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서울대학교, 기초과학연구원

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Dev. Cell, Published: March 23, 2021 | DOI:https://doi.org/10.1016/j.devcel.2021.03.006 RNA demethylation by FTO stabilizes the FOXJ1 mRNA for proper motile ciliogenesis

Hyunjoon Kim^1,2,6,*, Young-suk Lee^1,2,6,7, Seok-Min Kim^3,4, Soohyun Jang¹, Hyunji Choi², Jae-Won Lee⁵, Tae-Don Kim^3,4,*, V. Narry Kim^1,2,8,*

¹Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea
²School of the Biological Sciences, Seoul National University, Seoul 08826, Korea
³Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
⁴Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Korea
⁵Natural Medicine Research Center, KRIBB, Cheongju, Korea
⁶These authors contributed equally
⁷Present address: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
⁸Lead contact

^*Corresponding author

Abstract

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.

Keywords : N6-methyladenosine, m6A, RNA modification, FTO, FOXJ1, motile ciliogenesis, airway epithelium, airway epithelium

논문정보

형식Research article
게재일2021년 03월 (BRIC 등록일 2021-03-26)
연구진국내 연구진
분야 생명과학 > 세포생물학

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