Snhg26 long non-coding RNA regulates pluripotent cell states through a SINEB2-derived sequence

Abstract/SummaryLong-non coding RNAs (lncRNAs) are now well established players in gene expression regulation, but their detailed molecular mechanisms of action and underlying regulating sequences remain poorly understood. An emerging concept supports the idea that repeated sequences, more notably sequences derived from transposable elements (TEs), contribute to functional domains of lncRNAs. Here, we undertake the characterization of the function, interactors and functional domains of Snhg26, a lncRNA involved in reprogramming towards induced pluripotent stem cells (iPSCs) and maintenance of the pluripotent state of embryonic stem cells (ESCs). First, we show that modulation of Snhg26 expression levels affects expression and splicing of genes involved in pluripotency and chromatin remodeling during the early steps of reprogramming and in ESCs. We also find that down-regulation of Snhg26 increases the expression of SINEB2 transposable elements. Moreover, we identify hundreds of transcripts directly interacting with Snhg26 with a significant enrichment of RNAs containing SINEB2 elements. Strikingly, loss of a SINEB2 sequence embedded within Snhg26 abolishes its function in regulating pluripotent states. Our results thus support the idea that TEs constitute a source of functional units for lncRNAs and encourages further efforts to explore this concept.