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Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles
Open accessAbstract
Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). This RNA-binding protein is widely expressed in human and mouse tissues, and it is particularly abundant in the brain because of its high expression in neurons, where it localizes in the cell body and in granules throughout dendrites. Although FMRP is thought to regulate trafficking of repressed mRNA complexes and to influence local protein synthesis in synapses, it is not known whether it has additional functions in the control of translation in the cell body. Here, we have used recently developed approaches to investigate whether FMRP is associated with the translation apparatus. We demonstrate that, in the brain, FMRP is present in actively translating polyribosomes, and we show that this association is acutely sensitive to the type of detergent required to release polyribosomes from membranous structures. In addition, proteomic analyses of purified brain polyribosomes reveal the presence of several RNA-binding proteins that, similarly to FMRP, have been previously localized in neuronal granules. Our findings highlight the complex roles of FMRP both in actively translating polyribosomes and in repressed trafficking ribonucleoparticle granules.
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“FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus regarding either its RNA targets or mechanism of action.”
From FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism (2011) · cites this paper as Khandjian et al., 2004
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Metadata
- Authors
- Khandjian, E. W., Huot, M.-E., Tremblay, S., Davidovic, L., Mazroui, R., & Bardoni, B.
- Affiliations
- Unité de Recherche en Génétique Humaine et Moléculaire, Centre de Recherche Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Québec, QC, Canada G1L 3L5; Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec, QC, Canada G1K 7P4; and Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, BP 10142, 67404...
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Bardoni, Barbara
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-08-25
- Volume
- 101
- Issue
- 36
- Pages
- 13357-13362
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC516571
- OpenAlex
- W2049676741
- Cited by
- 178
- References
- 63
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 9 · 2016: 7 · 2015: 5 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- FMRP, polysomes, ribonucleoprotein particles, fragile X syndrome, RNA-binding proteins, translational regulation, mRNA trafficking, brain, detergent sensitivity
- MeSH terms
- Animals, Brain, Fragile X Syndrome, Intellectual Disability, Nerve Tissue Proteins, Polyribosomes, Ribonucleoproteins, Protein Biosynthesis, RNA-Binding Proteins, Mice, Fragile X Messenger Ribonucleoprotein 1
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