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

Eberhart, D.

doi:10.1093/hmg/5.8.1083

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

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

Eberhart, D.·1996·Human Molecular Genetics

DOI 10.1093/hmg/5.8.1083

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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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FMRP is an RNA-binding protein, and only its cytoplasmic function has been well characterized.
“FMRP is an RNA-binding protein, and, despite its clear shuttling from the nucleus to the cytoplasm (59,60), only the cytoplasmic function of FMRP has been well characterized.”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [59]

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Self-citation
Fragile X Mental Retardation Protein FMRP Binds mRNAs in the Nucleus
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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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