hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development
Growing oocytes accumulate maternal mRNA to support subsequent meiotic maturation and maternal-to-zygotic transition. However, the regulatory mechanisms governing the fate of these maternal mRNAs remain largely unknown. Here, we identified heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a critical regulator of pre-mRNA alternative splicing during mouse oocyte development. Genetic ablation of hnRNPM leads to severe cytoplasmic defects, meiotic arrest, and complete female infertility. Using SCAN-seq, we uncovered novel transcript isoforms and systematically characterized hnRNPM-regulated alternative splicing events. Furthermore, LACE-seq revealed hnRNPM-binding sites at single-nucleotide resolution in oocytes, linking its RNA-binding activity to splicing fidelity. Additionally, hnRNPM interacts with BCAS2, a known splicing factor critical for oocyte development, and modulates its binding to pre-mRNA loci to precisely control the alternative splicing. Overall, our study not only uncover an essential role of hnRNPM in mammalian oocyte development and female fertility but also unveils a critical regulatory network governing alternative splicing during oocyte development.
Authors
- Shiming Gan (ORCID: https://orcid.org/0000-0002-7508-4910)
- Yunlong Liu (ORCID: https://orcid.org/0000-0003-2158-4343)
- Ziqi Yu
- Fei Sun (ORCID: https://orcid.org/0000-0003-3562-1176)
- Haitao Zhang (ORCID: https://orcid.org/0000-0002-1639-4089)
- Hao Zhou (ORCID: https://orcid.org/0009-0005-2872-7097)
- Xuan Wu (ORCID: https://orcid.org/0000-0003-0239-7999)
- Chunhai Luo (ORCID: https://orcid.org/0000-0002-1490-7258)
- Heng-Yu Fan
- Ruibao Su
- Shuiqiao Yuan
- J Zhang
- Yifan Zhao
- Dalin Liu
- Zuoqi Deng
- Haoran Xu
- Shumin Zhou
Institutions
- Zhejiang International Studies University (CN)
- Army Medical University (CN)
- Jinan University (CN)
- Sir Run Run Shaw Hospital (CN)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Southwest Hospital (CN)
- Zhejiang University-University of Edinburgh Institute (CN)
- Hangzhou Medical College (CN)
- Huazhong University of Science and Technology (CN)
- Zhejiang University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-12
- DOI
- https://doi.org/10.1038/s41467-026-69176-8
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Agricultural University
- Chinese Academy of Sciences
- Zhejiang University
- Servier
- Directorate for Biological Sciences
- Institute of Zoology, Chinese Academy of Sciences