ArticleNucleic acids research2025
IRE1α RNase activity is critical for early embryo development by degrading maternal transcripts.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- When Fertilization Is Not Enough: Maternal-Zygotic Transition as a Determinant of Embryo Competence in IVF.International journal of molecular sciences · 2026Review
- Inhibition of IRE1α kinase increases ferroptosis resistance in triple-negative breast cancer cells.Oncology letters · 2026Article
- From the Understanding of Maternal Molecules and Mechanisms to Predicting Embryonic Development.Reproductive medicine and biologyReview
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Authors and funding
13 authors.
Funding
Abstract
During maternal-to-zygotic transition, oocytes and embryos undergo massive maternal mRNA degradation. Three key events are related to RNA degradation: oocyte meiotic resumption, fertilization, and zygotic genome activation (ZGA). In this study, we unexpectedly discover that the UPR (unfolded protein response) protein IRE1α is critical for post-fertilization maternal messenger mRNA (mRNA) degradation. IRE1α is specifically expressed from the metaphase II oocytes to four-cell embryos, with its translation dependent on the ERK1/2 pathway. Oocyte-specific deletion of the IRE1α RNase domain resulted in female infertility, characterized by embryonic developmental arrest at the one-cell or two-cell stage, and failure to degrade maternal mRNAs destined for elimination. Using IRE1α-Flag knock-in mouse model and LACE-seq, as well as in vitro analysis, we show that IRE1α can directly bind and cleave maternal mRNAs after fertilization. Moreover, IRE1α-mediated mRNA decay is essential for ZGA and histone modifications. This study unveils an important function of IRE1α in early embryonic development through regulated IRE1α-dependent decay, independent of the canonical IRE1α-XBP1 signaling pathway, thereby revealing a novel molecular mechanism underlying maternal mRNA degradation triggered by fertilization.
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Registered trials
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