Article | Published:

BTG4 is a meiotic cell cycle–coupled maternal-zygotic-transition licensing factor in oocytes

Nature Structural & Molecular Biology volume 23, pages 387394 (2016) | Download Citation

Abstract

The mRNAs stored in oocytes undergo general decay during the maternal-zygotic transition (MZT), and their stability is tightly interconnected with meiotic cell-cycle progression. However, the factors that trigger decay of maternal mRNA and couple this event to oocyte meiotic maturation remain elusive. Here, we identified B-cell translocation gene-4 (BTG4) as an MZT licensing factor in mice. BTG4 bridged CNOT7, a catalytic subunit of the CCR4–NOT deadenylase, to eIF4E, a key translation initiation factor, and facilitated decay of maternal mRNA. Btg4-null females produced morphologically normal oocytes but were infertile, owing to early developmental arrest. The intrinsic MAP kinase cascade in oocytes triggered translation of Btg4 mRNA stored in fully grown oocytes by targeting the 3′ untranslated region, thereby coupling CCR4–NOT deadenylase–mediated decay of maternal mRNA with oocyte maturation and fertilization. This is a key step in oocyte cytoplasmic maturation that determines the developmental potential of mammalian embryos.

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Acknowledgements

This study was funded by the National Basic Research Program of China (2012CB944403) and the National Natural Science Foundation of China (31528016, 91519313, and 31371449) to H.-Y.F. We thank B. Zhang (Peking University) for vectors.

Author information

Author notes

    • Chao Yu
    • , Shu-Yan Ji
    • , Qian-Qian Sha
    • , Yujiao Dang
    • , Jian-Jie Zhou
    •  & Yin-Li Zhang

    These authors contributed equally to this work.

Affiliations

  1. Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.

    • Chao Yu
    • , Shu-Yan Ji
    • , Qian-Qian Sha
    • , Jian-Jie Zhou
    • , Yin-Li Zhang
    • , Yang Liu
    •  & Heng-Yu Fan
  2. Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, China.

    • Yujiao Dang
    • , Boqiang Hu
    •  & Fuchou Tang
  3. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

    • Zhong-Wei Wang
    •  & Qing-Yuan Sun
  4. College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

    • Shao-Chen Sun

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Contributions

H.-Y.F. and C.Y. conceived the project. H.-Y.F., C.Y., S.-Y.J., Q.-Q.S., Y.D., Y.-L.Z., and F.T. designed and analyzed experiments. C.Y., S.-Y.J., Q.-Q.S., Y.D., Y.-L.Z., J.-J.Z., Y.L., B.H., and S.-C.S. performed experiments. Z.-W.W. and Q.-Y.S. assisted in microinjection of mouse embryos. C.Y., Y.-L.Z., and H.-Y.F. wrote the paper. C.Y., S.-Y.J., Q.-Q.S., Y.D., J.-J.Z., and Y.-L.Z. contributed equally to this work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Heng-Yu Fan.

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    Supplementary Figures 1–8 and Supplementary Tables 2–4

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    Supplementary Data Set 1

    Original images of gels and blots used in this study

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    Supplementary Table 1

    FPKM of RNA-seq results

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DOI

https://doi.org/10.1038/nsmb.3204

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