Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control

A fundamental challenge in molecular biology is to understand how evolving genomes can acquire new functions. Several recent studies have underscored how non-conserved sequences can contribute to organismal diversification in the primate lineage. Actively transcribed, non-coding parts of the genome provide a potential platform for the development of new functional sequences, but their biological and evolutionary roles remain largely unexplored. Here we show that a set of neutrally evolving long non-coding RNAs (lncRNA) arising from small nucleolar RNA Host Genes (SNHGs) are highly expressed in skin and dysregulated in inflammatory conditions. Using SNHG7 and human epidermal keratinocytes as a model, we describe a mechanism by which these lncRNAs can increase self-renewal and inhibit differentiation. SNHG7 lncRNA's activity has been acquired recently in the primate lineage and depends on a short sequence required for microRNA binding. Taken together, our results highlight the importance of understanding the role of fast-evolving transcripts in normal and diseased epithelia, and show how poorly conserved, actively transcribed non-coding sequences can participate in the evolution of genomic functionality. Overall design: Human primary keratinocytes were transfected with siRNA targeting SNHG7 or Scramble controls in duplicate. Samples were collected after 24 and 48h from the start of transfection and analyzed by RNA-seq