Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles.
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.
Khandjian
Edouard W
EW
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. edward.khandjian@crsfa.ulaval.ca
Huot
Marc-Etienne
ME
Tremblay
Sandra
S
Davidovic
Laetitia
L
Mazroui
Rachid
R
Bardoni
Barbara
B
D000818:Animals; D001921:Brain / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000378:metabolism*; D008607:Intellectual Disability / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012261:Ribonucleoproteins / Q000378:metabolism*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C497684:Fmr1 protein, mouse; C026452:messenger ribonucleoprotein