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. 1987 May;84(10):3171–3175. doi: 10.1073/pnas.84.10.3171

Aberrant splicing events that are induced by proviral integration: implications for myb oncogene activation.

D Rosson, D Dugan, E P Reddy
PMCID: PMC304830  PMID: 3033638

Abstract

Activation of the mouse c-myb oncogene in Abelson virus-induced plasmacytoid lymphosarcomas was studied using cDNA cloning and nucleotide sequence analysis. The results presented here show that viral integration in the myb locus generates splicing errors at the 5' and 3' regions. Viral integration results in transcriptional initiation within the viral long terminal repeat and generation of a chimeric mRNA that lacks the first three coding exons. The alterations at the 3' end are caused by an aberrant splicing event in which additional splice-donor and -acceptor sequences within intronic sequences are used to splice an additional 363 nucleotides into the myb transcripts. The resulting insertion of 121 amino acids is in a region of the protein where other activated forms of the myb gene product have deletions. These results suggest that alterations in the 3' end of the myb gene play a crucial role in the activation of this gene.

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Selected References

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

  1. Archibald A. L., Thompson N. A., Kvist S. A single nucleotide difference at the 3' end of an intron causes differential splicing of two histocompatibility genes. EMBO J. 1986 May;5(5):957–965. doi: 10.1002/j.1460-2075.1986.tb04309.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Bender T. P., Kuehl W. M. Murine myb protooncogene mRNA: cDNA sequence and evidence for 5' heterogeneity. Proc Natl Acad Sci U S A. 1986 May;83(10):3204–3208. doi: 10.1073/pnas.83.10.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  5. Cech T. R. RNA splicing: three themes with variations. Cell. 1983 Oct;34(3):713–716. doi: 10.1016/0092-8674(83)90527-5. [DOI] [PubMed] [Google Scholar]
  6. Gonda T. J., Gough N. M., Dunn A. R., de Blaquiere J. Nucleotide sequence of cDNA clones of the murine myb proto-oncogene. EMBO J. 1985 Aug;4(8):2003–2008. doi: 10.1002/j.1460-2075.1985.tb03884.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Klempnauer K. H., Gonda T. J., Bishop J. M. Nucleotide sequence of the retroviral leukemia gene v-myb and its cellular progenitor c-myb: the architecture of a transduced oncogene. Cell. 1982 Dec;31(2 Pt 1):453–463. doi: 10.1016/0092-8674(82)90138-6. [DOI] [PubMed] [Google Scholar]
  8. Kühne T., Wieringa B., Reiser J., Weissmann C. Evidence against a scanning model of RNA splicing. EMBO J. 1983;2(5):727–733. doi: 10.1002/j.1460-2075.1983.tb01492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lavu S., Reddy E. P. Structural organization and nucleotide sequence of mouse c-myb oncogene: activation in ABPL tumors is due to viral integration in an intron which results in the deletion of the 5' coding sequences. Nucleic Acids Res. 1986 Jul 11;14(13):5309–5320. doi: 10.1093/nar/14.13.5309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  11. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mushinski J. F., Bauer S. R., Potter M., Reddy E. P. Increased expression of myc-related oncogene mRNA characterizes most BALB/c plasmacytomas induced by pristane or Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1073–1077. doi: 10.1073/pnas.80.4.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mushinski J. F., Potter M., Bauer S. R., Reddy E. P. DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas. Science. 1983 May 20;220(4599):795–798. doi: 10.1126/science.6687762. [DOI] [PubMed] [Google Scholar]
  14. Nunn M. F., Seeburg P. H., Moscovici C., Duesberg P. H. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature. 1983 Nov 24;306(5941):391–395. doi: 10.1038/306391a0. [DOI] [PubMed] [Google Scholar]
  15. Potter M., Premkumar-Reddy E., Wivel N. A. Immunoglobulin production by lymphosarcomas induced by Abelson virus in mice. Natl Cancer Inst Monogr. 1978 May;(48):311–320. [PubMed] [Google Scholar]
  16. Potter M., Sklar M. D., Rowe W. P. Rapid viral induction of plasmacytomas in pristane-primed BALB-c mice. Science. 1973 Nov 9;182(4112):592–594. doi: 10.1126/science.182.4112.592. [DOI] [PubMed] [Google Scholar]
  17. Premkumar E., Potter M., Singer P. A., Sklar M. D. Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines. Cell. 1975 Oct;6(2):149–159. doi: 10.1016/0092-8674(75)90005-7. [DOI] [PubMed] [Google Scholar]
  18. Rosson D., Reddy E. P. Nucleotide sequence of chicken c-myb complementary DNA and implications for myb oncogene activation. Nature. 1986 Feb 13;319(6054):604–606. doi: 10.1038/319604a0. [DOI] [PubMed] [Google Scholar]
  19. Rushlow K. E., Lautenberger J. A., Papas T. S., Baluda M. A., Perbal B., Chirikjian J. G., Reddy E. P. Nucleotide sequence of the transforming gene of avian myeloblastosis virus. Science. 1982 Jun 25;216(4553):1421–1423. doi: 10.1126/science.6283631. [DOI] [PubMed] [Google Scholar]
  20. Shen-Ong G. L., Morse H. C., 3rd, Potter M., Mushinski J. F. Two modes of c-myb activation in virus-induced mouse myeloid tumors. Mol Cell Biol. 1986 Feb;6(2):380–392. doi: 10.1128/mcb.6.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shen-Ong G. L., Potter M., Mushinski J. F., Lavu S., Reddy E. P. Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas. Science. 1984 Nov 30;226(4678):1077–1080. doi: 10.1126/science.6093260. [DOI] [PubMed] [Google Scholar]
  22. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  23. Solnick D. Alternative splicing caused by RNA secondary structure. Cell. 1985 Dec;43(3 Pt 2):667–676. doi: 10.1016/0092-8674(85)90239-9. [DOI] [PubMed] [Google Scholar]
  24. Weinstein Y., Ihle J. N., Lavu S., Reddy E. P. Truncation of the c-myb gene by a retroviral integration in an interleukin 3-dependent myeloid leukemia cell line. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5010–5014. doi: 10.1073/pnas.83.14.5010. [DOI] [PMC free article] [PubMed] [Google Scholar]

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