Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells.
Fragile X mental retardation protein (FMRP) is an RNA binding protein encoded by the gene FMR1, whose expression is impaired in patients with fragile X mental retardation. The association of FMRP with polyribosomes in non-neural cell lines has previously suggested that FMRP is involved in translational regulation. However, the relevance of these studies to neuronal function has been questioned by the finding that FMRP in brain is not associated with polyribosomes, but is part of small ribonucleo-protein complexes that do not appear to include ribosomes. Here we optimize methods to analyze brain polyribosomes, allowing us to definitively demonstrate that FMRP forms complexes with cortical brain polyribosomes. Moreover, we demonstrate in neuroblastoma cells that the FMRP-polyribosome complexes are sensitive to puromycin, a drug that targets actively translating ribosomes. These data indicate that FMRP associates with functional polyribosomes in neurons.
Stefani
Giovanni
G
Howard Hughes Medical Institute and Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York 10021, USA.
Fraser
Claire E
CE
Darnell
Jennifer C
JC
Darnell
Robert B
RB
D000818:Animals; D001921:Brain / Q000166:cytology; D045744:Cell Line, Tumor; D051860:Fragile X Messenger Ribonucleoprotein 1; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D011132:Polyribosomes / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000032:analysis*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D016601:RNA-Binding Proteins; C497684:Fmr1 protein, mouse