1. STAT3-dependent long non-coding RNA Lncenc1 contributes to mouse ES cells pluripotency via stabilizing Klf4 mRNA.
- Author
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Monteleone, Emanuele, Corrieri, Paola, Provero, Paolo, Viavattene, Daniele, Pulvirenti, Lorenzo, Raggi, Laura, Carbognin, Elena, Bianchi, Marco E, Martello, Graziano, Oliviero, Salvatore, Pandolfi, Pier Paolo, and Poli, Valeria
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LINCRNA ,LEUKEMIA inhibitory factor ,GENE expression ,EMBRYONIC stem cells ,NON-coding RNA - Abstract
Embryonic stem cells (ESCs) preserve the unique ability to differentiate into any somatic cell lineage while maintaining their self-renewal potential, relying on a complex interplay of extracellular signals regulating the expression/activity of pluripotency transcription factors and their targets. Leukemia inhibitory factor (LIF)-activated STAT3 drives ESCs' stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors such as Klf4 and the maintenance of a stem-like epigenetic landscape. However, it is unknown if STAT3 directly controls stem-cell specific non-coding RNAs, crucial to balance pluripotency and differentiation. Applying a bioinformatic pipeline, here we identify Lncenc1 in mouse ESCs as an STAT3-dependent long non-coding RNA that supports pluripotency. Lncenc1 acts in the cytoplasm as a positive feedback regulator of the LIF–STAT3 axis by competing for the binding of microRNA-128 to the 3'UTR of the Klf4 core pluripotency factor mRNA, enhancing its expression. Our results unveil a novel non-coding RNA-based mechanism for LIF–STAT3-mediated pluripotency. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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