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首页> 外文期刊>The FEBS journal >Novel FMRP interaction networks linked to cellular stress
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Novel FMRP interaction networks linked to cellular stress

机译：与细胞应力相关联的新型FMRP交互网络

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Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities, with additional roles in increased viral infection, liver disease, and reduced cancer risk. FMRP plays critical roles in chromatin dynamics, RNA binding, mRNA transport, and mRNA translation. However, the underlying molecular mechanisms, including the (sub)cellular FMRP protein networks, remain elusive. Here, we employed affinity pull-down and quantitative LC-MS/MS analyses with FMRP. We identified known and novel candidate FMRP-binding proteins as well as protein complexes. FMRP interacted with 180 proteins, 28 of which interacted with its N terminus. Interaction with the C terminus of FMRP was observed for 102 proteins, and 48 proteins interacted with both termini. This FMRP interactome comprises known FMRP-binding proteins, including the ribosomal proteins FXR1P, NUFIP2, Caprin-1, and numerous novel FMRP candidate interacting proteins that localize to different subcellular compartments, including CARF, LARP1, LEO1, NOG2, G3BP1, NONO, NPM1, SKIP, SND1, SQSTM1, and TRIM28. Our data considerably expand the protein and RNA interaction networks of FMRP, which thereby suggest that, in addition to its known functions, FMRP participates in transcription, RNA metabolism, ribonucleoprotein stress granule formation, translation, DNA damage response, chromatin dynamics, cell cycle regulation, ribosome biogenesis, miRNA biogenesis, and mitochondrial organization. Thus, FMRP seems associated with multiple cellular processes both under normal and cell stress conditions in neuronal as well as non-neuronal cell types, as exemplified by its role in the formation of stress granules.
机译：脆性X智力低下1（FMR1）基因的沉默以及由此导致的FMR蛋白（FMRP）合成不足与脆性X综合征相关，脆性X综合征是最常见的遗传性智力残疾之一，在增加病毒感染、肝脏疾病和降低癌症风险方面具有额外作用。FMRP在染色质动力学、RNA结合、mRNA转运和mRNA翻译中起着关键作用。然而，潜在的分子机制，包括（亚）细胞FMRP蛋白网络，仍然难以捉摸。在这里，我们采用亲和下拉和定量LC-MS/MS分析与FMRP。我们确定了已知和新的候选FMRP结合蛋白以及蛋白复合物。FMRP与180种蛋白质相互作用，其中28种与其N末端相互作用。共观察到102个蛋白质与FMRP的C末端相互作用，48个蛋白质与两个末端相互作用。该FMRP相互作用组包含已知的FMRP结合蛋白，包括核糖体蛋白FXR1P、NUFIP2、Caprin-1，以及许多新的FMRP候选相互作用蛋白，它们定位于不同的亚细胞区，包括CARF、LARP1、LEO1、NOG2、G3BP1、NONO、NPM1、SKIP、SND1、SQSTM1和TRIM28。我们的数据极大地扩展了FMRP的蛋白质和RNA相互作用网络，从而表明，除了已知的功能外，FMRP还参与转录、RNA代谢、核糖核蛋白应激颗粒形成、翻译、DNA损伤反应、染色质动力学、细胞周期调节、核糖体生物发生、miRNA生物发生和线粒体组织。因此，FMRP似乎与神经细胞和非神经细胞类型的正常和细胞应激条件下的多个细胞过程有关，例如其在应激颗粒形成中的作用。

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