The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at Synapses
The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at Synapses
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DOI：
10.1016/s0092-8674(03)00079-5
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发表时间：
2003-02-07
期刊：
影响因子：
64.5
通讯作者：
Bagni, C
中科院分区：
文献类型：
--
作者：
Zalfa, F;Giorgi, M;Bagni, C
脆性X综合征是由功能性FMRP蛋白缺失引起的，是最常见的可遗传的智力低下形式。在这里，我们表明FMRP作为突触上特定mRNAs的翻译抑制因子。有趣的是，FMRP不仅与这些靶mRNAs有关，而且还与树突状的、不可翻译的RNABc1有关。阻断bc1可抑制FMRP与其靶向mRNAs的相互作用。此外，bc1直接与FMRP结合，在没有任何蛋白质的情况下，也可以与FMRP调控的mRNAs结合。这提示了一种机制，即BC1可以通过将调节的mRNAs与FMRP联系起来来确定FMRP功能的特异性。因此，当FMRP不存在时，突触上特定mRNAs翻译抑制的丢失可能导致脆性X患者的突触功能障碍表型。
The Fragile X syndrome, which results from the absence of functional FMRP protein, is the most common heritable form of mental retardation. Here, we show that FMRP acts as a translational repressor of specific mRNAs at synapses. Interestingly, FMRP associates not only with these target mRNAs, but also with the dendritic, non-translatable RNA BC1. Blocking of BC1 inhibits the interaction of FMRP with its target mRNAs. Furthermore, BC1 binds directly to FMRP and can also associate, in the absence of any protein, with the mRNAs regulated by FMRP. This suggests a mechanism where BC1 could determine the specificity of FMRP function by linking the regulated mRNAs and FMRP. Thus, when FMRP is not present, loss of translational repression of specific mRNAs at synapses could result in synaptic dysfunction phenotype of Fragile X patients.