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

## TL;DR

This study shows how a small RNA called Snord17 helps intestinal stem cells renew themselves by enabling the production of a key protein involved in cell signaling.

## Contribution

The study identifies a novel regulatory axis involving Snord17, Thoc3, Yy2, and Tead4 in intestinal stem cell self-renewal.

## Key findings

- Snord17 knockout disrupts stemness and epithelial regeneration in intestinal stem cells.
- Snord17 interacts with Thoc3 to enable Yy2 mRNA export and translation.
- Yy2 activates Tead4 transcription, which is essential for Hippo signaling and stem cell maintenance.

## 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.

Snord17, through interaction with Thoc3, promotes nuclear export and translation of Yy2 mRNA in Snord17
+/+ ISCs. The Yy2 protein subsequently binds the Tead4 promoter to promote its transcription, activating Hippo signaling, which is essential for ISC maintenance. In Snord17
−/− ISCs, impaired Yy2 mRNA export prevents translation, leading to suppressed Tead4 expression and disrupted Hippo signaling.