生物
核糖体生物发生
多嘧啶结合蛋白
RNA剪接
细胞生物学
核糖体蛋白
RNA结合蛋白
选择性拼接
核糖体
翻译(生物学)
核糖核酸
遗传学
信使核糖核酸
基因
作者
Matilda Rehn,Anne Wenzel,Anne-Katrine Frank,Mikkel Bruhn Schuster,Sachin Pundhir,Nanna K. Jørgensen,Kristoffer Vitting-Seerup,Ying Ge,Johan Jendholm,Magali Michaut,Erwin M. Schoof,Tanja Lyholm Jensen,Nicolas Rapin,Russell T Sapio,Kasper Langebjerg Andersen,Anders H. Lund,Michele Solimena,Martin Holzenberger,Dimitri G. Pestov,Bo T. Porse
出处
期刊:Cell Reports
[Elsevier]
日期:2022-05-01
卷期号:39 (6): 110793-110793
被引量:3
标识
DOI:10.1016/j.celrep.2022.110793
摘要
Ribosomopathies constitute a range of disorders associated with defective protein synthesis mainly affecting hematopoietic stem cells (HSCs) and erythroid development. Here, we demonstrate that deletion of poly-pyrimidine-tract-binding protein 1 (PTBP1) in the hematopoietic compartment leads to the development of a ribosomopathy-like condition. Specifically, loss of PTBP1 is associated with decreases in HSC self-renewal, erythroid differentiation, and protein synthesis. Consistent with its function as a splicing regulator, PTBP1 deficiency results in splicing defects in hundreds of genes, and we demonstrate that the up-regulation of a specific isoform of CDC42 partly mimics the protein-synthesis defect associated with loss of PTBP1. Furthermore, PTBP1 deficiency is associated with a marked defect in ribosome biogenesis and a selective reduction in the translation of mRNAs encoding ribosomal proteins. Collectively, this work identifies PTBP1 as a key integrator of ribosomal functions and highlights the broad functional repertoire of RNA-binding proteins.
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