Dataset Information
M1A demethylase Alkbh3 regulates neurogenesis through m1A demethylation of Mmp15 mRNA.
Ontology highlight
ABSTRACT: Background
N1-Methyladenosine (m1A) is an abundant modification of transcripts regulating mRNA structure and translation efficiency. However, the characteristics and biological functions of mRNA m1A modification in adult hippocampal neurogenesis remain enigmatic.Results
We found that m1A demethylase Alkbh3 was dramatically enriched in neurons and neuronal genesis. Functionally, depletion of Alkbh3 in neural stem cells (NSCs) significantly decreased m1A modification, neuronal differentiation and proliferation coupling with increasing gliogenesis, whereas overexpressing Alkbh3 facilitated neuronal differentiation and proliferation. Mechanistically, the m1A demethylation of Mmp15 mRNA by Alkbh3 improved its RNA stability and translational efficacy, which promoted neurogenesis. Therapeutically, the silencing of Alkbh3 reduced hippocampal neurogenesis and impaired spatial memory in the adult mice.Conclusions
We reveal a novel function of m1A demethylation on Mmp15 mRNA in Alkbh3-mediated neurogenesis, which shed light on advancing Alkbh3 regulation of neurogenesis as a novel neurotherapeutic strategy.
SUBMITTER: Wang H
PROVIDER: S-EPMC11246583 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
Publications
m<sup>1</sup>A demethylase Alkbh3 regulates neurogenesis through m<sup>1</sup>A demethylation of Mmp15 mRNA.
Cell & bioscience 20240714 1
<h4>Background</h4>N<sup>1</sup>-Methyladenosine (m<sup>1</sup>A) is an abundant modification of transcripts regulating mRNA structure and translation efficiency. However, the characteristics and biological functions of mRNA m<sup>1</sup>A modification in adult hippocampal neurogenesis remain enigmatic.<h4>Results</h4>We found that m<sup>1</sup>A demethylase Alkbh3 was dramatically enriched in neurons and neuronal genesis. Functionally, depletion of Alkbh3 in neural stem cells (NSCs) significant ...[more]