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. 1986 Jul;5(7):1625–1632. doi: 10.1002/j.1460-2075.1986.tb04405.x

Viral-encoded small RNAs in herpes virus saimiri induced tumors.

S Murthy, J Kamine, R C Desrosiers
PMCID: PMC1166988  PMID: 2427336

Abstract

DNA sequences from the left terminus of herpes virus saimiri L-DNA are essential for the oncogenic and transforming potential of the virus, but these sequences are not required for replication. RNA derived from 0.0 to 6.7 map units (7.4 kbp) on the herpes virus saimiri genome was studied by Northern blot hybridization and by nuclease protection analyses. Although several poly(A)-containing RNAs were detected from this region in permissively-infected monolayer cells in vitro, these RNAs could not be detected in cells taken directly from viral-induced lymphomas nor in the lymphoblastoid tumor cell line 1670. Instead, these transformed T-cells expressed four small RNAs of approximately 73, 105, 110 and 135 nt derived from this region. These small RNAs were not detected at all during the course of lytic infection of monolayer cells. Thus, synthesis of these RNAs is stringently regulated in a cell-type specific manner. Genomic coding sequences for each of these small RNAs were mapped to 0.5-1.2 kbp DNA fragments stretched over 4.3 kbp of viral genetic information. These findings together with the biological properties of mutants with deletions in this region have led us to speculate that one or more of these small RNAs play an essential role in cell growth transformation by herpes virus saimiri.

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Selected References

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

  1. Arrand J. R., Rymo L. Characterization of the major Epstein-Barr virus-specific RNA in Burkitt lymphoma-derived cells. J Virol. 1982 Feb;41(2):376–389. doi: 10.1128/jvi.41.2.376-389.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barta A., Richards R. I., Baxter J. D., Shine J. Primary structure and evolution of rat growth hormone gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4867–4871. doi: 10.1073/pnas.78.8.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhat R. A., Thimmappaya B. Construction and analysis of additional adenovirus substitution mutants confirm the complementation of VAI RNA function by two small RNAs encoded by Epstein-Barr virus. J Virol. 1985 Dec;56(3):750–756. doi: 10.1128/jvi.56.3.750-756.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheah M. S., Ley T. J., Tronick S. R., Robbins K. C. fgr proto-oncogene mRNA induced in B lymphocytes by Epstein-Barr virus infection. Nature. 1986 Jan 16;319(6050):238–240. doi: 10.1038/319238a0. [DOI] [PubMed] [Google Scholar]
  5. Desrosiers R. C., Bakker A., Kamine J., Falk L. A., Hunt R. D., King N. W. A region of the Herpesvirus saimiri genome required for oncogenicity. Science. 1985 Apr 12;228(4696):184–187. doi: 10.1126/science.2983431. [DOI] [PubMed] [Google Scholar]
  6. Desrosiers R. C., Burghoff R. L., Bakker A., Kamine J. Construction of replication-competent Herpesvirus saimiri deletion mutants. J Virol. 1984 Feb;49(2):343–348. doi: 10.1128/jvi.49.2.343-348.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Desrosiers R. C., Silva D. P., Waldron L. M., Letvin N. L. Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol. 1986 Feb;57(2):701–705. doi: 10.1128/jvi.57.2.701-705.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grinnell B. W., Wagner R. R. Inhibition of DNA-dependent transcription by the leader RNA of vesicular stomatitis virus: role of specific nucleotide sequences and cell protein binding. Mol Cell Biol. 1985 Oct;5(10):2502–2513. doi: 10.1128/mcb.5.10.2502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gutierrez-Hartmann A., Lieberburg I., Gardner D., Baxter J. D., Cathala G. G. Transcription of two classes of rat growth hormone gene-associated repetitive DNA: differences in activity and effects of tandem repeat structure. Nucleic Acids Res. 1984 Sep 25;12(18):7153–7173. doi: 10.1093/nar/12.18.7153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kamine J., Bakker A., Desrosiers R. C. Mapping of RNA transcribed from a region of the Herpesvirus saimiri genome required for oncogenicity. J Virol. 1984 Nov;52(2):532–540. doi: 10.1128/jvi.52.2.532-540.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knust E., Dietrich W., Fleckenstein B., Bodemer W. Virus-specific transcription in a Herpesvirus saimiri-transformed lymphoid tumor cell line. J Virol. 1983 Nov;48(2):377–383. doi: 10.1128/jvi.48.2.377-383.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koomey J. M., Mulder C., Burghoff R. L., Fleckenstein B., Desrosiers R. C. Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri. J Virol. 1984 May;50(2):662–665. doi: 10.1128/jvi.50.2.662-665.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lerner M. R., Andrews N. C., Miller G., Steitz J. A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1981 Feb;78(2):805–809. doi: 10.1073/pnas.78.2.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Milner R. J., Bloom F. E., Lai C., Lerner R. A., Sutcliffe J. G. Brain-specific genes have identifier sequences in their introns. Proc Natl Acad Sci U S A. 1984 Feb;81(3):713–717. doi: 10.1073/pnas.81.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Malley R. P., Mariano T. M., Siekierka J., Mathews M. B. A mechanism for the control of protein synthesis by adenovirus VA RNAI. Cell. 1986 Feb 14;44(3):391–400. doi: 10.1016/0092-8674(86)90460-5. [DOI] [PubMed] [Google Scholar]
  18. Rabin H., Hopkins R. F., 3rd, Desrosiers R. C., Ortaldo J. R., Djeu J. Y., Neubauer R. H. Transformation of owl monkey T cells in vitro with Herpesvirus saimiri. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4563–4567. doi: 10.1073/pnas.81.14.4563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reich P. R., Forget B. G., Weissman S. M. RNA of low molecular weight in KB cells infected with adenovirus type 2. J Mol Biol. 1966 Jun;17(2):428–439. doi: 10.1016/s0022-2836(66)80153-5. [DOI] [PubMed] [Google Scholar]
  20. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  21. Schaffer P. A., Falk L. A., Deinhardt F. Attenuation of herpesvirus saimiri for marmosets after successive passage in cell culture at 39 degrees C. J Natl Cancer Inst. 1975 Nov;55(5):1243–1246. doi: 10.1093/jnci/55.5.1243. [DOI] [PubMed] [Google Scholar]
  22. Schirm S., Müller I., Desrosiers R. C., Fleckenstein B. Herpesvirus saimiri DNA in a lymphoid cell line established by in vitro transformation. J Virol. 1984 Mar;49(3):938–946. doi: 10.1128/jvi.49.3.938-946.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schneider R. J., Safer B., Munemitsu S. M., Samuel C. E., Shenk T. Adenovirus VAI RNA prevents phosphorylation of the eukaryotic initiation factor 2 alpha subunit subsequent to infection. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4321–4325. doi: 10.1073/pnas.82.13.4321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schutzbank T., Robinson R., Oren M., Levine A. J. SV40 large tumor antigen can regulate some cellular transcripts in a positive fashion. Cell. 1982 Sep;30(2):481–490. doi: 10.1016/0092-8674(82)90245-8. [DOI] [PubMed] [Google Scholar]
  25. Singh K., Carey M., Saragosti S., Botchan M. Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells. Nature. 1985 Apr 11;314(6011):553–556. doi: 10.1038/314553a0. [DOI] [PubMed] [Google Scholar]
  26. Sutcliffe J. G., Milner R. J., Bloom F. E., Lerner R. A. Common 82-nucleotide sequence unique to brain RNA. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4942–4946. doi: 10.1073/pnas.79.16.4942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sutcliffe J. G., Milner R. J., Gottesfeld J. M., Lerner R. A. Identifier sequences are transcribed specifically in brain. Nature. 1984 Mar 15;308(5956):237–241. doi: 10.1038/308237a0. [DOI] [PubMed] [Google Scholar]
  28. Sutcliffe J. G., Milner R. J., Gottesfeld J. M., Reynolds W. Control of neuronal gene expression. Science. 1984 Sep 21;225(4668):1308–1315. doi: 10.1126/science.6474179. [DOI] [PubMed] [Google Scholar]
  29. Söderlund H., Pettersson U., Vennström B., Philipson L., Mathews M. B. A new species of virus-coded low molecular weight RNA from cells infected with adenovirus type 2. Cell. 1976 Apr;7(4):585–593. doi: 10.1016/0092-8674(76)90209-9. [DOI] [PubMed] [Google Scholar]
  30. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Turner P. Controlling roles for snurps. Nature. 1985 Jul 11;316(6024):105–106. doi: 10.1038/316105a0. [DOI] [PubMed] [Google Scholar]

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