YTHDF1-Mediated Translation Amplifies Wnt-Driven Intestinal Stemness

ABSTRACT: N6-methyladenosine (m6A) mRNA methylation has emerged as an important player in many biological processes by regulating gene expression. However, its roles in intestinal stem cell (ISC) homeostasis remain largely unknown. Here we report that YTHDF1, an m6A reader, is highly expressed in ISCs and its expression is upregulated by Wnt signaling at the translational level. Whereas YTHDF1 is dispensable for normal intestinal development in mice, genetic ablation of Ythdf1 dramatically blocks Wnt-driven regeneration and tumorigenesis with reduced ISC stemness. Mechanistically, YTHDF1 facilitates the translation of Wnt signaling effectors including TCF7L2/TCF4, while this process is enhanced during Wnt activation to augment ?-catenin activity. Targeting YTHDF1 in ISCs of established tumors leads

SUBMITTER: Bing Han 

PROVIDER: S-SCDT-EMBOR-2019-49229-T | biostudies-other |

REPOSITORIES: biostudies-other