Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1986 Dec 1;5(12):3297–3303. doi: 10.1002/j.1460-2075.1986.tb04643.x

A signal regulating mouse histone H4 mRNA levels in a mammalian cell cycle mutant and sequences controlling RNA 3' processing are both contained within the same 80-bp fragment.

C Stauber, B Lüscher, R Eckner, E Lötscher, D Schümperli
PMCID: PMC1167326  PMID: 3816761

Abstract

Fragments from the 3' end of a mouse histone H4 gene, when introduced into transcription units controlled by the SV40 early promoter, yield correctly processed RNA with histone-specific 3' ends, both in monkey and mouse cell lines. The processed RNA is regulated in parallel with endogenous H4 mRNAs in 21-Tb cells, a temperature-sensitive mouse mastocytoma cell cycle mutant that is specifically blocked in G1 phase at the non-permissive temperature. Mutational analyses of the H4 gene fragment indicate that the minimal sequences for this regulation and for RNA 3' processing are both contained within the same 80 bp. This fragment contains two histone-specific, highly conserved sequence elements that are located at the 3' end of histone mRNA and in the adjacent spacer region, respectively. Our data suggest that the observed cell cycle regulation is achieved either at RNA 3' processing or at some later step involving the conserved 3'-terminal sequence element of mature histone mRNA.

Full text

PDF
3297

Images in this article

3299Fig. 2.
on p.3299
3300Fig. 4.
on p.3300

Selected References

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

  1. Alterman R. B., Ganguly S., Schulze D. H., Marzluff W. F., Schildkraut C. L., Skoultchi A. I. Cell cycle regulation of mouse H3 histone mRNA metabolism. Mol Cell Biol. 1984 Jan;4(1):123–132. doi: 10.1128/mcb.4.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  3. Birchmeier C., Folk W., Birnstiel M. L. The terminal RNA stem-loop structure and 80 bp of spacer DNA are required for the formation of 3' termini of sea urchin H2A mRNA. Cell. 1983 Dec;35(2 Pt 1):433–440. doi: 10.1016/0092-8674(83)90176-9. [DOI] [PubMed] [Google Scholar]
  4. Birchmeier C., Grosschedl R., Birnstiel M. L. Generation of authentic 3' termini of an H2A mRNA in vivo is dependent on a short inverted DNA repeat and on spacer sequences. Cell. 1982 Apr;28(4):739–745. doi: 10.1016/0092-8674(82)90053-8. [DOI] [PubMed] [Google Scholar]
  5. Birchmeier C., Schümperli D., Sconzo G., Birnstiel M. L. 3' editing of mRNAs: sequence requirements and involvement of a 60-nucleotide RNA in maturation of histone mRNA precursors. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1057–1061. doi: 10.1073/pnas.81.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  7. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  8. Brush D., Dodgson J. B., Choi O. R., Stevens P. W., Engel J. D. Replacement variant histone genes contain intervening sequences. Mol Cell Biol. 1985 Jun;5(6):1307–1317. doi: 10.1128/mcb.5.6.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Busslinger M., Portmann R., Birnsteil M. L. A regulatory sequence near the 3' end of sea urchin histone genes. Nucleic Acids Res. 1979 Jul 11;6(9):2997–3008. doi: 10.1093/nar/6.9.2997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DeLisle A. J., Graves R. A., Marzluff W. F., Johnson L. F. Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts. Mol Cell Biol. 1983 Nov;3(11):1920–1929. doi: 10.1128/mcb.3.11.1920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Georgiev O., Birnstiel M. L. The conserved CAAGAAAGA spacer sequence is an essential element for the formation of 3' termini of the sea urchin H3 histone mRNA by RNA processing. EMBO J. 1985 Feb;4(2):481–489. doi: 10.1002/j.1460-2075.1985.tb03654.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gerster T., Picard D., Schaffner W. During B-cell differentiation enhancer activity and transcription rate of immunoglobulin heavy chain genes are high before mRNA accumulation. Cell. 1986 Apr 11;45(1):45–52. doi: 10.1016/0092-8674(86)90536-2. [DOI] [PubMed] [Google Scholar]
  13. Gick O., Krämer A., Keller W., Birnstiel M. L. Generation of histone mRNA 3' ends by endonucleolytic cleavage of the pre-mRNA in a snRNP-dependent in vitro reaction. EMBO J. 1986 Jun;5(6):1319–1326. doi: 10.1002/j.1460-2075.1986.tb04362.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  15. Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hentschel C. C., Birnstiel M. L. The organization and expression of histone gene families. Cell. 1981 Aug;25(2):301–313. doi: 10.1016/0092-8674(81)90048-9. [DOI] [PubMed] [Google Scholar]
  17. Imbert J., Lawrence J. J., Coulier F., Jeunet E., Billotey V., Birg F. Cell cycle-dependent expression of early viral genes in one group of simian virus 40-transformed rat cells. EMBO J. 1984 Nov;3(11):2587–2591. doi: 10.1002/j.1460-2075.1984.tb02178.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Krieg P. A., Robins A. J., Colman A., Wells J. R. Chicken histone H5 mRNA: the polyadenylated RNA lacks the conserved histone 3' terminator sequence. Nucleic Acids Res. 1982 Nov 11;10(21):6777–6785. doi: 10.1093/nar/10.21.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lüscher B., Stauber C., Schindler R., Schümperli D. Faithful cell-cycle regulation of a recombinant mouse histone H4 gene is controlled by sequences in the 3'-terminal part of the gene. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4389–4393. doi: 10.1073/pnas.82.13.4389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  21. Mulligan R. C., Berg P. Expression of a bacterial gene in mammalian cells. Science. 1980 Sep 19;209(4463):1422–1427. doi: 10.1126/science.6251549. [DOI] [PubMed] [Google Scholar]
  22. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nüesch J., Schümperli D. Structural and functional organization of the gpt gene region of Escherichia coli. Gene. 1984 Dec;32(1-2):243–249. doi: 10.1016/0378-1119(84)90052-0. [DOI] [PubMed] [Google Scholar]
  24. Plumb M., Stein J., Stein G. Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucleic Acids Res. 1983 Apr 25;11(8):2391–2410. doi: 10.1093/nar/11.8.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rassoulzadegan M., Binetruy B., Cuzin F. High frequency of gene transfer after fusion between bacteria and eukaryotic cells. Nature. 1982 Jan 21;295(5846):257–259. doi: 10.1038/295257a0. [DOI] [PubMed] [Google Scholar]
  26. Schaer J. C., Schindler R. The requirement of mammalian cell cultures for serum proteins. Growth-promoting activity of pepsin-digested serum albumin in different media. Biochim Biophys Acta. 1967 Sep 19;147(1):154–161. doi: 10.1016/0005-2795(67)90098-0. [DOI] [PubMed] [Google Scholar]
  27. Schaffner W. Direct transfer of cloned genes from bacteria to mammalian cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2163–2167. doi: 10.1073/pnas.77.4.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schümperli D. Cell-cycle regulation of histone gene expression. Cell. 1986 May 23;45(4):471–472. doi: 10.1016/0092-8674(86)90277-1. [DOI] [PubMed] [Google Scholar]
  29. Seiler-Tuyns A., Birnstiel M. L. Structure and expression in L-cells of a cloned H4 histone gene of the mouse. J Mol Biol. 1981 Oct 5;151(4):607–625. doi: 10.1016/0022-2836(81)90426-5. [DOI] [PubMed] [Google Scholar]
  30. Sittman D. B., Graves R. A., Marzluff W. F. Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1849–1853. doi: 10.1073/pnas.80.7.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Turner P. C., Woodland H. R. H3 and H4 histone cDNA sequences from Xenopus: a sequence comparison of H4 genes. Nucleic Acids Res. 1982 Jun 25;10(12):3769–3780. doi: 10.1093/nar/10.12.3769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weber F., de Villiers J., Schaffner W. An SV40 "enhancer trap" incorporates exogenous enhancers or generates enhancers from its own sequences. Cell. 1984 Apr;36(4):983–992. doi: 10.1016/0092-8674(84)90048-5. [DOI] [PubMed] [Google Scholar]
  34. Wells D. E. Compilation analysis of histones and histone genes. Nucleic Acids Res. 1986;14 (Suppl):r119–r149. doi: 10.1093/nar/14.suppl.r119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wells D., Kedes L. Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylylated mRNAs. Proc Natl Acad Sci U S A. 1985 May;82(9):2834–2838. doi: 10.1073/pnas.82.9.2834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zimmermann A., Schaer J. C., Muller D. E., Schneider J., Miodonski-Maculewicz N. M., Schindler R. Formation of mast cell granules in cell cycle mutants of an undifferentiated mastocytoma line: evidence for two different states of reversible proliferative quiescence. J Cell Biol. 1983 Jun;96(6):1756–1760. doi: 10.1083/jcb.96.6.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zimmermann A., Schaer J. C., Schneider J., Molo P., Schindler R. Dominant versus recessive behavior of a cold- and a heat-sensitive mammalian cell cycle variant in heterokaryons. Somatic Cell Genet. 1981 Sep;7(5):591–601. doi: 10.1007/BF01549661. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES