Abstract
A post-transcriptional control of gene expression was found to be responsible for a down-regulation of p53 mRNA accompanying the induced differentiation of murine erythroleukemia (MEL) cells. Such a post-transcriptional control was governed by the induced synthesis of an RNA species (inRNA). In an attempt to find a potential candidate for such a function, we have localized the post-transcriptional regulation of p53 mRNA in the nuclear compartment of the cells; the various fragments of the p53 gene were used as probes for induced RNA(s) susceptible to interacting with p53 pre-mRNA. This experimental approach allowed for the identification of a nuclear RNA molecule, approximately 1.3 kb long, which was recognized specifically by a PstI-HindIII fragment located in the 5' part of the first intervening sequence of the p53 gene. This RNA accumulated when cell were treated by the inducer concomitantly with high mol.wt p53 mRNA precursors. However this RNA was not a maturation product of p53 pre-mRNA as evidenced by its antisense orientation with respect to this RNA. Moreover it was markedly enriched in the poly(A)+ fraction. The complementary part of inRNA in the p53 gene has been sequenced over approximately 1200 bp; no extensive homology was found in gene data banks but three restricted areas of the sequence were found homologous to a limited number of genes; they were themselves partially homologous to known repetitive sequences. Possible implication of such a sequence in the regulation of p53 gene expression is discussed.
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- Adeniyi-Jones S., Zasloff M. Transcription, processing and nuclear transport of a B1 Alu RNA species complementary to an intron of the murine alpha-fetoprotein gene. Nature. 1985 Sep 5;317(6032):81–84. doi: 10.1038/317081a0. [DOI] [PubMed] [Google Scholar]
- Baxter-Gabbard K. L. A simple method for the large-scale preparation of sucrose gradients. FEBS Lett. 1972 Jan 15;20(1):117–119. doi: 10.1016/0014-5793(72)80031-0. [DOI] [PubMed] [Google Scholar]
- Ben-Dori R., Resnitzki D., Kimchi A. Reduction in p53 synthesis during differentiation of Friend-erythroleukemia cells. Correlation with the commitment to terminal cell division. FEBS Lett. 1983 Oct 17;162(2):384–389. doi: 10.1016/0014-5793(83)80792-3. [DOI] [PubMed] [Google Scholar]
- Bennett K. L., Hill R. E., Pietras D. F., Woodworth-Gutai M., Kane-Haas C., Houston J. M., Heath J. K., Hastie N. D. Most highly repeated dispersed DNA families in the mouse genome. Mol Cell Biol. 1984 Aug;4(8):1561–1571. doi: 10.1128/mcb.4.8.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bienz B., Zakut-Houri R., Givol D., Oren M. Analysis of the gene coding for the murine cellular tumour antigen p53. EMBO J. 1984 Sep;3(9):2179–2183. doi: 10.1002/j.1460-2075.1984.tb02110.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braithwaite A. W., Sturzbecher H. W., Addison C., Palmer C., Rudge K., Jenkins J. R. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature. 1987 Oct 1;329(6138):458–460. doi: 10.1038/329458a0. [DOI] [PubMed] [Google Scholar]
- Caffarelli E., Fragapane P., Gehring C., Bozzoni I. The accumulation of mature RNA for the Xenopus laevis ribosomal protein L1 is controlled at the level of splicing and turnover of the precursor RNA. EMBO J. 1987 Nov;6(11):3493–3498. doi: 10.1002/j.1460-2075.1987.tb02674.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dony C., Kessel M., Gruss P. Post-transcriptional control of myc and p53 expression during differentiation of the embryonal carcinoma cell line F9. Nature. 1985 Oct 17;317(6038):636–639. doi: 10.1038/317636a0. [DOI] [PubMed] [Google Scholar]
- Edwards D. R., Parfett C. L., Denhardt D. T. Transcriptional regulation of two serum-induced RNAs in mouse fibroblasts: equivalence of one species to B2 repetitive elements. Mol Cell Biol. 1985 Nov;5(11):3280–3288. doi: 10.1128/mcb.5.11.3280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Gannon J. V., Lane D. P. p53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature. 1987 Oct 1;329(6138):456–458. doi: 10.1038/329456a0. [DOI] [PubMed] [Google Scholar]
- Glaichenhaus N., Cuzin F. A role for ID repetitive sequences in growth- and transformation-dependent regulation of gene expression in rat fibroblasts. Cell. 1987 Sep 25;50(7):1081–1089. doi: 10.1016/0092-8674(87)90174-7. [DOI] [PubMed] [Google Scholar]
- Gudas J. M., Knight G. B., Pardee A. B. Nuclear posttranscriptional processing of thymidine kinase mRNA at the onset of DNA synthesis. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4705–4709. doi: 10.1073/pnas.85.13.4705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinds P., Finlay C., Levine A. J. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol. 1989 Feb;63(2):739–746. doi: 10.1128/jvi.63.2.739-746.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalb V. F., Glasser S., King D., Lingrel J. B. A cluster of repetitive elements within a 700 base pair region in the mouse genome. Nucleic Acids Res. 1983 Apr 11;11(7):2177–2184. doi: 10.1093/nar/11.7.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keppel F., Allet B., Eisen H. Appearance of a chromatin protein during the erythroid differentiation of Friend virus-transformed cells. Proc Natl Acad Sci U S A. 1977 Feb;74(2):653–656. doi: 10.1073/pnas.74.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khochbin S., Chabanas A., Lawrence J. J. Early events in murine erythroleukemia cells induced to differentiate: variation of the cell cycle parameters in relation to p53 accumulation. Exp Cell Res. 1988 Dec;179(2):565–574. doi: 10.1016/0014-4827(88)90294-7. [DOI] [PubMed] [Google Scholar]
- Khochbin S., Principaud E., Chabanas A., Lawrence J. J. Early events in murine erythroleukemia cells induced to differentiate. Accumulation and gene expression of the transformation-associated cellular protein p53. J Mol Biol. 1988 Mar 5;200(1):55–64. doi: 10.1016/0022-2836(88)90333-6. [DOI] [PubMed] [Google Scholar]
- Kohnoe S., Maehara Y., Endo H. A systematic survey of repetitive sequences abundantly expressed in rat tumors. Biochim Biophys Acta. 1987 Jul 14;909(2):107–114. doi: 10.1016/0167-4781(87)90032-7. [DOI] [PubMed] [Google Scholar]
- Lania L., Pannuti A., La Mantia G., Basilico C. The transcription of B2 repeated sequences is regulated during the transition from quiescent to proliferative state in cultured rodent cells. FEBS Lett. 1987 Jul 27;219(2):400–404. doi: 10.1016/0014-5793(87)80260-0. [DOI] [PubMed] [Google Scholar]
- Louis J. M., McFarland V. W., May P., Mora P. T. The phosphoprotein p53 is down-regulated post-transcriptionally during embryogenesis in vertebrates. Biochim Biophys Acta. 1988 Sep 7;950(3):395–402. doi: 10.1016/0167-4781(88)90136-4. [DOI] [PubMed] [Google Scholar]
- Mercer W. E., Nelson D., DeLeo A. B., Old L. J., Baserga R. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6309–6312. doi: 10.1073/pnas.79.20.6309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milner J., Milner S. SV40-53K antigen: a possible role for 53K in normal cells. Virology. 1981 Jul 30;112(2):785–788. doi: 10.1016/0042-6822(81)90327-5. [DOI] [PubMed] [Google Scholar]
- Munroe S. H. Antisense RNA inhibits splicing of pre-mRNA in vitro. EMBO J. 1988 Aug;7(8):2523–2532. doi: 10.1002/j.1460-2075.1988.tb03100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy D., Brickell P. M., Latchman D. S., Willison K., Rigby P. W. Transcripts regulated during normal embryonic development and oncogenic transformation share a repetitive element. Cell. 1983 Dec;35(3 Pt 2):865–871. doi: 10.1016/0092-8674(83)90119-8. [DOI] [PubMed] [Google Scholar]
- Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shen D. W., Real F. X., DeLeo A. B., Old L. J., Marks P. A., Rifkind R. A. Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5919–5922. doi: 10.1073/pnas.80.19.5919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shohat O., Greenberg M., Reisman D., Oren M., Rotter V. Inhibition of cell growth mediated by plasmids encoding p53 anti-sense. Oncogene. 1987;1(3):277–283. [PubMed] [Google Scholar]
- 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]
- 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]
- Ullu E., Tschudi C. Alu sequences are processed 7SL RNA genes. Nature. 1984 Nov 8;312(5990):171–172. doi: 10.1038/312171a0. [DOI] [PubMed] [Google Scholar]
- Vaessen R. T., Houweling A., van der Eb A. J. Post-transcriptional control of class I MHC mRNA expression in adenovirus 12-transformed cells. Science. 1987 Mar 20;235(4795):1486–1488. doi: 10.1126/science.3823900. [DOI] [PubMed] [Google Scholar]