Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 Dec;7(12):4505–4512. doi: 10.1128/mcb.7.12.4505

Induced heat shock mRNAs escape the nucleocytoplasmic transport block in adenovirus-infected HeLa cells.

M Moore 1, J Schaack 1, S B Baim 1, R I Morimoto 1, T Shenk 1
PMCID: PMC368135  PMID: 3437895

Abstract

Under conditions in which cytoplasmic accumulation of HeLa cell mRNAs has been blocked by adenovirus infection, hsp70 family mRNAs are transported from the nucleus to the cytoplasm at near normal efficiency subsequent to heat shock. Heat shock does not reverse the general virus-induced block to host cell mRNA transport. The heat shock mRNAs are translated within the cytoplasm of the infected cell but at substantially reduced efficiency compared with that of uninfected cells. Thus, the hsp70 family of mRNAs can escape the transport block but not the translational block instituted late after adenovirus infection. The beta-tubulin gene family is induced by the viral E1A gene after infection, and its mRNAs also accumulate in the cytoplasmic compartment. Given these two examples, it seems likely that the process of transcriptional induction allows the resulting mRNA to escape the viral block of transport.

Full text

PDF

Images in this article

4506Image
on p.4506
4507Image
on p.4507
4508Image
on p.4508
4509Image
on p.4509

Selected References

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

  1. Ashburner M., Bonner J. J. The induction of gene activity in drosophilia by heat shock. Cell. 1979 Jun;17(2):241–254. doi: 10.1016/0092-8674(79)90150-8. [DOI] [PubMed] [Google Scholar]
  2. Babich A., Feldman L. T., Nevins J. R., Darnell J. E., Jr, Weinberger C. Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination. Mol Cell Biol. 1983 Jul;3(7):1212–1221. doi: 10.1128/mcb.3.7.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Babiss L. E., Ginsberg H. S. Adenovirus type 5 early region 1b gene product is required for efficient shutoff of host protein synthesis. J Virol. 1984 Apr;50(1):202–212. doi: 10.1128/jvi.50.1.202-212.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Beltz G. A., Flint S. J. Inhibition of HeLa cell protein synthesis during adenovirus infection. Restriction of cellular messenger RNA sequences to the nucleus. J Mol Biol. 1979 Jun 25;131(2):353–373. doi: 10.1016/0022-2836(79)90081-0. [DOI] [PubMed] [Google Scholar]
  7. Blobel G. Gene gating: a hypothesis. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8527–8529. doi: 10.1073/pnas.82.24.8527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Craig E. A. The heat shock response. CRC Crit Rev Biochem. 1985;18(3):239–280. doi: 10.3109/10409238509085135. [DOI] [PubMed] [Google Scholar]
  10. Duncan R., Hershey J. W. Heat shock-induced translational alterations in HeLa cells. Initiation factor modifications and the inhibition of translation. J Biol Chem. 1984 Oct 10;259(19):11882–11889. [PubMed] [Google Scholar]
  11. Gaynor R. B., Hillman D., Berk A. J. Adenovirus early region 1A protein activates transcription of a nonviral gene introduced into mammalian cells by infection or transfection. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1193–1197. doi: 10.1073/pnas.81.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greenberg J. R. High stability of messenger RNA in growing cultured cells. Nature. 1972 Nov 10;240(5376):102–104. doi: 10.1038/240102a0. [DOI] [PubMed] [Google Scholar]
  13. Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Harrison G. S., Drabkin H. A., Kao F. T., Hartz J., Hart I. M., Chu E. H., Wu B. J., Morimoto R. I. Chromosomal location of human genes encoding major heat-shock protein HSP70. Somat Cell Mol Genet. 1987 Mar;13(2):119–130. doi: 10.1007/BF01534692. [DOI] [PubMed] [Google Scholar]
  17. Hearing P., Shenk T. Sequence-independent autoregulation of the adenovirus type 5 E1A transcription unit. Mol Cell Biol. 1985 Nov;5(11):3214–3221. doi: 10.1128/mcb.5.11.3214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hearing P., Shenk T. The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell. 1983 Jul;33(3):695–703. doi: 10.1016/0092-8674(83)90012-0. [DOI] [PubMed] [Google Scholar]
  19. Hickey E. D., Weber L. A. Modulation of heat-shock polypeptide synthesis in HeLa cells during hyperthermia and recovery. Biochemistry. 1982 Mar 30;21(7):1513–1521. doi: 10.1021/bi00536a008. [DOI] [PubMed] [Google Scholar]
  20. Hinds P. W., Finlay C. A., Frey A. B., Levine A. J. Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines. Mol Cell Biol. 1987 Aug;7(8):2863–2869. doi: 10.1128/mcb.7.8.2863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hofer E., Darnell J. E., Jr The primary transcription unit of the mouse beta-major globin gene. Cell. 1981 Feb;23(2):585–593. doi: 10.1016/0092-8674(81)90154-9. [DOI] [PubMed] [Google Scholar]
  22. Hunt C., Morimoto R. I. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6455–6459. doi: 10.1073/pnas.82.19.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hutchison N., Weintraub H. Localization of DNAase I-sensitive sequences to specific regions of interphase nuclei. Cell. 1985 Dec;43(2 Pt 1):471–482. doi: 10.1016/0092-8674(85)90177-1. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Kao H. T., Nevins J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol. 1983 Nov;3(11):2058–2065. doi: 10.1128/mcb.3.11.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kay R. J., Russnak R. H., Jones D., Mathias C., Candido E. P. Expression of intron-containing C. elegans heat shock genes in mouse cells demonstrates divergence of 3' splice site recognition sequences between nematodes and vertebrates, and an inhibitory effect of heat shock on the mammalian splicing apparatus. Nucleic Acids Res. 1987 May 11;15(9):3723–3741. doi: 10.1093/nar/15.9.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee M. G., Lewis S. A., Wilde C. D., Cowan N. J. Evolutionary history of a multigene family: an expressed human beta-tubulin gene and three processed pseudogenes. Cell. 1983 Jun;33(2):477–487. doi: 10.1016/0092-8674(83)90429-4. [DOI] [PubMed] [Google Scholar]
  28. Lin A. Y., Chang S. C., Lee A. S. A calcium ionophore-inducible cellular promoter is highly active and has enhancerlike properties. Mol Cell Biol. 1986 Apr;6(4):1235–1243. doi: 10.1128/mcb.6.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lindquist S. Regulation of protein synthesis during heat shock. Nature. 1981 Sep 24;293(5830):311–314. doi: 10.1038/293311a0. [DOI] [PubMed] [Google Scholar]
  30. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–1191. doi: 10.1146/annurev.bi.55.070186.005443. [DOI] [PubMed] [Google Scholar]
  31. Lowe D. G., Moran L. A. Molecular cloning and analysis of DNA complementary to three mouse Mr = 68,000 heat shock protein mRNAs. J Biol Chem. 1986 Feb 15;261(5):2102–2112. [PubMed] [Google Scholar]
  32. McCormick W., Penman S. Regulation of protein synthesis in HeLa cells: translation at elevated temperatures. J Mol Biol. 1969 Jan;39(2):315–333. doi: 10.1016/0022-2836(69)90320-9. [DOI] [PubMed] [Google Scholar]
  33. McKnight G. S., Palmiter R. D. Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct. J Biol Chem. 1979 Sep 25;254(18):9050–9058. [PubMed] [Google Scholar]
  34. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mues G. I., Munn T. Z., Raese J. D. A human gene family with sequence homology to Drosophila melanogaster Hsp70 heat shock genes. J Biol Chem. 1986 Jan 15;261(2):874–877. [PubMed] [Google Scholar]
  36. Munro S., Pelham H. R. An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell. 1986 Jul 18;46(2):291–300. doi: 10.1016/0092-8674(86)90746-4. [DOI] [PubMed] [Google Scholar]
  37. O'Malley K., Mauron A., Barchas J. D., Kedes L. Constitutively expressed rat mRNA encoding a 70-kilodalton heat-shock-like protein. Mol Cell Biol. 1985 Dec;5(12):3476–3483. doi: 10.1128/mcb.5.12.3476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pelham H. R. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986 Sep 26;46(7):959–961. doi: 10.1016/0092-8674(86)90693-8. [DOI] [PubMed] [Google Scholar]
  39. Philipson L., Pettersson U., Lindberg U., Tibbetts C., Vennström B., Persson T. RNA synthesis and processing in adenovirus-infected cells. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):447–456. doi: 10.1101/sqb.1974.039.01.057. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Sarnow P., Sullivan C. A., Levine A. J. A monoclonal antibody detecting the adenovirus type 5-E1b-58Kd tumor antigen: characterization of the E1b-58Kd tumor antigen in adenovirus-infected and -transformed cells. Virology. 1982 Jul 30;120(2):510–517. doi: 10.1016/0042-6822(82)90054-x. [DOI] [PubMed] [Google Scholar]
  43. Schlesinger M. J. Heat shock proteins: the search for functions. J Cell Biol. 1986 Aug;103(2):321–325. doi: 10.1083/jcb.103.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sierra F., Lichtler A., Marashi F., Rickles R., Van Dyke T., Clark S., Wells J., Stein G., Stein J. Organization of human histone genes. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1795–1799. doi: 10.1073/pnas.79.6.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Slater A., Cato A. C., Sillar G. M., Kioussis J., Burdon R. H. The pattern of protein synthesis induced by heat shock of HeLa cells. Eur J Biochem. 1981 Jul;117(2):341–346. doi: 10.1111/j.1432-1033.1981.tb06343.x. [DOI] [PubMed] [Google Scholar]
  46. Sorger P. K., Pelham H. R. Cloning and expression of a gene encoding hsc73, the major hsp70-like protein in unstressed rat cells. EMBO J. 1987 Apr;6(4):993–998. doi: 10.1002/j.1460-2075.1987.tb04850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stein R., Ziff E. B. HeLa cell beta-tubulin gene transcription is stimulated by adenovirus 5 in parallel with viral early genes by an E1a-dependent mechanism. Mol Cell Biol. 1984 Dec;4(12):2792–2801. doi: 10.1128/mcb.4.12.2792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Storti R. V., Scott M. P., Rich A., Pardue M. L. Translational control of protein synthesis in response to heat shock in D. melanogaster cells. Cell. 1980 Dec;22(3):825–834. doi: 10.1016/0092-8674(80)90559-0. [DOI] [PubMed] [Google Scholar]
  49. Wilson M. C., Nevins J. R., Blanchard J. M., Ginsberg H. S., Darnell J. E., Jr Metabolism of mRNA from the transforming region of adenovirus 2. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):447–455. doi: 10.1101/sqb.1980.044.01.048. [DOI] [PubMed] [Google Scholar]
  50. Wu B. J., Hurst H. C., Jones N. C., Morimoto R. I. The E1A 13S product of adenovirus 5 activates transcription of the cellular human HSP70 gene. Mol Cell Biol. 1986 Aug;6(8):2994–2999. doi: 10.1128/mcb.6.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wu B., Hunt C., Morimoto R. Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol. 1985 Feb;5(2):330–341. doi: 10.1128/mcb.5.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Yost H. J., Lindquist S. RNA splicing is interrupted by heat shock and is rescued by heat shock protein synthesis. Cell. 1986 Apr 25;45(2):185–193. doi: 10.1016/0092-8674(86)90382-x. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES