PDF(Pubmed)
Abstract：
It is currently not known whether mRNAs fulfill structural roles in the cytoplasm. Here, we report the fragile X-related protein 1 (FXR1) network, an mRNA-protein (mRNP) network present throughout the cytoplasm, formed by FXR1-mediated packaging of exceptionally long mRNAs. These mRNAs serve as an underlying condensate scaffold and concentrate FXR1 molecules. The FXR1 network contains multiple protein binding sites and functions as a signaling scaffold for interacting proteins. We show that it is necessary for RhoA signaling-induced actomyosin reorganization to provide spatial proximity between kinases and their substrates. Point mutations in FXR1, found in its homolog FMR1, where they cause fragile X syndrome, disrupt the network. FXR1 network disruption prevents actomyosin remodeling-an essential and ubiquitous process for the regulation of cell shape, migration, and synaptic function. Our findings uncover a structural role for cytoplasmic mRNA and show how the FXR1 RNA-binding protein as part of the FXR1 network acts as an organizer of signaling reactions.
摘要：
目前尚不清楚mRNA是否在细胞质中发挥结构作用。这里,我们报道了脆性X相关蛋白1(FXR1)网络，存在于整个细胞质中的mRNA蛋白（mRNP）网络，由FXR1介导的非常长的mRNA的包装形成。这些mRNA充当基础缩合物支架并浓缩FXR1分子。FXR1网络包含多个蛋白质结合位点，并充当相互作用蛋白质的信号支架。我们表明，RhoA信号诱导的肌动球蛋白重组必须在激酶及其底物之间提供空间接近性。FXR1的点突变，在其同源FMR1中发现，它们会导致脆性X综合征，扰乱网络。FXR1网络破坏可防止肌动球蛋白重塑-这是调节细胞形状的重要且普遍存在的过程，迁移,和突触功能。我们的发现揭示了细胞质mRNA的结构作用，并显示了FXR1RNA结合蛋白作为FXR1网络的一部分如何充当信号传导反应的组织者。
