Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31364-7
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Funding
- National Natural Science Foundation of China [81971444, 31900606, 31801237]
- Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals
- Chinese Academy of Sciences [FIRMSC200502 COV02]
- Science Technology and Innovation Commission of Shenzhen Municipality [JCYJ20170818160910316]
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This study reveals the mechanism of alternative splicing regulation by hnRNPH1 in germ cells and demonstrates its roles in both male and female germ cells, highlighting its importance in germ cell development.
Coordinated regulation of alternative splicing is essential for germ cell development. Here, the authors report that hnRNPH1 interacts with alternative splicing factors PTBP2 and SRSF3 in the germline to regulate pre-mRNA alternative splicing. Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the underlying molecular mechanism that controls alternative mRNA expression during germ cell development remains elusive. Herein, we show that hnRNPH1 is highly expressed in the reproductive system and recruits the PTBP2 and SRSF3 to modulate the alternative splicing in germ cells. Conditional knockout Hnrnph1 in spermatogenic cells causes many abnormal splicing events, thus affecting the genes related to meiosis and communication between germ cells and Sertoli cells. This is characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, which ultimately leads to male sterility. Markedly, Hnrnph1 germline-specific mutant female mice are also infertile, and Hnrnph1-deficient oocytes exhibit a similar defective synapsis and cell-cell junction as seen in Hnrnph1-deficient male germ cells. Collectively, our data support a molecular model wherein hnRNPH1 governs a network of alternative splicing events in germ cells via recruitment of PTBP2 and SRSF3.
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