title: Molecular dynamics of FMRP and other RNA-binding proteins in MEG-01 differentiation: the role of mRNP complexes in non-neuronal development.
abstract: Asymmetrically differentiating cells are formed with the aid of RNA-binding proteins (RBPs), which can bind, stabilize, regulate, and transport target mRNAs. The loss of RBPs in neurons may lead to severe neurodevelopmental diseases such as the Fragile X Syndrome with the absence of the Fragile X Mental Retardation Protein (FMRP). Because the latter is ubiquitous and shares many similarities with other RBPs involved in the development of peripheral cells, we suggest that FMRP would have a role in the differentiation of all tissues where it is expressed. A MEG-01 differentiation model was, therefore, established to study the global developmental functions of FMRP. PMA induction of MEG-01 cells causes important morphological changes driven by cytoskeletal dynamics. Cytoskeleton change and colocalization analyses were performed by confocal microscopy and sucrose gradient fractionation. Total cellular protein content and de novo synthesis were also analyzed. Microtubular transport mediates the displacement of FMRP and other RBP-containing mRNP complexes towards regions of the cell in development. De novo protein synthesis decreases significantly upon differentiation and total protein content composition is altered. Because those results are comparable with those obtained in neurons, the absence of FMRP would have significant consequences in cells everywhere in the body. The latter should be further investigated to give a better understanding of the systemic implications of imbalances of FMRP and other functionally similar RBPs.
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.|Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: McCoy
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.|Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Poliquin-Duchesneau
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.|Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Corbin
mesh_terms: D001692:Biological Transport; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human
keywords: FMRP; MEG-01; RNA-binding protein; cellular differentiation; cytoskeleton; cytosquelette; différenciation cellulaire; protéine de liaison à l’ARN