Vietri Rudan Matteo, Sipilä Kalle H, Philippeos Christina, Ganier Clarisse, Bhosale Priyanka G, Negri Victor A, Watt Fiona M
Centre for Gene Therapy and Regenerative Medicine, King's College London, Floor 28, Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
Directors' Unit, EMBL, Meyerhofstr. 1, 69117, Heidelberg, Germany.
EMBO J. 2024 Sep;43(18):4049-4067. doi: 10.1038/s44318-024-00172-8. Epub 2024 Jul 25.
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.
分子生物学中的一个基本挑战是理解不断进化的基因组如何获得新功能。基因组中活跃转录的非编码部分为新功能序列的发展提供了一个潜在平台，但其生物学和进化作用在很大程度上仍未得到探索。在这里，我们表明，一组内含子编码小核仁RNA的中性进化长链非编码RNA（lncRNA，即小核仁RNA宿主基因，SNHG）在皮肤中高度表达，在炎症条件下表达失调。以SNHG7和人表皮角质形成细胞为模型，我们描述了这些lncRNA增加自我更新和抑制分化的机制。SNHG7 lncRNA的活性最近在灵长类谱系中获得，并且依赖于微小RNA结合所需的短序列。综上所述，我们的结果强调了理解快速进化的转录本在正常和患病上皮细胞中的作用的重要性，并展示了保守性差、活跃转录的非编码序列如何参与基因组功能的进化。
