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. 1994 Nov 11;22(22):4660–4666. doi: 10.1093/nar/22.22.4660

Changes in the stem-loop at the 3' terminus of histone mRNA affects its nucleocytoplasmic transport and cytoplasmic regulation.

A S Williams 1, T C Ingledue 3rd 1, B K Kay 1, W F Marzluff 1
PMCID: PMC308515  PMID: 7984415

Abstract

The stem-loop structure at the 3' end of replication-dependent histone mRNA is required for efficient pre-mRNA processing, localization of histone mRNA to the polyribosomes, and regulation of histone mRNA degradation. A protein, the stem-loop binding protein (SLBP), binds the 3' end of histone mRNA and is thought to mediate some or all of these processes. A mutant histone mRNA with two nucleotide changes in the loop was constructed and found to be transported inefficiently to the cytoplasm. The mutant histone mRNA, unlike the wild-type histone mRNA, was not rapidly degraded when DNA synthesis is inhibited, and was not stabilized upon inhibition of protein synthesis. The stem-loop binding protein (SLBP) has between a 20-50 fold greater affinity for the wild type histone stem-loop structure than for the mutant stem-loop structure, suggesting that the alteration in the efficiency of transport and the normal degradation pathway in histone mRNA may be due to the reduced affinity of the mutant stem-loop for the SLBP.

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Selected References

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

  1. Baumbach L. L., Marashi F., Plumb M., Stein G., Stein J. Inhibition of DNA replication coordinately reduces cellular levels of core and H1 histone mRNAs: requirement for protein synthesis. Biochemistry. 1984 Apr 10;23(8):1618–1625. doi: 10.1021/bi00303a006. [DOI] [PubMed] [Google Scholar]
  2. Bond U. M., Yario T. A., Steitz J. A. Multiple processing-defective mutations in a mammalian histone pre-mRNA are suppressed by compensatory changes in U7 RNA both in vivo and in vitro. Genes Dev. 1991 Sep;5(9):1709–1722. doi: 10.1101/gad.5.9.1709. [DOI] [PubMed] [Google Scholar]
  3. Chaney W. G., Howard D. R., Pollard J. W., Sallustio S., Stanley P. High-frequency transfection of CHO cells using polybrene. Somat Cell Mol Genet. 1986 May;12(3):237–244. doi: 10.1007/BF01570782. [DOI] [PubMed] [Google Scholar]
  4. Chang D. D., Sharp P. A. Regulation by HIV Rev depends upon recognition of splice sites. Cell. 1989 Dec 1;59(5):789–795. doi: 10.1016/0092-8674(89)90602-8. [DOI] [PubMed] [Google Scholar]
  5. D'Agostino D. M., Felber B. K., Harrison J. E., Pavlakis G. N. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs. Mol Cell Biol. 1992 Mar;12(3):1375–1386. doi: 10.1128/mcb.12.3.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eckner R., Ellmeier W., Birnstiel M. L. Mature mRNA 3' end formation stimulates RNA export from the nucleus. EMBO J. 1991 Nov;10(11):3513–3522. doi: 10.1002/j.1460-2075.1991.tb04915.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans J. P., Kay B. K. Biochemical fractionation of oocytes. Methods Cell Biol. 1991;36:133–148. doi: 10.1016/s0091-679x(08)60275-7. [DOI] [PubMed] [Google Scholar]
  8. Gallwitz D. Kinetics of inactivation of histone mRNA in the cytoplasm after inhibition of DNA replication in synchronised HeLa cells. Nature. 1975 Sep 18;257(5523):247–248. doi: 10.1038/257247a0. [DOI] [PubMed] [Google Scholar]
  9. Gick O., Krämer A., Vasserot A., Birnstiel M. L. Heat-labile regulatory factor is required for 3' processing of histone precursor mRNAs. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8937–8940. doi: 10.1073/pnas.84.24.8937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graves R. A., Marzluff W. F. Rapid reversible changes in the rate of histone gene transcription and histone mRNA levels in mouse myeloma cells. Mol Cell Biol. 1984 Feb;4(2):351–357. doi: 10.1128/mcb.4.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graves R. A., Pandey N. B., Chodchoy N., Marzluff W. F. Translation is required for regulation of histone mRNA degradation. Cell. 1987 Feb 27;48(4):615–626. doi: 10.1016/0092-8674(87)90240-6. [DOI] [PubMed] [Google Scholar]
  12. Hamm J., Mattaj I. W. Monomethylated cap structures facilitate RNA export from the nucleus. Cell. 1990 Oct 5;63(1):109–118. doi: 10.1016/0092-8674(90)90292-m. [DOI] [PubMed] [Google Scholar]
  13. Harris M. E., Böhni R., Schneiderman M. H., Ramamurthy L., Schümperli D., Marzluff W. F. Regulation of histone mRNA in the unperturbed cell cycle: evidence suggesting control at two posttranscriptional steps. Mol Cell Biol. 1991 May;11(5):2416–2424. doi: 10.1128/mcb.11.5.2416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Hurt M. M., Chodchoy N., Marzluff W. F. The mouse histone H2a.2 gene from chromosome 3. Nucleic Acids Res. 1989 Nov 11;17(21):8876–8876. doi: 10.1093/nar/17.21.8876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Izaurralde E., Stepinski J., Darzynkiewicz E., Mattaj I. W. A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs. J Cell Biol. 1992 Sep;118(6):1287–1295. doi: 10.1083/jcb.118.6.1287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kay B. K. Xenopus laevis: Practical uses in cell and molecular biology. Injections of oocytes and embryos. Methods Cell Biol. 1991;36:663–669. [PubMed] [Google Scholar]
  18. Legrain P., Rosbash M. Some cis- and trans-acting mutants for splicing target pre-mRNA to the cytoplasm. Cell. 1989 May 19;57(4):573–583. doi: 10.1016/0092-8674(89)90127-x. [DOI] [PubMed] [Google Scholar]
  19. Levine B. J., Liu T. J., Marzluff W. F., Skoultchi A. I. Differential expression of individual members of the histone multigene family due to sequences in the 5' and 3' regions of the genes. Mol Cell Biol. 1988 May;8(5):1887–1895. doi: 10.1128/mcb.8.5.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lobo S. M., Marzluff W. F., Seufert A. C., Dean W. L., Schultz G. A., Simerly C., Schatten G. Localization and expression of U1 RNA in early mouse embryo development. Dev Biol. 1988 Jun;127(2):349–361. doi: 10.1016/0012-1606(88)90321-1. [DOI] [PubMed] [Google Scholar]
  21. Lund E., Bostock C., Robertson M., Christie S., Mitchen J. L., Dahlberg J. E. U1 small nuclear RNA genes are located on human chromosome 1 and are expressed in mouse-human hybrid cells. Mol Cell Biol. 1983 Dec;3(12):2211–2220. doi: 10.1128/mcb.3.12.2211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lund E., Dahlberg J. E., Forbes D. J. The two embryonic U1 small nuclear RNAs of Xenopus laevis are encoded by a major family of tandemly repeated genes. Mol Cell Biol. 1984 Dec;4(12):2580–2586. doi: 10.1128/mcb.4.12.2580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Malim M. H., Cullen B. R. Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes. Mol Cell Biol. 1993 Oct;13(10):6180–6189. doi: 10.1128/mcb.13.10.6180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marzluff W. F. Histone 3' ends: essential and regulatory functions. Gene Expr. 1992;2(2):93–97. [PMC free article] [PubMed] [Google Scholar]
  25. Melin L., Soldati D., Mital R., Streit A., Schümperli D. Biochemical demonstration of complex formation of histone pre-mRNA with U7 small nuclear ribonucleoprotein and hairpin binding factors. EMBO J. 1992 Feb;11(2):691–697. doi: 10.1002/j.1460-2075.1992.tb05101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Milligan J. F., Groebe D. R., Witherell G. W., Uhlenbeck O. C. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res. 1987 Nov 11;15(21):8783–8798. doi: 10.1093/nar/15.21.8783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mowry K. L., Steitz J. A. Both conserved signals on mammalian histone pre-mRNAs associate with small nuclear ribonucleoproteins during 3' end formation in vitro. Mol Cell Biol. 1987 May;7(5):1663–1672. doi: 10.1128/mcb.7.5.1663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pandey N. B., Marzluff W. F. The stem-loop structure at the 3' end of histone mRNA is necessary and sufficient for regulation of histone mRNA stability. Mol Cell Biol. 1987 Dec;7(12):4557–4559. doi: 10.1128/mcb.7.12.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pandey N. B., Sun J. H., Marzluff W. F. Different complexes are formed on the 3' end of histone mRNA with nuclear and polyribosomal proteins. Nucleic Acids Res. 1991 Oct 25;19(20):5653–5659. doi: 10.1093/nar/19.20.5653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pandey N. B., Williams A. S., Sun J. H., Brown V. D., Bond U., Marzluff W. F. Point mutations in the stem-loop at the 3' end of mouse histone mRNA reduce expression by reducing the efficiency of 3' end formation. Mol Cell Biol. 1994 Mar;14(3):1709–1720. doi: 10.1128/mcb.14.3.1709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roberts S. B., Emmons S. W., Childs G. Nucleotide sequences of Caenorhabditis elegans core histone genes. Genes for different histone classes share common flanking sequence elements. J Mol Biol. 1989 Apr 20;206(4):567–577. doi: 10.1016/0022-2836(89)90566-4. [DOI] [PubMed] [Google Scholar]
  32. Ross J., Kobs G., Brewer G., Peltz S. W. Properties of the exonuclease activity that degrades H4 histone mRNA. J Biol Chem. 1987 Jul 5;262(19):9374–9381. [PubMed] [Google Scholar]
  33. Ross J., Kobs G. H4 histone messenger RNA decay in cell-free extracts initiates at or near the 3' terminus and proceeds 3' to 5'. J Mol Biol. 1986 Apr 20;188(4):579–593. doi: 10.1016/s0022-2836(86)80008-0. [DOI] [PubMed] [Google Scholar]
  34. Ross J., Peltz S. W., Kobs G., Brewer G. Histone mRNA degradation in vivo: the first detectable step occurs at or near the 3' terminus. Mol Cell Biol. 1986 Dec;6(12):4362–4371. doi: 10.1128/mcb.6.12.4362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schwartz S., Felber B. K., Pavlakis G. N. Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing. Virology. 1991 Aug;183(2):677–686. doi: 10.1016/0042-6822(91)90996-o. [DOI] [PubMed] [Google Scholar]
  36. Shyu A. B., Greenberg M. E., Belasco J. G. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 1989 Jan;3(1):60–72. doi: 10.1101/gad.3.1.60. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Stimac E., Groppi V. E., Jr, Coffino P. Inhibition of protein synthesis stabilizes histone mRNA. Mol Cell Biol. 1984 Oct;4(10):2082–2090. doi: 10.1128/mcb.4.10.2082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sun J., Pilch D. R., Marzluff W. F. The histone mRNA 3' end is required for localization of histone mRNA to polyribosomes. Nucleic Acids Res. 1992 Nov 25;20(22):6057–6066. doi: 10.1093/nar/20.22.6057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Terns M. P., Dahlberg J. E., Lund E. Multiple cis-acting signals for export of pre-U1 snRNA from the nucleus. Genes Dev. 1993 Oct;7(10):1898–1908. doi: 10.1101/gad.7.10.1898. [DOI] [PubMed] [Google Scholar]
  41. Vasserot A. P., Schaufele F. J., Birnstiel M. L. Conserved terminal hairpin sequences of histone mRNA precursors are not involved in duplex formation with the U7 RNA but act as a target site for a distinct processing factor. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4345–4349. doi: 10.1073/pnas.86.12.4345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wellington C. L., Greenberg M. E., Belasco J. G. The destabilizing elements in the coding region of c-fos mRNA are recognized as RNA. Mol Cell Biol. 1993 Aug;13(8):5034–5042. doi: 10.1128/mcb.13.8.5034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wisdom R., Lee W. The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors. Genes Dev. 1991 Feb;5(2):232–243. doi: 10.1101/gad.5.2.232. [DOI] [PubMed] [Google Scholar]

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