Stefani Giovanni, Fraser Claire E, Darnell Jennifer C, Darnell Robert B
Howard Hughes Medical Institute and Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York 10021, USA.
J Neurosci. 2004 Aug 18;24(33):7272-6. doi: 10.1523/JNEUROSCI.2306-04.2004.
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.
脆性X智力低下蛋白（FMRP）是一种由FMR1基因编码的RNA结合蛋白，在脆性X智力低下患者中其表达受损。此前在非神经细胞系中FMRP与多核糖体的关联表明FMRP参与翻译调控。然而，这些研究与神经元功能的相关性受到了质疑，因为有研究发现大脑中的FMRP并不与多核糖体相关，而是小核糖核蛋白复合物的一部分，这些复合物似乎不包括核糖体。在此，我们优化了分析脑多核糖体的方法，从而能够确切证明FMRP与大脑皮质多核糖体形成复合物。此外，我们在神经母细胞瘤细胞中证明，FMRP-多核糖体复合物对嘌呤霉素敏感，嘌呤霉素是一种作用于活跃翻译核糖体的药物。这些数据表明FMRP在神经元中与功能性多核糖体相关联。
