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- Title
ALKBH3-dependent m<sup>1</sup>A demethylation of Aurora A mRNA inhibits ciliogenesis.
- 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
- Abstract
Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m1A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m1A modification remains largely unknown. Here we find that the m1A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m1A 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 m1A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.
- Subjects
CILIA &; ciliary motion; DEMETHYLATION; RNA metabolism; RNA modification &; restriction; RNA regulation; MESSENGER RNA
- Publication
Cell Discovery, 2022, Vol 8, Issue 1, p1
- ISSN
2056-5968
- Publication type
Article
- DOI
10.1038/s41421-022-00385-3