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

Author

Listed:
  • Long Bai

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Yu Xiang

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Minyue Tang

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Shuangying Liu

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Qingqing Chen

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Qichao Chen

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Min Zhang

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Shan Wan

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Yimiao Sang

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Qingfang Li

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Sisi Wang

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Zhekun Li

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Yang Song

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Xiaoling Hu

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Luna Mao

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Guofang Feng

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Long Cui

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Yinghui Ye

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Yimin Zhu

    (School of Medicine, Zhejiang University
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

Abstract

N6-methyladenosine (m6A) maintains maternal RNA stability in oocytes. One regulator of m6A, ALKBH5, reverses m6A 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 m6A dynamics demonstrated that ALKBH5-mediated m6A demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following Alkbh5−/− depletion. A distinct subset of transcripts with persistent m6A peaks are recognized by the m6A 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 m6A removal in maternal RNA decay.

Suggested Citation

  • Long Bai & Yu Xiang & Minyue Tang & Shuangying Liu & Qingqing Chen & Qichao Chen & Min Zhang & Shan Wan & Yimiao Sang & Qingfang Li & Sisi Wang & Zhekun Li & Yang Song & Xiaoling Hu & Luna Mao & Guofa, 2023. "ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42302-6
    DOI: 10.1038/s41467-023-42302-6
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    References listed on IDEAS

    as
    1. Jeesun Kim & Anup Kumar Singh & Yoko Takata & Kevin Lin & Jianjun Shen & Yue Lu & Marc A. Kerenyi & Stuart H. Orkin & Taiping Chen, 2015. "LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice," Nature Communications, Nature, vol. 6(1), pages 1-14, December.
    2. Huan Yao & Chun-Chun Gao & Danru Zhang & Jiawei Xu & Gege Song & Xiu Fan & Dao-Bo Liang & Yu-Sheng Chen & Qian Li & Yanjie Guo & Yu-Ting Cai & Lulu Hu & Yong-Liang Zhao & Ying-Pu Sun & Ying Yang & Jia, 2023. "scm6A-seq reveals single-cell landscapes of the dynamic m6A during oocyte maturation and early embryonic development," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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