STAT3-dependent Long Non-coding RNA Lncenc1 Contributes to Mouse ES Cells Pluripotency Via Stabilizing Klf4 MRNA

Overview

Journal Brief Funct Genomics

Publisher Oxford University Press

Date 2023 Oct 6

PMID 37801430

Authors

Emanuele Monteleone

Paola Corrieri

Paolo Provero

Daniele Viavattene

Lorenzo Pulvirenti

Laura Raggi

Elena Carbognin

Marco E Bianchi

Graziano Martello

Salvatore Oliviero

Pier Paolo Pandolfi

Valeria Poli

Affiliations

Soon will be listed here.

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.

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