Skip to main content
RNA logoLink to RNA
. 2002 Jan;8(1):83–96. doi: 10.1017/s1355838202013869

NMR structure and dynamics of the RNA-binding site for the histone mRNA stem-loop binding protein.

Eric S DeJong 1, William F Marzluff 1, Edward P Nikonowicz 1
PMCID: PMC1370231  PMID: 11871662

Abstract

The 3' end of replication-dependent histone mRNAs terminate in a conserved sequence containing a stem-loop. This 26-nt sequence is the binding site for a protein, stem-loop binding protein (SLBP), that is involved in multiple aspects of histone mRNA metabolism and regulation. We have determined the structure of the 26-nt sequence by multidimensional NMR spectroscopy. There is a 16-nt stem-loop motif, with a conserved 6-bp stem and a 4-nt loop. The loop is closed by a conserved U.A base pair that terminates the canonical A-form stem. The pyrimidine-rich 4-nt loop, UUUC, is well organized with the three uridines stacking on the helix, and the fourth base extending across the major groove into the solvent. The flanking nucleotides at the base of the hairpin stem do not assume a unique conformation, despite the fact that the 5' flanking nucleotides are a critical component of the SLBP binding site.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. Battle D. J., Doudna J. A. The stem-loop binding protein forms a highly stable and specific complex with the 3' stem-loop of histone mRNAs. RNA. 2001 Jan;7(1):123–132. doi: 10.1017/s1355838201001820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bikoff E. K., Gefter M. L. In vitro synthesis of transfer RNA. I. Purification of required components. J Biol Chem. 1975 Aug 25;250(16):6240–6247. [PubMed] [Google Scholar]
  3. 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]
  4. Bösl M., Kersten H. A novel RNA product of the tyrT operon of Escherichia coli. Nucleic Acids Res. 1991 Nov 11;19(21):5863–5870. doi: 10.1093/nar/19.21.5863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cai Z., Tinoco I., Jr Solution structure of loop A from the hairpin ribozyme from tobacco ringspot virus satellite. Biochemistry. 1996 May 14;35(19):6026–6036. doi: 10.1021/bi952985g. [DOI] [PubMed] [Google Scholar]
  6. Davanloo P., Rosenberg A. H., Dunn J. J., Studier F. W. Cloning and expression of the gene for bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2035–2039. doi: 10.1073/pnas.81.7.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deutscher M. P., Hilderman R. H. Isolation and partial characterization of Escherichia coli mutants with low levels of transfer ribonucleic acid nucleotidyltransferase. J Bacteriol. 1974 May;118(2):621–627. doi: 10.1128/jb.118.2.621-627.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deutscher M. P. Ribonucleases, tRNA nucleotidyltransferase, and the 3' processing of tRNA. Prog Nucleic Acid Res Mol Biol. 1990;39:209–240. doi: 10.1016/s0079-6603(08)60628-5. [DOI] [PubMed] [Google Scholar]
  9. Dieckmann T., Feigon J. Assignment methodology for larger RNA oligonucleotides: application to an ATP-binding RNA aptamer. J Biomol NMR. 1997 Apr;9(3):259–272. doi: 10.1023/a:1018622708674. [DOI] [PubMed] [Google Scholar]
  10. Dominski Z., Erkmann J. A., Greenland J. A., Marzluff W. F. Mutations in the RNA binding domain of stem-loop binding protein define separable requirements for RNA binding and for histone pre-mRNA processing. Mol Cell Biol. 2001 Mar;21(6):2008–2017. doi: 10.1128/MCB.21.6.2008-2017.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dominski Z., Marzluff W. F. Formation of the 3' end of histone mRNA. Gene. 1999 Oct 18;239(1):1–14. doi: 10.1016/s0378-1119(99)00367-4. [DOI] [PubMed] [Google Scholar]
  12. Dominski Z., Zheng L. X., Sanchez R., Marzluff W. F. Stem-loop binding protein facilitates 3'-end formation by stabilizing U7 snRNP binding to histone pre-mRNA. Mol Cell Biol. 1999 May;19(5):3561–3570. doi: 10.1128/mcb.19.5.3561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Draper D. E. Themes in RNA-protein recognition. J Mol Biol. 1999 Oct 22;293(2):255–270. doi: 10.1006/jmbi.1999.2991. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Furger A., Schaller A., Schümperli D. Functional importance of conserved nucleotides at the histone RNA 3' processing site. RNA. 1998 Mar;4(3):246–256. [PMC free article] [PubMed] [Google Scholar]
  16. Gabb H. A., Harris M. E., Pandey N. B., Marzluff W. F., Harvey S. C. Molecular modeling to predict the structural and biological effects of mutations in a highly conserved histone mRNA loop sequence. J Biomol Struct Dyn. 1992 Jun;9(6):1119–1130. doi: 10.1080/07391102.1992.10507983. [DOI] [PubMed] [Google Scholar]
  17. Ghora B. K., Apirion D. Structural analysis and in vitro processing to p5 rRNA of a 9S RNA molecule isolated from an rne mutant of E. coli. Cell. 1978 Nov;15(3):1055–1066. doi: 10.1016/0092-8674(78)90289-1. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Hennig M., Williamson J. R. Detection of N-H...N hydrogen bonding in RNA via scalar couplings in the absence of observable imino proton resonances. Nucleic Acids Res. 2000 Apr 1;28(7):1585–1593. doi: 10.1093/nar/28.7.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hsu L. M., Klee H. J., Zagorski J., Fournier M. J. Structure of an Escherichia coli tRNA operon containing linked genes for arginine, histidine, leucine, and proline tRNAs. J Bacteriol. 1984 Jun;158(3):934–942. doi: 10.1128/jb.158.3.934-942.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jucker F. M., Pardi A. Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif. Biochemistry. 1995 Nov 7;34(44):14416–14427. doi: 10.1021/bi00044a019. [DOI] [PubMed] [Google Scholar]
  23. Kelly K. O., Deutscher M. P. The presence of only one of five exoribonucleases is sufficient to support the growth of Escherichia coli. J Bacteriol. 1992 Oct;174(20):6682–6684. doi: 10.1128/jb.174.20.6682-6684.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Komine Y., Adachi T., Inokuchi H., Ozeki H. Genomic organization and physical mapping of the transfer RNA genes in Escherichia coli K12. J Mol Biol. 1990 Apr 20;212(4):579–598. doi: 10.1016/0022-2836(90)90224-A. [DOI] [PubMed] [Google Scholar]
  25. Li Z., Deutscher M. P. Maturation pathways for E. coli tRNA precursors: a random multienzyme process in vivo. Cell. 1996 Aug 9;86(3):503–512. doi: 10.1016/s0092-8674(00)80123-3. [DOI] [PubMed] [Google Scholar]
  26. Li Z., Deutscher M. P. The role of individual exoribonucleases in processing at the 3' end of Escherichia coli tRNA precursors. J Biol Chem. 1994 Feb 25;269(8):6064–6071. [PubMed] [Google Scholar]
  27. Li Z., Deutscher M. P. The tRNA processing enzyme RNase T is essential for maturation of 5S RNA. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6883–6886. doi: 10.1073/pnas.92.15.6883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Li Z., Pandit S., Deutscher M. P. 3' exoribonucleolytic trimming is a common feature of the maturation of small, stable RNAs in Escherichia coli. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2856–2861. doi: 10.1073/pnas.95.6.2856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Li Z., Pandit S., Deutscher M. P. Maturation of 23S ribosomal RNA requires the exoribonuclease RNase T. RNA. 1999 Jan;5(1):139–146. doi: 10.1017/s1355838299981669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Li Z., Pandit S., Deutscher M. P. RNase G (CafA protein) and RNase E are both required for the 5' maturation of 16S ribosomal RNA. EMBO J. 1999 May 17;18(10):2878–2885. doi: 10.1093/emboj/18.10.2878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lin-Chao S., Cohen S. N. The rate of processing and degradation of antisense RNAI regulates the replication of ColE1-type plasmids in vivo. Cell. 1991 Jun 28;65(7):1233–1242. doi: 10.1016/0092-8674(91)90018-t. [DOI] [PubMed] [Google Scholar]
  32. Lüscher B., Schümperli D. RNA 3' processing regulates histone mRNA levels in a mammalian cell cycle mutant. A processing factor becomes limiting in G1-arrested cells. EMBO J. 1987 Jun;6(6):1721–1726. doi: 10.1002/j.1460-2075.1987.tb02423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Martin F., Michel F., Zenklusen D., Müller B., Schümperli D. Positive and negative mutant selection in the human histone hairpin-binding protein using the yeast three-hybrid system. Nucleic Acids Res. 2000 Apr 1;28(7):1594–1603. doi: 10.1093/nar/28.7.1594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Martin F., Schaller A., Eglite S., Schümperli D., Müller B. The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein. EMBO J. 1997 Feb 17;16(4):769–778. doi: 10.1093/emboj/16.4.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Marzluff W. F. Histone 3' ends: essential and regulatory functions. Gene Expr. 1992;2(2):93–97. [PMC free article] [PubMed] [Google Scholar]
  36. McDowall K. J., Kaberdin V. R., Wu S. W., Cohen S. N., Lin-Chao S. Site-specific RNase E cleavage of oligonucleotides and inhibition by stem-loops. Nature. 1995 Mar 16;374(6519):287–290. doi: 10.1038/374287a0. [DOI] [PubMed] [Google Scholar]
  37. McDowall K. J., Lin-Chao S., Cohen S. N. A+U content rather than a particular nucleotide order determines the specificity of RNase E cleavage. J Biol Chem. 1994 Apr 8;269(14):10790–10796. [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Nikonowicz E. P., Sirr A., Legault P., Jucker F. M., Baer L. M., Pardi A. Preparation of 13C and 15N labelled RNAs for heteronuclear multi-dimensional NMR studies. Nucleic Acids Res. 1992 Sep 11;20(17):4507–4513. doi: 10.1093/nar/20.17.4507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Oubridge C., Ito N., Evans P. R., Teo C. H., Nagai K. Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature. 1994 Dec 1;372(6505):432–438. doi: 10.1038/372432a0. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. 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]
  44. Pardi A. Multidimensional heteronuclear NMR experiments for structure determination of isotopically labeled RNA. Methods Enzymol. 1995;261:350–380. doi: 10.1016/s0076-6879(95)61017-0. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Ray B. K., Apirion D. RNAase P is dependent on RNAase E action in processing monomeric RNA precursors that accumulate in an RNAase E- mutant of Escherichia coli. J Mol Biol. 1981 Jul 15;149(4):599–617. doi: 10.1016/0022-2836(81)90349-1. [DOI] [PubMed] [Google Scholar]
  47. Ray B. K., Apirion D. Transfer RNA precursors are accumulated in Escherichia coli in the absence of RNase E. Eur J Biochem. 1981 Mar;114(3):517–524. doi: 10.1111/j.1432-1033.1981.tb05175.x. [DOI] [PubMed] [Google Scholar]
  48. Reuven N. B., Deutscher M. P. Multiple exoribonucleases are required for the 3' processing of Escherichia coli tRNA precursors in vivo. FASEB J. 1993 Jan;7(1):143–148. doi: 10.1096/fasebj.7.1.8422961. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. Rossi J., Egan J., Hudson L., Landy A. The tyrT locus: termination and processing of a complex transcript. Cell. 1981 Nov;26(3 Pt 1):305–314. doi: 10.1016/0092-8674(81)90199-9. [DOI] [PubMed] [Google Scholar]
  51. Régnier P., Arraiano C. M. Degradation of mRNA in bacteria: emergence of ubiquitous features. Bioessays. 2000 Mar;22(3):235–244. doi: 10.1002/(SICI)1521-1878(200003)22:3<235::AID-BIES5>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  52. Sakano H., Shimura Y. Characterization and in vitro processing of transfer RNA precursors accumulated in a temperature-sensitive mutant of Escherichia coli. J Mol Biol. 1978 Aug 15;123(3):287–326. doi: 10.1016/0022-2836(78)90082-7. [DOI] [PubMed] [Google Scholar]
  53. Schedl P., Roberts J., Primakoff P. In vitro processing of E. coli tRNA precursors. Cell. 1976 Aug;8(4):581–594. doi: 10.1016/0092-8674(76)90226-9. [DOI] [PubMed] [Google Scholar]
  54. Sekiya T., Contreras R., Takeya T., Khorana H. G. Total synthesis of a tyrosine suppressor transfer RNA gene. XVII. Transcription, in vitro, of the synthetic gene and processing of the primary transcript to transfer RNA. J Biol Chem. 1979 Jul 10;254(13):5802–5816. [PubMed] [Google Scholar]
  55. Soldati D., Schümperli D. Structural and functional characterization of mouse U7 small nuclear RNA active in 3' processing of histone pre-mRNA. Mol Cell Biol. 1988 Apr;8(4):1518–1524. doi: 10.1128/mcb.8.4.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Steege D. A. Emerging features of mRNA decay in bacteria. RNA. 2000 Aug;6(8):1079–1090. doi: 10.1017/s1355838200001023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sullivan E., Santiago C., Parker E. D., Dominski Z., Yang X., Lanzotti D. J., Ingledue T. C., Marzluff W. F., Duronio R. J. Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression. Genes Dev. 2001 Jan 15;15(2):173–187. doi: 10.1101/gad.862801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Valegård K., Murray J. B., Stockley P. G., Stonehouse N. J., Liljas L. Crystal structure of an RNA bacteriophage coat protein-operator complex. Nature. 1994 Oct 13;371(6498):623–626. doi: 10.1038/371623a0. [DOI] [PubMed] [Google Scholar]
  59. Vögeli G., Stewart T. S., McCutchan T., Söll D. Isolation of Escherichia coli precursor tRNAs containing modified nucleoside Q. J Biol Chem. 1977 Apr 10;252(7):2311–2318. [PubMed] [Google Scholar]
  60. Wachi M., Umitsuki G., Shimizu M., Takada A., Nagai K. Escherichia coli cafA gene encodes a novel RNase, designated as RNase G, involved in processing of the 5' end of 16S rRNA. Biochem Biophys Res Commun. 1999 Jun 7;259(2):483–488. doi: 10.1006/bbrc.1999.0806. [DOI] [PubMed] [Google Scholar]
  61. Wang Z. F., Whitfield M. L., Ingledue T. C., 3rd, Dominski Z., Marzluff W. F. The protein that binds the 3' end of histone mRNA: a novel RNA-binding protein required for histone pre-mRNA processing. Genes Dev. 1996 Dec 1;10(23):3028–3040. doi: 10.1101/gad.10.23.3028. [DOI] [PubMed] [Google Scholar]
  62. Whitfield M. L., Zheng L. X., Baldwin A., Ohta T., Hurt M. M., Marzluff W. F. Stem-loop binding protein, the protein that binds the 3' end of histone mRNA, is cell cycle regulated by both translational and posttranslational mechanisms. Mol Cell Biol. 2000 Jun;20(12):4188–4198. doi: 10.1128/mcb.20.12.4188-4198.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. 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]
  64. Williams A. S., Marzluff W. F. 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. Nucleic Acids Res. 1995 Feb 25;23(4):654–662. doi: 10.1093/nar/23.4.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Zanier Katia, Luyten Ingrid, Crombie Catriona, Muller Berndt, Schümperli Daniel, Linge Jens P., Nilges Michael, Sattler Michael. Structure of the histone mRNA hairpin required for cell cycle regulation of histone gene expression. RNA. 2002 Jan;8(1):29–46. doi: 10.1017/s1355838202014061. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from RNA are provided here courtesy of The RNA Society

RESOURCES