生物
应力颗粒
甲基化
细胞质
精氨酸
突变体
颗粒(地质)
分子生物学
细胞生物学
基因
生物化学
氨基酸
信使核糖核酸
翻译(生物学)
古生物学
作者
Daiki Kawahara,Toshiharu Suzuki,Tadashi Nakaya
摘要
Abstract Many mutations in the fused in sarcoma (FUS) gene have been identified as genetic causative factors of amyotrophic lateral sclerosis (ALS). As a certain number of mutants form aberrant cytoplasmic granules under specific conditions, granule forming ability of FUS is believed to be linked to the pathogenesis of ALS. However, molecular mechanisms underlying this property remain unclear. An ALS‐linked FUS mutant, R495X, shows extensive cytoplasmic localization and forms granules in neurons. In the present study, using R495X domain deletion constructs, we showed that deletion of any of Gly‐rich, RGG1 or RGG2 significantly suppressed granule formation. Furthermore, when neurons expressing EGFP‐R495X were treated with an arginine methylation inhibitor, the number of cells displaying R495X granules was significantly reduced. When FLAG‐tagged arginine N‐methyltransferase 8 (PRMT8) was co‐expressed with EGFP‐R495X to facilitate its methylation, the number of cells with granules was significantly increased. Collectively, these findings suggest that cytoplasmic granule formation by R495X is attributable to the arginine methylation in all Gly‐rich, RGG1 and RGG2 domains.
科研通智能强力驱动
Strongly Powered by AbleSci AI