Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1995 Feb 25;23(4):654–662. doi: 10.1093/nar/23.4.654

The sequence of the stem and flanking sequences at the 3' end of histone mRNA are critical determinants for the binding of the stem-loop binding protein.

A S Williams 1, W F Marzluff 1
PMCID: PMC306734  PMID: 7899087

Abstract

Complexes of different electrophoretic mobility containing the stem-loop binding protein, a 45 kDa protein, bound to the stem-loop at the 3' end of histone mRNA, are present in both nuclear and cytoplasmic extracts from mammalian cells. We have determined the effect of changes in the loop, in the stem and in the flanking sequences on the affinity of the SLBP for the 3' end of histone mRNA. The sequence of the stem is particularly critical for SLBP binding. Specific sequences both 5' and 3' of the stem-loop are also required for high-affinity binding. Expanding the four base loop by one or two uridines reduced but did not abolish SLBP binding. RNA footprinting experiments show that the flanking sequences on both sides of the stem-loop are critical for efficient binding, but that cleavages in the loop do not abolish binding. Thus all three regions of the RNA sequence contribute to SLBP binding, suggesting that the 26 nt at the 3' end of histone mRNA forms a defined tertiary structure recognized by the SLBP.

Full text

PDF
654

Images in this article

656Image
on p.656
658Image
on p.658
659Image
on p.659
659Image
on p.659
660Image
on p.660
660Image
on p.660

Selected References

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

  1. 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]
  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. Churcher M. J., Lamont C., Hamy F., Dingwall C., Green S. M., Lowe A. D., Butler J. G., Gait M. J., Karn J. High affinity binding of TAR RNA by the human immunodeficiency virus type-1 tat protein requires base-pairs in the RNA stem and amino acid residues flanking the basic region. J Mol Biol. 1993 Mar 5;230(1):90–110. doi: 10.1006/jmbi.1993.1128. [DOI] [PubMed] [Google Scholar]
  4. Cotten M., Gick O., Vasserot A., Schaffner G., Birnstiel M. L. Specific contacts between mammalian U7 snRNA and histone precursor RNA are indispensable for the in vitro 3' RNA processing reaction. EMBO J. 1988 Mar;7(3):801–808. doi: 10.1002/j.1460-2075.1988.tb02878.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Frankel A. D., Mattaj I. W., Rio D. C. RNA-protein interactions. Cell. 1991 Dec 20;67(6):1041–1046. doi: 10.1016/0092-8674(91)90282-4. [DOI] [PubMed] [Google Scholar]
  7. Gait M. J., Karn J. RNA recognition by the human immunodeficiency virus Tat and Rev proteins. Trends Biochem Sci. 1993 Jul;18(7):255–259. doi: 10.1016/0968-0004(93)90176-n. [DOI] [PubMed] [Google Scholar]
  8. 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]
  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. Hall K. B. Interaction of RNA hairpins with the human U1A N-terminal RNA binding domain. Biochemistry. 1994 Aug 23;33(33):10076–10088. doi: 10.1021/bi00199a035. [DOI] [PubMed] [Google Scholar]
  11. Hamy F., Asseline U., Grasby J., Iwai S., Pritchard C., Slim G., Butler P. J., Karn J., Gait M. J. Hydrogen-bonding contacts in the major groove are required for human immunodeficiency virus type-1 tat protein recognition of TAR RNA. J Mol Biol. 1993 Mar 5;230(1):111–123. doi: 10.1006/jmbi.1993.1129. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Jaffrey S. R., Haile D. J., Klausner R. D., Harford J. B. The interaction between the iron-responsive element binding protein and its cognate RNA is highly dependent upon both RNA sequence and structure. Nucleic Acids Res. 1993 Sep 25;21(19):4627–4631. doi: 10.1093/nar/21.19.4627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jessen T. H., Oubridge C., Teo C. H., Pritchard C., Nagai K. Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA. EMBO J. 1991 Nov;10(11):3447–3456. doi: 10.1002/j.1460-2075.1991.tb04909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Marzluff W. F. Histone 3' ends: essential and regulatory functions. Gene Expr. 1992;2(2):93–97. [PMC free article] [PubMed] [Google Scholar]
  17. Marzluff W. F., Pandey N. B. Multiple regulatory steps control histone mRNA concentrations. Trends Biochem Sci. 1988 Feb;13(2):49–52. doi: 10.1016/0968-0004(88)90027-8. [DOI] [PubMed] [Google Scholar]
  18. McLaren R. S., Ross J. Individual purified core and linker histones induce histone H4 mRNA destabilization in vitro. J Biol Chem. 1993 Jul 15;268(20):14637–14644. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Mowry K. L., Oh R., Steitz J. A. Each of the conserved sequence elements flanking the cleavage site of mammalian histone pre-mRNAs has a distinct role in the 3'-end processing reaction. Mol Cell Biol. 1989 Jul;9(7):3105–3108. doi: 10.1128/mcb.9.7.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mowry K. L., Steitz J. A. Identification of the human U7 snRNP as one of several factors involved in the 3' end maturation of histone premessenger RNA's. Science. 1987 Dec 18;238(4834):1682–1687. doi: 10.1126/science.2825355. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. Puglisi J. D., Tan R., Calnan B. J., Frankel A. D., Williamson J. R. Conformation of the TAR RNA-arginine complex by NMR spectroscopy. Science. 1992 Jul 3;257(5066):76–80. doi: 10.1126/science.1621097. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. 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]
  30. Sachs A. B., Deardorff J. A. Translation initiation requires the PAB-dependent poly(A) ribonuclease in yeast. Cell. 1992 Sep 18;70(6):961–973. doi: 10.1016/0092-8674(92)90246-9. [DOI] [PubMed] [Google Scholar]
  31. Scharl E. C., Steitz J. A. The site of 3' end formation of histone messenger RNA is a fixed distance from the downstream element recognized by the U7 snRNP. EMBO J. 1994 May 15;13(10):2432–2440. doi: 10.1002/j.1460-2075.1994.tb06528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stauber C., Lüscher B., Eckner R., Lötscher E., Schümperli D. 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. EMBO J. 1986 Dec 1;5(12):3297–3303. doi: 10.1002/j.1460-2075.1986.tb04643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stauber C., Schümperli D. 3' processing of pre-mRNA plays a major role in proliferation-dependent regulation of histone gene expression. Nucleic Acids Res. 1988 Oct 25;16(20):9399–9414. doi: 10.1093/nar/16.20.9399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stern S., Powers T., Changchien L. M., Noller H. F. RNA-protein interactions in 30S ribosomal subunits: folding and function of 16S rRNA. Science. 1989 May 19;244(4906):783–790. doi: 10.1126/science.2658053. [DOI] [PubMed] [Google Scholar]
  35. Streit A., Koning T. W., Soldati D., Melin L., Schümperli D. Variable effects of the conserved RNA hairpin element upon 3' end processing of histone pre-mRNA in vitro. Nucleic Acids Res. 1993 Apr 11;21(7):1569–1575. doi: 10.1093/nar/21.7.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Tsai D. E., Harper D. S., Keene J. D. U1-snRNP-A protein selects a ten nucleotide consensus sequence from a degenerate RNA pool presented in various structural contexts. Nucleic Acids Res. 1991 Sep 25;19(18):4931–4936. doi: 10.1093/nar/19.18.4931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Williams A. S., Ingledue T. C., 3rd, Kay B. K., Marzluff W. F. Changes in the stem-loop at the 3' terminus of histone mRNA affects its nucleocytoplasmic transport and cytoplasmic regulation. Nucleic Acids Res. 1994 Nov 11;22(22):4660–4666. doi: 10.1093/nar/22.22.4660. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES