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YTHDF 1‐mediated translation amplifies Wnt‐driven intestinal stemness by Han, Bing; Yan, Sujun; Wei, Saisai; Xiang, Jie; Liu, Kangli; Chen, Zhanghui; Bai, Rongpan; Sheng, Jinghao; Xu, Zhengping; Gao, Xiangwei is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is YTHDF 1‐mediated translation amplifies Wnt‐driven intestinal stemness about?

N6-methyladenosine (m A) 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 m A 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 β-catenin activity. Targeting YTHDF1 in ISCs of established tumors leads to tumor shrinkage and prolonged survival. Collectively, our studies unveil YTHDF1 as an amplifier of Wnt/β-catenin signaling at the translational level, which is required for the maintenance of ISCs during regeneration and tumorigenesis.

Who reads YTHDF 1‐mediated translation amplifies Wnt‐driven intestinal stemness?

Author

Han, Bing; Yan, Sujun; Wei, Saisai; Xiang, Jie; Liu, Kangli; Chen, Zhanghui; Bai, Rongpan; Sheng, Jinghao; Xu, Zhengping; Gao, Xiangwei

Publisher

Nature Publishing Group; Wiley (John Wiley & Sons); Wiley-Blackwell; EMBO; Wiley; Springer Science and Business Media LLC (ISSN 1469-221X)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)