Key Laboratory of Genetic Network Biology, Institute of Genetics and Developmental Biology, Innovation Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
RNA Biol. 2021 Jun;18(6):875-887. doi: 10.1080/15476286.2020.1827591. Epub 2020 Oct 23.
The pluripotency of embryonic stem cells (ESCs) is controlled by a multilayer regulatory network, of which the key factors include core pluripotency genes and , and multiple microRNAs (miRNAs). Recently, long noncoding RNAs (lncRNAs) have been discovered as a class of new regulators for ESCs, and some lncRNAs could function as competing endogenous RNAs (ceRNAs) to regulate mRNAs by competitively binding to miRNAs. Here, we identify mmu-miR-139-5p as a new regulator for by targeting 3' untranslated region (UTR) to repress expression in mouse ESCs and embryos. Such regulation could be released by an ESC-specifically expressed ceRNA named . The expression of is activated by OCT4, SOX2, as well as NANOG through promoter binding. Downregulation of reduces abundance, which leads to decreased pluripotency of mouse ESCs and embryonic lethality. These results reveal as a new regulator for in mouse ESCs, and uncover a feed-forward regulatory loop of through the participation of .
胚胎干细胞（ESCs）的多能性由一个多层次的调控网络控制，其中关键因素包括核心多能性基因和，以及多个 microRNAs（miRNAs）。最近，长非编码 RNA（lncRNA）被发现是 ESCs 的一类新的调控因子，一些 lncRNA 可以作为竞争性内源 RNA（ceRNA）通过竞争性结合 miRNAs 来调节 mRNAs。在这里，我们鉴定出 mmu-miR-139-5p 是通过靶向 3'非翻译区（UTR）来抑制小鼠 ESCs 和胚胎中表达的新的 调节剂。这种调节可以通过一种 ESC 特异性表达的 ceRNA 释放，该 ceRNA 名为 。的表达通过启动子结合被 OCT4、SOX2 和 NANOG 激活。下调会降低 的丰度，导致小鼠 ESCs 多能性降低和胚胎致死。这些结果揭示了 在小鼠 ESCs 中作为 的新调节剂，并揭示了 通过 的参与的正反馈调节环。
