2. Academic Validation
  3. hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development

hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development

  • Nat Commun. 2026 Feb 12;17(1):2681. doi: 10.1038/s41467-026-69176-8.
Shumin Zhou # 1,  Dalin Liu # 1,  Shiming Gan # 2,  Ziqi Yu # 1,  Ruibao Su # 3,  Hao Zhou 1 4,  Jiaqi Zhang 5,  Haoran Xu 1,  Yifan Zhao 1 4,  Hua Zhang 6,  Zuoqi Deng 6,  Xuan Wu 6,  Chunhai Luo 1,  Yunlong Liu 1,  Shuiqiao Yuan 7,  Heng-Yu Fan 8 9,  Fei Sun 10 11
Affiliations

Affiliations

  • 1 Department of Urology & Andrology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Center for Reproductive Medicine, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University, Yiwu, China.
  • 3 Center for Reproductive Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 4 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 5 Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China.
  • 6 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
  • 7 Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 8 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
  • 9 Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 10 Department of Urology & Andrology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
  • 11 Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 41680151 DOI: 10.1038/s41467-026-69176-8
Abstract

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.

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