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<p>Intestinal epithelium relies on intestinal stem cells (ISCs) for rapid and precise tissue replenishment to maintain gut normal function. The self-renewal maintenance of ISCs is finely regulated by multiple stemness factors and signaling pathways. However, the transcription mechanisms of some key stemness factors remain poorly understood. Here, we identify that small nucleolar RNA <i>Snora61</i> is highly expressed in ISCs. <i>Snora61</i> is mainly distributed in the nucleoplasm. <i>Snora61</i> knockout impairs ISC self-renewal and intestinal regeneration. Mechanistically, <i>Snora61</i> binds to the promoter region of <i>Lgr5</i> gene and engages with RNA-binding protein RBMX to recruit HMGB2 onto <i>Lgr5</i> promoter, leading to <i>Lgr5</i> transcription and expression. <i>Snora61</i> promotes the self-renewal of small intestinal stem cells, which in turn enhances the proliferation of differentiated epithelial cells, thereby contributing to the maintenance of intestinal homeostasis. Conversely, <i>Snora61</i> knockout causes reduced LGR5 expression. Deletion of <i>Lgr5</i> with <i>Snora61</i> displays more severely impaired ISC self-renewal and intestinal regeneration. Our findings reveal a regulatory mechanism of <i>Lgr5</i> transcription underlying ISC self-renewal maintenance.</p>

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Small nucleolar RNA Snora61 drives self-renewal of intestinal stem cells via initiation of Lgr5 transcription

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月7日

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  • Jiacheng He,
  • Yufei Lan,
  • Yuwei Xu,
  • Zhen Xiong,
  • Zhibin Yi,
  • Hui Guo,
  • Jiahang Zhang,
  • Ziheng Zhou,
  • Ying Du,
  • Fan Pan,
  • Zusen Fan

摘要

Intestinal epithelium relies on intestinal stem cells (ISCs) for rapid and precise tissue replenishment to maintain gut normal function. The self-renewal maintenance of ISCs is finely regulated by multiple stemness factors and signaling pathways. However, the transcription mechanisms of some key stemness factors remain poorly understood. Here, we identify that small nucleolar RNA Snora61 is highly expressed in ISCs. Snora61 is mainly distributed in the nucleoplasm. Snora61 knockout impairs ISC self-renewal and intestinal regeneration. Mechanistically, Snora61 binds to the promoter region of Lgr5 gene and engages with RNA-binding protein RBMX to recruit HMGB2 onto Lgr5 promoter, leading to Lgr5 transcription and expression. Snora61 promotes the self-renewal of small intestinal stem cells, which in turn enhances the proliferation of differentiated epithelial cells, thereby contributing to the maintenance of intestinal homeostasis. Conversely, Snora61 knockout causes reduced LGR5 expression. Deletion of Lgr5 with Snora61 displays more severely impaired ISC self-renewal and intestinal regeneration. Our findings reveal a regulatory mechanism of Lgr5 transcription underlying ISC self-renewal maintenance.