Abstract
The interactions of adenovirus with differentiated human cells have been investigated in human myeloma cells. Relative to HeLa cells, the E1A and E1B genes, but not other viral genes, were markedly repressed by differential RNA stabilization, resulting in 20- to 50-fold less E1A and E1B mRNAs at steady state late in infection. The reduced E1A level corresponded to an approximately 200-fold-lower abundance of E1A polypeptides, which were nonetheless capable of efficient transactivation of E1A-dependent viral genes and were necessary for productive infection. The E1B gene was further regulated posttranscriptionally, yielding altered molar representation of alternatively spliced 22S and 13S mRNAs early in infection of myeloma cells. Taken together, these results suggested that repression and altered expression of E1A and E1B genes may provide a molecular basis of delayed kinetics of infection of lymphoid cells with adenovirus (D. Lavery, S. M. Fu, T. Lufkin, and S. Chen-Kiang, J. Virol. 61:1466-1472, 1987). The molecular mechanisms by which E1A and E1B are regulated and by which E1A transactivates viral genes in lymphoid cells are discussed.
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Selected References
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- Aleström P., Akusjärvi G., Perricaudet M., Mathews M. B., Klessig D. F., Pettersson U. The gene for polypeptide IX of adenovirus type 2 and its unspliced messenger RNA. Cell. 1980 Mar;19(3):671–681. doi: 10.1016/s0092-8674(80)80044-4. [DOI] [PubMed] [Google Scholar]
- Babich A., Nevins J. R. The stability of early adenovirus mRNA is controlled by the viral 72 kd DNA-binding protein. Cell. 1981 Nov;26(3 Pt 1):371–379. doi: 10.1016/0092-8674(81)90206-3. [DOI] [PubMed] [Google Scholar]
- Babiss L. E., Ginsberg H. S., Darnell J. E., Jr Adenovirus E1B proteins are required for accumulation of late viral mRNA and for effects on cellular mRNA translation and transport. Mol Cell Biol. 1985 Oct;5(10):2552–2558. doi: 10.1128/mcb.5.10.2552. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berk A. J. Adenovirus promoters and E1A transactivation. Annu Rev Genet. 1986;20:45–79. doi: 10.1146/annurev.ge.20.120186.000401. [DOI] [PubMed] [Google Scholar]
- Bhat B. M., Brady H. A., Pursley M. H., Wold W. S. Deletion mutants that alter differential RNA processing in the E3 complex transcription unit of adenovirus. J Mol Biol. 1986 Aug 20;190(4):543–557. doi: 10.1016/0022-2836(86)90240-8. [DOI] [PubMed] [Google Scholar]
- Brewer G., Ross J. Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system. Mol Cell Biol. 1988 Apr;8(4):1697–1708. doi: 10.1128/mcb.8.4.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunet L. J., Berk A. J. Concentration dependence of transcriptional transactivation in inducible E1A-containing human cells. Mol Cell Biol. 1988 Nov;8(11):4799–4807. doi: 10.1128/mcb.8.11.4799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen-Kiang S., Lavery D. J. Preparation of precursors to mRNA from mammalian cell nuclei. Methods Enzymol. 1989;180:69–82. doi: 10.1016/0076-6879(89)80093-x. [DOI] [PubMed] [Google Scholar]
- Chen-Kiang S., Lavery D. J. Pulse labeling of heterogeneous nuclear RNA in isolated nuclei. Methods Enzymol. 1989;180:82–96. doi: 10.1016/0076-6879(89)80094-1. [DOI] [PubMed] [Google Scholar]
- Chen-Kiang S., Wolgemuth D. J., Hsu M. T., Darnell J. E., Jr Transcription and accurate polyadenylation in vitro of RNA from the major late adenovirus 2 transcription unit. Cell. 1982 Mar;28(3):575–584. doi: 10.1016/0092-8674(82)90212-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Engel D. A., Hardy S., Shenk T. cAMP acts in synergy with E1A protein to activate transcription of the adenovirus early genes E4 and E1A. Genes Dev. 1988 Dec;2(12A):1517–1528. doi: 10.1101/gad.2.12a.1517. [DOI] [PubMed] [Google Scholar]
- Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
- Flint J., Shenk T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. doi: 10.1146/annurev.ge.23.120189.001041. [DOI] [PubMed] [Google Scholar]
- Flint J. The topography and transcription of the adenovirus genome. Cell. 1977 Feb;10(2):153–166. doi: 10.1016/0092-8674(77)90211-2. [DOI] [PubMed] [Google Scholar]
- Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gingeras T. R., Sciaky D., Gelinas R. E., Bing-Dong J., Yen C. E., Kelly M. M., Bullock P. A., Parsons B. L., O'Neill K. E., Roberts R. J. Nucleotide sequences from the adenovirus-2 genome. J Biol Chem. 1982 Nov 25;257(22):13475–13491. [PubMed] [Google Scholar]
- 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]
- 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]
- Harlow E., Franza B. R., Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. doi: 10.1128/jvi.55.3.533-546.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hearing P., Shenk T. The adenovirus type 5 E1A enhancer contains two functionally distinct domains: one is specific for E1A and the other modulates all early units in cis. Cell. 1986 Apr 25;45(2):229–236. doi: 10.1016/0092-8674(86)90387-9. [DOI] [PubMed] [Google Scholar]
- Jones N., Shenk T. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell. 1979 Jul;17(3):683–689. doi: 10.1016/0092-8674(79)90275-7. [DOI] [PubMed] [Google Scholar]
- Kovesdi I., Reichel R., Nevins J. R. E1A transcription induction: enhanced binding of a factor to upstream promoter sequences. Science. 1986 Feb 14;231(4739):719–722. doi: 10.1126/science.2935935. [DOI] [PubMed] [Google Scholar]
- Lavery D., Fu S. M., Lufkin T., Chen-Kiang S. Productive infection of cultured human lymphoid cells by adenovirus. J Virol. 1987 May;61(5):1466–1472. doi: 10.1128/jvi.61.5.1466-1472.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malter J. S. Identification of an AUUUA-specific messenger RNA binding protein. Science. 1989 Nov 3;246(4930):664–666. doi: 10.1126/science.2814487. [DOI] [PubMed] [Google Scholar]
- Matsuoka Y., Moore G. E., Yagi Y., Pressman D. Production of free light chains of immunoglobulin by a hematopoietic cell line derived from a patient with multiple myeloma. Proc Soc Exp Biol Med. 1967 Aug-Sep;125(4):1246–1250. doi: 10.3181/00379727-125-32327. [DOI] [PubMed] [Google Scholar]
- Moran E., Mathews M. B. Multiple functional domains in the adenovirus E1A gene. Cell. 1987 Jan 30;48(2):177–178. doi: 10.1016/0092-8674(87)90418-1. [DOI] [PubMed] [Google Scholar]
- Osborne T. F., Berk A. J. Far upstream initiation sites for adenovirus early region 1A transcription are utilized after the onset of viral DNA replication. J Virol. 1983 Feb;45(2):594–599. doi: 10.1128/jvi.45.2.594-599.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pei R., Calame K. Differential stability of c-myc mRNAS in a cell-free system. Mol Cell Biol. 1988 Jul;8(7):2860–2868. doi: 10.1128/mcb.8.7.2860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peltz S. W., Ross J. Autogenous regulation of histone mRNA decay by histone proteins in a cell-free system. Mol Cell Biol. 1987 Dec;7(12):4345–4356. doi: 10.1128/mcb.7.12.4345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perricaudet M., Akusjärvi G., Virtanen A., Pettersson U. Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses. Nature. 1979 Oct 25;281(5733):694–696. doi: 10.1038/281694a0. [DOI] [PubMed] [Google Scholar]
- Perricaudet M., Le Moullec J. M., Pettersson U. Predicted structure of two adenovirus tumor antigens. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3778–3782. doi: 10.1073/pnas.77.7.3778. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilder S., Moore M., Logan J., Shenk T. The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs. Mol Cell Biol. 1986 Feb;6(2):470–476. doi: 10.1128/mcb.6.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pugh B. F., Tjian R. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell. 1990 Jun 29;61(7):1187–1197. doi: 10.1016/0092-8674(90)90683-6. [DOI] [PubMed] [Google Scholar]
- Ruether J. E., Maderious A., Lavery D., Logan J., Fu S. M., Chen-Kiang S. Cell-type-specific synthesis of murine immunoglobulin mu RNA from an adenovirus vector. Mol Cell Biol. 1986 Jan;6(1):123–133. doi: 10.1128/mcb.6.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarnow P., Ho Y. S., Williams J., Levine A. J. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell. 1982 Feb;28(2):387–394. doi: 10.1016/0092-8674(82)90356-7. [DOI] [PubMed] [Google Scholar]
- Shenk T., Jones N., Colby W., Fowlkes D. Functional analysis of adenovirus-5 host-range deletion mutants defective for transformation of rat embryo cells. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):367–375. doi: 10.1101/sqb.1980.044.01.041. [DOI] [PubMed] [Google Scholar]
- Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Virtanen A., Gilardi P., Näslund A., LeMoullec J. M., Pettersson U., Perricaudet M. mRNAs from human adenovirus 2 early region 4. J Virol. 1984 Sep;51(3):822–831. doi: 10.1128/jvi.51.3.822-831.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White E., Grodzicker T., Stillman B. W. Mutations in the gene encoding the adenovirus early region 1B 19,000-molecular-weight tumor antigen cause the degradation of chromosomal DNA. J Virol. 1984 Nov;52(2):410–419. doi: 10.1128/jvi.52.2.410-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson M. C., Darnell J. E., Jr Control of messenger RNA concentration by differential cytoplasmic half-life. Adenovirus messenger RNAs from transcription units 1A and 1B. J Mol Biol. 1981 May 25;148(3):231–251. doi: 10.1016/0022-2836(81)90537-4. [DOI] [PubMed] [Google Scholar]
- Wu L., Rosser D. S., Schmidt M. C., Berk A. A TATA box implicated in E1A transcriptional activation of a simple adenovirus 2 promoter. Nature. 1987 Apr 2;326(6112):512–515. doi: 10.1038/326512a0. [DOI] [PubMed] [Google Scholar]