Cited by 178Genetics and Neurodevelopmental DisordersRNA and protein synthesis mechanismsRNA Research and Splicing

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Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles

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Khandjian, Edouard W., Huot, Marc-Etienne, Tremblay, Sandra, Davidovic, Laetitia, Mazroui, Rachid, Bardoni, Barbara·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0405398101PMC PMC516571

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Abstract

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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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
DOI: 10.1073/pnas.0405398101
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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Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles

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