Article | Published:

Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance and oocyte growth by mediating rRNA processing

Cell Death & Differentiation (2018) | Download Citation

Abstract

During mammalian oocyte growth, chromatin configuration transition from the nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role in the regulation of gene expression and acquisition of meiotic and developmental competence by the oocyte. Nonetheless, the mechanism underlying chromatin configuration maturation in oocytes is poorly understood. Here we show that nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)-processing complex and is essential for oocyte NSN–SN transition in mice. A conditional knockout of Dcaf13 in oocytes led to the arrest of oocyte development in the NSN configuration, follicular atresia, premature ovarian failure, and female sterility. The DCAF13 deficiency resulted in pre-rRNA accumulation in oocytes, whereas the total mRNA level was not altered. Further exploration showed that DCAF13 participated in the 18S rRNA processing in growing oocytes. The lack of 18S rRNA because of DCAF13 deletion caused a ribosome assembly disorder and then reduced global protein synthesis. DCAF13 interacted with a protein of the core box C/D ribonucleoprotein, fibrillarin, i.e., a factor of early pre-rRNA processing. When fibrillarin was knocked down in the oocytes from primary follicles, follicle development was inhibited as well, indicating that an rRNA processing defect in the oocyte indeed stunts chromatin configuration transition and follicle development. Taken together, these results elucidated the in vivo function of novel nucleolar protein DCAF13 in maintaining mammalian oogenesis.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Edited by H. Zhang

References

  1. 1.

    Adhikari D, Liu K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev. 2009;30:438–64.

  2. 2.

    Liu K, Rajareddy S, Liu L, Jagarlamudi K, Boman K, Selstam G, et al. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: new roles for an old timer. Dev Biol. 2006;299:1–11.

  3. 3.

    Tan JH, Wang HL, Sun XS, Liu Y, Sui HS, Zhang J. Chromatin configurations in the germinal vesicle of mammalian oocytes. Mol Hum Reprod. 2009;15:1–9.

  4. 4.

    Yu C, Xu YW, Sha QQ, Fan HY. CRL4DCAF1 is required in activated oocytes for follicle maintenance and ovulation. Mol Hum Reprod. 2015;21:195–205.

  5. 5.

    Yu C, Zhang YL, Pan WW, Li XM, Wang ZW, Ge ZJ, et al. CRL4 complex regulates mammalian oocyte survival and reprogramming by activation of TET proteins. Science. 2013;342:1518–21.

  6. 6.

    Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature. 2011;477:606–10.

  7. 7.

    Lee J, Zhou P. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol Cell. 2007;26:775–80.

  8. 8.

    Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006;443:590–3.

  9. 9.

    Xu YW, Cao LR, Wang M, Xu Y, Wu X, Liu J, et al. Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice. J Cell Sci. 2017;130:3297–307.

  10. 10.

    Yu C, Ji SY, Sha QQ, Sun QY, Fan HY. CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. Nat Commun. 2015;6:8017.

  11. 11.

    Zhang YL, Zhao LW, Zhang J, Le R, Ji SY, Chen C, et al. DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development. EMBO J. 2018;37:e98981.

  12. 12.

    Zuccotti M, Giorgi Rossi P, Martinez A, Garagna S, Forabosco A, Redi CA. Meiotic and developmental competence of mouse antral oocytes. Biol Reprod. 1998;58:700–4.

  13. 13.

    Ma JY, Li M, Luo YB, Song S, Tian D, Yang J, et al. Maternal factors required for oocyte developmental competence in mice: transcriptome analysis of non-surrounded nucleolus (NSN) and surrounded nucleolus (SN) oocytes. Cell Cycle. 2013;12:1928–38.

  14. 14.

    Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szollosi MS, Debey P. Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biol Reprod. 1999;60:580–7.

  15. 15.

    Kageyama S, Liu H, Kaneko N, Ooga M, Nagata M, Aoki F. Alterations in epigenetic modifications during oocyte growth in mice. Reproduction. 2007;133:85–94.

  16. 16.

    Lodde V, Modina S, Maddox-Hyttel P, Franciosi F, Lauria A, Luciano AM. Oocyte morphology and transcriptional silencing in relation to chromatin remodeling during the final phases of bovine oocyte growth. Mol Reprod Dev. 2008;75:915–24.

  17. 17.

    Rodriguez-Corona U, Sobol M, Rodriguez-Zapata LC, Hozak P, Castano E. Fibrillarin from Archaea to human. Biol Cell. 2015;107:159–74.

  18. 18.

    Duncan FE, Jasti S, Paulson A, Kelsh JM, Fegley B, Gerton JL. Age-associated dysregulation of protein metabolism in the mammalian oocyte. Aging Cell. 2017;16:1381–93.

  19. 19.

    Bax R, Vos HR, Raue HA, Vos JC. Saccharomyces cerevisiae Sof1p associates with 35S Pre-rRNA independent from U3 snoRNA and Rrp5p. Eukaryot Cell. 2006;5:427–34.

  20. 20.

    Lan ZJ, Xu X, Cooney AJ. Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice. Biol Reprod. 2004;71:1469–74.

Download references

Acknowledgements

This study is funded by the National Key Research and Developmental Program of China (2017YFC1001500, 2016YFC1000600, and 2017YFC1001100), National Natural Science Foundation of China (31528016, 31371449, and 31671558), and the Key Research and Development Program of Zhejiang Province (2017C03022).

Author information

Author notes

  1. These authors contributed equally: Jue Zhang, Yin-Li Zhang, Long-Wen Zhao

Affiliations

  1. Life Sciences Institute, Zhejiang University, 310058, Hangzhou, China

    • Jue Zhang
    • , Long-Wen Zhao
    • , Jing-Xin Guo
    • , Jia-Li Yu
    • , Shu-Yan Ji
    • , Lan-Rui Cao
    • , Li Shen
    •  & Heng-Yu Fan
  2. Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310016, Hangzhou, China

    • Yin-Li Zhang
    • , Song-Ying Zhang
    •  & Heng-Yu Fan
  3. Assisted Reproduction Unit, Second Hospital of Guangdong Province, China Southern Medical University, Guangzhou, China

    • Xiang-Hong Ou

Authors

  1. Search for Jue Zhang in:

  2. Search for Yin-Li Zhang in:

  3. Search for Long-Wen Zhao in:

  4. Search for Jing-Xin Guo in:

  5. Search for Jia-Li Yu in:

  6. Search for Shu-Yan Ji in:

  7. Search for Lan-Rui Cao in:

  8. Search for Song-Ying Zhang in:

  9. Search for Li Shen in:

  10. Search for Xiang-Hong Ou in:

  11. Search for Heng-Yu Fan in:

Conflict of interest

The authors declare that they have no conflict of interest

Corresponding author

Correspondence to Heng-Yu Fan.

Electronic supplementary material

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41418-018-0203-7