Small Nucleolar RNA Snord17 Promotes Self-Renewal of Intestinal Stem Cells through Yy2 mRNA Export and Tead4 Activation

Advanced Science, 4 January, 2026, DOI：https://doi.org/10.1002/advs.202512029

Small Nucleolar RNA Snord17 Promotes Self-Renewal of Intestinal Stem Cells through Yy2 mRNA Export and Tead4 Activation

Peikang Zhang, Yuwei Xu, Yufei Lan, Zhen Xiong, Zhibin Yi, Runyuan Wu, Cunzhen Li, Ying Du, Hui Guo, Yingchi Yang, Zusen Fan

Abstract

The intestinal epithelium possesses a profound capacity for regeneration, which is fueled by the proliferation and differentiation of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-expressing intestinal stem cells (ISCs) located at the base of the crypts. However, how small nucleolar RNAs (snoRNAs) regulate the self-renewal of ISCs remains elusive. Here, we identified a small nucleolar RNA Snord17 that is highly expressed in ISCs. Snord17 knockout abrogates stemness of ISCs and impairs epithelial regeneration. Mechanistically, Snord17 interacts with THO complex 3 (Thoc3) to facilitate nuclear export of Yin yang 2 transcription factor (Yy2) mRNA for its subsequent translation. Yy2 protein enriches on the promoter of TEA domain family member 4 (Tead4) to activate its transcription, leading to activation of Hippo signaling for self-renewal maintenance of ISCs. Of note, Tead4 deficiency impairs self-renewal of ISCs and intestinal regeneration. Our findings reveal that the Snord17-Thoc3-Yy2-Tead4 axis is required for self-renewal maintenance of ISCs and gut regeneration.

文章链接：https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202512029