Skip to main content
SpringerLink
Log in

TFIIIA: A Sophisticated Zinc Finger Protein

  • Chapter
Zinc Finger Proteins

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

Abstract

Transcription factor IIIA (TFIIIA) is widely regarded as the archetypal zinc finger protein. It is a member of a very large multigene family of eukaryotic DNA-binding proteins. More than two decades of research have been dedicated to understanding its interaction with the 5S ribosomal RNA gene (5S DNA). TFIIIA has nine tandem C2H2 zinc fingers along the peptide sequence. The three-dimensional structure of the N-terminal 6 zinc fingers bound to 31 base pairs of DNA shows that not all fingers are equal. Four of them make contacts located on both DNA strands while two fingers act as spacers. Individual fingers can recognize overlapping and interlocking base pair quartets. Side chains in the short alpha helices of fingers contact bases in the major groove. It is likely that the linker sequences connecting adjacent zinc fingers evolved to dictate which fingers bind to DNA. Signals essential for transcription initiation of 5S DNA, nuclear localization, and nucleocytoplasmic transport of 5S ribosomal RNA (5S rRNA) are located in the C-terminal part of TFIIIA.

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

Access this chapter

Log in via an institution
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. Mattaj IW, Lienhard S, Zeller R et al. Nuclear exclusion of transcription factor IIIA and the 42S particle transfer RNA-binding protein in Xenopus oocytes: A possible mechanism for gene control? J Cell Biol 1983; 97(4):1261–1265.

    Article  PubMed  CAS  Google Scholar 

  2. 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 

  3. Rincon-Guzman A, Beltran-Pena E, Ortiz-Lopez A et al. Ribonucleoprotein particles of quiescent maize embryonic axes. Plant Mol Biol 1998; 38(3):357–364.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Honda BM, Roeder RG. Association of a 5S gene transcription factor with 5S RNA and altered levels of the factor during cell differentiation. Cell 1980; 22(1 Pt 1):119–126.

    Article  PubMed  CAS  Google Scholar 

  6. Mathieu O, Yukawa Y, Prieto J-L et al. Identification and characterization of transcription factor IIIA and ribosomal protein L5 from Arabidopsis thaliana. Nucleic Acids Res 2003; 31(9):2424–2433.

    Article  PubMed  CAS  Google Scholar 

  7. Huang Y, Maraia RJ. Comparison of the RNA polymerase III transcription machinery in Schizosaccharomyces pombe, Saccharomyces cerevisiae and human. Nucleic Acids Res 2001; 29(13):2675–2690.

    Article  PubMed  CAS  Google Scholar 

  8. Xing YY, Worcel A. The C-terminal domain of transcription factor IIIA interacts differently with different 5S RNA genes. Mol Cell Biol 1989; 9(2):499–514.

    PubMed  CAS  Google Scholar 

  9. Pelham HR, Wormington WM, Brown DD. Related 5S RNA transcription factors in Xenopus oocytes and somatic cells. Proc Natl Acad Sci USA 1981; 78(3):1760–1764.

    Article  PubMed  CAS  Google Scholar 

  10. Kim SH, Darby MK, Joho KE et al. The characterization of the TFIIIA synthesized in somatic cells of Xenopus laevis. Genes Dev 1990; 4(9):1602–1610.

    PubMed  CAS  Google Scholar 

  11. 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 

  12. Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J 1985; 4:1609–1614.

    PubMed  CAS  Google Scholar 

  13. Hanas JS, Hazuda DJ, Bogenhagen DF et al. Xenopus transcription factor A requires zinc for binding to the 5S RNA gene. J Biol Chem 1983; 258(23):14120–14125.

    PubMed  CAS  Google Scholar 

  14. Wingender E, Dilloo D, Seifart KH, Zinc ions are differentially required for the transcription of ribosomal 5S RNA and tRNA in a HeLa-cell extract. Nucleic Acids Res 1984; 12(23):8971–8985.

    Article  PubMed  CAS  Google Scholar 

  15. Diakun GP, Fairall L, Klug A. EXAFS study of the zinc-binding sites in the protein transcription factor IIIA. Nature 1986; 324(6098):698–699.

    Article  PubMed  CAS  Google Scholar 

  16. Brown RS. Structural investigation of the Xenopus 7S Ribonucleoprotein complex. PhD Thesis 1990. London University, Great Britain.

    Google Scholar 

  17. Ginsberg AM, King BO, Roeder RG. Xenopus 5S gene transcription factor, TFIIIA: characterization of a cDNA clone and measurement of RNA levels throughout development. Cell 1984; 39(3 Pt 2):479–489.

    Article  PubMed  CAS  Google Scholar 

  18. Brown RS, Sander C, Argos P. The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett 1985; 186(2):271–274.

    Article  PubMed  CAS  Google Scholar 

  19. Rosenberg UB, Schroeder C, Preiss A et al. Structural homology of the product of the Drosophila Krueppel gene with Xenopus transcription factor IIIA. Nature 1986; 319:336–339.

    Article  CAS  Google Scholar 

  20. Fridell RA, Fischer U, Luhrmann R et al. Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Proc Natl Acad Sci USA 1996; 93(7):2936–2940.

    Article  PubMed  CAS  Google Scholar 

  21. Rudt F, Pieler T. Cytoplasmic retention and nuclear import of 5S ribosomal RNA containing RNPs. EMBO J 1996; 15(6):1383–91.

    PubMed  CAS  Google Scholar 

  22. Mao X, Darby MK. A position-dependent transcription-activating domain in TFIIIA. Mol Cell Biol 1993; 13(12):7496–7506.

    PubMed  CAS  Google Scholar 

  23. Tso JY, Van Den Berg DJ, Korn LJ. Structure of the gene for Xenopus transcription factor TFIIIA. Nucleic Acids Res 1986; 14(5):2187–2200.

    Article  PubMed  CAS  Google Scholar 

  24. Taylor W, Jackson IJ, Siegel N et al. The developmental expression of the gene for TFIIIA in Xenopus laevis. Nucleic Acids Res 1986; 14(15):6185–6195.

    Article  PubMed  CAS  Google Scholar 

  25. Gaskins CJ, Hanas JS. Sequence variation in transcription factor IIIA. Nucleic Acids Res 1990; 18(8):2117–2123.

    Article  PubMed  CAS  Google Scholar 

  26. Gaskins CJ, Smith JF, Ogilvie MK et al. Comparison of the sequence and structure of transcription factor IIIA from Bufo americanus and Rana pipiens. Gene 1992; 120(2):197–206.

    Article  PubMed  CAS  Google Scholar 

  27. Ogilvie MK, Hanas JS. Molecular biology of vertebrate transcription factor IIIA: Cloning and characterization of TEIIIA from channel catfish oocytes. Gene 1997; 203(2):103–112.

    Article  PubMed  CAS  Google Scholar 

  28. Hanas JS, Hocker JR, Cheng YG et al. cDNA cloning, DNA binding, and evolution of mammalian transcription factor IIIA. Gene 2002; 282(1–2):43–52.

    Article  PubMed  CAS  Google Scholar 

  29. Arakawa H, Nagase H, Hayashi N et al. Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA. Cytogenet Cell Genet 1995; 70(3–4):235–238.

    PubMed  CAS  Google Scholar 

  30. Drew PD, Nagle JW, Canning RD et al. Cloning and expression analysis of a human cDNA homologous to Xenopus TFIIIA. Gene 1995; 159(2):215–218.

    Article  PubMed  CAS  Google Scholar 

  31. Archambault J, Milne CA, Schappert KT et al. The deduced sequence of the transcription factor TFIIIA from Saccharomyces cerevisiae reveals extensive divergence from Xenopus TFIIIA. J Biol Chem 1992; 267(5):3282–3288.

    PubMed  CAS  Google Scholar 

  32. Schulman DB, Setzer DR. Identification and characterization of transcription factor IIIA from Schizosaccharomyces pombe. Nucleic Acids Res 2002; 30(13):2772–2781.

    Article  PubMed  CAS  Google Scholar 

  33. Mathieu O, Yukawa Y, Prieto JL et al. Identification and characterization of transcription factor IIIA and ribosomal protein L5 from Arabidopsis thaliana. Nucleic Acids Res 2003; 31(9):2424–2433.

    Article  PubMed  CAS  Google Scholar 

  34. Wyszko E, Barciszewska M. Purification and characterization of transcription factor IIIA from higher plants. Eur J Biochem 1997; 249(1):107–112.

    Article  PubMed  CAS  Google Scholar 

  35. Wyszko E, Radlowski M, Bartkowiak S et al. Maize TF IIIA—the first transcription factor IIIA from monocotyledons. Purification and properties. Acta Biochim Pol 1997; 44(3):579–589.

    PubMed  CAS  Google Scholar 

  36. Polakowski N, Paule MR. Purification and characterization of transcription factor IIIA from Acanthamoeba castellanii. Gene 1997; 203(2):103–112.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. 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 

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

    PubMed  CAS  Google Scholar 

  40. Pieler T, Hamm J, Roeder RG. The 5S gene internal control region is composed of three distinct sequence elements, organized as two functional domains with variable spacing. Cell 1987; 48(1):91–100.

    Article  PubMed  CAS  Google Scholar 

  41. Clemens KR, Zhang P, Liao X et al. Relative contributions of the zinc fingers of transcription factor IIIA to the energetics of DNA binding. J Mol Biol 1994; 244(1):23–35.

    Article  PubMed  CAS  Google Scholar 

  42. Wu C. An exonuclease protection assay reveals heat-shock element and TATA box DNA-binding proteins in crude nuclear extracts. Nature 1985; 317(6032):84–87.

    Article  PubMed  CAS  Google Scholar 

  43. Nikolaev LG, Glotov BO, Belyavsky AV et al. Identification of sequence-specific DNA-binding factors by label transfer: Application to the adenovirus-2 major late promoter. Nucleic Acids Res 1988; 16(2):519–535.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  45. Fairall L, Rhodes D, Klug A. Mapping of the sites of protection on a 5 S RNA gene by the Xenopus transcription factor IIIA. A model for the interaction. J Mol Biol 1986; 192(3):577–591.

    Article  PubMed  CAS  Google Scholar 

  46. Clemens KR, Liao X, Wolf V et al. Definition of the binding sites of individual zinc fingers in the transcription factor IIIA-5S RNA gene complex. Proc Natl Acad Sci USA 1992; 89(22):10822–10826.

    Article  PubMed  CAS  Google Scholar 

  47. Hayes JJ, Tullius TD. Structure of the TFIIIA-5 S DNA complex. J Mol Biol 1992; 227(2):407–417.

    Article  PubMed  CAS  Google Scholar 

  48. Nolte RT, Conlin RM, Harrison SC et al. Differing roles for zinc fingers in DNA recognition: Structure of a six-finger transcription factor IIIA complex. Proc Natl Acad Sci USA 1998; 95(6):2938–2943.

    Article  PubMed  CAS  Google Scholar 

  49. 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 

  50. Brown RS, Argos P. Fingers and helices. Nature 1986; 324(6094):215.

    Article  PubMed  CAS  Google Scholar 

  51. 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 

  52. Wolfe SA, Nekludova L, Pabo CO. DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct 2000; 29:183–212.

    Article  PubMed  CAS  Google Scholar 

  53. Laity JH, Dyson HJ, Wright PE. DNA-induced alpha-helix capping in conserved linker sequences is a determinant of binding affinity in Cys(2)-His(2) zinc fingers. J Mol Biol 2000; 295(4):719–727.

    Article  PubMed  CAS  Google Scholar 

  54. 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 

  55. 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 

  56. 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 

  57. Hanas JS, Koelsch G, Moreland RM et al. Differential requirements of basic amino acids in transcription factor IIIA-5S gene interaction. Biochim Biophys Acta 1998; 1398(3):256–264.

    PubMed  CAS  Google Scholar 

  58. Zang WQ, Veldhoen N, Romaniuk PJ. Effects of zinc finger mutations on the nucleic acid binding activities of Xenopus transcription factor IIIA. Biochemistry 1995; 34(47):15545–15552.

    Article  PubMed  CAS  Google Scholar 

  59. Bumbulis MJ, Wroblewski G, McKean D et al. Genetic analysis of Xenopus transcription factor IIIA. J Mol Biol 1998; 284(5):1307–1322.

    Article  PubMed  CAS  Google Scholar 

  60. Moreland RJ, Dresser ME, Rodgers JS et al. Identification of a transcription factor IIIA-interacting protein. Nucleic Acids Res 2000; 28(9):1986–1993.

    Article  PubMed  CAS  Google Scholar 

  61. Cassiday LA, Maher LJ 3rd. Having it both ways: Transcription factors that bind DNA and RNA. Nucleic Acids Res 2002; 30(19):4118–4126.

    Article  PubMed  CAS  Google Scholar 

  62. Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis 1997; 18(15):2714–2723.

    Article  PubMed  CAS  Google Scholar 

  63. Pov-Ray™ (http://www.povray.org).

    Google Scholar 

  64. Bernstein HJ. Recent changes to RasMol, recombining the variants. Trends Biochem Sci 2000; 25(9):453–455.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Experimental Medicine Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts, USA

    Raymond S. Brown

  2. Department of Molecular Biology Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA

    Jane Flint

Authors
  1. Raymond S. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jane Flint
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

Rights and permissions

Reprints and permissions

Copyright information

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

About this chapter

Cite this chapter

Brown, R.S., Flint, J. (2005). TFIIIA: A Sophisticated Zinc Finger Protein. 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_3

Download citation

Publish with us

Policies and ethics

Search

Navigation