Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression.
Absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein, is responsible for the Fragile X syndrome, the most common form of inherited mental retardation. FMRP is a cytoplasmic protein associated with mRNP complexes containing poly(A)+mRNA. As a step towards understanding FMRP function(s), we have established the immortal STEK Fmr1 KO cell line and showed by transfection assays with FMR1-expressing vectors that newly synthesized FMRP accumulates into cytoplasmic granules. These structures contain mRNAs and several other RNA-binding proteins. The formation of these cytoplasmic granules is dependent on determinants located in the RGG domain. We also provide evidence that FMRP acts as a translation repressor following co-transfection with reporter genes. The FMRP-containing mRNPs are dynamic structures that oscillate between polyribosomes and cytoplasmic granules reminiscent of the Stress Granules that contain repressed mRNAs. We speculate that, in neurons, FMRP plays a role as a mRNA repressor in incompetent mRNP granules that have to be translocated from the cell body to distal locations such as dendritic spines and synaptosomes.
Mazroui
Rachid
R
Unité de Recherche en Génétique Humaine et Moléculaire, Centre de recherche Hôpital Saint François d'Assise, 10 rue de l'Espinay, Québec G1L 3L5, PQ, Canada.
Huot
Marc-Etienne
ME
Tremblay
Sandra
S
Filion
Christine
C
Labelle
Yves
Y
Khandjian
Edouard W
EW
D003594:Cytoplasmic Granules / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
C096916:FXR1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins