Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1991 Dec;65(12):6782–6789. doi: 10.1128/jvi.65.12.6782-6789.1991

Translational control of human cytomegalovirus gp48 expression.

M R Schleiss 1, C R Degnin 1, A P Geballe 1
PMCID: PMC250765  PMID: 1658374

Abstract

Posttranscriptional controls modulate the expression of several human cytomegalovirus genes. Previous studies have shown that one cytomegalovirus gene transcript leader contains AUG codons which inhibit translation of a downstream reading frame. However, two other cytomegalovirus gene transcript leaders of similar structure do not inhibit translation. We have extended these studies to the analysis of the structural glycoprotein gp48, whose predominant transcript contains three upstream AUG codons. The 5' leader of this transcript strongly inhibits downstream translation in fibroblasts. Analyses of deletions and point mutations identify the second upstream AUG codon as an essential component of the inhibitory signal. Other leader sequences, but neither the first nor the third AUG codon, are also required. Intriguingly, the inhibitory signal appears also to depend on the amino acid coding information of the short reading frame associated with the second AUG codon. Insights derived from these studies are germane to understanding the translational regulation of other viral and cellular genes of similar structure.

Full text

PDF
6782

Images in this article

6783Image
on p.6783
6785Image
on p.6785
6785Image
on p.6785
6786Image
on p.6786
6787Image
on p.6787

Selected References

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

  1. Barkan A., Mertz J. E. The number of ribosomes on simian virus 40 late 16S mRNA is determined in part by the nucleotide sequence of its leader. Mol Cell Biol. 1984 Apr;4(4):813–816. doi: 10.1128/mcb.4.4.813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biegalke B. J., Geballe A. P. Translational inhibition by cytomegalovirus transcript leaders. Virology. 1990 Aug;177(2):657–667. doi: 10.1016/0042-6822(90)90531-u. [DOI] [PubMed] [Google Scholar]
  3. Brawerman G. mRNA decay: finding the right targets. Cell. 1989 Apr 7;57(1):9–10. doi: 10.1016/0092-8674(89)90166-9. [DOI] [PubMed] [Google Scholar]
  4. Chang C. P., Malone C. L., Stinski M. F. A human cytomegalovirus early gene has three inducible promoters that are regulated differentially at various times after infection. J Virol. 1989 Jan;63(1):281–290. doi: 10.1128/jvi.63.1.281-290.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C. P., Vesole D. H., Nelson J., Oldstone M. B., Stinski M. F. Identification and expression of a human cytomegalovirus early glycoprotein. J Virol. 1989 Aug;63(8):3330–3337. doi: 10.1128/jvi.63.8.3330-3337.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
  7. Cleveland D. W., Yen T. J. Multiple determinants of eukaryotic mRNA stability. New Biol. 1989 Nov;1(2):121–126. [PubMed] [Google Scholar]
  8. Demarchi J. M. Human cytomegalovirus DNA: restriction enzyme cleavage maps and map locations for immediate-early, early, and late RNAs. Virology. 1981 Oct 15;114(1):23–38. doi: 10.1016/0042-6822(81)90249-x. [DOI] [PubMed] [Google Scholar]
  9. Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fajardo J. E., Shatkin A. J. Translation of bicistronic viral mRNA in transfected cells: regulation at the level of elongation. Proc Natl Acad Sci U S A. 1990 Jan;87(1):328–332. doi: 10.1073/pnas.87.1.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Geballe A. P., Leach F. S., Mocarski E. S. Regulation of cytomegalovirus late gene expression: gamma genes are controlled by posttranscriptional events. J Virol. 1986 Mar;57(3):864–874. doi: 10.1128/jvi.57.3.864-874.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Geballe A. P., Mocarski E. S. Translational control of cytomegalovirus gene expression is mediated by upstream AUG codons. J Virol. 1988 Sep;62(9):3334–3340. doi: 10.1128/jvi.62.9.3334-3340.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Geballe A. P., Spaete R. R., Mocarski E. S. A cis-acting element within the 5' leader of a cytomegalovirus beta transcript determines kinetic class. Cell. 1986 Sep 12;46(6):865–872. doi: 10.1016/0092-8674(86)90068-1. [DOI] [PubMed] [Google Scholar]
  14. Goins W. F., Stinski M. F. Expression of a human cytomegalovirus late gene is posttranscriptionally regulated by a 3'-end-processing event occurring exclusively late after infection. Mol Cell Biol. 1986 Dec;6(12):4202–4213. doi: 10.1128/mcb.6.12.4202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Greenaway P. J., Wilkinson G. W. Nucleotide sequence of the most abundantly transcribed early gene of human cytomegalovirus strain AD169. Virus Res. 1987 Feb;7(1):17–31. doi: 10.1016/0168-1702(87)90055-4. [DOI] [PubMed] [Google Scholar]
  16. Kozak M. Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems. Mol Cell Biol. 1989 Nov;9(11):5073–5080. doi: 10.1128/mcb.9.11.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kozak M. Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8301–8305. doi: 10.1073/pnas.87.21.8301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
  21. McDonough S. H., Spector D. H. Transcription in human fibroblasts permissively infected by human cytomegalovirus strain AD169. Virology. 1983 Feb;125(1):31–46. doi: 10.1016/0042-6822(83)90061-2. [DOI] [PubMed] [Google Scholar]
  22. Miller P. F., Hinnebusch A. G. Sequences that surround the stop codons of upstream open reading frames in GCN4 mRNA determine their distinct functions in translational control. Genes Dev. 1989 Aug;3(8):1217–1225. doi: 10.1101/gad.3.8.1217. [DOI] [PubMed] [Google Scholar]
  23. Mulligan R. C., Berg P. Factors governing the expression of a bacterial gene in mammalian cells. Mol Cell Biol. 1981 May;1(5):449–459. doi: 10.1128/mcb.1.5.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peabody D. S., Berg P. Termination-reinitiation occurs in the translation of mammalian cell mRNAs. Mol Cell Biol. 1986 Jul;6(7):2695–2703. doi: 10.1128/mcb.6.7.2695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peabody D. S., Subramani S., Berg P. Effect of upstream reading frames on translation efficiency in simian virus 40 recombinants. Mol Cell Biol. 1986 Jul;6(7):2704–2711. doi: 10.1128/mcb.6.7.2704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sedman S. A., Gelembiuk G. W., Mertz J. E. Translation initiation at a downstream AUG occurs with increased efficiency when the upstream AUG is located very close to the 5' cap. J Virol. 1990 Jan;64(1):453–457. doi: 10.1128/jvi.64.1.453-457.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sedman S. A., Good P. J., Mertz J. E. Leader-encoded open reading frames modulate both the absolute and relative rates of synthesis of the virion proteins of simian virus 40. J Virol. 1989 Sep;63(9):3884–3893. doi: 10.1128/jvi.63.9.3884-3893.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spaete R. R., Mocarski E. S. Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J Virol. 1985 Oct;56(1):135–143. doi: 10.1128/jvi.56.1.135-143.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spaete R. R., Mocarski E. S. The alpha sequence of the cytomegalovirus genome functions as a cleavage/packaging signal for herpes simplex virus defective genomes. J Virol. 1985 Jun;54(3):817–824. doi: 10.1128/jvi.54.3.817-824.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Spaete R. R., Thayer R. M., Probert W. S., Masiarz F. R., Chamberlain S. H., Rasmussen L., Merigan T. C., Pachl C. Human cytomegalovirus strain Towne glycoprotein B is processed by proteolytic cleavage. Virology. 1988 Nov;167(1):207–225. doi: 10.1016/0042-6822(88)90071-2. [DOI] [PubMed] [Google Scholar]
  31. Stamminger T., Puchtler E., Fleckenstein B. Discordant expression of the immediate-early 1 and 2 gene regions of human cytomegalovirus at early times after infection involves posttranscriptional processing events. J Virol. 1991 May;65(5):2273–2282. doi: 10.1128/jvi.65.5.2273-2282.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stenberg R. M., Depto A. S., Fortney J., Nelson J. A. Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region. J Virol. 1989 Jun;63(6):2699–2708. doi: 10.1128/jvi.63.6.2699-2708.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stinski M. F. Sequence of protein synthesis in cells infected by human cytomegalovirus: early and late virus-induced polypeptides. J Virol. 1978 Jun;26(3):686–701. doi: 10.1128/jvi.26.3.686-701.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wathen M. W., Stinski M. F. Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol. 1982 Feb;41(2):462–477. doi: 10.1128/jvi.41.2.462-477.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Werner M., Feller A., Messenguy F., Piérard A. The leader peptide of yeast gene CPA1 is essential for the translational repression of its expression. Cell. 1987 Jun 19;49(6):805–813. doi: 10.1016/0092-8674(87)90618-0. [DOI] [PubMed] [Google Scholar]
  36. Wright D. A., Spector D. H. Posttranscriptional regulation of a class of human cytomegalovirus phosphoproteins encoded by an early transcription unit. J Virol. 1989 Jul;63(7):3117–3127. doi: 10.1128/jvi.63.7.3117-3127.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES