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. 1994 Feb;68(2):697–703. doi: 10.1128/jvi.68.2.697-703.1994

trans complementation by RNA of defective foot-and-mouth disease virus internal ribosome entry site elements.

J Drew 1, G J Belsham 1
PMCID: PMC236505  PMID: 8289373

Abstract

A region of about 435 bases from the 5' noncoding region of foot-and-mouth disease virus RNA directs internal initiation of protein synthesis. This region, termed the internal ribosome entry site (IRES), is predicted to contain extensive secondary structure. Precise deletion of five predicted secondary structure features has been performed. The mutant IRES elements have been constructed into vectors which express bicistronic mRNAs and assayed within cells. Each of the modified IRES elements was defective in directing internal initiation when assayed alone. However, coexpression of an intact foot-and-mouth disease virus IRES complemented four of these defective elements to an efficiency of up to 80% of wild-type activity. No complementation was observed with the structurally analogous element from encephalomyocarditis virus. The role of RNA-RNA interactions in the function of the picornavirus IRES is discussed.

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Selected References

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  1. Belsham G. J., Brangwyn J. K. 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. J Virol. 1990 Nov;64(11):5389–5395. doi: 10.1128/jvi.64.11.5389-5395.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belsham G. J. Dual initiation sites of protein synthesis on foot-and-mouth disease virus RNA are selected following internal entry and scanning of ribosomes in vivo. EMBO J. 1992 Mar;11(3):1105–1110. doi: 10.1002/j.1460-2075.1992.tb05150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borman A., Howell M. T., Patton J. G., Jackson R. J. The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation. J Gen Virol. 1993 Sep;74(Pt 9):1775–1788. doi: 10.1099/0022-1317-74-9-1775. [DOI] [PubMed] [Google Scholar]
  4. Borovjagin A. V., Ezrokhi M. V., Rostapshov V. M., Ugarova TYu, Bystrova T. F., Shatsky I. N. RNA--protein interactions within the internal translation initiation region of encephalomyocarditis virus RNA. Nucleic Acids Res. 1991 Sep 25;19(18):4999–5005. doi: 10.1093/nar/19.18.4999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown E. A., Day S. P., Jansen R. W., Lemon S. M. The 5' nontranslated region of hepatitis A virus RNA: secondary structure and elements required for translation in vitro. J Virol. 1991 Nov;65(11):5828–5838. doi: 10.1128/jvi.65.11.5828-5838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duke G. M., Hoffman M. A., Palmenberg A. C. Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation. J Virol. 1992 Mar;66(3):1602–1609. doi: 10.1128/jvi.66.3.1602-1609.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fütterer J., Kiss-László Z., Hohn T. Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA. Cell. 1993 May 21;73(4):789–802. doi: 10.1016/0092-8674(93)90257-q. [DOI] [PubMed] [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jackson R. J., Howell M. T., Kaminski A. The novel mechanism of initiation of picornavirus RNA translation. Trends Biochem Sci. 1990 Dec;15(12):477–483. doi: 10.1016/0968-0004(90)90302-r. [DOI] [PubMed] [Google Scholar]
  12. Jang S. K., Kräusslich 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 Aug;62(8):2636–2643. doi: 10.1128/jvi.62.8.2636-2643.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  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 Sep;4(9):1560–1572. doi: 10.1101/gad.4.9.1560. [DOI] [PubMed] [Google Scholar]
  14. Kaminski A., Howell M. T., Jackson R. J. Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism. EMBO J. 1990 Nov;9(11):3753–3759. doi: 10.1002/j.1460-2075.1990.tb07588.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kühn R., Luz N., Beck E. Functional analysis of the internal translation initiation site of foot-and-mouth disease virus. J Virol. 1990 Oct;64(10):4625–4631. doi: 10.1128/jvi.64.10.4625-4631.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Luz N., Beck E. Interaction of a cellular 57-kilodalton protein with the internal translation initiation site of foot-and-mouth disease virus. J Virol. 1991 Dec;65(12):6486–6494. doi: 10.1128/jvi.65.12.6486-6494.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martínez-Salas E., Sáiz J. C., Dávila M., Belsham G. J., 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. doi: 10.1128/jvi.67.7.3748-3755.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meerovitch K., Pelletier J., Sonenberg N. A cellular protein that binds to the 5'-noncoding region of poliovirus RNA: implications for internal translation initiation. Genes Dev. 1989 Jul;3(7):1026–1034. doi: 10.1101/gad.3.7.1026. [DOI] [PubMed] [Google Scholar]
  20. Meerovitch K., Svitkin Y. V., Lee H. S., Lejbkowicz F., Kenan D. J., Chan E. K., Agol V. I., Keene J. D., Sonenberg N. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J Virol. 1993 Jul;67(7):3798–3807. doi: 10.1128/jvi.67.7.3798-3807.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicholson R., Pelletier J., Le S. Y., Sonenberg N. Structural and functional analysis of the ribosome landing pad of poliovirus type 2: in vivo translation studies. J Virol. 1991 Nov;65(11):5886–5894. doi: 10.1128/jvi.65.11.5886-5894.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Parks G. D., Duke G. M., Palmenberg A. C. Encephalomyocarditis virus 3C protease: efficient cell-free expression from clones which link viral 5' noncoding sequences to the P3 region. J Virol. 1986 Nov;60(2):376–384. doi: 10.1128/jvi.60.2.376-384.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Patton J. G., Mayer S. A., Tempst P., Nadal-Ginard B. Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. Genes Dev. 1991 Jul;5(7):1237–1251. doi: 10.1101/gad.5.7.1237. [DOI] [PubMed] [Google Scholar]
  24. Pelletier J., Flynn M. E., Kaplan G., Racaniello V., Sonenberg N. Mutational analysis of upstream AUG codons of poliovirus RNA. J Virol. 1988 Dec;62(12):4486–4492. doi: 10.1128/jvi.62.12.4486-4492.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pelletier J., Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988 Jul 28;334(6180):320–325. doi: 10.1038/334320a0. [DOI] [PubMed] [Google Scholar]
  26. Percy N., Belsham G. J., Brangwyn J. K., Sullivan M., Stone D. M., Almond J. W. Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis. J Virol. 1992 Mar;66(3):1695–1701. doi: 10.1128/jvi.66.3.1695-1701.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pestova T. V., Hellen C. U., Wimmer E. Translation of poliovirus RNA: role of an essential cis-acting oligopyrimidine element within the 5' nontranslated region and involvement of a cellular 57-kilodalton protein. J Virol. 1991 Nov;65(11):6194–6204. doi: 10.1128/jvi.65.11.6194-6204.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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 Jul 25;17(14):5701–5711. doi: 10.1093/nar/17.14.5701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pilipenko E. V., Blinov V. M., Romanova L. I., Sinyakov A. N., Maslova S. V., Agol V. I. 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. doi: 10.1016/0042-6822(89)90259-6. [DOI] [PubMed] [Google Scholar]
  30. Pilipenko E. V., Gmyl A. P., Maslova S. V., Svitkin Y. V., Sinyakov A. N., Agol V. I. Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell. 1992 Jan 10;68(1):119–131. doi: 10.1016/0092-8674(92)90211-t. [DOI] [PubMed] [Google Scholar]
  31. Skinner M. A., Racaniello V. R., Dunn G., Cooper J., Minor P. D., Almond J. W. 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. 1989 May 20;207(2):379–392. doi: 10.1016/0022-2836(89)90261-1. [DOI] [PubMed] [Google Scholar]
  32. Standart N., Dale M., Stewart E., Hunt T. Maternal mRNA from clam oocytes can be specifically unmasked in vitro by antisense RNA complementary to the 3'-untranslated region. Genes Dev. 1990 Dec;4(12A):2157–2168. doi: 10.1101/gad.4.12a.2157. [DOI] [PubMed] [Google Scholar]
  33. Stone D. M., Almond J. W., Brangwyn J. K., Belsham G. J. trans complementation of cap-independent translation directed by poliovirus 5' noncoding region deletion mutants: evidence for RNA-RNA interactions. J Virol. 1993 Oct;67(10):6215–6223. doi: 10.1128/jvi.67.10.6215-6223.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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