Article
FMR1 KH0-KH1 domains coordinate m6A binding and phase separation in Fragile X syndrome.
Experimental cell research - 15 Jul 2025
Zhou Xian, Guo Chen-Jun, Wang Rui, Li Yi-Lan, Zhang Tianyi, Qiu Zhuangyi, Gao Shaorong, Liu Ji-Long, Gao Yawei
Abstract excerpt
Fragile X messenger ribonucleoprotein 1 (FMR1) regulates neurodevelopment through m6A RNA interactions, yet the domain-specific roles of KH0 and KH1 in RNA binding and disease pathogenesis remain poorly understood. Using mutagenesis and AlphaFold3 structural modeling, we identify KH1 as the primary m6A-binding interface, while the KH0 domain (particularly Arg138) modulates liquid-liquid phase separation (LLPS)....
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