmyl, A. P., Maslova, S. V., Svitkin, Y. V., Sinyakov, A. N., and Agol, V. I. (1992). Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell 68, 119–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Robertson, M. E., Seamons, R. A., and Belsham, G. J. (1999). A selection system for functional internal ribosome entry site (IRES) elements: analysis of the requirement for a conserved GNRA tetraloop in the encephalomyocarditis virus IRES. RNA 5, 1167–79.PubMedCrossRefGoogle Scholar
  48. 48.
    Zhao and WimmerGoogle Scholar
  49. 49.
    Kaminski, A., Howell, M. T., and Jackson, R. J. (1990). Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism. Embo J 9, 3753–9.PubMedGoogle Scholar
  50. 50.
    Kaminski, A., Belsham, G. J., and Jackson, R. J. (1994). Translation of encephalomyocarditis virus RNA: parameters influencing the selection of the internal initiation site. Embo J /3, 1673–81.Google Scholar
  51. 51.
    Pestova, T. V., Hellen, C. U., and Wimmer, E. (1994). A conserved AUG triplet in the 5’ nontranslated region of poliovirus can function as an initiation codon in vitro and in vivo. Virology 204, 729–37.PubMedCrossRefGoogle Scholar
  52. 52.
    Ohlmann, T., and Jackson, R. J. (1999). The properties of chimeric picornavirus IRESes show that discrimination between internal translation initiation sites is influenced by the identity of the IRES and not just the context of the AUG codon. RNA 5, 764–78.PubMedCrossRefGoogle Scholar
  53. 53.
    Pelletier, J., Flynn, M. E., Kaplan, G., Racaniello, V., and Sonenberg, N. (1988). Mutational analysis of upstream AUG codons of poliovirus RNA. J Virol 62, 4486–92.PubMedGoogle Scholar
  54. 54.
    Kuge, S., Kawamura, N., and Nomoto, A. (1989). Strong inclination toward transition mutation in nucleotide substitutions by poliovirus replicase. J Mol Bio! 207, 175–82.CrossRefGoogle Scholar
  55. 55.
    Hellen, C. U., Pestova, T. V., and Wimmer, E. (1994). Effect of mutations downstream of the internal ribosome entry site on initiation of poliovirus protein synthesis. J Virol 68, 6312–22.PubMedGoogle Scholar
  56. 56.
    Futterer, J., Kiss-Laszlo, Z., and Hohn, T. (1993). Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA. Cell 73, 789–802.PubMedCrossRefGoogle Scholar
  57. 57.
    Kuge, S., and Nomoto, A. (1987). Construction of viable deletion and insertion mutants of the Sabin strain of type 1 poliovirus: function of the 5’ noncoding sequence in viral replication. J Viro! 61, 1478–87.Google Scholar
  58. 58.
    Pestova, T. V., Shatsky, I. N., and Hellen, C. U. (1996). 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 Bio116, 6870–8.Google Scholar
  59. 59.
    Borman, A. M., Bailly, J. L., Girard, M., and Kean, K. M. (1995). Picornavirus internal ribosome entry segments: comparison of translation efficiency and the requirements for optimal internal initiation of translation in vitro. Nucleic Acids Res 23, 3656–63.PubMedCrossRefGoogle Scholar
  60. 60.
    Borman, A. M., and Kean, K. M. (1997). Intact eukaryotic initiation factor 4G is required for hepatitis A virus internal initiation of translation. Virology 237, 129–36.PubMedCrossRefGoogle Scholar
  61. 61.
    Borman, A. M., Le Mercier, P., Girard, M., and Kean, K. M. (1997). Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins. Nucleic Acids Res 25, 925–32.PubMedCrossRefGoogle Scholar
  62. 62.
    Pestova, T. V., Shatsky, I. N., Fletcher, S. P., Jackson, R. J., and Hellen, C. U. (1998). 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 12, 67–83.PubMedCrossRefGoogle Scholar
  63. 63.
    Pestova, T. V., and Hellen, C. U. (1999). Internal initiation of translation of bovine viral diarrhea virus RNA. Virology 258, 249–56.PubMedCrossRefGoogle Scholar
  64. 64.
    Kolupaeva, V. G., Pestova, T. V., and Hellen, C. U. (2000). An enzymatic footprinting analysis of the interaction of 40S ribosomal subunits with the infernal ribosomal entry site of hepatitis C virus. J Virol 74, 6242–50.PubMedCrossRefGoogle Scholar
  65. 65.
    Buratti, E., Tisminetzky, S., Zotti, M., and Baralle, F. E. (1998). Functional analysis of the interaction between HCV 5’UTR and putative subunits of eukaryotic translation initiation factor eIF3. Nucleic Acids Res 26, 3179–87.PubMedCrossRefGoogle Scholar
  66. 66.
    Sizova, D. V., Kolupaeva, V. G., Pestova, T. V., Shatsky, I. N., and Hellen, C. U. (1998). Specific interaction of eukaryotic translation initiation factor 3 with the 5’ nontranslated regions of hepatitis C virus and classical swine fever virus RNAs. J Virol 72, 4775–82.PubMedGoogle Scholar
  67. 67.
    Pestova, T. V., Hellen, C. U., and Shatsky, I. N. (1996). Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry. Mol Cell Biol 16, 6859–69.PubMedGoogle Scholar
  68. 68.
    Kolupaeva, V. G., Pestova, T. V., Hellen, C. U., and Shatsky, I. N. (1998). Translation eukaryotic initiation factor 4G recognizes a specific structural element within the internal ribosome entry site of encephalomyocarditis virus RNA. J Biol Chem 273, 18599–604.PubMedCrossRefGoogle Scholar
  69. 69.
    Lomakin, I. B., Hellen, C. U., and Pestova, T. V. (2000). 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 20, 6019–29.PubMedCrossRefGoogle Scholar
  70. 70.
    Lopez de Quinto, S., and Martinez-Salas, E. (2000). Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo [In Process Citation]. RNA 6, 1380–92.CrossRefGoogle Scholar
  71. 71.
    Meyer, K., Petersen, A., Niepmann, M., and Beck, E. (1995). Interaction of eukaryotic initiation factor eIF-4B with a picornavirus internal translation initiation site. J Virol 69, 2819–24.PubMedGoogle Scholar
  72. 72.
    Rust, R. C., Ochs, K., Meyer, K., Beck, E., and Niepmann, M. (1999). Interaction of eukaryotic initiation factor eIF4B with the internal ribosome entry site of foot-and-mouth disease virus is independent of the polypyrimidine tract-binding protein. J Virol 73, 6111–3.PubMedGoogle Scholar
  73. 73.
    Brown, B. A., and Ehrenfeld, E. (1979). Translation of poliovirus RNA in vitro: changes in cleavage pattern and initiation sites by ribosomal salt wash. Virology 97, 396–405.PubMedCrossRefGoogle Scholar
  74. 74.
    Dorner, A. J., Semler, B. L., Jackson, R. J., Hanecak, R., Duprey, E., and Wimmer, E. (1984). In vitro translation of poliovirus RNA: utilization of internal initiation sites in reticulocyte lysate. J Virol 50, 507–14.PubMedGoogle Scholar
  75. 75.
    Phillips, B. A., and Emmert, A. (1986). Modulation of the expression of poliovirus proteins in reticulocyte lysates. Virology 148, 255–67.PubMedCrossRefGoogle Scholar
  76. 76.
    Borman, A., Howell, M. T., Patton, J. G., and Jackson, R. J. (1993). The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation. J Gen Virol 74, 1775–88.PubMedCrossRefGoogle Scholar
  77. 77.
    Roberts, L. O., Seamons, R. A., and Belsham, G. J. (1998). Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. RNA 4, 520–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Meerovitch, K., Pelletier, J., and Sonenberg, N. (1989). A cellular protein that binds to the 5’-noncoding region of poliovirus RNA: implications for internal translation initiation. Genes Dev 3, 1026–34.PubMedCrossRefGoogle Scholar
  79. 79.
    Meerovitch, K., Svitkin, Y. V., Lee, H. S., Lejbkowicz, F., Kenan, D. J., Chan, E. K., Agol, V. I., Keene, J. D., and Sonenberg, N. (1993). La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J Virol 67, 3798807.Google Scholar
  80. 80.
    Shiroki, K., Isoyama, T., Kuge, S., Ishii, T., Ohmi, S., Hata, S., Suzuki, K., Takasaki, Y., and Nomoto, A. (1999). Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro-mediated cleavage. J Virol 73, 2193–200.PubMedGoogle Scholar
  81. 81.
    Ali, N., and Siddiqui, A. (1997). The La antigen binds 5’ noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation. Proc Natl Acad Sci U S A 94, 224954.Google Scholar
  82. 82.
    Ali, N., Pruijn, G. J., Kenan, D. J., Keene, J. D., and Siddiqui, A. (2000). Human La antigen is required for the hepatitis C virus internal ribosome entry site-mediated translation. J Biol Chem 275, 27531–40.PubMedGoogle Scholar
  83. 83.
    Holcik, M., and Korneluk, R. G. (2000). Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: role of La autoantigen in XIAP translation. Mol Cell Biol 20, 4648–57.PubMedCrossRefGoogle Scholar
  84. 84.
    Holcik, M., Yeh, C., Korneluk, R. G., and Chow, T. (2000). Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 19, 4174–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Carter, M. S., and Sarnow, P. (2000). Distinct mRNAs that encode La autoantigen are differentially expressed and contain internal ribosome entry sites. J Biol Chem 275, 28301–7.PubMedGoogle Scholar
  86. 86.
    Hellen, C. U., Witherell, G. W., Schmid, M., Shin, S. H., Pestova, T. V., Gil, A., and Wimmer, E. (1993). 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 90, 7642–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Kaminski, A., Hunt, S. L., Patton, J. G., and Jackson, R. J. (1995). Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA. RNA 1, 924–38.PubMedGoogle Scholar
  88. 88.
    Kaminski, A., and Jackson, R. J. (1998). The polypyrimidine tract binding protein ( PTB) requirement for internal initiation of translation of cardiovirus RNAs is conditional rather than absolute. RNA 4, 626–38.Google Scholar
  89. 89.
    Niepmann, M., Petersen, A., Meyer, K., and Beck, E. (1997). 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 71, 8330–9.PubMedGoogle Scholar
  90. 90.
    Hunt, S. L., and Jackson, R. J. (1999). Polypyrimidine-tract binding protein (PTB) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 RNA. RNA 5, 344–59.PubMedCrossRefGoogle Scholar
  91. 91.
    Hunt, S. L., Hsuan, J. J., Totty, N., and Jackson, R. J. (1999). unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA. Genes Dev 13, 437–48.Google Scholar
  92. 92.
    Boussadia, O., Jacquemin-Sablon, H., and Dautry, F. (1993). Exon skipping in the expression of the gene immediately upstream of N-ras (unr/NRU). Biochim Biophys Acta 1172, 64–72.PubMedCrossRefGoogle Scholar
  93. 93.
    Jacquemin-Sablon, H., Triqueneaux, G., Deschamps, S., le Maire, M., Doniger, J., and Dautry, F. (1994). Nucleic acid binding and intracellular localization of unr, a protein with five cold shock domains. Nucleic Acids Res 22, 2643–50.PubMedCrossRefGoogle Scholar
  94. 94.
    Boussadia, O., Amiot, F., Cases, S., Triqueneaux, G., Jacquemin-Sablon, H., and Dautry, F. (1997). Transcription of unr (upstream of N-ras) down-modulates N-ras expression in vivo. FEBS Lett 420, 20–4.PubMedCrossRefGoogle Scholar
  95. 95.
    Ali, N., and Siddiqui, A. (1995). Interaction of polypyrimidine tract-binding protein with the 5’ noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation. J Virol 69, 6367–75.PubMedGoogle Scholar
  96. 96.
    Anwar, A., Ali, N., Tanveer, R., and Siddiqui, A. (2000). Demonstration of functional requirement of polypyrimidine tract-binding protein by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated translation initiation [In Process Citation]. J Biol Chem 275, 34231–5.PubMedCrossRefGoogle Scholar
  97. 97.
    Gosert, R., Chang, K. H., Rijnbrand, R., Yi, M., Sangar, D. V., and Lemon, S. M. (2000). Transient expression of cellular polypyrimidine-tract binding protein stimulates cap-independent translation directed by both picornaviral and flaviviral internal ribosome entry sites In vivo. Mol Cell Biol 20, 1583–95.PubMedCrossRefGoogle Scholar
  98. 98.
    Schultz, D. E., Hardin, C. C., and Lemon, S. M. (1996). Specific interaction of glyceraldehyde 3-phosphate dehydrogenase with the 5’-nontranslated RNA of hepatitis A virus. J Biol Chem 271, 14134–42.PubMedCrossRefGoogle Scholar
  99. 99.
    Yi, M., Schultz, D. E., and Lemon, S. M. (2000). Functional significance of the interaction of hepatitis A virus RNA with glyceraldehyde 3-phosphate dehydrogenase (GAPDH): opposing effects of GAPDH and polypyrimidine tract binding protein on internal ribosome entry site function. J Virol 74, 6459–68.PubMedCrossRefGoogle Scholar
  100. 100.
    Kim, Y. K., Hahm, B., and Jong, S. K. (2000). Polypyrimidine tract-binding protein inhibits translation of bip mRNA [In Process Citation]. J Mol Biol 304, 119–33.PubMedCrossRefGoogle Scholar
  101. 101.
    Huez, I., Creancier, L., Audigier, S., Gensac, M. C., Prats, A. C., and Prats, H. (1998). Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA. Mol Cell Biol 18, 6178–90.PubMedGoogle Scholar
  102. 102.
    Blyn, L. B., Swiderek, K. M., Richards, O., Stahl, D. C., Semler, B. L., and Ehrenfeld, E. (1996). Poly(rC) binding protein 2 binds to stem-loop IV of the poliovirus RNA 5’ noncoding region: identification by automated liquid chromatography-tandem mass spectrometry. Proc Natl Acad Sci U S A 93, 11115–20.PubMedCrossRefGoogle Scholar
  103. 103.
    Blyn, L. B., Towner, J. S., Semler, B. L., and Ehrenfeld, E. (1997). Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA. J Virol 71, 6243–6.PubMedGoogle Scholar
  104. 104.
    Walter, B. L., Nguyen, J. H., Ehrenfeld, E., and Semler, B. L. (1999). Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements. RNA 5, 1570–85.PubMedCrossRefGoogle Scholar
  105. 105.
    Silvera, D., Gamarnik, A. V., and Andino, R. (1999). The N-terminal K homology domain of the poly(rC)-binding protein is a major determinant for binding to the poliovirus 5’-untranslated region and acts as an inhibitor of viral translation. J Biol Chem 274, 38163–70.PubMedCrossRefGoogle Scholar
  106. 106.
    Parsley, T. B., Towner, J. S., Blyn, L. B., Ehrenfeld, E., and Semler, B. L. (1997). Poly (rC) binding protein 2 forms a ternary complex with the 5’-terminal sequences of poliovirus RNA and the viral 3CD proteinase. RNA 3, 1124–34.PubMedGoogle Scholar
  107. 107.
    Gamarnik, A. V., and Andino, R. (1998). Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev 12, 2293–304.PubMedCrossRefGoogle Scholar
  108. 108.
    Gamarnik, A. V., and Andino, R. (2000). Interactions of viral protein 3CD and Poly(rC) binding protein with the 5’ untranslated region of the poliovirus genome [In Process Citation]. J Virol 74, 2219–26.PubMedCrossRefGoogle Scholar
  109. 109.
    Agol, V. I., Paul, A. V., and Wimmer, E. (1999). Paradoxes of the replication of picornaviral genomes. Virus Res 62, 129–47.PubMedCrossRefGoogle Scholar
  110. 110.
    Graff, J., Cha, J., Blyn, L. B., and Ehrenfeld, E. (1998). Interaction of poly(rC) binding protein 2 with the 5’ noncoding region of hepatitis A virus RNA and its effects on translation. J Virol 72, 9668–75.PubMedGoogle Scholar
  111. 111.
    Spangberg, K., Goobar-Larsson, L., Wahren-Herlenius, M., and Schwartz, S. (1999). The La protein from human liver cells interacts specifically with the U-rich region in the hepatitis C virus 3’ untranslated region. J Hum Virol 2, 296–307.PubMedGoogle Scholar
  112. 112.
    Radomski, N., and Jost, E. (1995). Molecular cloning of a murine cDNA encoding a novel protein, p38–2G4, which varies with the cell cycle. Exp Cell Res 220, 434–45.PubMedCrossRefGoogle Scholar
  113. 113.
    Nakagawa, Y., Watanabe, S., Akiyama, K., Sarker, A. H., Tsutsui, K., Inoue, H., and Seki, S. (1997). cDNA cloning, sequence analysis and expression of a mouse 44-kDa nuclear protein copurified with DNA repair factors for acid-depurinated DNA. Acta Med Okayama 51, 195–206.Google Scholar
  114. 114.
    Pilipenko, E. V., Pestova, T. V., Kolupaeva, V. G., Khitrina, E. V., Poperechnaya, A. N., Agol, V. I., and Hellen, C. U. (2000). A cell cycle-dependent protein serves as a template-specific translation initiation factor. Genes Dev 14, 2028–45.PubMedGoogle Scholar
  115. 115.
    Gromeier, M., Lachmann, S., Rosenfeld, M. R., Gutin, P. H., and Wimmer, E. (2000). Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci U S A 97, 6803–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Hahm, B., Kim, Y. K., Kim, J. H., Kim, T. Y., and Jang, S. K. (1998). Heterogeneous nuclear ribonucleoprotein L interacts with the 3’ border of the internal ribosomal entry site of hepatitis C virus. J Virol 72, 8782–8.PubMedGoogle Scholar
  117. 117.
    Reynolds, J. E., Kaminski, A., Kettinen, H. J., Grace, K., Clarke, B. E., Carroll, A. R., Rowlands, D. J., and Jackson, R. J. (1995). Unique features of internal initiation of hepatitis C virus RNA translation. Embo J 14, 6010–20.PubMedGoogle Scholar
  118. 118.
    Peek, R., Pruijn, G. J., and Van Venrooij, W. J. (1996). Interaction of the La (SS-B) autoantigen with small ribosomal subunits. Eur J Biochem 236, 649–55.PubMedCrossRefGoogle Scholar
  119. 119.
    Kim, J. H., Hahm, B., Kim, Y. K., Choi, M., and Jang, S. K. (2000). Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm. J Mol Biol 298, 395–405.PubMedCrossRefGoogle Scholar
  120. 120.
    Krecic, A. M., and Swanson, M. S. (1999). hnRNP complexes: composition, structure, and function. Curr Opin Cell Biol 11, 363–71.Google Scholar
  121. 121.
    Shyu, A. B., and Wilkinson, M. F. (2000). The double lives of shuttling mRNA binding proteins. Cell 102, 135–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Gamarnik, A. V., and Andino, R. (1996). Replication of poliovirus in Xenopus oocytes requires two human factors. Embo J 15, 5988–98.PubMedGoogle Scholar
  123. 123.
    Toyoda, H., Koide, N., Kamiyama, M., Tobita, K., Mizumoto, K., and Imura, N. (1994). Host factors required for internal initiation of translation on poliovirus RNA. Arch Virol 138, 1–15.Google Scholar
  124. 124.
    Yoo, C. J., and Wolin, S. L. (1997). The yeast La protein is required for the 3’ endonucleolytic cleavage that matures tRNA precursors. Cell 89, 393–402.PubMedCrossRefGoogle Scholar
  125. 125.
    Pannone, B. K., Xue, D., and Wolin, S. L. (1998). A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcripts. Embo J 17, 7442–53.PubMedCrossRefGoogle Scholar
  126. 126.
    Xue, D., Rubinson, D. A., Pannone, B. K., Yoo, C. J., and Wolin, S. L. (2000). U snRNP assembly in yeast involves the La protein [published erratum appears in EMBO J 2000 Jun 1;19(11):2763]. Embo J 19, 1650–60.Google Scholar
  127. 127.
    McClure, W. R. (1985). Mechanism and control of transcription initiation in prokaryotes. Annu Rev Biochem 54, 171–204.PubMedCrossRefGoogle Scholar
  128. 128.
    Struhl, K. (1999). Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell 98, 1–4.PubMedCrossRefGoogle Scholar
  129. 129.
    Steitz, J. A., and Jakes, K. (1975). How ribosomes select initiator regions in mRNA: base pair formation between the 3’ terminus of 16S rRNA and the mRNA during initiation of protein synthesis in Escherichia coli. Proc Natl Acad Sci U S A 72, 47348.CrossRefGoogle Scholar
  130. 130.
    Boni, I. V., Isaeva, D. M., Musychenko, M. L., and Tzareva, N. V. (1991). Ribosome-messenger recognition: mRNA target sites for ribosomal protein 51. Nucleic Acids Res 19, 155–62.PubMedCrossRefGoogle Scholar
  131. 131.
    Pugh, B. F. (2000). Control of gene expression through regulation of the TATA-binding protein [In Process Citation]. Gene 255, 1–14.PubMedCrossRefGoogle Scholar
  132. 132.
    Henry, R. W., Sadowski, C. L., Kobayashi, R., and Hernandez, N. (1995). A TBPTAF complex required for transcription of human snRNA genes by RNA polymerase II and III. Nature 374, 653–6.PubMedCrossRefGoogle Scholar
  133. 133.
    Verrijzer, C. P., Yokomori, K., Chen, J. L., and Tjian, R. (1994). Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA. Science 264, 933–41.PubMedCrossRefGoogle Scholar
  134. 134.
    Burke, T. W., and Kadonaga, J. T. (1997). The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila. Genes Dev 11, 3020–31.PubMedCrossRefGoogle Scholar
  135. 135.
    Goodrich, J. A., Hoey, T., Thut, C. J., Admon, A., and Tjian, R. (1993). Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor TFIIB. Cell 75, 519–30.PubMedCrossRefGoogle Scholar
  136. 136.
    Farmer, G., Colgan, J., Nakatani, Y., Manley, J. L., and Prives, C. (1996). Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo. Mol Cell Biol 16, 4295–304.PubMedGoogle Scholar
  137. 137.
    Hoey, T., Weinzierl, R. O., Gill, G., Chen, J. L., Dynlacht, B. D., and Tjian, R. (1993). Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Cell 72, 247–60.PubMedCrossRefGoogle Scholar
  138. 138.
    Chen, J. L., Attardi, L. D., Verrijzer, C. P., Yokomori, K., and Tjian, R. (1994). Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell 79, 93–105.PubMedCrossRefGoogle Scholar
  139. 139.
    May, M., Mengus, G., Lavigne, A. C., Chambon, P., and Davidson, I. (1996). Human TAF(1128) promotes transcriptional stimulation by activation function 2 of the retinoid X receptors. Embo J 15, 3093–104.PubMedGoogle Scholar
  140. 140.
    Jacq, X., Brou, C., Lutz, Y., Davidson, I., Chambon, P., and Tora, L. (1994). Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 79, 107–17.PubMedCrossRefGoogle Scholar
  141. 141.
    Mengus, G., May, M., Carre, L., Chambon, P., and Davidson, I. (1997). Human TAF(II)135 potentiates transcriptional activation by the AF-2s of the retinoic acid, vitamin D3, and thyroid hormone receptors in mammalian cells. Genes Dev 11, 138195.Google Scholar
  142. 142.
    Chiang, C. M., and Roeder, R. G. (1995). Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science 267, 531–6.PubMedCrossRefGoogle Scholar
  143. 143.
    Fletcher, C. M., Pestova, T. V., Hellen, C. U., and Wagner, G. (1999). Structure and interactions of the translation initiation factor elFI. Embo J 18, 2631–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Bandyopadhyay, X., and Maitra, U. (1999). Cloning and characterization of the p42 subunit of mammalian translation initiation factor 3 (eIF3): demonstration that eIF3 interacts with eIF5 in mammalian cells. Nucleic Acids Res 27, 1331–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Lamphear, B. J., Kirchweger, R., Skern, T., and Rhoads, R. E. (1995). Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J Biol Chem 270, 21975–83.PubMedCrossRefGoogle Scholar
  146. 146.
    Tarin, S. Z., Jr., and Sachs, A. B. (1997). Binding of eukaryotic translation initiation factor 4E (eIF4E) to eIF4G represses translation of uncapped mRNA. Mol Cell Biol 17, 6876–86.Google Scholar
  147. 147.
    Christensen, A. K., Kahn, L. E., and Boume, C. M. (1987). Circular polysomes predominate on the rough endoplasmic reticulum of somatotropes and mammotropes in the rat anterior pituitary. Am J Anat 178, 1–10.PubMedCrossRefGoogle Scholar
  148. 148.
    Wells, S. E., Hillner, P. E., Vale, R. D., and Sachs, A. B. (1998). Circularization of mRNA by eukaryotic translation initiation factors. Mol Cell 2, 135–40.PubMedCrossRefGoogle Scholar
  149. 149.
    Tarun, S. Z., Jr., and Sachs, A. B. (1995). A common function for mRNA 5’ and 3’ ends in translation initiation in yeast. Genes Dev 9, 2997–3007.PubMedCrossRefGoogle Scholar
  150. 150.
    Tanin, S. Z., Jr., Wells, S. E., Deardorff, J. A., and Sachs, A. B. (1997). Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation. Proc Natl Acad Sci U S A 94, 9046–51.CrossRefGoogle Scholar
  151. 151.
    Carey, M., Lin, Y. S., Green, M. R., and Ptashne, M. (1990). A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature 345, 361–4.PubMedCrossRefGoogle Scholar
  152. 152.
    De Gregorio, E., Preiss, T., and Hentze, M. W. (1999). Translation driven by an eIF4G core domain in vivo. Embo J 18, 4865–74.PubMedCrossRefGoogle Scholar
  153. 153.
    Chappell, S. A., Edelman, G. M., and Mauro, V. P. (2000). A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity. Proc Natl Acad Sci U S A 97, 1536–41.PubMedCrossRefGoogle Scholar
  154. 154.
    Coldwell, M. J., Mitchell, S. A., Stoneley, M., MacFarlane, M., and Willis, A. E. (2000). Initiation of Apaf-1 translation by internal ribosome entry. Oncogene 19, 899905.Google Scholar
  155. 155.
    Cornelis, S., Bruynooghe, Y., Denecker, G., Van Huffel, S., Tinton, S., and Beyaert, R. (2000). Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol Cell 5, 597–605.PubMedCrossRefGoogle Scholar
  156. 156.
    Henis-Korenblit, S., Strumpf, N. L., Goldstaub, D., and Kimchi, A. (2000). A novel form of DAPS protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation. Mol Cell Biol 20, 496–506.PubMedCrossRefGoogle Scholar
  157. 157.
    Lauring, S. A., and Overbaugh, J. (2000). Evidence that an IRES within the Notch2 coding region can direct expression of a nuclear form of the protein.[In Process Citation]. Mol Cell 6, 939–45.PubMedCrossRefGoogle Scholar
  158. 158.
    Pyronnet, S., Pradayrol, L., and Sonenberg, N. (2000). A cell cycle-dependent internal ribosome entry site. Mol Cell 5, 607–16.PubMedCrossRefGoogle Scholar
  159. 159.
    Sella, O., Gerlitz, G., Le, S. Y., and Elroy-Stein, O. (1999). Differentiation-induced internal translation of c-sis mRNA: analysis of the cis elements and their differentiation-linked binding to the hnRNP C protein. Mol Cell Biol 19, 5429–40.PubMedGoogle Scholar
  160. 160.
    Galy, B., Maret, A., Prats, A. C., and Prats, H. (1999). Cell transformation results in the loss of the density-dependent translational regulation of the expression of fibroblast growth factor 2 isoforms. Cancer Res 59, 165–71.PubMedGoogle Scholar
  161. 161.
    van der Velden, A. W., and Thomas, A. A. (1999). The role of the 5’ untranslated region of an mRNA in translation regulation during development. Int J Biochem Cell Biol 31, 87–106.PubMedCrossRefGoogle Scholar
  162. 162.
    Fernandez, J., Yaman, I., Mishra, R., Merrick, W. C., Snider, M. D., Lamers, W. H., and Hatzoglou, M. (2001). IRES-mediated translation of a mammalian mRNA is regulated by amino acid availability. J Biol Chem, in press.Google Scholar
  163. 163.
    Johannes, G., Carter, M. S., Eisen, M. B., Brown, P. 0., and Sarnow, P. (1999). Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Proc Natl Acad Sci U S A 96, 131 1823.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Sung Key Jang
    • 1
  • Eckard Wimmer
    • 2
  1. 1.Pohang University of Science and TechnologyPohangKorea
  2. 2.Stony Brook School of Medicine Stony BrookSUNYUSA

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