A reduction in A-to-I RNA editing by ADAR disrupts Pumilio-mediated inhibition of MAPK signaling to drive intestinal stem cell aging.

Qian Zhang, Yuedan Zhu, Yi Chen, Wenhao Hou, Aolong Sun, La Yan, Xingzhu Liu, Yu Yuan, Chaoxin Gao, Junfeng Xie, Rui Zhang, Haiyang Chen

West China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. · pubmed

Paper

Abstract

Aging impairs intestinal stem cell (ISC) function, disrupting epithelial homeostasis and regenerative repair. Loss of ISC quiescence promotes intestinal dysfunction and contributes to organismal aging. Here, we report an epitranscriptomic mechanism through which a decrease in adenosine-to-inosine (A-to-I) RNA editing by the adenosine deaminase ADAR in ISCs during aging disrupts a conserved signaling axis that maintains ISC quiescence. In

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Research summary

A reduction in ADAR-mediated A-to-I RNA editing disrupts Pumilio-mediated inhibition of MAPK signaling, leading to the loss of intestinal stem cell quiescence and driving organismal aging. This paper identifies a specific epitranscriptomic mechanism linking RNA editing to stem cell maintenance, offering a potential target for modulating aging-related tissue dysfunction.

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