假尿苷
红细胞生成
翻译(生物学)
生物
突变体
铁粒细胞性贫血
转移RNA
细胞生物学
突变
分子生物学
生物化学
核糖核酸
贫血
基因
信使核糖核酸
内科学
医学
作者
Deyang Shi,Bichen Wang,Haoyuan Li,Yu Lian,Qiuyi Ma,Tong Liu,Mutian Cao,Yuanwu Ma,Shi Lei,Weiping Yuan,Jun Shi,Yajing Chu
出处
期刊:iScience
[Elsevier]
日期:2024-03-01
卷期号:27 (3): 109265-109265
标识
DOI:10.1016/j.isci.2024.109265
摘要
Pseudouridylation plays a regulatory role in various physiological and pathological processes. A prime example is the mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA), characterized by defective pseudouridylation resulting from genetic mutations in pseudouridine synthase 1 (PUS1). However, the roles and mechanisms of pseudouridylation in normal erythropoiesis and MLASA-related anemia remain elusive. We established a mouse model carrying a point mutation (R110W) in the enzymatic domain of PUS1, mimicking the common mutation in human MLASA. Pus1-mutant mice exhibited anemia at 4 weeks old. Impaired mitochondrial oxidative phosphorylation was also observed in mutant erythroblasts. Mechanistically, mutant erythroblasts showed defective pseudouridylation of targeted tRNAs, altered tRNA profiles, decreased translation efficiency of ribosomal protein genes, and reduced globin synthesis, culminating in ineffective erythropoiesis. Our study thus provided direct evidence that pseudouridylation participates in erythropoiesis in vivo. We demonstrated the critical role of pseudouridylation in regulating tRNA homeostasis, cytoplasmic translation, and erythropoiesis.
科研通智能强力驱动
Strongly Powered by AbleSci AI