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. 1990 Dec;87(24):9543–9547. doi: 10.1073/pnas.87.24.9543

Adenovirus early region 4 stimulates mRNA accumulation via 5' introns.

K Nordqvist 1, G Akusjärvi 1
PMCID: PMC55208  PMID: 2263609

Abstract

The adenovirus major late transcription unit accounts for most virus-specific transcription late after infection. All mRNAs expressed from this unit carry a short spliced leader, the so-called tripartite leader, attached to their 5' ends. Here we describe a function for an adenovirus gene product in the control of major late mRNA abundance. We show that early region 4 (E4) stimulates mRNA accumulation from tripartite leader intron-containing transcription units approximately 10-fold in short-term transfection assays. The effect was already detectable in nuclear RNA and was not due to a transcriptional activation through any of the major late promoter elements or through an effect at nuclear to cytoplasmic mRNA transport. A surprising positional effect of the intron was noted. To be E4 responsive, the intron had to be placed close to the pre-mRNA 5' end. The same intron located far downstream in the 3' untranslated region of the mRNA was not E4 responsive. The E4 enhancement was not dependent on specific virus exon or intron sequences. These results suggest that E4 modulates a general pathway in mammalian mRNA formation.

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Selected References

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

  1. Babiss L. E. The cellular transcription factor E2f requires viral E1A and E4 gene products for increased DNA-binding activity and functions to stimulate adenovirus E2A gene expression. J Virol. 1989 Jun;63(6):2709–2717. doi: 10.1128/jvi.63.6.2709-2717.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beyer A. L., Osheim Y. N. Splice site selection, rate of splicing, and alternative splicing on nascent transcripts. Genes Dev. 1988 Jun;2(6):754–765. doi: 10.1101/gad.2.6.754. [DOI] [PubMed] [Google Scholar]
  3. Bridge E., Ketner G. Interaction of adenoviral E4 and E1b products in late gene expression. Virology. 1990 Feb;174(2):345–353. doi: 10.1016/0042-6822(90)90088-9. [DOI] [PubMed] [Google Scholar]
  4. Bridge E., Ketner G. Redundant control of adenovirus late gene expression by early region 4. J Virol. 1989 Feb;63(2):631–638. doi: 10.1128/jvi.63.2.631-638.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buchman A. R., Berg P. Comparison of intron-dependent and intron-independent gene expression. Mol Cell Biol. 1988 Oct;8(10):4395–4405. doi: 10.1128/mcb.8.10.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Callis J., Fromm M., Walbot V. Introns increase gene expression in cultured maize cells. Genes Dev. 1987 Dec;1(10):1183–1200. doi: 10.1101/gad.1.10.1183. [DOI] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Cutt J. R., Shenk T., Hearing P. Analysis of adenovirus early region 4-encoded polypeptides synthesized in productively infected cells. J Virol. 1987 Feb;61(2):543–552. doi: 10.1128/jvi.61.2.543-552.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Falgout B., Ketner G. Adenovirus early region 4 is required for efficient virus particle assembly. J Virol. 1987 Dec;61(12):3759–3768. doi: 10.1128/jvi.61.12.3759-3768.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goding C., Jalinot P., Zajchowski D., Boeuf H., Kédinger C. Sequence-specific trans-activation of the adenovirus EIIa early promoter by the viral EIV transcription unit. EMBO J. 1985 Jun;4(6):1523–1528. doi: 10.1002/j.1460-2075.1985.tb03812.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  12. Halbert D. N., Cutt J. R., Shenk T. Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J Virol. 1985 Oct;56(1):250–257. doi: 10.1128/jvi.56.1.250-257.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hardy S., Engel D. A., Shenk T. An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity. Genes Dev. 1989 Jul;3(7):1062–1074. doi: 10.1101/gad.3.7.1062. [DOI] [PubMed] [Google Scholar]
  14. Hemström C., Nordqvist K., Pettersson U., Virtanen A. Gene product of region E4 of adenovirus type 5 modulates accumulation of certain viral polypeptides. J Virol. 1988 Sep;62(9):3258–3264. doi: 10.1128/jvi.62.9.3258-3264.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang M. M., Hearing P. Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection. J Virol. 1989 Jun;63(6):2605–2615. doi: 10.1128/jvi.63.6.2605-2615.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang M. M., Hearing P. The adenovirus early region 4 open reading frame 6/7 protein regulates the DNA binding activity of the cellular transcription factor, E2F, through a direct complex. Genes Dev. 1989 Nov;3(11):1699–1710. doi: 10.1101/gad.3.11.1699. [DOI] [PubMed] [Google Scholar]
  17. Huang M. T., Gorman C. M. Intervening sequences increase efficiency of RNA 3' processing and accumulation of cytoplasmic RNA. Nucleic Acids Res. 1990 Feb 25;18(4):937–947. doi: 10.1093/nar/18.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jansen-Durr P., Mondésert G., Kédinger C. Replication-dependent activation of the adenovirus major late promoter is mediated by the increased binding of a transcription factor to sequences in the first intron. J Virol. 1989 Dec;63(12):5124–5132. doi: 10.1128/jvi.63.12.5124-5132.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klinz F. J., Gallwitz D. Size and position of intervening sequences are critical for the splicing efficiency of pre-mRNA in the yeast Saccharomyces cerevisiae. Nucleic Acids Res. 1985 Jun 11;13(11):3791–3804. doi: 10.1093/nar/13.11.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leong K., Lee W., Berk A. J. High-level transcription from the adenovirus major late promoter requires downstream binding sites for late-phase-specific factors. J Virol. 1990 Jan;64(1):51–60. doi: 10.1128/jvi.64.1.51-60.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lewis E. D., Manley J. L. Control of adenovirus late promoter expression in two human cell lines. Mol Cell Biol. 1985 Sep;5(9):2433–2442. doi: 10.1128/mcb.5.9.2433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mansour S. L., Grodzicker T., Tjian R. Downstream sequences affect transcription initiation from the adenovirus major late promoter. Mol Cell Biol. 1986 Jul;6(7):2684–2694. doi: 10.1128/mcb.6.7.2684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moore M. A., Shenk T. The adenovirus tripartite leader sequence can alter nuclear and cytoplasmic metabolism of a non-adenovirus mRNA within infected cells. Nucleic Acids Res. 1988 Mar 25;16(5):2247–2262. doi: 10.1093/nar/16.5.2247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Patzelt E., Thalmann E., Hartmuth K., Blaas D., Kuechler E. Assembly of pre-mRNA splicing complex is cap dependent. Nucleic Acids Res. 1987 Feb 25;15(4):1387–1399. doi: 10.1093/nar/15.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Reichel R., Neill S. D., Kovesdi I., Simon M. C., Raychaudhuri P., Nevins J. R. The adenovirus E4 gene, in addition to the E1A gene, is important for trans-activation of E2 transcription and for E2F activation. J Virol. 1989 Sep;63(9):3643–3650. doi: 10.1128/jvi.63.9.3643-3650.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sandler A. B., Ketner G. Adenovirus early region 4 is essential for normal stability of late nuclear RNAs. J Virol. 1989 Feb;63(2):624–630. doi: 10.1128/jvi.63.2.624-630.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sarnow P., Hearing P., Anderson C. W., Halbert D. N., Shenk T., Levine A. J. Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells. J Virol. 1984 Mar;49(3):692–700. doi: 10.1128/jvi.49.3.692-700.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Svensson C., Akusjärvi G. A novel effect of adenovirus VA RNA1 on cytoplasmic mRNA abundance. Virology. 1990 Feb;174(2):613–617. doi: 10.1016/0042-6822(90)90116-9. [DOI] [PubMed] [Google Scholar]
  29. Svensson C., Akusjärvi G. Adenovirus 2 early region 1A stimulates expression of both viral and cellular genes. EMBO J. 1984 Apr;3(4):789–794. doi: 10.1002/j.1460-2075.1984.tb01886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Svensson C., Akusjärvi G. Adenovirus VA RNAI mediates a translational stimulation which is not restricted to the viral mRNAs. EMBO J. 1985 Apr;4(4):957–964. doi: 10.1002/j.1460-2075.1985.tb03724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Svensson C., Pettersson U., Akusjärvi G. Splicing of adenovirus 2 early region 1A mRNAs is non-sequential. J Mol Biol. 1983 Apr 15;165(3):475–495. doi: 10.1016/s0022-2836(83)80214-9. [DOI] [PubMed] [Google Scholar]
  32. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weinberg D. H., Ketner G. Adenoviral early region 4 is required for efficient viral DNA replication and for late gene expression. J Virol. 1986 Mar;57(3):833–838. doi: 10.1128/jvi.57.3.833-838.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]
  35. van Ooyen A., van den Berg J., Mantei N., Weissmann C. Comparison of total sequence of a cloned rabbit beta-globin gene and its flanking regions with a homologous mouse sequence. Science. 1979 Oct 19;206(4416):337–344. doi: 10.1126/science.482942. [DOI] [PubMed] [Google Scholar]

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