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. 1989 Nov;9(11):5234–5238. doi: 10.1128/mcb.9.11.5234

The 5' noncoding region of the human leukemia-associated oncogene BCR/ABL is a potent inhibitor of in vitro translation.

A J Muller 1, O N Witte 1
PMCID: PMC363679  PMID: 2601719

Abstract

The mRNA encoding the chimeric BCR/ABL oncogene, which is transcribed from the Philadelphia chromosome in human chronic myelogenous leukemia, has a 5' noncoding sequence greater than 500 bases in length which is highly GC rich and contains a short open reading frame. This untranslated sequence has a dramatic inhibitory effect upon translational efficiency in vitro. However, when BCR/ABL message is expressed in certain cell types such as the NIH 3T3 cell line, the 5' noncoding region has little inhibitory effect on translational efficiency.

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Selected References

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  1. Chamberlain J. P. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. doi: 10.1016/0003-2697(79)90716-4. [DOI] [PubMed] [Google Scholar]
  2. Clark S. S., Crist W. M., Witte O. N. Molecular pathogenesis of Ph-positive leukemias. Annu Rev Med. 1989;40:113–122. doi: 10.1146/annurev.me.40.020189.000553. [DOI] [PubMed] [Google Scholar]
  3. Contreras R., Cheroutre H., Degrave W., Fiers W. Simple, efficient in vitro synthesis of capped RNA useful for direct expression of cloned eukaryotic genes. Nucleic Acids Res. 1982 Oct 25;10(20):6353–6362. doi: 10.1093/nar/10.20.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daley G. Q., McLaughlin J., Witte O. N., Baltimore D. The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science. 1987 Jul 31;237(4814):532–535. doi: 10.1126/science.2440107. [DOI] [PubMed] [Google Scholar]
  5. Freier S. M., Kierzek R., Jaeger J. A., Sugimoto N., Caruthers M. H., Neilson T., Turner D. H. Improved free-energy parameters for predictions of RNA duplex stability. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9373–9377. doi: 10.1073/pnas.83.24.9373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Godeau F., Persson H., Gray H. E., Pardee A. B. C-myc expression is dissociated from DNA synthesis and cell division in Xenopus oocyte and early embryonic development. EMBO J. 1986 Dec 20;5(13):3571–3577. doi: 10.1002/j.1460-2075.1986.tb04684.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hariharan I. K., Adams J. M. cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia. EMBO J. 1987 Jan;6(1):115–119. doi: 10.1002/j.1460-2075.1987.tb04727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Konarska M. M., Padgett R. A., Sharp P. A. Recognition of cap structure in splicing in vitro of mRNA precursors. Cell. 1984 Oct;38(3):731–736. doi: 10.1016/0092-8674(84)90268-x. [DOI] [PubMed] [Google Scholar]
  9. Konopka J. B., Davis R. L., Watanabe S. M., Ponticelli A. S., Schiff-Maker L., Rosenberg N., Witte O. N. Only site-directed antibodies reactive with the highly conserved src-homologous region of the v-abl protein neutralize kinase activity. J Virol. 1984 Jul;51(1):223–232. doi: 10.1128/jvi.51.1.223-232.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Konopka J. B., Watanabe S. M., Singer J. W., Collins S. J., Witte O. N. Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1810–1814. doi: 10.1073/pnas.82.6.1810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konopka J. B., Watanabe S. M., Witte O. N. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984 Jul;37(3):1035–1042. doi: 10.1016/0092-8674(84)90438-0. [DOI] [PubMed] [Google Scholar]
  12. Konopka J. B., Witte O. N. Activation of the abl oncogene in murine and human leukemias. Biochim Biophys Acta. 1985 Nov 12;823(1):1–17. doi: 10.1016/0304-419x(85)90012-5. [DOI] [PubMed] [Google Scholar]
  13. Konopka J. B., Witte O. N. Detection of c-abl tyrosine kinase activity in vitro permits direct comparison of normal and altered abl gene products. Mol Cell Biol. 1985 Nov;5(11):3116–3123. doi: 10.1128/mcb.5.11.3116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kozak M. Bifunctional messenger RNAs in eukaryotes. Cell. 1986 Nov 21;47(4):481–483. doi: 10.1016/0092-8674(86)90609-4. [DOI] [PubMed] [Google Scholar]
  16. Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. doi: 10.1128/mr.47.1.1-45.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kozak M. Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes. Mol Cell Biol. 1987 Oct;7(10):3438–3445. doi: 10.1128/mcb.7.10.3438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kozak M. Influences of mRNA secondary structure on initiation by eukaryotic ribosomes. Proc Natl Acad Sci U S A. 1986 May;83(9):2850–2854. doi: 10.1073/pnas.83.9.2850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  20. Kozak M. Selection of initiation sites by eucaryotic ribosomes: effect of inserting AUG triplets upstream from the coding sequence for preproinsulin. Nucleic Acids Res. 1984 May 11;12(9):3873–3893. doi: 10.1093/nar/12.9.3873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lifshitz B., Fainstein E., Marcelle C., Shtivelman E., Amson R., Gale R. P., Canaani E. bcr genes and transcripts. Oncogene. 1988 Feb;2(2):113–117. [PubMed] [Google Scholar]
  23. Liu C. C., Simonsen C. C., Levinson A. D. Initiation of translation at internal AUG codons in mammalian cells. Nature. 1984 May 3;309(5963):82–85. doi: 10.1038/309082a0. [DOI] [PubMed] [Google Scholar]
  24. Marth J. D., Overell R. W., Meier K. E., Krebs E. G., Perlmutter R. M. Translational activation of the lck proto-oncogene. Nature. 1988 Mar 10;332(6160):171–173. doi: 10.1038/332171a0. [DOI] [PubMed] [Google Scholar]
  25. McLaughlin J., Chianese E., Witte O. N. In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6558–6562. doi: 10.1073/pnas.84.18.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Mes-Masson A. M., McLaughlin J., Daley G. Q., Paskind M., Witte O. N. Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9768–9772. doi: 10.1073/pnas.83.24.9768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Parkin N., Darveau A., Nicholson R., Sonenberg N. cis-acting translational effects of the 5' noncoding region of c-myc mRNA. Mol Cell Biol. 1988 Jul;8(7):2875–2883. doi: 10.1128/mcb.8.7.2875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Peabody D. S., Berg P. Termination-reinitiation occurs in the translation of mammalian cell mRNAs. Mol Cell Biol. 1986 Jul;6(7):2695–2703. doi: 10.1128/mcb.6.7.2695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Peabody D. S., Subramani S., Berg P. Effect of upstream reading frames on translation efficiency in simian virus 40 recombinants. Mol Cell Biol. 1986 Jul;6(7):2704–2711. doi: 10.1128/mcb.6.7.2704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pelletier J., Kaplan G., Racaniello V. R., Sonenberg N. Translational efficiency of poliovirus mRNA: mapping inhibitory cis-acting elements within the 5' noncoding region. J Virol. 1988 Jul;62(7):2219–2227. doi: 10.1128/jvi.62.7.2219-2227.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pelletier J., Sonenberg N. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell. 1985 Mar;40(3):515–526. doi: 10.1016/0092-8674(85)90200-4. [DOI] [PubMed] [Google Scholar]
  33. Pelletier J., Sonenberg N. The involvement of mRNA secondary structure in protein synthesis. Biochem Cell Biol. 1987 Jun;65(6):576–581. doi: 10.1139/o87-074. [DOI] [PubMed] [Google Scholar]
  34. Pendergast A. M., Clark R., Kawasaki E. S., McCormick F. P., Witte O. N. Baculovirus expression of functional P210 BCR-ABL oncogene product. Oncogene. 1989 Jun;4(6):759–766. [PubMed] [Google Scholar]
  35. Schwartz R. C., Stanton L. W., Riley S. C., Marcu K. B., Witte O. N. Synergism of v-myc and v-Ha-ras in the in vitro neoplastic progression of murine lymphoid cells. Mol Cell Biol. 1986 Sep;6(9):3221–3231. doi: 10.1128/mcb.6.9.3221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shatkin A. J. Capping of eucaryotic mRNAs. Cell. 1976 Dec;9(4 Pt 2):645–653. doi: 10.1016/0092-8674(76)90128-8. [DOI] [PubMed] [Google Scholar]
  37. Taylor M. V., Gusse M., Evan G. I., Dathan N., Mechali M. Xenopus myc proto-oncogene during development: expression as a stable maternal mRNA uncoupled from cell division. EMBO J. 1986 Dec 20;5(13):3563–3570. doi: 10.1002/j.1460-2075.1986.tb04683.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zuker M., Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. doi: 10.1093/nar/9.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]

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