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Updated: Sep 19, 2025
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Determining the Role of Maternally-Expressed Genes in Early Development with Maternal Crispants
Published on: December 21, 2021
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IRE1α RNase activity is critical for early embryo development by degrading maternal transcripts
Chao Li1,2, Yong-Peng Tan2, Di Gao2
1Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Guangzhou 510317, China.
Nucleic Acids Research
|June 18, 2025
Summary
The unfolded protein response protein IRE1α is crucial for degrading maternal mRNA after fertilization, ensuring proper embryonic development and zygotic genome activation. This discovery reveals a new role for IRE1α in early embryogenesis.
Area of Science:
- Reproductive Biology
- Molecular Embryology
- RNA Biology
Background:
- Maternal mRNA degradation is vital during the maternal-to-zygotic transition.
- This degradation is linked to oocyte maturation, fertilization, and zygotic genome activation (ZGA).
Purpose of the Study:
- To investigate the role of the unfolded protein response (UPR) protein IRE1α in maternal mRNA degradation post-fertilization.
- To elucidate the molecular mechanism by which IRE1α regulates early embryonic development.
Main Methods:
- Utilized an IRE1α-Flag knock-in mouse model.
- Employed LACE-seq and in vitro analyses.
- Generated oocyte-specific IRE1α RNase domain deletion mutants.
Main Results:
- IRE1α is expressed in oocytes and early embryos, with translation dependent on the ERK1/2 pathway.
- Oocyte-specific deletion of IRE1α's RNase domain caused female infertility and embryonic arrest.
- IRE1α directly binds and cleaves maternal mRNAs post-fertilization, essential for ZGA and histone modifications.
Conclusions:
- IRE1α plays a critical, previously unrecognized role in maternal mRNA decay after fertilization.
- This function is independent of the canonical IRE1α-XBP1 signaling pathway.
- IRE1α-mediated decay is essential for successful early embryonic development and zygotic genome activation.
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