hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells

Shenglei Feng, Jinmei Li, Hui Wen, Kuan Liu, Yiqian Gui, Yujiao Wen, Xiaoli Wang and Shuiqiao Yuan ()
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Shenglei Feng: Huazhong University of Science and Technology
Jinmei Li: Huazhong University of Science and Technology
Hui Wen: Huazhong University of Science and Technology
Kuan Liu: Huazhong University of Science and Technology
Yiqian Gui: Huazhong University of Science and Technology
Yujiao Wen: Huazhong University of Science and Technology
Xiaoli Wang: Huazhong University of Science and Technology
Shuiqiao Yuan: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31364-7

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