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
  • 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.

Products
Inhibitors & Agonists
Other Products