Skip to main content

RNA Binding by Single Zinc Fingers

  • Chapter
Zinc Finger Proteins

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

RNA-protein complexes have important functions in gene expression and regulation. Zinc fingers of the Cys-Cys-His-His (C2H2) class that bind RNA do so via contacts with amino acid side chains in the α-helical portion of the zinc finger, similar to their interaction with DNA. In general, two or more tandem zinc fingers are present in naturally occurring zinc finger proteins. In vitro selection and recombination techniques have isolated single zinc fingers that bind complex RNA structures with high affinity and specificity. These zinc fingers may ultimately find use as pharmaceutical or agricultural agents designed specifically to modify the function of cellular or viral RNA.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Simons RW, Grunberg-Manago M. RNA structure and function. Plainview. NY: Cold Spring Harbor Laboratory Press, 1998.

    Google Scholar 

  2. Query CC, Bentley RC, Keene JD. A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell Apr 7 1989; 57(1):89–101.

    Article  CAS  Google Scholar 

  3. Siomi H, Matunis MJ, Michael WM et al. The premRNA binding K protein contains a novel evolutionarily conserved motif. Nucleic Acids Res 1993; 21(5):1193–1198.

    Article  PubMed  CAS  Google Scholar 

  4. St Johnston D, Brown NH, Gall JG et al. A conserved double-stranded RNA-binding domain. Proc Natl Acad Sci USA 1992; 89(22):10979–10983.

    Article  PubMed  CAS  Google Scholar 

  5. Calnan BJ, Tidor B, Biancalana S et al. Arginine-mediated RNA recognition: The arginine fork. Science 1991; 252(5010):1167–1171.

    Article  PubMed  CAS  Google Scholar 

  6. Laity JH, Lee BM, Wright PE. Zinc finger proteins: New insights into structural and functional diversity. Curr Opin Struct Biol 2001; 11(1):39–46.

    Article  PubMed  CAS  Google Scholar 

  7. Pavletich NP, Pabo CO. Zinc finger-DNA recognition: Crystal structure of a Zif268-DNA complex at 2.1 A. Science 1991; 252(5007):809–817.

    Article  PubMed  CAS  Google Scholar 

  8. Rebar EJ, Pabo CO. Zinc finger phage: Affinity selection of fingers with new DNA-binding specificities. Science 1994; 263(5147):671–673.

    Article  PubMed  CAS  Google Scholar 

  9. Choo Y, Klug A. Physical basis of a protein-DNA recognition code. Curr Opin Struct Biol 1997; 7(1):117–125.

    Article  PubMed  CAS  Google Scholar 

  10. Choo Y, Sanchez-Garcia I, Klug A. In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. Nature 1994; 372(6507):642–645.

    Article  PubMed  CAS  Google Scholar 

  11. Jamieson AC, Miller JC, Pabo CO. Drug discovery with engineered zinc-finger proteins. Nat Rev Drug Discov 2003; 2(5):361–368.

    Article  PubMed  CAS  Google Scholar 

  12. Ordiz MI, Barbas 3rd CF, Beachy RN. Regulation of transgene expression in plants with polydactyl zinc finger transcription factors. Proc Natl Acad Sci USA 2002; 99(20):13290–13295.

    Article  PubMed  CAS  Google Scholar 

  13. Friesen WJ, Darby MK. Specific RNA binding proteins constructed from zinc fingers. Nat Struct Biol 1998; 5(7):543–546.

    Article  PubMed  CAS  Google Scholar 

  14. Steitz T. Similarities and Differences between RNA and DNA Recognition by Proteins. In: Gesteland R, Atkins J, eds. The RNA World. Vol Monograph 24. Cold Spring Harbor: CSHL Press, 1993:219–237.

    Google Scholar 

  15. Leulliot N, Varani G. Current topics in RNA-protein recognition: Control of specificity and biological function through induced fit and conformational capture. Biochemistry 2001; 40(27):7947–7956.

    Article  PubMed  CAS  Google Scholar 

  16. Williamson JR. Induced fit in RNA-protein recognition. Nat Struct Biol Oct 2000;7(10):834–837.

    Article  CAS  Google Scholar 

  17. Schuh R, Aicher W, Gaul U et al. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell 1986; 47(6):1025–1032.

    Article  PubMed  CAS  Google Scholar 

  18. Bardeesy N, Pelletier J. Overlapping RNA and DNA binding domains of the wt1 tumor suppressor gene product. Nucleic Acids Res 1998; 26(7):1784–1792.

    Article  PubMed  CAS  Google Scholar 

  19. Zhai G, Iskandar M, Barilla K et al. Characterization of RNA aptamer binding by the Wilms’ tumor suppressor protein WT1. Biochemistry 2001; 40(7):2032–2040.

    Article  PubMed  CAS  Google Scholar 

  20. Pelham HR, Brown DD. A specific transcription factor that can bind either the 5S RNA gene or 5S RNA. Proc Natl Acad Sci USA 1980; 77(7):4170–4174.

    Article  PubMed  CAS  Google Scholar 

  21. Engelke DR, Ng SY, Shastry BS et al. Specific interaction of a purified transcription factor with an internal control region of 5S RNA genes. Cell 1980; 19(3):717–728.

    Article  PubMed  CAS  Google Scholar 

  22. Picard B, Wegnez M. Isolation of a 7S particle from Xenopus laevis oocytes: A 5S RNA-protein complex. Proc Natl Acad Sci USA 1979; 76(1):241–245.

    Article  PubMed  CAS  Google Scholar 

  23. Vrana KE, Churchill ME, Tullius TD et al. Mapping functional regions of transcription factor TFIIIA. Mol Cell Biol 1988; 8(4):1684–1696.

    PubMed  CAS  Google Scholar 

  24. Smith DR, Jackson IJ, Brown DD. Domains of the positive transcription factor specific for the Xenopus 5S RNA gene. Cell 1984;37(2):645–652.

    Article  PubMed  CAS  Google Scholar 

  25. Joho KE, Darby MK, Crawford ET et al. A finger protein structurally similar to TFIIIA that binds exclusively to 5S RNA in Xenopus. Cell 1990;61(2):293–300.

    Article  PubMed  CAS  Google Scholar 

  26. Picard B, le Maire M, Wegnez M et al. Biochemical Research on oogenesis. Composition of the 42-S storage particles of Xenopus laevix oocytes. Eur J Biochem 1980; 109(2):359–368.

    Article  PubMed  CAS  Google Scholar 

  27. Hamilton TB, Turner J, Barilla K et al. Contribution of individual amino acids to the nucleic acid binding activities of the Xenopus zinc finger proteins TFIIIIA and p43. Biochemistry 2001; 40(20):6093–6101.

    Article  PubMed  CAS  Google Scholar 

  28. Sands MS, Bogenhagen DF. Two zinc finger proteins from Xenopus laevis bind the same region of 5S RNA but with different nuclease protection patterns. Nucleic Acids Res 1991; 19(8):1797–1803.

    Article  PubMed  CAS  Google Scholar 

  29. Darby MK, Joho KE. Differential binding of zinc fingers from Xenopus TFIIIA and p43 to 5S RNA and the 5S RNA gene. Mol Cell Biol 1992; 12(7):3155–3164.

    PubMed  CAS  Google Scholar 

  30. Zang WQ, Romaniuk PJ. Characterization of the 5 S RNA binding activity of Xenopus zinc finger protein p43. J Mol Biol 1995; 245(5):549–558.

    Article  PubMed  CAS  Google Scholar 

  31. Ryan RF, Darby MK. The role of zinc finger linkers in p43 and TFIIIA binding to 5S rRNA and DNA. Nucleic Acids Res 1998; 26(3):703–709.

    Article  PubMed  CAS  Google Scholar 

  32. Theunissen O, Rudt F, Guddat U et al. RNA and DNA binding zinc fingers in Xenopus TFIIIA. Cell 1992;71(4):679–690.

    Article  PubMed  CAS  Google Scholar 

  33. Clemens KR, Wolf V, McBryant SJ et al. Molecular basis for specific recognition of both RNA and DNA by a zinc finger protein. Science 1993; 260(5107):530–533.

    Article  PubMed  CAS  Google Scholar 

  34. Choo Y, Klug A. A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA. Nucleic Acids Res 1993; 21(15):3341–3346.

    Article  PubMed  CAS  Google Scholar 

  35. Searles MA, Lu D, Klug A. The role of the central zinc fingers of transcription factor IIIA in binding to 5 S RNA. J Mol Biol 2000;301(1):47–60.

    Article  PubMed  CAS  Google Scholar 

  36. Neely LS, Lee BM, Xu J et al. Identification of a minimal domain of 5 S ribosomal RNA sufficient for high affinity interactions with the RNA-specific zinc fingers of transcription factor IIIA. J Mol Biol 1999; 291(3):549–560.

    Article  PubMed  CAS  Google Scholar 

  37. Friesen WJ, Darby MK. Phage display of RNA binding zinc fingers from transcription factor IIIA. J Biol Chem 1997; 272(17):10994–10997.

    Article  PubMed  CAS  Google Scholar 

  38. Smith GP, Scott JK. Libraries of peptides and proteins displayed on filamentous phage. Methods Enzymol 1993; 217:228–257.

    Article  PubMed  CAS  Google Scholar 

  39. Nardelli J, Gibson TJ, Vesque C et al. Base sequence discrimination by zinc-finger DNA-binding domains. Nature 1991; 349(6305):175–178.

    Article  PubMed  CAS  Google Scholar 

  40. Wolfe SA, Greisman HA, Ramm EI et al. Analysis of zinc fingers optimized via phage display: Evaluating the utility of a recognition code. J Mol Biol 1999; 285(5):1917–1934.

    Article  PubMed  CAS  Google Scholar 

  41. Pabo CO, Peisach E, Grant RA. Design and selection of novel Cys2His2 zinc finger proteins. Annu Rev Biochem 2001; 70:313–340.

    Article  PubMed  CAS  Google Scholar 

  42. Liu Q, Segal DJ, Ghiara JB et al. Design of polydactyl zinc-finger proteins for unique addressing within complex genomes. Proc Natl Acad Sci USA 1997; 94(11):5525–5530.

    Article  PubMed  CAS  Google Scholar 

  43. Christiansen J, Brown RS, Sproat BS et al. Xenopus transcription factor IIIA binds primarily at junctions between double helical stems and internal loops in oocyte 5S RNA. Embo J 1987; 6(2):453–460.

    PubMed  CAS  Google Scholar 

  44. Pieler T, Erdmann VA, Appel B. Structural requirements for the interaction of 5S rRNA with the eukaryotic transcription factor IIIA. Nucleic Acids Res 1984; 12(22):8393–8406.

    Article  PubMed  CAS  Google Scholar 

  45. Theunissen O, Rudt F, Pieler T. Structural determinants in 5S RNA and TFIIIA for 7S RNP formation. Eur J Biochem 1998; 258(2):758–767.

    Article  PubMed  CAS  Google Scholar 

  46. Setzer DR, Menezes SR, Del Rio S et al. Functional interactions between the zinc fingers of Xenopus transcription factor IIIA during 5S rRNA binding. RNA 1996; 2(12):1254–1269.

    PubMed  CAS  Google Scholar 

  47. Darsillo P, Huber PW. The use of chemical nucleases to analyze RNA-protein interactions. The TFIIIA-5 S rRNA complex. J Biol Chem 1991; 266(31):21075–21082.

    PubMed  CAS  Google Scholar 

  48. Kjems J, Calnan BJ, Frankel AD et al. Specific binding of a basic peptide from HIV-1 Rev. EMBO Journal 1992; 11(3):1119–1129.

    PubMed  CAS  Google Scholar 

  49. Pollard VW, Malim MH. The HIV-1 Rev protein. Annu Rev Microbiol 1998;52:491–532.

    Article  PubMed  CAS  Google Scholar 

  50. Sodroski J, Goh WC, Rosen C et al. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature 1986; 321(6068):412–417.

    Article  PubMed  CAS  Google Scholar 

  51. Hope T, Pomerantz RJ. The human immunodeficiency virus type 1 Rev protein: A pivotal protein in the viral life cycle. Curr Top Microbiol Immunol 1995; 193:91–105.

    PubMed  CAS  Google Scholar 

  52. Malim MH, Cullen BR. HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: Implications for HIV-1 latency. Cell 1991; 65(2):241–248.

    Article  PubMed  CAS  Google Scholar 

  53. Pasquinelli AE, Ernst RK, Lund E et al. The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. Embo J 1997; 16(24):7500–7510.

    Article  PubMed  CAS  Google Scholar 

  54. Tan R, Chen L, Buettner JA et al. RNA recognition by an isolated alpha helix. Cell 1993; 73(5):1031–1040.

    Article  PubMed  CAS  Google Scholar 

  55. Wuttke DS, Foster MP, Case DA et al. Solution structure of the first three zinc fingers of TFIIIA bound to the cognate DNA sequence: Determinants of affinity and sequence specificity. J Mol Biol 1997; 273(1):183–206.

    Article  PubMed  CAS  Google Scholar 

  56. Stemmer WP. DNA shuffling by random fragmentation and reassembly: In vitro recombination for molecular evolution. Proc Natl Acad Sci USA 1994; 91(22):10747–10751.

    Article  PubMed  CAS  Google Scholar 

  57. Stemmer WP. Rapid evolution of a protein in vitro by DNA shuffling. Nature 1994; 370(6488):389–391.

    Article  PubMed  CAS  Google Scholar 

  58. Friesen WJ, Darby MK. Specific RNA binding by a single C2H2 zinc finger. J Biol Chem 2001;276(3):1968–1973.

    Article  PubMed  CAS  Google Scholar 

  59. Southgate C, Zapp ML, Green MR. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature 1990; 345(6276):640–642.

    Article  PubMed  CAS  Google Scholar 

  60. Brigati C, Giacca M, Noonan DM et al. HIV Tat, its TARgets and the control of viral gene expression. FEMS Microbiol Lett 2003; 220(1):57–65.

    Article  PubMed  CAS  Google Scholar 

  61. Darby MK, Germann MW. Unpublished.

    Google Scholar 

  62. McColl DJ, Honchell CD, Frankel AD. Structure-based design of an RNA-binding zinc finger. Proc Natl Acad Sci USA 1999; 96(17):9521–9526.

    Article  PubMed  CAS  Google Scholar 

  63. Blancafort P, Steinberg SV, Paquin B et al. The recognition of a noncanonical RNA base pair by a zinc finger protein. Chem Biol 1999; 6(8):585–597.

    Article  PubMed  CAS  Google Scholar 

  64. Greisman HA, Pabo CO. A general strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites. Science 1997; 275(5300):657–661.

    Article  PubMed  CAS  Google Scholar 

  65. Blackshear PJ. Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover. Biochem Soc Trans 2002; 30(Pt 6):945–952.

    Article  PubMed  CAS  Google Scholar 

  66. Lai WS, Carballo E, Strum JR et al. Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA. Mol Cell Biol 1999; 19(6):4311–4323.

    PubMed  CAS  Google Scholar 

  67. Michel SL, Guerrerio AL, Berg JM. Selective RNA binding by a single CCCH zinc-binding domain from Nup475 (Tristetraprolin). Biochemistry 2003; 42(16):4626–4630.

    Article  PubMed  CAS  Google Scholar 

  68. Blackshear PJ, Lai WS, Kennington EA et al. Characteristics of the interaction of a synthetic human tristetraprolin tandem zinc finger peptide with AU-rich element-containing RNA substrates. J Biol Chem 2003(Please add the missing information)

    Google Scholar 

  69. Lai WS, Carballo E, Thorn J et al. Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA. J Biol Chem 2000; 275(23):17827–17837.

    Article  PubMed  CAS  Google Scholar 

  70. Shastry BS. Transcription factor IIIA (TFIIIA) in the second decade. J Cell Sci 1996; 109(Pt 3):535–539.

    PubMed  CAS  Google Scholar 

  71. Caricasole A, Duarte A, Larsson SH et al. RNA binding by the Wilms tumor suppressor zinc finger proteins. Proc Natl Acad Sci USA 1996; 93(15):7562–7566.

    Article  PubMed  CAS  Google Scholar 

  72. Mendez-Vidal C, Wilhelm MT, Hellborg F et al. The p53-induced mouse zinc finger protein wig-1 binds double-stranded RNA with high affinity. Nucleic Acids Res 2002; 30(9):1991–1996.

    Article  PubMed  CAS  Google Scholar 

  73. Finerty Jr PJ, Bass BL. A Xenopus zinc finger protein that specifically binds dsRNA and RNA-DNA hybrids. J Mol Biol 1997; 271(2):195–208.

    Article  PubMed  CAS  Google Scholar 

  74. Yang M, May WS, Ito T. JAZ requires the double-stranded RNA-binding zinc finger motifs for nuclear localization. J Biol Chem 1999; 274(39):27399–27406.

    Article  PubMed  CAS  Google Scholar 

  75. Arranz V, Harper F, Florentin Y et al. Human and mouse MOK2 proteins are associated with nuclear ribonucleoprotein components and bind specifically to RNA and DNA through their zinc finger domains. Mol Cell Biol 1997; 17(4):2116–2126.

    PubMed  CAS  Google Scholar 

  76. Bardoni B, Schenck A, Mandel JL. A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein. Hum Mol Genet 1999; 8(13):2557–2566.

    Article  PubMed  CAS  Google Scholar 

  77. Klocke B, Koster M, Hille S et al. The FAR domain defines a new Xenopus laevis zinc finger protein subfamily with specific RNA homopolymer binding activity. Biochim Biophys Acta 1994; 1217(1):81–89.

    PubMed  CAS  Google Scholar 

  78. Grondin B, Bazinet M, Aubry M. The KRAB zinc finger gene ZNF74 encodes an RNA-binding protein tightly associated with the nuclear matrix. J Biol Chem 1996; 271(26):15458–15467.

    Article  PubMed  CAS  Google Scholar 

  79. Amero SA, Elgin SC, Beyer AL. A unique zinc finger protein is associated preferentially with active ecdysone-responsive loci in Drosophila. Genes Dev 1991; 5(2):188–200.

    PubMed  CAS  Google Scholar 

  80. Hovemann BT, Reim I, Werner S et al. The protein Hrb57A of Drosophila melanogaster closely related to hnRNP K from vertebrates is present at sites active in transcription and coprecipitates with four RNA-binding proteins. Gene 2000; 245(1):127–137.

    Article  PubMed  CAS  Google Scholar 

  81. Dominski Z, Erkmann JA, Yang X et al. A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone premRNP to stimulate 3′-end processing. Genes Dev 2002; 16(1):58–71.

    Article  PubMed  CAS  Google Scholar 

  82. Koster M, Kuhn U, Bouwmeester T et al. Structure, expression and in vitro functional characterization of a novel RNA binding zinc finger protein from Xenopus. Embo J 1991; 10(10):3087–3093.

    PubMed  CAS  Google Scholar 

  83. Gorelick RJ, Henderson LE, Hanser JP et al. Point mutants of Moloney murine leukemia virus that fail to package viral RNA: Evidence for specific RNA recognition by a “zinc finger-like” protein sequence. Proc Natl Acad Sci USA 1988; 85(22):8420–8424.

    Article  PubMed  CAS  Google Scholar 

  84. Curtis D, Treiber DK, Tao F et al. A CCHC metal-binding domain in Nanos is essential for translational regulation. Embo J 1997; 16(4):834–843.

    Article  PubMed  CAS  Google Scholar 

  85. Worthington MT, Amann BT, Nathans D et al. Metal binding properties and secondary structure of the zinc-binding domain of Nup475. Proc Natl Acad Sci USA 1996; 93(24):13754–13759.

    Article  PubMed  CAS  Google Scholar 

  86. Barabino SM, Hubner W, Jenny A et al. The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins. Genes Dev 1997; 11(13):1703–1716.

    PubMed  CAS  Google Scholar 

  87. Ogura K, Kishimoto N, Mitani S et al. Translational control of maternal glp-1 mRNA by POS-1 and its interacting protein SPN-4 in Caenorhabditis elegans. Development 2003; 130(11):2495–2503.

    Article  PubMed  CAS  Google Scholar 

  88. Tabara H, Hill RJ, Mello CC et al. pos-1 encodes a cytoplasmic zinc-finger protein essential for germline specification in C. elegans. Development 1999; 126(1):1–11.

    PubMed  CAS  Google Scholar 

  89. Plambeck CA, Kwan AH, Adams DJ et al. The structure of the zinc finger domain from human splicing factor ZNF265 fold. J Biol Chem 2003; 278(25):22805–22811.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Landes Bioscience/Eurekah.com and Kluwer Academic/Plenum Publishers

About this chapter

Cite this chapter

Darby, M.K. (2005). RNA Binding by Single Zinc Fingers. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_11

Download citation

Publish with us

Policies and ethics