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hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development.
Shumin Zhou1, Dalin Liu1, Shiming Gan2
1Department of Urology & Andrology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Nature Communications
|February 12, 2026
Summary
Heterogeneous nuclear ribonucleoprotein M (hnRNPM) is crucial for mouse oocyte development and female fertility. Its absence causes meiotic arrest and infertility by disrupting alternative splicing regulation.
Area of Science:
- Reproductive biology
- Molecular genetics
- RNA biology
Background:
- Oocytes require maternal mRNA for development, but regulatory mechanisms are poorly understood.
- Alternative splicing is vital for oocyte maturation and the maternal-to-zygotic transition.
Purpose of the Study:
- To identify key regulators of alternative splicing in mouse oocytes.
- To elucidate the role of hnRNPM in oocyte development and female fertility.
Main Methods:
- Genetic ablation of hnRNPM in mice.
- SCAN-seq to identify transcript isoforms and splicing events.
- LACE-seq to map hnRNPM binding sites.
- Co-immunoprecipitation to study protein interactions.
Main Results:
- hnRNPM deficiency causes severe oocyte defects, meiotic arrest, and infertility.
- hnRNPM regulates alternative splicing of numerous genes in oocytes.
- hnRNPM binds pre-mRNA and interacts with BCAS2 to control splicing fidelity.
Conclusions:
- hnRNPM is essential for mammalian oocyte development and female fertility.
- hnRNPM plays a critical role in regulating alternative splicing networks during oogenesis.
- This study reveals a novel regulatory mechanism for maternal mRNA fate in oocytes.
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