52
Views
73
CrossRef citations to date
0
Altmetric
Article

Fragile X Mental Retardation Protein FMRP Binds mRNAs in the Nucleus

, &
Pages 214-228 | Received 30 Aug 2008, Accepted 09 Oct 2008, Published online: 21 Mar 2023

REFERENCES

  • Adinolfi, S., C. Bagni, G. Musco, T. Gibson, L. Mazzarella, and A. Pastore. 1999. Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains. RNA 5:1248–1258.
  • Adinolfi, S., A. Ramos, S. R. Martin, F. Dal Piaz, P. Pucci, B. Bardoni, J. L. Mandel, and A. Pastore. 2003. The N-terminus of the fragile X mental retardation protein contains a novel domain involved in dimerization and RNA binding. Biochemistry 42:10437–10444.
  • Antar, L. N., R. Afroz, J. B. Dictenberg, R. C. Carroll, and G. J. Bassell. 2004. Metabotropic glutamate receptor activation regulates fragile X mental retardation protein and Fmr1 mRNA localization differentially in dendrites and at synapses. J. Neurosci. 24:2648–2655.
  • Arttamangkul, S., V. Alvarez-Maubecin, G. Thomas, J. T. Williams, and D. K. Grandy. 2000. Binding and internalization of fluorescent opioid peptide conjugates in living cells. Mol. Pharmacol. 58:1570–1580.
  • Ashley, C. T., J. S. Sutcliffe, C. B. Kunst, H. A. Leiner, E. E. Eichler, D. L. Nelson, and S. T. Warren. 1993. Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nat. Genet. 4:244–251.
  • Ashley, C. T., K. D. Wilkinson, D. Reines, and S. T. Warren. 1993. FMR1 protein: conserved RNP family domains and selective RNA binding. Science 262:563–566.
  • Bardoni, B., A. Sittler, Y. Shen, and J. L. Mandel. 1997. Analysis of domains affecting intracellular localization of the FMRP protein. Neurobiol. Dis. 4:329–336.
  • Beenders, B., P. L. Jones, and M. Bellini. 2007. The tripartite motif of nuclear factor 7 is required for its association with transcriptional units. Mol. Cell. Biol. 27:2615–2624.
  • Blonden, L., S. van't Padje, L. A. Severijnen, O. Destree, B. A. Oostra, and R. Willemsen. 2005. Two members of the Fxr gene family, Fmr1 and Fxr1, are differentially expressed in Xenopus tropicalis. Int. J. Dev. Biol. 49:437–441.
  • Bor, Y., J. Swartz, A. Morrison, D. Rekosh, M. Ladomery, and M.-L. Hammarskjold. 2006. The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron. Genes Dev. 20:1597–1608.
  • Braun, I. C., E. Rohrbach, C. Schmitt, and E. Izaurralde. 1999. TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus. EMBO J. 18:1953–1965.
  • Brown, V., P. Jin, S. Ceman, J. C. Darnell, W. T. O'Donnell, S. A. Tenenbaum, X. Jin, Y. Feng, K. D. Wilkinson, J. D. Keene, R. B. Darnell, and S. T. Warren. 2001. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107:477–487.
  • Ceman, S., V. Brown, and S. T. Warren. 1999. Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex. Mol. Cell. Biol. 19:7925–7932.
  • Ceman, S., F. Zhang, T. Johnson, and S. T. Warren. 2003. Development and characterization of antibodies that immunoprecipitate the FMR1 protein. Methods Mol. Biol. 217:345–354.
  • Conti, E., and E. Izaurralde. 2001. Nucleocytoplasmic transport enters the atomic age. Curr. Opin. Cell Biol. 13:310–319.
  • Cook, J. R., J.-H. Lee, Z.-H. Yang, C. D. Krause, N. Herth, R. Hoffmann, and S. Pestka. 2006. FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues. Biochem. Biophys. Res. Commun. 342:472–481.
  • Darnell, J. C., C. E. Fraser, O. Mostovetsky, G. Stefani, T. A. Jones, S. R. Eddy, and R. B. Darnell. 2005. Kissing complex RNAs mediate interaction between the fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev. 19:903–918.
  • Darnell, J. C., K. B. Jensen, P. Jin, V. Brown, S. T. Warren, and R. B. Darnell. 2001. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107:489–499.
  • Davidovic, L., X. H. Jaglin, A.-M. Lepagnol-Bestel, S. Tremblay, M. Simonneau, B. Bardoni, and E. W. Khandjian. 2007. The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules. Hum. Mol. Genet. 16:3047–3058.
  • De Boulle, K., A. J. M. H. Verkerk, E. Reyniers, L. Vits, J. Hendrickx, B. Van Roy, F. Van den Bos, E. de Graaff, B. A. Oostra, and P. J. Willems. 1993. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat. Genet. 3:31–35.
  • De Diego Otero, Y., L.-A. Severijnen, G. van Cappellen, M. Schrier, B. Oostra, and R. Willemsen. 2002. Transport of fragile X mental retardation protein via granules in neurites of PC12 cells. Mol. Cell. Biol. 22:8332–8341.
  • Devys, D., Y. Lutz, N. Rouyer, J.-P. Bellocq, and J.-L. Mandel. 1993. The FMR-1 protein is cytoplasmic, most abundant in neurons, and appears normal in carriers of the fragile X premutation. Nat. Genet. 4:335–340.
  • Didiot, M.-C., Z. Tian, C. Schaeffer, M. Subramanian, J.-L. Mandel, and H. Moine. 2008. The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer. Nucleic Acids Res. 36:4902–4912.
  • Eberhart, D. E., H. E. Malter, Y. Feng, and S. T. Warren. 1996. The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum. Mol. Genet. 5:1083–1091.
  • Eberhart, D. E., and S. T. Warren. 1996. The molecular basis of fragile X syndrome. Cold Spring Harb. Symp. Quant. Biol. 61:679–687.
  • Eichler, E. E., S. Richards, R. A. Gibbs, and D. L. Nelson. 1993. Fine structure of the human FMR1 gene. Hum. Mol. Genet. 2:1147–1153.
  • Elbashir, S. M., J. Harborth, K. Weber, and T. Tuschl. 2002. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199–212.
  • Farina, K. L., and R. H. Singer. 2002. The nuclear connection in RNA transport and localization. Trends Cell Biol. 12:466–472.
  • Feng, Y., D. Absher, D. E. Eberhart, V. Brown, H. Malter, and S. T. Warren. 1997. FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol. Cell 1:109–118.
  • Feng, Y., C.-A. Gutekunst, D. E. Eberhart, H. Yi, S. T. Warren, and S. M. Hersch. 1997. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J. Neurosci. 17:1539–1547.
  • Fridell, R., R. Benson, J. Hua, H. Bogerd, and B. Cullen. 1996. A nuclear role for the fragile X mental retardation protein. EMBO J. 15:5408–5414.
  • Fu, Y.-H., D. P. Kuhl, A. Pizzuti, M. Pieretti, J. S. Sutcliffe, S. Richards, A. J. M. H. Verkerk, J. J. A. Holden, R. G. Fenwick, Jr., S. T. Warren, B. A. Oostra, D. L. Nelson, and C. T. Caskey. 1991. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047–1058.
  • Fukuda, M., S. Asano, T. Nakamura, M. Adachi, M. Yoshida, M. Yanagida, and E. Nishida. 1997. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390:308–311.
  • Garber, K., K. T. Smith, D. Reines, and S. T. Warren. 2006. Transcription, translation and fragile X syndrome. Curr. Opin. Genet. Dev. 16:270–275.
  • Gonzalez-Reyes, A., H. Elliott, and D. St Johnston. 1995. Polarization of both major body axes in Drosophila by gurken-torpedo signalling. Nature 375:654–658.
  • Gruter, P., C. Tabernero, C. von Kobbe, C. Schmitt, C. Saavedra, A. Bachi, M. Wilm, B. K. Felber, and E. Izaurralde. 1998. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol. Cell 1:649–659.
  • Hachet, O., and A. Ephrussi. 2001. Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport. Curr. Biol. 11:1666–1674.
  • Hamilton, B. J., R. C. Nichols, H. Tsukamoto, R. J. Boado, W. M. Pardridge, and W. F. C. Rigby. 1999. hnRNP A2 and hnRNP L bind the 3′ UTR of glucose transporter 1 mRNA and exist as a complex in vivo. Biochem. Biophys. Res. Commun. 261:646–651.
  • Hodel, M. R., A. H. Corbett, and A. E. Hodel. 2001. Dissection of a nuclear localization signal. J. Biol. Chem. 276:1317–1325.
  • Hornstra, I. K., D. L. Nelson, S. T. Warren, and T. P. Yang. 1993. High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome. Hum. Mol. Genet. 2:1659–1665.
  • Huang, Y., R. Gattoni, J. Stevenin, and J. A. Steitz. 2003. SR splicing factors serve as adapter proteins for TAP-dependent mRNA export. Mol. Cell 11:837–843.
  • Huang, Y., and J. A. Steitz. 2005. SRprises along a messenger's journey. Mol. Cell 17:613–615.
  • Huttelmaier, S., D. Zenklusen, M. Lederer, J. Dictenberg, M. Lorenz, X. Meng, G. J. Bassell, J. Condeelis, and R. H. Singer. 2005. Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1. Nature 438:512–515.
  • Izaurralde, E. 2002. A novel family of nuclear transport receptors mediates the export of messenger RNA to the cytoplasm. Eur. J. Cell Biol. 81:577–584.
  • Jin, L., B. W. Guzik, Y.-C. Bor, D. Rekosh, and M.-L. Hammarskjold. 2003. Tap and NXT promote translation of unspliced mRNA. Genes Dev. 17:3075–3086.
  • Jin, P., R. S. Alisch, and S. T. Warren. 2004. RNA and microRNAs in fragile X mental retardation. Nat. Cell Biol. 6:1048–1053.
  • Kalderon, D., W. D. Richardson, A. F. Markham, and A. E. Smith. 1984. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature 311:33–38.
  • Kalderon, D., B. L. Roberts, W. D. Richardson, and A. E. Smith. 1984. A short amino acid sequence able to specify nuclear location. Cell 39:499–509.
  • Kang, Y., and B. R. Cullen. 1999. The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev. 13:1126–1139.
  • Kataoka, N., J. Yong, V. N. Kim, F. Velazquez, R. A. Perkinson, F. Wang, and G. Dreyfuss. 2000. Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol. Cell 6:673–682.
  • Lai, D., D. Sakkas, and Y. Huang. 2006. The fragile X mental retardation protein interacts with a distinct mRNA nuclear export factor NXF2. RNA 12:1446–1449.
  • Le Hir, H., D. Gatfield, E. Izaurralde, and M. J. Moore. 2001. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 20:4987–4997.
  • Le Hir, H., E. Izaurralde, L. E. Maquat, and M. J. Moore. 2000. The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 19:6860–6869.
  • Levesque, L., Y.-C. Bor, L. H. Matzat, L. Jin, S. Berberoglu, D. Rekosh, M.-L. Hammarskjold, and B. M. Paschal. 2006. Mutations in Tap uncouple RNA export activity from translocation through the nuclear pore complex. Mol. Biol. Cell 17:931–943.
  • Li, Y., Y.-C. Bor, Y. Misawa, Y. Xue, D. Rekosh, and M.-L. Hammarskjold. 2006. An intron with a constitutive transport element is retained in a Tap messenger RNA. Nature 443:234–237.
  • Mattaj, I. W., and L. Englmeier. 1998. Nucleocytoplasmic transport: the soluble phase. Ann. Rev. Biochem. 67:265–306.
  • Matzat, L. H., S. Berberoglu, and L. Levesque. 2007. Formation of a Tap/NXF1 homotypic complex is mediated through the amino-terminal domain of Tap and enhances interaction with nucleoporins. Mol. Biol. Cell 19:327–338.
  • Mazroui, R., M. E. Huot, S. Tremblay, C. Filion, Y. Labelle, and E. W. Khandjian. 2002. Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11:3007–3017.
  • Miyashiro, K. Y., A. Beckel-Mitchener, T. K. Purk, K. G. Becker, T. Barret, L. Liu, S. Carbonetto, I. J. Weiler, W. T. Greenough, and J. Eberwine. 2003. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37:417–431.
  • Monzo, K., O. Papoulas, G. T. Cantin, Y. Wang, J. R. Yates, III, and J. C. Sisson. 2006. Fragile X mental retardation protein controls trailer hitch expression and cleavage furrow formation in Drosophila embryos. Proc. Natl. Acad. Sci. USA 103:18160–18165.
  • Morgan, G. T. 2002. Lampbrush chromosomes and associated bodies: new insights into principles of nuclear structure and function. Chromosome Res. 10:177–200.
  • Nakielny, S., and G. Dreyfuss. 1999. Transport of proteins and RNAs in and out of the nucleus. Cell 99:677–690.
  • Newport, J., and M. Kirschner. 1982. A major developmental transition in early Xenopus embryos. I. Characterization and timing of cellular changes at the midblastula stage. Cell 30:675–686.
  • Niranjanakumari, S., E. Lasda, R. Brazas, and M. A. Garcia-Blanco. 2002. Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo. Methods 26:182–190.
  • Oberlé, I., F. Rousseau, D. Heitz, C. Kretz, D. Devys, A. Hanauer, J. Boué, M. F. Bertheas, and J. L. Mandel. 1991. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252:1097–1102.
  • Ossareh-Nazari, B., F. Bachelerie, and C. Dargemont. 1997. Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science 278:141–144.
  • Patel, S. B., N. Novikova, and M. Bellini. 2007. Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts. J. Cell Biol. 178:937–949.
  • Prasanth, K. V., S. G. Prasanth, Z. Xuan, S. Hearn, S. M. Freier, C. F. Bennett, M. Q. Zhang, and D. L. Spector. 2005. Regulating gene expression through RNA nuclear retention. Cell 123:249.
  • Rodrigues, J. P., M. Rode, D. Gatfield, B. J. Blencowe, M. Carmo-Fonseca, and E. Izaurralde. 2001. REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus. Proc. Natl. Acad. Sci. USA 98:1030–1035.
  • Schaeffer, C., B. Bardoni, J. L. Mandel, B. Ehresmann, C. Ehresmann, and H. Moine. 2001. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J. 20:4803–4813.
  • Siomi, H., M. Choi, M. C. Siomi, R. L. Nussbaum, and G. Dreyfuss. 1994. Essential role for KH domains in RNA binding: impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. Cell 77:33–39.
  • Siomi, H., M. C. Siomi, R. L. Nussbaum, and G. Dreyfuss. 1993. The protein product of the fragile X gene, FMR1, has characteristics of an RNA binding protein. Cell 74:291–298.
  • Siomi, M. C., Y. Zhang, H. Siomi, and G. Dreyfuss. 1996. Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Mol. Cell. Biol. 16:3825–3832.
  • Sittler, A., D. Devys, C. Weber, and J.-L. Mandel. 1996. Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Hum. Mol. Genet. 5:95–102.
  • Stade, K., C. S. Ford, C. Guthrie, and K. Weis. 1997. Exportin 1 (Crm1p) is an essential nuclear export factor. Cell 90:1041–1050.
  • Stetler, A., C. Winograd, J. Sayegh, A. Cheever, E. Patton, X. Zhang, S. Clarke, and S. Ceman. 2006. Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp. Hum Mol. Genet. 15:87–96.
  • Stutz, F., A. Bachi, T. Doerks, I. C. Braun, B. Seraphin, M. Wilm, P. Bork, and E. Izaurralde. 2000. REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA 6:638–650.
  • Sutcliffe, J. S., D. L. Nelson, F. Zhang, M. Pieretti, C. T. Caskey, D. Saxe, and S. T. Warren. 1992. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1:397–400.
  • Tamanini, F., C. Bontekoe, C. E. Bakker, L. van Unen, B. Anar, R. Willemsen, M. Yoshida, H. Galjaard, B. Oostra, and A. T. Hoogeveen. 1999. Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations. Hum. Mol. Genet. 8:863–869.
  • Tan, W., A. S. Zolotukhin, I. Tretyakova, J. Bear, S. Lindtner, S. V. Smulevitch, and B. K. Felber. 2005. Identification and characterization of the mouse nuclear export factor (Nxf) family members. Nucleic Acids Res. 33:3855–3865.
  • Tran, E. J., and S. R. Wente. 2006. Dynamic nuclear pore complexes: life on the edge. Cell 125:1041–1053.
  • van′t Padje, S., B. Engels, L. Blonden, L. A. Severijnen, F. Verheijen, B. A. Oostra, and R. Willemsen. 2005. Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 gene. Dev. Genes Evol. 215:198–206.
  • Varadi, A., and G. A. Rutter. 2002. Dynamic imaging of endoplasmic reticulum Ca2+ concentration in insulin-secreting MIN6 cells using recombinant targeted cameleons: roles of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2 and ryanodine receptors. Diabetes 51:S190–S201.
  • Vasudevan, S., and J. A. Steitz. 2007. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 128:1105–1118.
  • Verkerk, A. J. M. H., M. Pieretti, J. S. Sutcliffe, Y.-H. Fu, D. P. A. Kuhl, A. Pizutti, O. Reiner, S. Richards, M. F. Victoria, F. Zhang, B. E. Eussen, G. J. B. van Ommen, L. A. J. Blonden, G. J. Riggins, J. L. Chastain, C. B. Kunst, H. Galjaard, C. T. Caskey, D. L. Nelson, B. A. Oostra, and S. T. Warren. 1991. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914.
  • Wilkie, G. S., V. Zimyanin, R. Kirby, C. Korey, H. Francis-Lang, D. Van Vactor, and I. Davis. 2001. Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development. RNA 7:1781–1792.
  • Zalfa, F., S. Adinolfi, I. Napoli, E. Kuhn-Holsken, H. Urlaub, T. Achsel, A. Pastore, and C. Bagni. 2005. Fragile X mental retardation protein (FMRP) binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA-binding motif. J. Biol. Chem. 280:33403–33410.
  • Zhang, M., Q. Wang, and Y. Huang. 2007. Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells. Proc. Natl. Acad. Sci. USA 104:10057–10062.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.