Cited by 390Genetics and Neurodevelopmental DisordersRNA Research and SplicingRNA and protein synthesis mechanisms

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The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals

Eberhart, D.·1996·Human Molecular Genetics

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Abstract

Fragile X syndrome is a frequent cause of mental retardation resulting from the absence of FMRP, the protein encoded by the FMR1 gene. FMRP is an RNA-binding protein of unknown function which is associated with ribosomes. To gain insight into FMRP function, we performed immunolocalization analysis of FMRP truncation and fusion constructs which revealed a nuclear localization signal (NLS) in the amino terminus of FMRP as well as a nuclear export signal (NES) encoded by exon 14. A 17 amino acid peptide containing the FMRP NES, which closely resembles the NES motifs recently described for HIV-1 Rev and PKI, is sufficient to direct nuclear export of a microinjected protein conjugate. Sucrose gradient analysis shows that FMRP ribosome association is RNA-dependent and FMRP is found in ribonucleoprotein (RNP) particles following EDTA treatment. These data are consistent with nascent FMRP entering the nucleus to assemble into mRNP particles prior to export back into the cytoplasm and suggests that fragile X syndrome may result from altered translation of transcripts which normally bind to FMRP.

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Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481
Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080
Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M. F., & Mandel, J. L. (1991) · Science · doi:10.1126/science.252.5009.1097 · Cited by 1,499
Identification of a signal for rapid export of proteins from the nucleus
Wen, W., Meinkotht, J. L., Tsien, R. Y., & Taylor, S. S. (1995) · Cell · doi:10.1016/0092-8674(95)90435-2 · Cited by 1,190
The HIV-1 Rev Activation Domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs
Fischer, U., Huber, J., Boelens, W. C., Mattaj, I. W., & Lührmann, R. (1995) · Cell · doi:10.1016/0092-8674(95)90436-0 · Cited by 1,140
Nucleocytoplasmic Transport
Görlich, D., & Mattaj, I. W. (1996) · Science · doi:10.1126/science.271.5255.1513 · Cited by 1,081
The FMR–1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation
Devys, D., Lutz, Y., Rouyer, N., Bellocq, J., & Mandel, J. (1993) · Nature Genetics · doi:10.1038/ng0893-335 · Cited by 781
FMR1 Protein: Conserved RNP Family Domains and Selective RNA Binding
Ashley, C. T., Wilkinson, K. D., Reines, D., & Warren, S. T. (1993) · Science · doi:10.1126/science.7692601 · Cited by 752
DNA methylation represses FMR-1 transcription in fragile X syndrome
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.397 · Cited by 680
The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
Siomi, H., Siomi, M. C., Nussbaum, R. L., & Dreyfuss, G. (1993) · Cell · doi:10.1016/0092-8674(93)90420-u · Cited by 641
A point mutation in the FMR-1 gene associated with fragile X mental retardation
Boulle, K. D., Verkerk, A. J. M. H., Reyniers, E., Vits, L., Hendrickx, J., Roy, B. V., Bos, F. V. D., de Graaff, E., Oostra, B. A., & Willems, P. J. (1993) · Nature Genetics · doi:10.1038/ng0193-31 · Cited by 624
How proteins enter the nucleus
Silver, P. A. (1991) · Cell · doi:10.1016/0092-8674(91)90233-o · Cited by 553
A nuclear export signal in hnRNP A1: A signal-mediated, temperature-dependent nuclear protein export pathway
Michael, W. M., Choi, M., & Dreyfuss, G. (1995) · Cell · doi:10.1016/0092-8674(95)90119-1 · Cited by 528
The translation machinery and 70 kd heat shock protein cooperate in protein synthesis
Nelson, R., Ziegelhoffer, T., Nicolet, C. M., Werner‐Washburne, M., & Craig, E. A. (1992) · Cell · doi:10.1016/0092-8674(92)90269-i · Cited by 512
A nuclear localization domain in the hnRNP A1 protein.
Siomi, H., & Dreyfuss, G. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.3.551 · Cited by 498
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
Siomi, H., Choi, M., Siomi, M. C., Nussbaum, R. L., & Dreyfuss, G. (1994) · Cell · doi:10.1016/0092-8674(94)90232-1 · Cited by 446
Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome
Hinds, H. L., Ashley, C. T., Sutcliffe, J. S., Nelson, D. L., Warren, S. T., Housman, D. E., & Schalling, M. (1993) · Nature Genetics · doi:10.1038/ng0193-36 · Cited by 396
Translational Suppression by Trinucleotide Repeat Expansion at FMR1
Feng, Y., Zhang, F., Lokey, L. K., Chastain, J. L., Lakkis, L., Eberhart, D., & Warren, S. T. (1995) · Science · doi:10.1126/science.7732383 · Cited by 358
Self-citation
Characterization and localization of the FMR-1 gene product associated with fragile X syndrome
Verheij, C., Bakker, C. E., de Graaff, E., Keulemans, J., Willemsen, R., Verkerk, A. J. M. H., Galjaard, H., Reuser, A. J. J., Hoogeveen, A. T., & Oostra, B. A. (1993) · Nature · doi:10.1038/363722a0 · Cited by 343
The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.
Zhang, Y., O'Connor, J. P., Siomi, M. C., Srinivasan, S., Dutra, A., Nussbaum, R. L., & Dreyfuss, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00220.x · Cited by 337
Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins
Bogerd, H. P., Fridell, R. A., Madore, S. J., & Cullen, B. R. (1995) · Cell · doi:10.1016/0092-8674(95)90437-9 · Cited by 305
Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain
Abitbol, M. M., Ménini, C., Delezoide, A., Rhyner, T. A., Vekemans, M. J. J., & Mallet, J. J. (1993) · Nature Genetics · doi:10.1038/ng0693-147 · Cited by 284
Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG–repeat
Ashley, C. T., Sutcliffe, J. S., Kunst, C. B., Leiner, H. A., Eichler, E. E., Nelson, D. L., & Warren, S. T. (1993) · Nature Genetics · doi:10.1038/ng0793-244 · Cited by 269
A human nucleoporin-like protein that specifically interacts with HIV Rev
Fritz, C., Zapp, M. L., & Green, M. R. (1995) · Nature · doi:10.1038/376530a0 · Cited by 264
Nuclear localization signals (NLS).
Boulikas, T. (1993) · PubMed · Cited by 255
The fragile X mental retardation protein is associated with ribosomes
Khandjian, E. W., Corbin, F., Woerly, S., & Rousseau, F. (1996) · Nature Genetics · doi:10.1038/ng0196-91 · Cited by 251
Fluorescence microphotolysis to measure nucleocytoplasmic transport and intracellular mobility
Peters, R. (1986) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(86)90003-1 · Cited by 246
Structure and Function of Nuclear and Cytoplasmic Ribonucleoprotein Particles
Dreyfuss, G. (1986) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.2.1.459 · Cited by 243
FXR1, an autosomal homolog of the fragile X mental retardation gene.
Siomi, M. C., Siomi, H., Sauer, W. H., Srinivasan, S., Nussbaum, R. L., & Dreyfuss, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07237.x · Cited by 241
Nuclear export signals and the fast track to the cytoplasm
Gerace, L. (1995) · Cell · doi:10.1016/0092-8674(95)90420-4 · Cited by 233
Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast
Stutz, F., Neville, M. C., & Rosbash, M. (1995) · Cell · doi:10.1016/0092-8674(95)90438-7 · Cited by 224
A Pre-mRNA-Binding Protein Accompanies the RNA from the Gene through the Nuclear Pores and into Polysomes
Visa, N., Alzhanova-Ericsson, A. T., Sun, X., Владимировна, К. Е., Björkroth, B., Wurtz, T., & Daneholt, B. (1996) · Cell · doi:10.1016/s0092-8674(00)80980-0 · Cited by 218
The effect of protein context on nuclear location signal function
Roberts, B., Richardson, W. D., & Smith, A. E. (1987) · Cell · doi:10.1016/0092-8674(87)90500-9 · Cited by 212
Advances in Molecular Analysis of Fragile X Syndrome
Warren, S. T. (1994) · JAMA · doi:10.1001/jama.1994.03510310066040 · Cited by 204
Alternative Splicing of Exon 14 Determines Nuclear or Cytoplasmic Localisation of FMR1 Protein Isoforms
Sittler, A., Devys, D., Weber, C., & Mandel, J.-L. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.1.95 · Cited by 198
Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome
Lugenbeel, K. A., Peier, A. M., Carson, N. L., Chudley, A. E., & Nelson, D. L. (1995) · Nature Genetics · doi:10.1038/ng0895-483 · Cited by 165
Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway
Nielsen, F. C., Østergaard, L., Nielsen, J., & Christiansen, J. (1995) · Nature · doi:10.1038/377358a0 · Cited by 163
A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture
Khandjian, E. W., Anny, F., Thibodeau, A., Tremblay, S., Côté, F., Devys, D., Mandel, J.-L., & Rousseau, F. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.5.783 · Cited by 145
Alternative splicing in the fragile X gene FMR1
Verkerk, A. J. M. H., de Graaff, E., Boulle, K. D., Eichler, E. E., Konecki, D. S., Reyniers, E., Manca, A., Poustka, A., Willems, P. J., Nelson, D. L., et al. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.8.1348 · Cited by 138
Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation
Scott, J. A., Wenger, S. L., Steele, M. W., & Chakravarti, A. (1995) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320560115 · Cited by 130
A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome
Meljer, H., de Graaff, E., Merckx, D. M. L., Jongbloed, R. J. E., de Die-Smulders, C. E. M., Engelen, J. J. M., Fryns, J., Curfs, P. M. G., & Oostra, B. A. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.4.615 · Cited by 129
Intracellular distribution of the U1A protein depends on active transport and nuclear binding to U1 snRNA.
Kambach, C., & Mattaj, I. W. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.118.1.11 · Cited by 128
High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome
Hornstra, L. K., Nelson, D. L., Warren, S. T., & Yang, T. P. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.10.1659 · Cited by 127
Context affects nuclear protein localization in Saccharomyces cerevisiae.
Nelson, M. K., & Silver, P. A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.2.384 · Cited by 123
Translational discrimination of mRNAs coding for human insulin-like growth factor II.
Nielsen, F. C., Gammeltoft, S., & Christiansen, J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77363-8 · Cited by 106
Characterization of FMR1 proteins isolated from different tissues
Verhelj, C., de Graaff, E., Bakker, C. E., Willemsen, R., Willems, P. J., Meijer, N., GALJAARD, H., Reuser, A. J. J., Oostra, B. A., & Hoogeveen, A. T. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.5.895 · Cited by 85
Highly conserved 3′ UTR and expression pattern of FXR1 points to a divergent gene regulation of FXR1 and FMR1
Coy, J. F., Sedláček, Z., Bächner, D., Hameister, H., Joos, S., Lichter, P., Delius, H., & Poustka, A. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2209 · Cited by 74
Triplet repeat expansion mutations: the example of fragile X syndrome.
Warren, S. T., & Ashley, C. T. (1995) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.18.030195.000453 · Cited by 74
The human 18S ribosomal RNA gene: evolution and stability.
Gonzalez, I. L., & Schmickel, R. D. (1986) · PubMed · Cited by 73
Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice
Hergersberg, M., Matsuo, K., Gassmann, M., Schaffner, W., Lüscher, B., Rülicke, T., & Aguzzi, A. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.3.359 · Cited by 71
Use of a general purpose mammalian expression vector for studying intracellular protein targeting: identification of critical residues in the nuclear lamin A/C nuclear localization signal
Frangioni, J. V., & Neel, B. G. (1993) · Journal of Cell Science · doi:10.1242/jcs.105.2.481 · Cited by 54
The ChickenFMR1Gene Is Highly Conserved with a CCT 5′-Untranslated Repeat and Encodes an RNA-Binding Protein
Price, D. K., Zhang, F. P., Ashley, C. T., & Warren, S. T. (1996) · Genomics · doi:10.1006/geno.1996.0002 · Cited by 46
Advances in molecular analysis of fragile X syndrome
Warren, S. T. (1994) · JAMA · doi:10.1001/jama.271.7.536 · Cited by 44
Antiribosomal S10 antibodies in humans and MRL/lpr mice with systemic lupus erythematosus
Bonfá, E., Parnassa, A. P., Rhoads, D. D., Roufa, D. J., Wool, I. G., & Elkon, K. B. (1989) · Arthritis & Rheumatism · doi:10.1002/anr.1780321010 · Cited by 38
Triplet Repeat Expansion Mutations: The Example of Fragile X Syndrome
Warren, S. (1995) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.18.1.77 · Cited by 3

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See all 390

Authors: Eberhart, D.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Eberhart, D.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 1996-08-01
Volume: 5
Issue: 8
Pages: 1083-1091
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/5.8.1083
OpenAlex: W2106239245
Cited by: 390
References: 53
Citations by year: 2026: 3 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 17 · 2013: 21 · 2012: 21
FWCI: 9.58
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 20521)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: fragile X syndrome, FMRP, FMR1 gene, nuclear localization signal, nuclear export signal, ribonucleoprotein, RNA-binding proteins, ribosome association, exon 14, protein localization, translational regulation
MeSH terms: Amino Acid Sequence, Animals, Biological Transport, Active, Cell Nucleus, Exons, Fragile X Syndrome, Humans, Models, Biological, Molecular Sequence Data, Nerve Tissue Proteins, Recombinant Fusion Proteins, Ribonucleoproteins, Ribosomes, Transfection, RNA-Binding Proteins, COS Cells, Protein Sorting Signals, Fragile X Messenger Ribonucleoprotein 1

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The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals

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