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Original Article | Open Access

METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis

Qiuchan Xiong1, Caojie Liu1, Xin Zheng1 , Xinyi Zhou1, Kexin Lei1, Xiaohan Zhang1, Qian Wang1, Weimin Lin1, Ruizhan Tong2, Ruoshi Xu1( ), Quan Yuan1 ( )
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
Department of Thoracic Oncology, Cancer Center, and Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, China
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Abstract

The dorsal lingual epithelium, which is composed of taste buds and keratinocytes differentiated from K14+ basal cells, discriminates taste compounds and maintains the epithelial barrier. N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotic cells. How METTL3-mediated m6A modification regulates K14+ basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear. Here we show knockout of Mettl3 in K14+ cells reduced the taste buds and enhanced keratinocytes. Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds. Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization, but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery. Mechanically, we revealed that the most frequent m6A modifications were enriched in Hippo and Wnt signaling, and specific peaks were observed near the stop codons of Lats1 and FZD7. Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.

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International Journal of Oral Science
Volume 14,
2022
Article number: 26
DOI: 10.1038/s41368-022-00176-2

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Cite this article:
Xiong Q, Liu C, Zheng X, et al. METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis. International Journal of Oral Science, 2022, 14: 26. https://doi.org/10.1038/s41368-022-00176-2

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Accepted: 21 April 2022
Published: 17 May 2022
© The Author(s) 2022

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