A lncRNA fine tunes the dynamics of a cell state transition involving Lin28 , let-7 and de novo DNA methylation

Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) hereafter ( ), that modulates the dynamics of exit from naïve pluripotency. deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of , expression is reduced which results in persistence of the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. deletion retards ES cell transition, correlating with delayed promoter methylation and phenocopying loss of or . The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. illustrates how lncRNAs may introduce species-specific network modulations.