RNA剪接
基因敲除
选择性拼接
内含子
拼接因子
信使核糖核酸
细胞生物学
生物
剪接体
基因
化学
遗传学
核糖核酸
作者
Mingxuan Li,Qian Fang,Pingping Xiao,Zhinang Yin,Guang-Bo Mei,Cheng Wang,Ying Xiang,Xuejun Zhao,Lihua Qu,Tian Xu,Jiaxi Zhang,Liu Ke-jun,Xiaoqing Li,Hui‐Fen Dong,R. Xiao,Rui Zhou
标识
DOI:10.1038/s41419-024-06886-1
摘要
Abstract Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.
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