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Revisiting ZAR proteins: the understudied regulator of female fertility and beyond

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Abstract

Putative RNA-binding proteins (RBPs), zygote arrested-1 (ZAR1), and ZAR2 (also known as ZAR1L), have been identified as maternal factors that mainly function in oogenesis and embryogenesis. Despite divergence in their spatio-temporal expression among species, the CxxC structure of the C-terminus of ZAR proteins is highly conserved and is reported to be the functional domain for the activity of the RBPs of ZAR proteins. In oocytes from Xenopus laevis and zebrafish, ZAR proteins have been reported to bind to maternal transcripts and inhibit translation in immature growing oocytes, whereas in fully grown mouse oocytes, they promote the translation during meiotic maturation. Thus, ZAR1 and ZAR2 may be required for the maternal-to-zygotic transition by stabilizing the maternal transcriptome in oocytes with partial functional redundancy. In addition, recent studies have suggested non-ovarian expression and function of ZAR proteins, particularly their involvement in tumorigenesis. ZAR proteins are potentially associated with tumor suppressors and can serve as epigenetically inactivated cancer biomarkers. In this review, studies on Zar1/2 are systematically summarized, and some issues that require discussion and further investigation are introduced as perspectives.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2021YFC2700100), the National Natural Science Foundation of China (Award Numbers: 31930031 and 31890781), the National Ten-Thousands Talents Program of China, the Natural Science Foundation of Zhejiang Province, China [D22C68649], and the Key Research and Development Program of Zhejiang Province (2021C03098 and 2021C03100). We thank Drs Shu-Yan Ji and Yan Rong for their contributions to the ZAR1/2 studies and helpful discussions. We thank Editage (www.editage.cn) for English language editing.

Funding

This work was funded by the National Natural Science Foundation of China (Award Numbers: 31930031 and 31890781).

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  1. Life Sciences Institute, Zhejiang University, 866 Yu Hang Tang Rd., Hangzhou, 310058, China

    Yu-Ke Wu & Heng-Yu Fan

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WYK wrote the manuscript and prepared the figures. FHY conceived and revised the manuscript.

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Wu, YK., Fan, HY. Revisiting ZAR proteins: the understudied regulator of female fertility and beyond. Cell. Mol. Life Sci. 79, 92 (2022). https://doi.org/10.1007/s00018-022-04141-4

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