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ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation
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ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation
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Journal Article
ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation
2023
Overview
N
6
-methyladenosine (m
6
A) maintains maternal RNA stability in oocytes. One regulator of m
6
A, ALKBH5, reverses m
6
A deposition and is essential in RNA metabolism. However, the specific role of ALKBH5 in oocyte maturation remains elusive. Here, we show that
Alkbh5
depletion causes a wide range of defects in oocyte meiosis and results in female infertility. Temporal profiling of the maternal transcriptomes revealed striking RNA accumulation in
Alkbh5
−/−
oocytes during meiotic maturation. Analysis of m
6
A dynamics demonstrated that ALKBH5-mediated m
6
A demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following
Alkbh5
−/−
depletion. A distinct subset of transcripts with persistent m
6
A peaks are recognized by the m
6
A reader IGF2BP2 and thus remain stabilized, resulting in impaired RNA clearance. Additionally, reducing IGF2BP2 in
Alkbh5
-depleted oocytes partially rescued these defects. Overall, this work identifies ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m
6
A removal in maternal RNA decay.
N6-methyladenosine (m6A) maintains maternal RNA stability in oocytes. Here, the authors identify demethylase ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m6A removal in maternal RNA decay.
