RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and - Independent Functions
RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and - Independent Functions
复制标题
RNA 解旋酶 DDX5 通过基于 miRNA 的 RYBP 抑制及其 PRC1 依赖性和独立功能来抑制重编程为多能性。
DOI：
10.1016/j.stem.2016.12.002
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发表时间：
2017-04-06
期刊：
影响因子：
23.9
通讯作者：
Yao, Hongjie
中科院分区：
文献类型：
--
作者：
Li, Huanhuan;Lai, Ping;Yao, Hongjie
RNA结合蛋白（RBP）除了在细胞内稳态中发挥作用外，还在谱系特化和维持细胞身份方面发挥重要作用。尽管它们的多样性和基本功能，几乎涉及RNA代谢的所有方面，但RBP在体细胞重编程中的作用知之甚少。在这里，我们表明，死亡盒RBP DDX 5抑制重编程的表达和功能的非典型polycomb复合物1（PRC 1）亚基RYBP。破坏Ddx 5表达提高了iPSC生成的效率，并阻碍了miR-125 b的加工，导致Rybp上调，并通过H2 AK 119的RYBP依赖性泛素化抑制谱系特异性基因。此外，RYBP需要PRC 1独立的招募OCT 4的启动子Kdm 2b，组蛋白脱甲基酶基因，促进重编程通过重新激活内源性多能性基因。总之，这些结果揭示了DDX 5在调节重编程中的重要功能，并突出了Ddx 5-miR 125 b-Rybp轴在控制细胞命运中的重要性。
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.