biostudies-literatureJiapaer ZShanghai Municipal Medical and Health Discipline ConstructionFundamental Research Funds for the Central UniversitiesMinistry of EducationMinistry of Science and TechnologyScience and Technology Commission of Shanghai MunicipalityNational Natural Science Foundation of China395-409https://www.ebi.ac.uk/biostudies/studies/S-EPMC6092693biostudies-literatureUnknown11(2)Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from the naïve state to the primed state, whereas ectopic LincU expression maintains mESCs in the naïve state. Mechanistically, we demonstrate that LincU binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naïve state. Importantly, we reveal the functional role of LincU to be evolutionarStem cell reportsLincU Preserves Naive Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.PMC6092693IRT_15R512017ZZ02015816006753172100331571390151521904015JC1403201317715062016YFA01013003157151920002310002316715333170111031571529151521903931471250815300421500219106Li GSu DLi JGuo XZhu FDu YWang GWan XBai MChen WYe DJia WKang JJiapaer ZYu YfalseLincU Preserves Naive Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from the naïve state to the primed state, whereas ectopic LincU expression maintains mESCs in the naïve state. Mechanistically, we demonstrate that LincU binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naïve state. Importantly, we reveal the functional role of LincU to be evolutionar2018-01-01T00:00:00Z2018 Aug2026-05-05T22:46:37.036Z2019-03-26T23:51:24ZS-EPMC60926933001782010.1016/j.stemcr.2018.06.010