RNA demethylation by FTO stabilizes the FOXJ1 mRNA for proper motile ciliogenesis

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Adenosine N6-methylation (m6A) is one of the most pervasive mRNA modifications, and yet the physiological significance of m6A removal (demethylation) remains elusive. Here, we report that the m6A demethylase FTO functions as a conserved regulator of motile ciliogenesis. Mechanistically, FTO demethylates and thereby stabilizes the mRNA that encodes the master ciliary transcription factor FOXJ1. Depletion of Fto in Xenopus laevis embryos caused widespread motile cilia defects, and Foxj1 was identified as one of the major phenocritical targets. In primary human airway epithelium, FTO depletion also led to FOXJ1 mRNA destabilization and a severe loss of ciliated cells with an increase of neighboring goblet cells. Consistently, Fto knockout mice showed strong asthma-like phenotypes upon allergen challenge, a result owing to defective ciliated cells in the airway epithelium. Altogether, our study reveals a conserved role of the FTO-FOXJ1 axis in embryonic and homeostatic motile ciliogenesis.
Publisher
CELL PRESS
Issue Date
2021-04
Language
English
Article Type
Article
Citation

DEVELOPMENTAL CELL, v.56, no.8, pp.1118 - +

ISSN
1534-5807
DOI
10.1016/j.devcel.2021.03.006
URI
http://hdl.handle.net/10203/285348
Appears in Collection
BiS-Journal Papers(저널논문)
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