RNA颗粒是通过蛋白质-蛋白质和蛋白质-RNA相互作用聚集的显微镜可见的细胞结构。以应力颗粒为例,我们讨论了RNA颗粒形成的原理,这依赖于RNA和多结构域蛋白质的多价以及具有朊病毒样/低复杂性结构域的蛋白质之间的低亲和力相互作用(例如FUS和TDP-43)。然后,我们探索RNA颗粒形成的失调与神经退行性疾病的关系,如肌萎缩侧索硬化(ALS)和额颞叶变性(FTLD),并讨论治疗干预的可能策略。
RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions between proteins with prion-like/low-complexity domains (e.g. FUS and TDP-43). We then explore how dysregulation of RNA granule formation is linked to neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), and discuss possible strategies for therapeutic intervention.