An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity.
An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity.
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DOI：
10.1093/nar/gkac1084
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发表时间：
2022-11-28
影响因子：
14.9
通讯作者：
Wang, Jianlong
中科院分区：
文献类型：
--
作者：
Li, Dan;Yang, Jihong;Malik, Vikas;Huang, Yuting;Huang, Xin;Zhou, Hongwei;Wang, Jianlong
RNA解旋酶参与了RNA代谢的多个步骤，以指导其在基因表达中的作用，但其在多能性控制中的功能在很大程度上仍未被探索。从RNA解旋酶的RNA干扰(RNAi)筛选开始，我们确定eIF4A3是外显子连接复合体(EJC)的死盒(DDX)解旋酶成分，对胚胎干细胞(ESCs)的维持是必不可少的。从机制上讲，我们证明了eIF4A3转录后控制与多能性相关的细胞周期调节因子，并且它的缺失通过细胞周期失调导致多能性丧失。具体地说，eIF4A3是有效的Ccnb1mRNA核输出所必需的，Ccnb1编码Cyclin B1，Cyclin B1是ESCs细胞周期进程中多潜能促进途径的关键组成部分。我们的结果揭示了eIF4A3及其相关的EJC在通过转录后控制细胞周期维持干细胞多能性方面以前未被认识到的作用。
RNA helicases are involved in multiple steps of RNA metabolism to direct their roles in gene expression, yet their functions in pluripotency control remain largely unexplored. Starting from an RNA interference (RNAi) screen of RNA helicases, we identified that eIF4A3, a DEAD-box (Ddx) helicase component of the exon junction complex (EJC), is essential for the maintenance of embryonic stem cells (ESCs). Mechanistically, we show that eIF4A3 post-transcriptionally controls the pluripotency-related cell cycle regulators and that its depletion causes the loss of pluripotency via cell cycle dysregulation. Specifically, eIF4A3 is required for the efficient nuclear export of Ccnb1 mRNA, which encodes Cyclin B1, a key component of the pluripotency-promoting pathway during the cell cycle progression of ESCs. Our results reveal a previously unappreciated role for eIF4A3 and its associated EJC in maintaining stem cell pluripotency through post-transcriptional control of the cell cycle.
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影响因子：
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作者：
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