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

EMBO J. 2024 Sep;43(18):4049-4067. doi: 10.1038/s44318-024-00172-8. Epub 2024 Jul 25.

Abstract

A fundamental challenge in molecular biology is to understand how evolving genomes can acquire new functions. 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 (lncRNAs) whose introns encode small nucleolar RNAs (snoRNA 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. The activity of SNHG7 lncRNA has been recently acquired 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.

Keywords: Evolution; Skin; lncRNA.

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Evolution, Molecular*
  • Humans
  • Keratinocytes* / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Small Nucleolar* / genetics
  • RNA, Small Nucleolar* / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Small Nucleolar
  • MicroRNAs