REVIEW article
Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1599487
ALKBH5 in Development: Decoding the Multifaceted Roles of m6A Demethylation in Biological Processes
Provisionally accepted
- 1School of Stomatology, Wuhan University, Wuhan, Hubei Province, China
- 2Hospital of Stomatology, Sun Yat-sen University, Guangdong, China
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N6-methyladenosine (m6A), an abundant internal RNA modification in eukaryotes, serves as a dynamic post-transcriptional regulator of gene expression by influencing RNA splicing, stability, translation, and decay. This reversible epitranscriptomic mechanism, which is mediated by methyltransferase (writers), demethylase (erasers), and m6A-binding proteins (readers), is pivotal in diverse biological contexts. Among m6A erasers, alkylation repair homolog protein 5 (ALKBH5), an Fe(II)/α-ketoglutarate-dependent dioxygenase, is the second to be discovered and one of the most significant demethylases. Mounting evidence underscores ALKBH5's role in modulating developmental programming, where it coordinates processes such as lineage specification, organogenesis, and tissue homeostasis. This review systematically deciphers the multifaceted contributions of ALKBH5-mediated m6A demethylation to developmental biology. We synthesize recent advances elucidating how ALKBH5-driven m6A erasure dynamically regulates transcriptomic rewiring during embryogenesis, reproductive development, cardiac development, central nervous system development, immune system development, pancreatic organogenesis, osteogenic/odontogenic differentiation, adipogenesis, and angiogenesis. These revelations not only deepen our understanding of epitranscriptomic regulation in ontogeny but also illuminate therapeutic avenues for developmental anomalies and regenerative medicine.
Keywords: ALKBH5, m6A demethylation, development, Organogenesis, Therapeutics
Received: 29 Mar 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Zhang, Zhou, Tian and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huangheng Tao, School of Stomatology, Wuhan University, Wuhan, 430079, Hubei Province, China
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