Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Nat Rev Neurosci. 2021 Apr;22(4):209-222. doi: 10.1038/s41583-021-00432-0. Epub 2021 Feb 19.
Fragile X mental retardation protein (FMRP) is the product of the fragile X mental retardation 1 gene (FMR1), a gene that - when epigenetically inactivated by a triplet nucleotide repeat expansion - causes the neurodevelopmental disorder fragile X syndrome (FXS). FMRP is a widely expressed RNA-binding protein with activity that is essential for proper synaptic plasticity and architecture, aspects of neural function that are known to go awry in FXS. Although the neurophysiology of FXS has been described in remarkable detail, research focusing on the molecular biology of FMRP has only scratched the surface. For more than two decades, FMRP has been well established as a translational repressor; however, recent whole transcriptome and translatome analyses in mouse and human models of FXS have shown that FMRP is involved in the regulation of nearly all aspects of gene expression. The emerging mechanistic details of the mechanisms by which FMRP regulates gene expression may offer ways to design new therapies for FXS.
脆性 X 智力低下蛋白（FMRP）是脆性 X 智力低下 1 基因（FMR1）的产物，该基因在三核苷酸重复扩展导致神经发育障碍脆性 X 综合征（FXS）时，通过表观遗传失活。FMRP 是一种广泛表达的 RNA 结合蛋白，其活性对于正常的突触可塑性和结构至关重要，而神经功能的这些方面在 FXS 中是失调的。尽管 FXS 的神经生理学已经被描述得非常详细，但专注于 FMRP 分子生物学的研究只是触及了表面。二十多年来，FMRP 已被很好地确立为翻译抑制剂；然而，最近在 FXS 的小鼠和人类模型中的全转录组和翻译组分析表明，FMRP 参与了几乎所有基因表达方面的调控。FMRP 调节基因表达的机制的出现的机制细节可能为 FXS 的新疗法设计提供途径。
