Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The fragile X mental retardation protein FMRP is an RNA binding protein that associates with a large collection of mRNAs. Since FMRP was previously shown to be a nucleocytoplasmic shuttling protein, we examined the hypothesis that FMRP binds its cargo mRNAs in the nucleus. The enhanced green fluorescent protein-tagged FMRP construct (EGFP-FMRP) expressed in Cos-7 cells was efficiently exported from the nucleus in the absence of its nuclear export sequence and in the presence of a strong nuclear localization sequence (the simian virus 40 [SV40] NLS), suggesting an efficient mechanism for nuclear export. We hypothesized that nuclear FMRP exits the nucleus through its bound mRNAs. Using silencing RNAs to the bulk mRNA exporter Tap/NXF1, we observed a significantly increased number of cells containing EGFP-FMRP in the nucleus, which was further augmented by removal of FMRP's nuclear export sequence. Nuclear-retained SV40-FMRP could be released upon treatment with RNase. Further, Tap/NXF1 coimmunoprecipitated with EGFP-FMRP in an RNA-dependent manner and contained the FMR1 mRNA. To determine whether FMRP binds pre-mRNAs cotranscriptionally, we expressed hemagglutinin-SV40 FMRP in amphibian oocytes and found it, as well as endogenous Xenopus FMRP, on the active transcription units of lampbrush chromosomes. Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus.
Adinolfi,
Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains.
1999, Pubmed
Adinolfi,
Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains.
1999,
Pubmed Adinolfi,
The N-terminus of the fragile X mental retardation protein contains a novel domain involved in dimerization and RNA binding.
2003,
Pubmed Antar,
Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses.
2004,
Pubmed Arttamangkul,
Binding and internalization of fluorescent opioid peptide conjugates in living cells.
2000,
Pubmed Ashley,
FMR1 protein: conserved RNP family domains and selective RNA binding.
1993,
Pubmed Ashley,
Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat.
1993,
Pubmed Bardoni,
Analysis of domains affecting intracellular localization of the FMRP protein.
1997,
Pubmed Beenders,
The tripartite motif of nuclear factor 7 is required for its association with transcriptional units.
2007,
Pubmed
,
Xenbase Blonden,
Two members of the Fxr gene family, Fmr1 and Fxr1, are differentially expressed in Xenopus tropicalis.
2005,
Pubmed
,
Xenbase Bor,
The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron.
2006,
Pubmed Braun,
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.
1999,
Pubmed
,
Xenbase Brown,
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome.
2001,
Pubmed Ceman,
Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex.
1999,
Pubmed Ceman,
Development and characterization of antibodies that immunoprecipitate the FMR1 protein.
2003,
Pubmed Conti,
Nucleocytoplasmic transport enters the atomic age.
2001,
Pubmed Cook,
FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues.
2006,
Pubmed Darnell,
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes.
2005,
Pubmed Darnell,
Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function.
2001,
Pubmed Davidovic,
The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules.
2007,
Pubmed De Boulle,
A point mutation in the FMR-1 gene associated with fragile X mental retardation.
1993,
Pubmed De Diego Otero,
Transport of fragile X mental retardation protein via granules in neurites of PC12 cells.
2002,
Pubmed Devys,
The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation.
1993,
Pubmed Didiot,
The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer.
2008,
Pubmed Eberhart,
The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals.
1996,
Pubmed Eberhart,
The molecular basis of fragile X syndrome.
1996,
Pubmed Eichler,
Fine structure of the human FMR1 gene.
1993,
Pubmed Elbashir,
Analysis of gene function in somatic mammalian cells using small interfering RNAs.
2002,
Pubmed Farina,
The nuclear connection in RNA transport and localization.
2002,
Pubmed Feng,
Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes.
1997,
Pubmed Feng,
FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association.
1997,
Pubmed Fridell,
A nuclear role for the Fragile X mental retardation protein.
1996,
Pubmed Fu,
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.
1991,
Pubmed Fukuda,
CRM1 is responsible for intracellular transport mediated by the nuclear export signal.
1997,
Pubmed
,
Xenbase Garber,
Transcription, translation and fragile X syndrome.
2006,
Pubmed González-Reyes,
Polarization of both major body axes in Drosophila by gurken-torpedo signalling.
1995,
Pubmed Grüter,
TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus.
1998,
Pubmed
,
Xenbase Hachet,
Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport.
2001,
Pubmed Hamilton,
hnRNP A2 and hnRNP L bind the 3'UTR of glucose transporter 1 mRNA and exist as a complex in vivo.
1999,
Pubmed Hodel,
Dissection of a nuclear localization signal.
2001,
Pubmed Hornstra,
High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome.
1993,
Pubmed Huang,
SR splicing factors serve as adapter proteins for TAP-dependent mRNA export.
2003,
Pubmed
,
Xenbase Huang,
SRprises along a messenger's journey.
2005,
Pubmed Hüttelmaier,
Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1.
2005,
Pubmed Izaurralde,
A novel family of nuclear transport receptors mediates the export of messenger RNA to the cytoplasm.
2002,
Pubmed Jin,
RNA and microRNAs in fragile X mental retardation.
2004,
Pubmed Jin,
Tap and NXT promote translation of unspliced mRNA.
2003,
Pubmed Kalderon,
Sequence requirements for nuclear location of simian virus 40 large-T antigen.
,
Pubmed Kalderon,
A short amino acid sequence able to specify nuclear location.
1984,
Pubmed Kang,
The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences.
1999,
Pubmed Kataoka,
Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm.
2000,
Pubmed
,
Xenbase Lai,
The fragile X mental retardation protein interacts with a distinct mRNA nuclear export factor NXF2.
2006,
Pubmed Le Hir,
The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay.
2001,
Pubmed
,
Xenbase Le Hir,
The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions.
2000,
Pubmed
,
Xenbase Lévesque,
Mutations in tap uncouple RNA export activity from translocation through the nuclear pore complex.
2006,
Pubmed Li,
An intron with a constitutive transport element is retained in a Tap messenger RNA.
2006,
Pubmed Mattaj,
Nucleocytoplasmic transport: the soluble phase.
1998,
Pubmed Matzat,
Formation of a Tap/NXF1 homotypic complex is mediated through the amino-terminal domain of Tap and enhances interaction with nucleoporins.
2008,
Pubmed Mazroui,
Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression.
2002,
Pubmed Miyashiro,
RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice.
2003,
Pubmed Monzo,
Fragile X mental retardation protein controls trailer hitch expression and cleavage furrow formation in Drosophila embryos.
2006,
Pubmed Morgan,
Lampbrush chromosomes and associated bodies: new insights into principles of nuclear structure and function.
2002,
Pubmed Nakielny,
Transport of proteins and RNAs in and out of the nucleus.
1999,
Pubmed Newport,
A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage.
1982,
Pubmed
,
Xenbase Niranjanakumari,
Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo.
2002,
Pubmed Oberlé,
Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome.
1991,
Pubmed Ossareh-Nazari,
Evidence for a role of CRM1 in signal-mediated nuclear protein export.
1997,
Pubmed Patel,
Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts.
2007,
Pubmed
,
Xenbase Prasanth,
Regulating gene expression through RNA nuclear retention.
2005,
Pubmed Rodrigues,
REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus.
2001,
Pubmed
,
Xenbase Schaeffer,
The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif.
2001,
Pubmed
,
Xenbase Siomi,
The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
1993,
Pubmed Siomi,
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.
1996,
Pubmed Siomi,
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.
1994,
Pubmed Sittler,
Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms.
1996,
Pubmed Stade,
Exportin 1 (Crm1p) is an essential nuclear export factor.
1997,
Pubmed Stetler,
Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp.
2006,
Pubmed Stutz,
REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export.
2000,
Pubmed
,
Xenbase Sutcliffe,
DNA methylation represses FMR-1 transcription in fragile X syndrome.
1992,
Pubmed Tamanini,
Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations.
1999,
Pubmed Tan,
Identification and characterization of the mouse nuclear export factor (Nxf) family members.
2005,
Pubmed Tran,
Dynamic nuclear pore complexes: life on the edge.
2006,
Pubmed van 't Padje,
Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 gene.
2005,
Pubmed Varadi,
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.
2002,
Pubmed Vasudevan,
AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2.
2007,
Pubmed Verkerk,
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.
1991,
Pubmed Wilkie,
Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development.
2001,
Pubmed Zalfa,
Fragile X mental retardation protein (FMRP) binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA-binding motif.
2005,
Pubmed Zhang,
Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells.
2007,
Pubmed
