1887

Abstract

(ERBV) has recently been classified as an , a new genus in the family. ERBV is distantly related to members of the and genera which utilize a type II internal ribosome entry sequence (IRES) to initiate translation. We show that ERBV also possesses the core stem–loop structures (H–L) of a type II IRES. The function of the ERBV IRES was characterized using bicistronic plasmids that were analysed both by transfection into BHK-21 cells and by transcription and translation in rabbit reticulocyte lysates. In both systems, a region encompassed by nucleotides (nt) 189–920 downstream of the poly(C) tract was required for maximal translation. This sequence includes stem–loops H–L as well as four additional upstream stem–loops. Nt 904 corresponds to the second of three in-frame AUG codons located immediately downstream of the polypyrimidine tract (nucleotides 869–880). Site-directed mutagenesis demonstrated that AUG2 is the major initiation codon despite the appropriate positioning of AUG1 16 nt downstream of the polypyrimidine tract. In direct IRES competition experiments, the ERBV IRES was able to compete strongly for translation factors with the IRES of (EMCV). This was true when the assays were performed (with the IRESs competing either in or ) and (with the IRESs competing in ). A comparative analysis of the strength of several IRESs revealed that the ERBV IRES, like that of the EMCV, is a powerful inducer of translation and may have similar potential for use in mammalian expression systems.

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2001-09-01
2019-09-18
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References

  1. Agol, V. I. ( 1991; ). The 5′-untranslated region of picornaviral genomes. Advances in Virus Research 40, 103-180.
    [Google Scholar]
  2. Andino, R., Boddeker, N., Silvera, D. & Gamarnik, A. V. ( 1999; ). Intracellular determinants of picornavirus replication. Trends in Microbiology 7, 76-82.[CrossRef]
    [Google Scholar]
  3. Bae, Y. S., Eun, H. M. & Yoon, J. W. ( 1989; ). Genomic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus. Virology 170, 282-287.[CrossRef]
    [Google Scholar]
  4. Beck, E., Fross, S., Strebel, K., Cattaneo, R. & Feil, G. ( 1983; ). Structure of the FMDV translation initiation site and of the structural proteins. Nucleic Acids Research 11, 7873-7885.[CrossRef]
    [Google Scholar]
  5. Belsham, G. J. & Brangwyn, J. K. ( 1990; ). A region of the 5′ noncoding region of foot-and-mouth disease virus RNA directs efficient internal initiation of protein synthesis within cells: involvement with the role of L protease in translational control. Journal of Virology 64, 5389-5395.
    [Google Scholar]
  6. Belsham, G. J. & Sonenberg, N. ( 1996; ). RNA-protein interactions in regulation of picornavirus RNA translation. Microbiological Reviews 60, 499-511.
    [Google Scholar]
  7. Brown, E. A., Day, S. P., Jansen, R. W. & Lemon, S. M. ( 1991; ). The 5′ nontranslated region of Hepatitis A virus RNA: secondary structure and elements required for translation in vitro. Journal of Virology 65, 5828-5838.
    [Google Scholar]
  8. Burrows, R. ( 1978; ). Equine rhinovirus and adenovirus infections. Proceedings of the 24th Annual Convention of the American Association of Equine Practitioners 299–306.
    [Google Scholar]
  9. Carman, S., Rosendal, S., Huber, L., Gyles, C., McKee, S., Willoughby, R. A., Dubovi, E., Thorsen, J. & Lein, D. ( 1997; ). Infectious agents in acute respiratory disease in horses in Ontario. Journal of Veterinary Diagnostic Investigation 9, 17-23.[CrossRef]
    [Google Scholar]
  10. Clarke, B. E., Sangar, D. V., Burroughs, J. N., Newton, S. E., Carroll, A. R. & Rowlands, D. J. ( 1985; ). Two initiation sites for foot-and-mouth disease virus polyprotein in vivo. Journal of General Virology 66, 2615-2626.[CrossRef]
    [Google Scholar]
  11. Davies, M. V. & Kaufman, R. J. ( 1992; ). The sequence context of the initiation codon in the Encephalomyocarditis Virus leader modulates efficiency of internal translation initiation. Journal of Virology 66, 1924-1932.
    [Google Scholar]
  12. De Quinto, S. L. & Martinez-Salas, E. ( 1997; ). Conserved structural motifs located in distal loops of aphthovirus internal ribosome entry site domain 3 are required for internal initiation of translation. Journal of Virology 71, 4171-4175.
    [Google Scholar]
  13. De Quinto, S. L. & Martinez-Salas, E. ( 1999; ). Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection. Virology 255, 324-336.[CrossRef]
    [Google Scholar]
  14. Duke, G. M., Hoffman, M. A. & Palmenberg, A. C. ( 1992; ). Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation. Journal of Virology 66, 1602-1609.
    [Google Scholar]
  15. Fuerst, T. R., Niles, E. G., Studier, W. & Moss, B. ( 1986; ). Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proceedings of the National Academy of Sciences, USA 83, 8122-8126.[CrossRef]
    [Google Scholar]
  16. Hinton, T. M., Li, F. & Crabb, B. S. ( 2000; ). Internal ribosomal entry site-mediated translation initiation in equine rhinitis A virus: similarities to and differences from that of foot-and-mouth disease virus. Journal of Virology 74, 11708-11716.[CrossRef]
    [Google Scholar]
  17. Jang, S. K. & 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 & Development 4, 1560-1572.[CrossRef]
    [Google Scholar]
  18. Kaminski, A., Belsham, G. J. & Jackson, R. J. ( 1994; ). Translation of encephalomyocarditis virus RNA: parameters influencing the selection of the internal initiation site. EMBO Journal 13, 1673-1681.
    [Google Scholar]
  19. King, A. M. Q., Brown, F., Christian, P., Hovi, T., Hyypiä, T., Knowles, N. J., Lemon, S. M., Minor, P. D., Palmenberg, A. C., Skern, T. & Stanway, G. ( 2000; ). Picornaviridae. In Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses , pp. 657-673. Edited by M. H. V. van Regenmortel, C. M. Fauquet, D. H. L. Bishop, E. B. Carstens, M. K. Estes, S. M. Lemon, J. Maniloff, M. A. Mayo, D. J. McGeoch, C. R. Pringle & R. B. Wickner. San Diego:Academic Press.
  20. Kong, W.-P. & Roos, R. P. ( 1991; ). Alternative translation initiation site in the DA strain of Theiler’s murine encephalomyelitis virus. Journal of Virology 65, 3395-3399.
    [Google Scholar]
  21. Le, S.-Y., Chen, J.-H., Sonenberg, N. & Maizel, J. V. ( 1993; ). Conserved structural elements in the 5′ nontranslated region of cardiovirus, aphthovirus and hepatitis A virus RNAs. Nucleic Acids Research 21, 2445-2451.[CrossRef]
    [Google Scholar]
  22. Li, F., Browning, G. F., Studdert, M. J. & Crabb, B. S. ( 1996; ). Equine rhinovirus 1 is more closely related to foot-and-mouth disease virus than to other picornaviruses. Proceedings of the National Academy of Sciences, USA 93, 990-995.[CrossRef]
    [Google Scholar]
  23. McCollum, W. H. & Timoney, P. J. (1992). Studies of the seroprevalence and frequency of equine rhinovirus-I and II infection in normal horse. In Equine Infectious Diseases VI, pp. 83–87. Edited by W. Plowright, P. D. Rossdale & J. F. Wadw.
  24. Mathews, D. H., Sabina, J., Zuker, M. & Turner, D. H. ( 1999; ). Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. Journal of Molecular Biology 288, 911-940.[CrossRef]
    [Google Scholar]
  25. Moss, B., Elroy-Stein, O., Mizukami, T., Alexander, W. A. & Fuerst, T. R. ( 1990; ). New mammalian expression vectors. Nature 348, 91-92.[CrossRef]
    [Google Scholar]
  26. Mumford, I. A. & Thomson, G. R. ( 1978; ). Studies on picornaviruses isolated from the respiratory tract of horses. In Equine Infectious Diseases , pp. 419-429. Edited by J. T. Bryans & H. Gerber. Basel:Karger.
  27. Nateri, A. S., Hughes, P. J. & Stanway, G. ( 2000; ). In vivo and in vitro identification of structural and sequence elements of the human parechovirus 5′ untranslated region required for internal initiation. Journal of Virology 74, 6269-6277.[CrossRef]
    [Google Scholar]
  28. Palmenberg, A. C. & Sgro, J.-Y. ( 1997; ). Topological organization of picornaviral genomes: statistical prediction of RNA structural signals. Seminars in Virology 8, 231-241.[CrossRef]
    [Google Scholar]
  29. Palmenberg, A. C., Kirby, E. M., Tanda, M. R., Drake, N. L., Duke, G. M., Pottratz, K. F. & Collett, M. S. ( 1984; ). The nucleotide and deduced amino acid sequence of the encephalomyocarditis viral polyprotein coding region. Nucleic Acids Research 12, 2969-2985.[CrossRef]
    [Google Scholar]
  30. Pestova, T. V., Hellen, C. U. & Shatsky, I. N. ( 1996; ). Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry. Molecular Cell Biology 16, 6859-6869.
    [Google Scholar]
  31. Pevear, D. C., Calenoff, M., Rozhon, E. & Lipton, H. ( 1987; ). Analysis of the complete nucleotide sequence of the picornavirus Theiler’s murine encephalomyelitis virus indicates that it is closely related to cardioviruses. Journal of Virology 61, 1507-1516.
    [Google Scholar]
  32. Piccone, M. E., Rieder, E., Mason, P. W. & Grubman, M. J. ( 1995; ). The foot-and-mouth disease virus leader proteinase gene is not required for viral replication. Journal of Virology 69, 5376-5382.
    [Google Scholar]
  33. Pilipenko, E. V., Blinov, V. M., Dmitrieva, T. M. & Agol, V. I. ( 1989; ). Conservation of the secondary structure elements of the 5′-untranslated region of cardio- and aphthovirus RNAs. Nucleic Acids Research 17, 5701-5711.[CrossRef]
    [Google Scholar]
  34. Pilipenko, E. V., Gmyl, A. P., Maslova, S. V., Svitkin, Y. V., Sinyakov, A. N. & Agol, V. I. ( 1992; ). Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell 68, 119-131.[CrossRef]
    [Google Scholar]
  35. Pringle, C. R. ( 1999; ). Virus taxonomy at the XIth International Congress of Virology, Sydney, Australia. Archives of Virology 144, 2065-2070.[CrossRef]
    [Google Scholar]
  36. Robertson, B. H., Grubman, M. J., Weddell, G. N., Moore, D. M., Welsh, D., Fischer, T., Dowbenko, D. J., Yansura, D. G., Small, B. & Kleid, D. G. ( 1985; ). Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. Journal of Virology 54, 651-660.
    [Google Scholar]
  37. Robertson, M. E., Seamons, R. A. & 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, 1167-1179.[CrossRef]
    [Google Scholar]
  38. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  39. Stewart, S. R. & Semler, B. L. ( 1997; ). RNA determinants of picornavirus cap-independent translation initiation. Seminars in Virology 8, 242-255.[CrossRef]
    [Google Scholar]
  40. Thompson, J. D., Higgins, D. G. & Gibson, T. J. ( 1994; ). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22, 4673-4680.[CrossRef]
    [Google Scholar]
  41. Thorsen, J. ( 1991; ). Equine rhinoviruses. Equine Practice 13, 19-22.
    [Google Scholar]
  42. Wutz, G., Auer, H., Nowotny, N., Grosse, B., Skern, T. & Kuechler, E. ( 1996; ). Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses. Journal of General Virology 77, 1719-1730.[CrossRef]
    [Google Scholar]
  43. Yamasaki, K., Weihl, C. C. & Roos, R. P. ( 1999; ). Alternative translation initiation of Theiler’s murine encephalomyelitis virus. Journal of Virology 73, 8519-8526.
    [Google Scholar]
  44. Zuker, M., Mathews, D. H. & Turner, D. H. ( 1998; ). Algorithms and thermodynamics for RNA secondary structure prediction: a practical guide. In RNA Biochemistry and Biotechnology , pp. 11-43. Edited by J. Barciszewski & B. F. C. Clark. Dordrecht:Kluwer.
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