Fragile X mental retardation protein: Many partners and multiple targets for a promiscuous function

Current Genomics

Volumn 6, Issue 7, 2005, Pages 515-522

  Khandjian, E W ^a   Bechara, E ^b   Davidovic, L ^a   Bardoni, B ^b  

^a UNIVERSITÉ LAVAL   (Canada)

^b UNIVERSITÉ CÔTE D'AZUR   (France)

Author keywords

Fragile X syndrome; G quartet; Kissing complex; Mental retardation; MRNP complexes; Rac pathway; RNA binding domains; RNA binding proteins

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; ADENOVIRUS VECTOR; COMPLEMENTARY DNA; FRAGILE X MENTAL RETARDATION PROTEIN; MESSENGER RNA; RNA BINDING PROTEIN;

AMINO TERMINAL SEQUENCE; BINDING SITE; BLOOD BRAIN BARRIER; CELL BASED GENE THERAPY; DRUG DELIVERY SYSTEM; DRUG PURIFICATION; DRUG UPTAKE; FRAGILE X SYNDROME; GENE IDENTIFICATION; GENE SILENCING; GENE THERAPY; GENETIC CODE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MENTAL DEFICIENCY; NONHUMAN; NUCLEAR EXPORT SIGNAL; NUCLEAR LOCALIZATION SIGNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; RNA BINDING; RNA METABOLISM; RNA STRUCTURE; VIRAL GENE DELIVERY SYSTEM;

ADENOVIRIDAE;

EID: 29944433844     PISSN: 13892029     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920205775067701     Document Type: Review

References (74)

1. Verkek, A.J., Pieretti, M., Sutcliffe, J.S., Fu, Y.H., Kuhl, D.P., Pizzuti, A., Reiner, O., Richards, S., Victoria, M.F., Zhang, F.P., Nelson, L.D., Oostra, B., Warren, S.T. Identification of a gene (FMR-1) containing CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65: 905-914.
2. Hagerman, R.J., Cronister, A. Fragile X Syndrome: Diagnosis, treatement and Research. Edited by University of Baltimore; 1996.
3. Greenough, W.T., Klintsova, A.Y., Irwin, S.A., Galvez, R., Bates, E., Weiler, I.J. Synaptic regulation of protein synthesis and the fragile X protein. Proc. Nat. Acad. Sci. USA 2001; 98: 7101-7106.
4. Bear, M.F., Huber, K.M., Warren, ST. The mGluR theory of Fragile X mental retardation. Trends Neurosci., 2004; 27: 370-377.
5. Stoyanova, V., Rossetti, S., Van Unen, L., Oostra, B., Hoogeveen, AT. Loss of FMR1 hypermethylation in somatic cell heterokaryons. FASEB J., 2004; 18: 1964-1966.
6. Bardoni, B., Mandel, J.L., Fisch, GS. FMR1 gene and fragile X syndrome. Am. J. Med. Genet. 2000; 97: 153-163.
7. Tassone, F., Hagerman, R.J., Garcia-Arocena, D., Khandjian, E.W., Greco, CM., Hagerman, P.J. Intranuclear inclusions in neural cells with premutation alleles in fragile X associated tremor/ataxia syndrome. J. Med. Genet. 2004; 41: e43.
8. Hundscheid, R.D., Smits, A.P., Thomas, C.M., Kiemeney, L.A., Braat, D.D. Females carriers of fragile X premutations have no increased risk for additional diseases other that premature ovarian failure. Am. J. med. Genet. 2003; 117: 6-9.
9. Goodlin-Jones, B.L., Tassone, F., Gane, L.W., Hagerman, P.J. Autistic spectrum disorder and the fragile X premutation. Dev. Behav. Pediatr. 2004; 25: 1-7.
10. Siomi, H., Siomi, M.C., Nussbaum, R.L., Dreyfuss, G. The protein product of the fragile X gene, FMR1, has characteristics of an RNA binding protein. Cell 1993; 77: 33-39.
11. Sittler, A., Devys, D., Weber, C., Mandel, J.L. Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Hum. Mol. Genet. 1996; 5: 95-102.
12. Rackham, O., Brown, C.M. Visualization of RNA-protein interactions in living cells: FMRP and IMP1 interact on mRNAs. EMBO J. 2004; 23: 3346-3355.
13. Darnell, J.C., Jensen, K.B., Jin, P., Brown, V., Warren, S.T., Darnell, RB. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 2001; 107: 489-499.
14. Ramos, A., Hollingworth, D., Pastore, A. G-quartet-dependent recognition between the FMRP RGG box and RNA. RNA 2003; 9: 1198-1207.
15. Musco, G., Stier, G., Joseph, C., Castiglione Morelli, MA., Nilges, M., Gibson, TJ., Pastore, A. Three dimentional structure and stability of the KH domain: molecular insights into the fragile X syndrome. Cell 1996; 85: 237-245.
16. Darnell, J.C., Fraser, C.E., Mostovetsky, O., Stefani, G., Jones, T.A., Eddy S.R., Darnell R.B. Kissing complex RNAs mediate interaction between the Fragile X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev. 2005; 19: 903-918.
17. Adinolfi, S., Ramos, A., Martin, S.R., Dal Piaz, F., Pucci, P., Bardoni, B., Mandel, J.L., Pastore, A. The N-terminus of the fragile X mental retardation protein contains a novel domain involved in dimerization and RNA binding. Biochemistry 2003; 42: 10437-10444.
18. Zalfa, F., Adinolfi, S., Napoli, I., Künn-Hölsken, E., Henning, U., Achsel, T., Pastore, A., Bagni, C. FMRP binds specifically to the brain cytoplasmic BC1/BC200 via a novel RNA binding motif. J. Biol. Chem. 2005; M504286200.
19. Bardoni, B., Schenck, A., Mandel, J.L. A novel RNA binding protein that interacts with the fragile X mental retardation (FMR1) protein. Hum. Mol. Genet. 1999; 8: 2557-2566.
20. Ashley, C.T., Wilkinson, K.D., Reines, D., Warren, S.T. FMR1 protein. conserved RNP family domains and selmective RNA binding. Science, 1993; 262: 563-566.
21. Sung, Y.J., Conti, J., Currie, J.R., Brown, W.T., Denman, R.B. RNAs that interact with the fragile X syndrome RNA binding protein FMRP. Biochem. Biophys. Res. Commun. 2000; 275: 973-980.
22. Schaeffer, C., Bardoni, B., Mandel, J.L., Ehresmann, B., Ehresmann, C., Moine, H. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J. 2001; 20: 4803-4813.
23. Brown, V., Jin, P., Ceman, S., Darnell, J.C., O'Donnell, W.T., Tenebaum, S.A., Jin, X., Feng, Y., Wilkinson, K.D., Keene, J.D., Darnell, R.B., Warren, S.T. Microarray identification of FMRP-associated brain mRNA and altered mRNA translational profiles in fragile X syndrome. Cell 2001; 107.
24. Todd, P.K., Mack, K.J., Malter, J.S. The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD 95. Proc. Nat. Acad. Sci. USA 2003; 100: 14374-14378.
25. Castets, M., Schaeffer, C., Bechara, E., Schenck, A., Khandjian, E.W., Luche, S., Moine, H., Rabilloud, T., Mandel, J.L., Bardoni, B. FMRP interferes with Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts;. Hum. Mol. Genet. 2005, 14: 835-844.
26. Mazroui, R., Huot, M.E., Tremblay, S., Boilard, N., Labelle, Y., Khandjian, E.W. Fragile X mental retardation protein determinants required for its association with polyribosomal ribonucleoparticles. Hum. Mol. Genet. 2003; 12: 3087-3096.
27. Chen, L., Yun, S-W., Seto, J., Liu, W., Toth M: The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequenses. Neuroscience 2003; 120: 1005-10017.
28. Gabus, C., Mazroui, R., Tremblay, S., Khandjian, E.W., Darlix, J.L. The fragile X mental retardation protein has nucleic acid chaperone properties. Nucleic Acids Res. 2004: 32: 2623-2631.
29. Dolzhanskaya, N., Sung, Y.J., Conti, J., Currie, J.R., Denman, R.B. The fragile X mental retardation protein interacts with U-rich RNAs in a yeast three-hybrid system. Biochem. Biophys. Res. Commun. 2003; 305: 434-441.
30. D'Agata, V., Warren, S.T., Zhao, W., Torre, E.R., Alkon, D.L., Cavallaro, S. Gene expression profiles in a transgenic animal model of fragile X syndrome. Neurobiol. Dis. 2002; 10: 211-218.
31. Miyashiro, K.Y., Beckel-Mitchener, A., Purk, T.P., Becker, K.G., Barret, T., Liu, L., Carbonetto, S., Weiler, I.J., Greenough, W.T., Eberwine, J. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 2003; 37: 417-431.
32. Lu, R., Wang, H., Iiang, Z., O'donnell, W.T., Li, W., Warren, S.T., Feng, Y. The fragile X protein controls microtubules-associated protein 1B translation and microtubule stability in brain neuron development. Proc. Nat. Acad. Sci. USA 2004; 101: 15201-15206.
33. Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S.A., Oostra, B., Bagni, C. The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell 2003; 112: 317-327.
34. Zhang, Y.Q., Matthies, H.J., Mancuso, J., Andrews, H.K., Woodruff, E., Friedman, D., Broadie, K. The Drosophila fragile X-related gene regulates axoneme differentiation during spermatogenesis. Dev. Biol. 2004; 270: 290-307.
35. Zhang, Y.Q., Bailey, A.M., Matthies, H.J., Renden, R.B., Smith, M.A., Speese, S.D., Rubin, G.M., Broadie, K. Drosophila fragile X-related gene regulates MAP1B homolog FUTSCH to control synaptic structure and function. Cell 2001; 107: 591-603.
36. Costa, A., Wang, Y., Dockendorff, T.C., Erdjiument-Bromage, H., Tempst, P., Schedl, P., Jongens, T.A. The Drosophila fragile X protein functions as a negative regulator in the orb autoregulatory pathway. Dev. Biol. 2005; 8: 331-342.
37. Reeve, S.P., Bassetto, L., Genova, G.K., Kleyner, Y., Leyssen, M., Jackson, F.R., Hassan, B.A. The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain. Curr. Biol. 2005; 15: 1156-1163.
38. Lee, A., Li, W., Xu, K., Bogert, BA., Su, K, Gao, FB. Control of dendritic development by the Drosophila fragile-X related gene involves the smal GTPase Rac1. Development 2003; 130: 5543-5552.
39. Zhang, Y., O'Connor, J.P., Siomi, M.C., Srinivasan, S., Dutra, A., Nussbaum, R.L., Dreyfuss, G. The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J. 1995; 14: 5358-5366.
40. Bardoni, B., Sittler, A., Shen, Y., Mandel JL. Analysis of domains affecting intracellular localization of the FMRP protein. Neurobiol. Dis. 1997; 4: 329-336.
41. Tamanini, F., Willemsen, R., Van Unen, L., Bontekoe, C., Galjaard, H., Oostra, B., Hoogeveen, A.T. Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. Hum. Mol. Genet. 1997; 6: 1315-1322.
42. Tamanini, F., Bontekoe, C., Bakker, C., Van Unen, L., Anar, B., Willemsen, R., Yoshida, M., Galjaard, H., Oostra, B., Hoogeveen, A.T. Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations. Hum. Mol. Genet. 1999; 8: 863-869.
43. Tamanini, F., Kirkpatrick, L.L., Schonkeren, J., Van Unen, L., Bontekoe, C., Bakker, C., Nelson, D.L., Galjaard, H., Oostra, B., Hoogeveen, A.T. The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins. Hum. Mol. Genet. 2000; 9: 1487-1493.
44. Khandjian, E.W., Bardoni, B., Corbin, F., Sittler, A., Giroux, S., Heitz, D., Tremblay, S., Pinset, C., Montarras, D., Rousseau, F., Mandel, J.L. Novel isoform of the fragile X related protein FXR1P are expressed during myogenesis. Hum. Mol. Genet. 1998; 7: 2121-2128.
45. Dubé, M., Huot, M.E., Khandjian, E.W. Muscle specific fragile X related protein 1 isoforms are sequestred in the nucleus of undifferentiated myoblast. BMC Genet. 2000; 1: 4.
46. Mientjes, E.J., Willemsen, R., Kirkpatrick, L.L., Nieuwenhuizen, I.M., Hoogeveen-Westerveld, M., Verwzeij, M., Reis, S.A., Bardoni, B., Hoogeveen, A.T., Oostra, B., Nelson, D.L. Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo. Hum. Mol. Genet. 2004; 13: 1291-1302.
47. Huot, M.E., Bisson, N., Davidovic, L., Mazroui, R., Labelle, Y., Moss, T., Khandjian, E.W. The RNA-binding protein fragile X-related 1 regulates somite formation in Xenopus laevis. Mol. Biol. Cell 2005; 10: 4350-4361.
48. Bardoni, B., Castets, M., Huot, M.E., Schenck, A., Adinolfi, S., Corbin, F., Pastore, A., Khandjian, E.W., Mandel, J.L. 82-FIP, a novel FMRP (Fragile X mental retardation protein) interacting protein, shows a cell cycle-dependent intracellular localization. Hum. Mol. Genet. 2003; 12: 1689-1698.
49. Bardoni, B., Willemsen, R., Weiler, I.J., Schenck, A., Severijnen, L.A., Hindelang, C., Lalli, E., Mandel, J.L. NUFIP1 is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes. Exp. Cell Res. 2003; 289: 95-107.
50. Schenck, A., Bardoni, B., Moro, A., Bagni, C., Mandel, J.L. A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displayng selective interaction with FMRP-related proteins FXR1P and FXR2P. Proc. Nat. Acad. Sci. USA 2001; 98: 8844-8849.
51. Ivanyi-Nagy, I., Davidovic, L., Khandjian, E.W., Darlix, J.L. Disordered RNA chaperone proteins: from functions to disease. Cell Mol. Life 2005; 62: 1409-1417.
52. Ceman, S., Brown, V., Warren, S.T. Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related components of the complex. Mol. Biol. Cell 1999; 19: 7925-7932.
53. Ceman, S., Nelson, R., Warren, S.T. Identification of mouse YB1/p5O as a component of the FMRP-associated mRNP particle. Biochem. Biophys. Res. Commun. 2000; 279: 904-908.
54. Ohashi, S., Koike, K., Omori, A., Ichinose, S., Ohara, S., Kobayashi, S., Sato, T.A., Anzai, K. Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. J. Biol. Chem. 2002; 277: 7804-37810.
55. Caudy, A.A., Myers, M., Hannon, G.J., Hammond, S.M. Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev. 2002; 16: 2491-2496.
56. Ishizuka, A., Siomi, M.C., Siomi, H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 2002; 16: 2497-2507.
57. Jin, P., Zarnescu, D.C., Ceman, S., Nakamoto, M., Mowrey, J., Jongens, T.A., Nelson, D.L., Moses, K., Warren, S.T. Biochemical and genetic interaction between the fragile X mental retardation protein and microRNA patway. Nat. Neurosci. 2004; 7: 113-117.
58. Okamura, K., Ishizuka, A., Siomi, H., Siomi, M.C. Distinct roles for Argonaute proteins in small RNA-directed cleavage pathways. Genes Dev. 2004; 18: 1655-1666.
59. Mazroui, R., Huot, M.E., Tremblay, S., Filion, C., Labelle, Y., Khandjian, E.W. Trapping of messenger RNA by fragile X mental retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 2002; 11: 3007-3017.
60. Menon, R.P., Gibson, T.J., Pastore A. The C terminus of fragile x mental retardation protein interacts with the multi-domain Ran-binding protein in the microtubule organizing centre. J. Mol. Biol. 2004; 344: 43-53.
61. Zarnescu, D.C., Jin, P., Betschinger, J., Nakamoto, M., Wang, Y., Dockendorff, T.C,, Feng, Y., Jongens, T.A., Sisson, J.C., Knoblich, J.A., Warren, S.T., Moses, K. Fragile X protein functions with lgl and the par complex in flies and mice. Dev. Cell 2005; 8: 43-52.
62. Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.L., Giangrande, A. CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein. Neuron 2003; 38: 887-898.
63. Corbin, F., M. B., Fortin, A., Morin, S., Rousseau, F., Khandjian, E.W. The fragile X mental retardation protein is associated with poly (A)+mRNA in actively translating polyribosomes. Hum. Mol. Genet. 1997; 6: 401-410.
64. Khandjian, E.W., Huot, M.E., Tremblay, S., Davidovic, L., Mazroui, R., Bardoni, B. Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc. Nat. Acad. Sci. USA 2004; 101: 13357-13362.
65. Stefani, G., Fraser, C.E., Darnell, J.C., Darnell, R.B. Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells. J. Neurosci. 2004; 24: 9272-9276.
66. Siomi, M.C., Siomi H: Identification of components of RNAi pathways using the tandem affinity purification method. Methods Mol. Biol. 2005; 309: 1-10.
67. Antar, L.N., Afroz, R., Dictemberg, J.B., Carroll, R.C., Bassell, G.J. Metabotropic glutamate receptor activation regulates Fragile X mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J. Neurosci. 2004; 24: 2648-2655.
68. De Diego Otero, Y., Severijnen, L-A., Van Cappellen, G., Schrier, M., Oostra, B., Willemsen, R. Transport of Fragile X Mental Retardation Protein via granules in neurites of PC12 cells. Mol. Cell. Biol. 2002, 22: 8332-8341.
69. Ling, S.C., Fahrner, P.S., Greenough, W.T., Gelfald V.I. Transport of Drosophila fragile X mental retardation protein-containing ribonucleoprotein by kinesin-1 and cytoplasmic dynein. Proc. Nat. Acad. Sci. USA 2004; 101: 17428-17433.
70. Rattazzi, M., LaFauci, G., Brown, W.T. Prospect for gene theray in the fragile X syndrome. Ment. Retard. Dev. Disabil. Res. Rev. 2004; 44: 191-194.
71. Reis, S.A., Willemsen, R., Van Unen, L., Hoogeveen, A.T,, Oostra B: Prospect of TAT-mediated protein therapy for fragile X syndrome. J. Mol. Histol. 2004; 35: 389-395.
72. Aschrafi, A., Cunningham, B.A., Edelman, G.M., Vanderlish, P.W. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate level of mRNA granules in brain. Proc. Nat. Acad. Sci. USA 2005; 102: 2180-2185.
73. Yan, Q.J., Rammal, M., Tranfaglia, M., Bauchwitz, R.P. Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 2005; doi: 10.1016.
74. McBride, S.M., Choi, C.H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K.K., Dockendorff, T.C., Nguyen, H.T., McDonald, T.V., Jongens, T.A. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body, defects in a Drosophila model of fragile X syndrome. Neuron 2005; 45: 753-764.