Long Noncoding RNA Q Associates with Sox2 and Is Involved in the Maintenance of Pluripotency in Mouse Embryonic Stem Cells

Large intergenic noncoding RNAs (lincRNAs) in embryonic stem cells may play an important role in the maintenance of pluripotency. The identification of stem cell-specific lincRNAs and their interacting partners will deepen our understanding of the maintenance of stem cell pluripotency. We identified a lincRNA, LincQ, which is specifically expressed in embryonic stem cells and is regulated by core pluripotent transcription factors. It was rapidly downregulated during the differentiation process. Knockdown of LincQ in embryonic stem cells led to differentiation, downregulation of pluripotency-related genes, and upregulation of differentiation-related genes. We found that exon 1 of LincQ can specifically bind to Sox2. The Soxp region in Sox2, rather than the HMG domain, is responsible for LincQ binding. Importantly, the interaction between LincQ and Sox2 is required for the maintenance of pluripotency in embryonic stem cells and the transcription of pluripotency genes. Esrrb and Tfcp2l1 are key downstream targets of LincQ and Sox2, since overexpression of Esrrb and Tfcp2l1 can restore the loss of embryonic stem cell pluripotency that is induced by LincQ depletion. In summary, we found that LincQ specifically interacts with Sox2 and contributes to the maintenance of pluripotency, highlighting the critical role of lincRNA in the pluripotency regulatory network. (c) AlphaMed Press 2020 SIGNIFICANCE STATEMENT: This study shows that the long intergenic noncoding RNA LincQ is critical for embryonic stem cell (ESC) pluripotency maintenance. LincQ is highly expressed in ESCs and is downregulated during differentiation. Further, its inhibition leads to ESC differentiation. LincQ binds to Sox2 to regulate the transcription of pluripotency genes. Esrrb and Tfcp2l1 are the main downstream targets of LincQ/Sox2 that are involved in ESC maintenance.