Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1997 Jul 1;16(13):4107–4116. doi: 10.1093/emboj/16.13.4107

A viral sequence in the 3'-untranslated region mimics a 5' cap in facilitating translation of uncapped mRNA.

S Wang 1, K S Browning 1, W A Miller 1
PMCID: PMC1170033  PMID: 9233819

Abstract

For recognition by the translational machinery, most eukaryotic cellular mRNAs have a 5' cap structure [e.g. m7G(5')ppp(5')N]. We describe a translation enhancer sequence (3'TE) located in the 3'-untranslated region (UTR) of the genome of the PAV barley yellow dwarf virus (BYDV-PAV) which stimulates translation from uncapped mRNA by 30- to 100-fold in vitro and in vivo to a level equal to that of efficient capped mRNAs. A four base duplication within the 3'TE destroyed the stimulatory activity. Efficient translation was recovered by addition of a 5' cap to this mRNA. Translation of both uncapped mRNA containing the 3'TE in cis and capped mRNA lacking any BYDV-PAV sequence was inhibited specifically by added 3'TE RNA in trans. This inhibition was reversed by adding initiation factor 4F (eIF4F), suggesting that the 3'TE, like the 5' cap, mediates eIF4F-dependent translation initiation. The BYDV-PAV 5'UTR was necessary for the 3'TE to function, except when the 3'TE itself was moved to the 5'UTR. Thus, the 3'TE is sufficient for recruiting the translation factors and ribosomes, while the viral 5'UTR may serve only for the long distance 3'-5' communication. Models are proposed to explain this novel mechanism of cap-independent translation initiation facilitated by the 3'UTR.

Full Text

The Full Text of this article is available as a PDF (529.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carrington J. C., Freed D. D. Cap-independent enhancement of translation by a plant potyvirus 5' nontranslated region. J Virol. 1990 Apr;64(4):1590–1597. doi: 10.1128/jvi.64.4.1590-1597.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chalhoub B. A., Kelly L., Robaglia C., Lapierre H. D. Sequence variability in the genome-3'-terminal region of BYDV for 10 geographically distinct PAV-like isolates of barley yellow dwarf virus: analysis of the ORF6 variation. Arch Virol. 1994;139(3-4):403–416. doi: 10.1007/BF01310801. [DOI] [PubMed] [Google Scholar]
  3. Curtis D., Lehmann R., Zamore P. D. Translational regulation in development. Cell. 1995 Apr 21;81(2):171–178. doi: 10.1016/0092-8674(95)90325-9. [DOI] [PubMed] [Google Scholar]
  4. Danthinne X., Seurinck J., Meulewaeter F., Van Montagu M., Cornelissen M. The 3' untranslated region of satellite tobacco necrosis virus RNA stimulates translation in vitro. Mol Cell Biol. 1993 Jun;13(6):3340–3349. doi: 10.1128/mcb.13.6.3340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinesh-Kumar S. P., Miller W. A. Control of start codon choice on a plant viral RNA encoding overlapping genes. Plant Cell. 1993 Jun;5(6):679–692. doi: 10.1105/tpc.5.6.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dubnau J., Struhl G. RNA recognition and translational regulation by a homeodomain protein. Nature. 1996 Feb 22;379(6567):694–699. doi: 10.1038/379694a0. [DOI] [PubMed] [Google Scholar]
  7. Fletcher L., Corbin S. D., Browning K. S., Ravel J. M. The absence of a m7G cap on beta-globin mRNA and alfalfa mosaic virus RNA 4 increases the amounts of initiation factor 4F required for translation. J Biol Chem. 1990 Nov 15;265(32):19582–19587. [PubMed] [Google Scholar]
  8. Gallie D. R., Lewis N. J., Marzluff W. F. The histone 3'-terminal stem-loop is necessary for translation in Chinese hamster ovary cells. Nucleic Acids Res. 1996 May 15;24(10):1954–1962. doi: 10.1093/nar/24.10.1954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gallie D. R. The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev. 1991 Nov;5(11):2108–2116. doi: 10.1101/gad.5.11.2108. [DOI] [PubMed] [Google Scholar]
  10. Gallie D. R., Walbot V. RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a poly(A) tail in plant and animal cells. Genes Dev. 1990 Jul;4(7):1149–1157. doi: 10.1101/gad.4.7.1149. [DOI] [PubMed] [Google Scholar]
  11. Jackson R. J., Kaminski A. Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond. RNA. 1995 Dec;1(10):985–1000. [PMC free article] [PubMed] [Google Scholar]
  12. Leathers V., Tanguay R., Kobayashi M., Gallie D. R. A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation. Mol Cell Biol. 1993 Sep;13(9):5331–5347. doi: 10.1128/mcb.13.9.5331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lesnaw J. A., Reichmann M. E. Identity of the 5'-terminal RNA nucleotide sequence of the satellite tobacco necrosis virus and its helper virus: possible role of the 5'-terminus in the recognition by virus-specific RNA replicase. Proc Natl Acad Sci U S A. 1970 May;66(1):140–145. doi: 10.1073/pnas.66.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Merrick W. C. Eukaryotic protein synthesis: an in vitro analysis. Biochimie. 1994;76(9):822–830. doi: 10.1016/0300-9084(94)90183-x. [DOI] [PubMed] [Google Scholar]
  15. Miller W. A., Rasochová L. Barley yellow dwarf viruses. Annu Rev Phytopathol. 1997;35:167–190. doi: 10.1146/annurev.phyto.35.1.167. [DOI] [PubMed] [Google Scholar]
  16. Miller W. A., Waterhouse P. M., Gerlach W. L. Sequence and organization of barley yellow dwarf virus genomic RNA. Nucleic Acids Res. 1988 Jul 11;16(13):6097–6111. doi: 10.1093/nar/16.13.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mohan B. R., Dinesh-Kumar S. P., Miller W. A. Genes and cis-acting sequences involved in replication of barley yellow dwarf virus-PAV RNA. Virology. 1995 Sep 10;212(1):186–195. doi: 10.1006/viro.1995.1467. [DOI] [PubMed] [Google Scholar]
  18. Muhlrad D., Decker C. J., Parker R. Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript. Genes Dev. 1994 Apr 1;8(7):855–866. doi: 10.1101/gad.8.7.855. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Pestova T. V., Hellen C. U., Shatsky I. N. Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry. Mol Cell Biol. 1996 Dec;16(12):6859–6869. doi: 10.1128/mcb.16.12.6859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Sheets M. D., Wu M., Wickens M. Polyadenylation of c-mos mRNA as a control point in Xenopus meiotic maturation. Nature. 1995 Apr 6;374(6522):511–516. doi: 10.1038/374511a0. [DOI] [PubMed] [Google Scholar]
  23. Standart N., Jackson R. J. Regulation of translation by specific protein/mRNA interactions. Biochimie. 1994;76(9):867–879. doi: 10.1016/0300-9084(94)90189-9. [DOI] [PubMed] [Google Scholar]
  24. Tanguay R. L., Gallie D. R. Isolation and characterization of the 102-kilodalton RNA-binding protein that binds to the 5' and 3' translational enhancers of tobacco mosaic virus RNA. J Biol Chem. 1996 Jun 14;271(24):14316–14322. doi: 10.1074/jbc.271.24.14316. [DOI] [PubMed] [Google Scholar]
  25. Tarun S. Z., Jr, Sachs A. B. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 1996 Dec 16;15(24):7168–7177. [PMC free article] [PubMed] [Google Scholar]
  26. Tsukiyama-Kohara K., Iizuka N., Kohara M., Nomoto A. Internal ribosome entry site within hepatitis C virus RNA. J Virol. 1992 Mar;66(3):1476–1483. doi: 10.1128/jvi.66.3.1476-1483.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wang S., Miller W. A. A sequence located 4.5 to 5 kilobases from the 5' end of the barley yellow dwarf virus (PAV) genome strongly stimulates translation of uncapped mRNA. J Biol Chem. 1995 Jun 2;270(22):13446–13452. doi: 10.1074/jbc.270.22.13446. [DOI] [PubMed] [Google Scholar]
  28. Xiong Z., Lommel S. A. The complete nucleotide sequence and genome organization of red clover necrotic mosaic virus RNA-1. Virology. 1989 Aug;171(2):543–554. doi: 10.1016/0042-6822(89)90624-7. [DOI] [PubMed] [Google Scholar]
  29. Yueh A., Schneider R. J. Selective translation initiation by ribosome jumping in adenovirus-infected and heat-shocked cells. Genes Dev. 1996 Jun 15;10(12):1557–1567. doi: 10.1101/gad.10.12.1557. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES