Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly
Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly
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DOI：
10.1091/mbc.e08-07-0737
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Moine, Herve
中科院分区：
文献类型：
--
作者：
Didiot, Marie-Cecile;Subramanian, Murugan;Moine, Herve
脆性X智力低下蛋白（FMRP）是一种参与mRNA代谢的RNA结合蛋白。神经元中FMRP的缺失会导致突触可塑性改变，这可能是翻译调控缺陷的结果。FMRP在翻译调控中所起作用的确切分子机制一直不清楚。发现FMRP与RNA干扰沉默复合物（RISC，一种翻译调控的关键物质）之间存在相互作用，这表明这两种调控因子可能在功能上相关联。我们在此对这种关联进行了研究，结果表明FMRP在物理和功能上与RISC机制几乎没有重叠，排除了FMRP对RISC功能的直接影响。我们的数据表明，FMRP和RISC与不同的mRNA池相关联。与RISC机制不同，FMRP与在细胞应激时最终进入应激颗粒的mRNA池相关联。此外，我们发现FMRP在这一过程中起积极作用，因为FMRP的缺失或导致严重脆性X综合征的点突变会改变应激颗粒的形成。我们的数据支持这样一种观点，即FMRP在翻译停滞之后对mRNA的命运起控制作用。
The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP and the RNA interference silencing complex (RISC), a master of translation regulation, has suggested that both regulators could be functionally linked. We investigated here this link, and we show that FMRP exhibits little overlap both physically and functionally with the RISC machinery, excluding a direct impact of FMRP on RISC function. Our data indicate that FMRP and RISC are associated to distinct pools of mRNAs. FMRP, unlike RISC machinery, associates with the pool of mRNAs that eventually goes into stress granules upon cellular stress. Furthermore, we show that FMRP plays a positive role in this process as the lack of FMRP or a point mutant causing a severe fragile X alter stress granule formation. Our data support the proposal that FMRP plays a role in controlling the fate of mRNAs after translation arrest.