PDF(Pubmed)
Abstract：
Silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene and a consequent lack of FMR protein (FMRP) synthesis are associated with fragile X syndrome, one of the most common inherited intellectual disabilities. FMRP is a multifunctional protein that is involved in many cellular functions in almost all subcellular compartments under both normal and cellular stress conditions in neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and it is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes the recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.
摘要：
脆性X信使核糖核蛋白1（FMR1）基因的沉默和随之而来的FMR蛋白（FMRP）合成的缺乏与脆性X综合征有关，最常见的遗传性智力障碍之一。FMRP是一种多功能蛋白，在神经元和非神经元细胞类型的正常和细胞应激条件下，在几乎所有亚细胞区室中都参与许多细胞功能。这是通过其贩运信号实现的，核定位信号(NLS)，核输出信号（NES），和核仁定位信号(NoLS)，以及它的RNA和蛋白质结合域，它受到各种翻译后修饰的调节，如磷酸化，泛素化，sumoylation,和甲基化。这篇综述总结了在理解FMRP相互作用网络方面的最新进展，特别关注FMRP压力相关功能，包括应力颗粒的形成，线粒体和内质网可塑性，核糖体生物发生，细胞周期控制，和DNA损伤反应。
