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PMID: 12202751 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Distinct domains in the CArG-box binding factor A destabilize tetraplex forms of the fragile X expanded sequence d(CGG)n.

Nucleic acids research ·Vol. 30 ·No. 17 ·2002-09-01 ·Pages 3672-81

Weisman-Shomer P, Cohen E, Fry M

Abstract

Formation of hairpin or tetraplex structures of the FMR1 gene d(CGG)n sequence triggers its expansion, setting off fragile X syndrome. In searching for proteins that destabilize d(CGG)n secondary structures we purified from rat liver quadruplex telomeric DNA binding protein 42 (qTBP42) that disrupts G'2 bimolecular tetraplex d(CGG)n while paradoxically stabilizing the G'2 structure of the telomeric sequence d(TTAGGG)n. Based on peptide sequence homology of qTBP42 and mouse CArG-box binding factor A (CBF-A), we provide direct evidence that recombinant CBF-A protein is physically and immunochemically indistinguishable from qTBP42 and that it too destabilizes G'2 d(CGG)n while stabilizing G'2 d(TTAGGG)n. We inquired whether CBF-A employs the same or different domains to differentially interact with G'2 d(CGG)n and G'2 d(TTAGGG)n. Mutant CBF-A proteins that lack each or combinations of its five conserved motifs: RNP1(1), RNP1(2), RNP2(1), RNP2(2) and ATP/GTP-binding box were tested for their G'2 d(CGG)n destabilization and G'2 d(TTAGGG)n stabilization activities. We find that either RNP1(1) or the ATP/GTP motifs are necessary and sufficient for G'2 d(CGG)n destabilization whereas RNP2(1) suppresses destabilization by either one of these two motifs. Neither RNP1(1) nor the ATP/GTP motif are required for G'2 d(TTAGGG)n stabilization. Hence, CBF-A employs different domains to destabilize G'2 d(CGG)n or stabilize G'2 d(TTAGGG)n.

MeSH Terms
Animals Base Sequence Binding Sites/genetics Cell Cycle Proteins DNA/chemistry,genetics,metabolism DNA-Binding Proteins/genetics,immunology,metabolism Fragile X Mental Retardation Protein G-Quadruplexes Heterogeneous-Nuclear Ribonucleoprotein Group A-B Hot Temperature Immune Sera/immunology Mice Mutation Nerve Tissue Proteins/genetics Nucleic Acid Conformation Protein Binding RNA-Binding Proteins Rats Repressor Proteins/genetics,immunology,metabolism Ribonucleoproteins Transcription Factors Trinucleotide Repeats/genetics
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Fmr1 protein, mouse Fmr1 protein, rat Heterogeneous-Nuclear Ribonucleoprotein Group A-B Hnrnpab protein, rat Immune Sera Nerve Tissue Proteins RNA-Binding Proteins Repressor Proteins Ribonucleoproteins Transcription Factors Fragile X Mental Retardation Protein Hnrnpab protein, mouse DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Weisman-Shomer Pnina
Unit of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, PO Box 9649, Haifa 31096, Israel.
Cohen Esther
Fry Michael
References (56)
56 references, click to expand
  1. Sequence-specific binding protein of single-stranded and unimolecular quadruplex telomeric DNA from rat hepatocytes.
    J Biol Chem. 1997 Jun 20;272(25):15881-90 PMID: 9188487
  2. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs.
    Cell. 1987 Dec 24;51(6):899-908 PMID: 3690664
  3. DNA tetraplex formation in the control region of c-myc.
    Nucleic Acids Res. 1998 Mar 1;26(5):1167-72 PMID: 9469822
  4. Purification, characterization and molecular cloning of TGP1, a novel G-DNA binding protein from Tetrahymena thermophila.
    Nucleic Acids Res. 1998 Apr 1;26(7):1613-20 PMID: 9512530
  5. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis.
    Nature. 1988 Jul 28;334(6180):364-6 PMID: 3393228
  6. Monovalent cation-induced structure of telomeric DNA: the G-quartet model.
    Cell. 1989 Dec 1;59(5):871-80 PMID: 2590943
  7. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops.
    Nature. 1989 Dec 14;342(6251):825-9 PMID: 2601741
  8. A Tetrahymena thermophila G4-DNA binding protein with dihydrolipoamide dehydrogenase activity.
    Biochemistry. 1998 Mar 24;37(12):4224-34 PMID: 9521745
  9. Purification and characterization of a protein binding to the SP6 kappa promoter. A potential role for CArG-box binding factor-A in kappa transcription.
    J Biol Chem. 1998 Jul 24;273(30):18881-90 PMID: 9668064
  10. The Bloom's syndrome helicase unwinds G4 DNA.
    J Biol Chem. 1998 Oct 16;273(42):27587-92 PMID: 9765292
  11. The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs.
    Nucleic Acids Res. 1999 May 1;27(9):1978-84 PMID: 10198430
  12. Human werner syndrome DNA helicase unwinds tetrahelical structures of the fragile X syndrome repeat sequence d(CGG)n.
    J Biol Chem. 1999 Apr 30;274(18):12797-802 PMID: 10212265
  13. Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA.
    Genes Dev. 1999 May 1;13(9):1102-15 PMID: 10323862
  14. Characterization of CArG-binding protein A initially identified by differential display.
    Neuroscience. 1999;94(2):637-49 PMID: 10579224
  15. Tetrahelical forms of the fragile X syndrome expanded sequence d(CGG)(n) are destabilized by two heterogeneous nuclear ribonucleoprotein-related telomeric DNA-binding proteins.
    J Biol Chem. 2000 Jan 21;275(3):2231-8 PMID: 10636930
  16. Changes in CArG-binding protein A expression levels following injection(s) of the D1-dopamine agonist SKF-82958 in the intact and 6-hydroxydopamine-lesioned rat.
    Neuroscience. 2000;98(1):69-78 PMID: 10858613
  17. In vitro properties of the conserved mammalian protein hnRNP D suggest a role in telomere maintenance.
    Mol Cell Biol. 2000 Aug;20(15):5425-32 PMID: 10891483
  18. CArG binding factor A (CBF-A) is involved in transcriptional regulation of the rat Ha-ras promoter.
    Nucleic Acids Res. 2000 Oct 1;28(19):3762-70 PMID: 11000268
  19. Interaction of hnRNP A2/B1 isoforms with telomeric ssDNA and the in vitro function.
    Biochem Biophys Res Commun. 2001 Jan 26;280(3):625-30 PMID: 11162566
  20. Functional and dysfunctional roles of quadruplex DNA in cells.
    Chem Biol. 2001 Mar;8(3):221-30 PMID: 11306347
  21. Interactions between the Werner syndrome helicase and DNA polymerase delta specifically facilitate copying of tetraplex and hairpin structures of the d(CGG)n trinucleotide repeat sequence.
    J Biol Chem. 2001 May 11;276(19):16439-46 PMID: 11279038
  22. G-quadruplex DNA structures--variations on a theme.
    Biol Chem. 2001 Apr;382(4):621-8 PMID: 11405224
  23. S1 proteins C2 and D2 are novel hnRNPs similar to the transcriptional repressor, CArG box motif-binding factor A.
    Eur J Biochem. 2001 Jul;268(13):3654-63 PMID: 11432731
  24. The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases.
    Nucleic Acids Res. 2001 Jul 1;29(13):2843-9 PMID: 11433031
  25. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif.
    EMBO J. 2001 Sep 3;20(17):4803-13 PMID: 11532944
  26. Cloning and sequence analysis of a human type A/B hnRNP protein.
    FEBS Lett. 1991 Sep 23;290(1-2):159-61 PMID: 1717314
  27. MyoD binds to the guanine tetrad nucleic acid structure.
    J Biol Chem. 1992 Jul 5;267(19):13714-8 PMID: 1320026
  28. A protein binding to CArG box motifs and to single-stranded DNA functions as a transcriptional repressor.
    Gene. 1992 Oct 1;119(2):229-36 PMID: 1398104
  29. hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn.
    Nucleic Acids Res. 1992 Dec 25;20(24):6461-4 PMID: 1282701
  30. QUAD, a protein from hepatocyte chromatin that binds selectively to guanine-rich quadruplex DNA.
    J Biol Chem. 1993 Feb 15;268(5):3306-12 PMID: 8429007
  31. Polynucleotide binding to macrophage scavenger receptors depends on the formation of base-quartet-stabilized four-stranded helices.
    J Biol Chem. 1993 Feb 15;268(5):3546-54 PMID: 8429030
  32. Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3157-61 PMID: 8475054
  33. Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n.
    Mol Cell Biol. 1993 Jul;13(7):4301-10 PMID: 8321232
  34. hnRNP proteins and the biogenesis of mRNA.
    Annu Rev Biochem. 1993;62:289-321 PMID: 8352591
  35. The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA.
    Cell. 1993 Sep 10;74(5):875-85 PMID: 8374954
  36. Characterization of a G-quartet formation reaction promoted by the beta-subunit of the Oxytricha telomere-binding protein.
    Biochemistry. 1993 Nov 2;32(43):11646-57 PMID: 8218232
  37. A protein from Tetrahymena thermophila that specifically binds parallel-stranded G4-DNA.
    Biochemistry. 1994 Mar 1;33(8):2240-6 PMID: 7509637
  38. The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure.
    Proc Natl Acad Sci U S A. 1994 May 24;91(11):4950-4 PMID: 8197163
  39. The yeast KEM1 gene encodes a nuclease specific for G4 tetraplex DNA: implication of in vivo functions for this novel DNA structure.
    Cell. 1994 Jul 1;77(7):1083-92 PMID: 8020096
  40. Stabilization of tetrahelical DNA by the quadruplex DNA binding protein QUAD.
    Biochem Biophys Res Commun. 1994 Nov 30;205(1):305-11 PMID: 7999041
  41. cDNA encoding a chicken protein (CRP1) with homology to hnRNP type A/B.
    Biochim Biophys Acta. 1995 Apr 4;1261(2):290-2 PMID: 7711075
  42. A yeast gene product, G4p2, with a specific affinity for quadruplex nucleic acids.
    J Biol Chem. 1995 Apr 21;270(16):9413-9 PMID: 7721866
  43. A novel yeast gene product, G4p1, with a specific affinity for quadruplex nucleic acids.
    J Biol Chem. 1995 Sep 1;270(35):20692-7 PMID: 7657649
  44. Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat.
    J Mol Biol. 1995 Dec 8;254(4):638-56 PMID: 7500339
  45. The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism.
    Bioessays. 1996 Sep;18(9):747-56 PMID: 8831291
  46. Structure-function correlations of the insulin-linked polymorphic region.
    J Mol Biol. 1996 Dec 6;264(3):534-45 PMID: 8969303
  47. Purification and characterization of qTBP42, a new single-stranded and quadruplex telomeric DNA-binding protein from rat hepatocytes.
    J Biol Chem. 1997 Feb 14;272(7):4474-82 PMID: 9020172
  48. A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates.
    J Cell Biol. 1997 Feb 24;136(4):761-73 PMID: 9049243
  49. Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs.
    Structure. 1997 Apr 15;5(4):559-70 PMID: 9115444
  50. Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution.
    Nat Struct Biol. 1997 Mar;4(3):215-22 PMID: 9164463
  51. A human nuclease specific for G4 DNA.
    Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12444-9 PMID: 11675489
  52. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome.
    Cell. 2001 Nov 16;107(4):477-87 PMID: 11719188
  53. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function.
    Cell. 2001 Nov 16;107(4):489-99 PMID: 11719189
  54. Yeast hnRNP K-like genes are involved in regulation of the telomeric position effect and telomere length.
    Mol Cell Biol. 2002 Jan;22(1):286-97 PMID: 11739741
  55. Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins.
    Mol Cell Biol. 1987 May;7(5):1731-9 PMID: 3110598
  56. Telomeric and tetraplex DNA binding properties of qTBP42: a homologue of the CArG box binding protein CBF-A.
    Biochem Biophys Res Commun. 1997 Aug 28;237(3):617-23 PMID: 9299414
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkf506
Published
2002-09-01
Pages
3672-81
Language
English
Region
England
NLM ID
0411011
PMCID
PMC137428
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkf506 PMC Full Text View journal details
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