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

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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  • FMRP is a neuronal RNA-binding protein that is largely associated with polyribosomes.

    “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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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
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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