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

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