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  • Long noncoding RNA lnc-NAP ...
    Xie, Dongfang; Tong, Man; Xia, Baolong; Feng, Guihai; Wang, Leyun; Li, Ang; Luo, Guanzheng; Wan, Haifeng; Zhang, Zeyu; Zhang, Hao; Yang, Yun-Gui; Zhou, Qi; Wang, Meng; Wang, Xiu-Jie

    RNA biology, 06/2021, Volume: 18, Issue: 6
    Journal Article

    The pluripotency of embryonic stem cells (ESCs) is controlled by a multilayer regulatory network, of which the key factors include core pluripotency genes Oct4, Sox2 and Nanog, 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 Nanog by targeting Nanog 3′ untranslated region (UTR) to repress Nanog expression in mouse ESCs and embryos. Such regulation could be released by an ESC-specifically expressed ceRNA named lnc-NAP. The expression of lnc-NAP is activated by OCT4, SOX2, as well as NANOG through promoter binding. Downregulation of lnc-NAP reduces Nanog abundance, which leads to decreased pluripotency of mouse ESCs and embryonic lethality. These results reveal lnc-NAP as a new regulator for Nanog in mouse ESCs, and uncover a feed-forward regulatory loop of Nanog through the participation of lnc-NAP.