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RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions

tshuang319 添加于 2018/8/31 20:29:07  368次阅读 | 0次推荐 | 0个评论

RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b, a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.

作 者:Li Huanhuan, Lai Ping, Jia Jinping, Song Yawei, Xia Qing, Huang Kaimeng, He Na, Ping Wangfang, Chen Jiayu, Yang Zhongzhou, Li Jiao, Yao Mingze, Dong Xiaotao, Zhao Jicheng, Hou Chunhui, Esteban MA, Gao Shaorong, Pei Duanqing, Hutchins AP, Yao Hongjie.
期刊名称: Cell Stem Cell
期卷页: 2017/4/6 第20卷 第4期 462-477页
学科领域:生命科学 » 细胞生物学 » 细胞增殖、生长与分化
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原文链接:https://www.ncbi.nlm.nih.gov/pubmed/28111200
DOI: 10.1016/j.stem.2016.12.002
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