Snord15b Maintains Stemness of Intestinal Stem Cells via Enhancement of Alternative Splicing of Btrc Short Isoform for Suppression of β-Catenin Ubiquitination.

ABSTRACT: Intestinal epithelium is derived from Lgr5⁺ intestinal stem cells (ISCs) located at the crypt base. However, how small nucleolar RNAs (snoRNAs) regulate ISC stemness remains elusive. Here, a conserved snoRNA, Snord15b, that is highly expressed in ISCs is identified. Snord15b knockout abolishes the self-renewal capacity of ISCs and impairs epithelial regeneration. Mechanistically, Snord15b interacts with interleukin enhancer-binding factor 2 (Ilf2) to recruit splicing factors, which mediates alternative splicing of Btrc to form a short isoform of Btrc, resulting in abrogation of E3 ligase complex formation for ubiquitination of β-catenin. Subsequently, stable β-catenin translocates into the nucleus of ISCs for activation of the Wnt/β-catenin signaling pathway, leading to ISC stem

SUBMITTER: Xu Y 

PROVIDER: S-EPMC12667501 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature