ALKBH3-dependent m1A demethylation of Aurora A mRNA inhibits ciliogenesis

Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m 1 A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m 1 A modification remains largely u...

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Published inCell discovery Vol. 8; no. 1; p. 25
Main Authors Kuang, Wenjun, Jin, Hao, Yang, Feng, Chen, Xiying, Liu, Jianzhao, Li, Ting, Chang, Yongxia, Liu, Min, Xu, Zhangqi, Huo, Chunxiao, Yan, Xiaoyi, Yang, Yuehong, Liu, Wei, Shu, Qiang, Xie, Shanshan, Zhou, Tianhua
Format Journal Article
LanguageEnglish
Published Singapore Springer Singapore 11.03.2022
Springer Nature B.V
Nature Publishing Group
Subjects
631/337/1645/2570
631/80/128/1383
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Cycle Analysis
Cell Physiology
Cilia
Demethylation
Ectopic expression
Edema
Embryogenesis
Gene expression
Life Sciences
Mammalian cells
mRNA turnover
Otoliths
RNA modification
Stem Cells
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Summary:Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m 1 A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m 1 A modification remains largely unknown. Here we find that the m 1 A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m 1 A sites on mRNA of Aurora A , a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3 , but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m 1 A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.
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ISSN:2056-5968
2056-5968
DOI:10.1038/s41421-022-00385-3