ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N (6)-methyladenosine methylation

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.