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hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells
Nature Communications ( IF 14.7 ) Pub Date : 2022-06-23 , DOI: 10.1038/s41467-022-31364-7
Shenglei Feng 1 , Jinmei Li 1 , Hui Wen 1 , Kuan Liu 1 , Yiqian Gui 1 , Yujiao Wen 1 , Xiaoli Wang 1 , Shuiqiao Yuan 1, 2, 3
Affiliation  

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.



中文翻译:

hnRNPH1 招募 PTBP2 和 SRSF3 来调节生殖细胞中的选择性剪接

替代前体 mRNA 剪接的协调调节对于生殖细胞发育至关重要。然而,在生殖细胞发育过程中控制替代 mRNA 表达的潜在分子机制仍然难以捉摸。在此,我们表明 hnRNPH1 在生殖系统中高度表达,并招募 PTBP2 和 SRSF3 来调节生殖细胞中的选择性剪接。条件性敲除生精细胞中的Hnrnph1会导致许多异常剪接事件,从而影响与减数分裂相关的基因以及生殖细胞和支持细胞之间的通讯。其特征是染色体不联会和胚芽-支持细胞通讯受损,最终导致雄性不育。显着地,Hnrnph1种系特异性突变的雌性小鼠也是不育的,Hnrnph1缺陷的卵母细胞表现出与Hnrnph1缺陷的雄性生殖细胞相似的缺陷突触和细胞-细胞连接。总的来说,我们的数据支持一个分子模型,其中 hnRNPH1 通过募集 PTBP2 和 SRSF3 来控制生殖细胞中的可变剪接事件网络。

更新日期:2022-06-23
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