hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells.
hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells.
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hnRNPH1 招募 PTBP2 和 SRSF3 来调节生殖细胞中的选择性剪接
DOI：
10.1038/s41467-022-31364-7
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发表时间：
2022-06-23
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
选择性前体mRNA剪接的协调调节对于生殖细胞发育是必不可少的。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，我们发现hnRNPH 1在生殖系统中高度表达，并招募PTBP 2和SRSF 3来调节生殖细胞中的选择性剪接。生精细胞中的条件性敲除Hnrnph 1引起许多异常剪接事件，从而影响减数分裂相关基因以及生殖细胞与支持细胞之间的通讯。其特征是染色体不联会和生殖细胞-支持细胞通讯受损，最终导致雄性不育。明显地，Hnrnph 1生殖系特异性突变的雌性小鼠也是不育的，并且Hnrnph 1缺陷的卵母细胞表现出类似于在Hnrnph 1缺陷的雄性生殖细胞中所见的有缺陷的突触和细胞-细胞连接。总的来说，我们的数据支持一个分子模型，其中hnRNPH 1通过招募PTBP 2和SRSF 3来管理生殖细胞中的选择性剪接事件网络。选择性剪接的协调调节对生殖细胞发育至关重要。在这里，作者报告说，hnRNPH 1与选择性剪接因子PTBP 2和SRSF 3在种系中相互作用，以调节前mRNA选择性剪接。
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. 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.
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影响因子：
8.8
作者：
Hannigan MM;Zagore LL;Licatalosi DD
通讯作者：
Licatalosi DD
影响因子：
16.6
作者：
Liu W;Wang F;Xu Q;Shi J;Zhang X;Lu X;Zhao ZA;Gao Z;Ma H;Duan E;Gao F;Gao S;Yi Z;Li L
通讯作者：
Li L
影响因子：
64.5
作者：
Ji X;Zhou Y;Pandit S;Huang J;Li H;Lin CY;Xiao R;Burge CB;Fu XD
通讯作者：
Fu XD
影响因子：
9
作者：
Cesari, Eleonora;Loiarro, Maria;Sette, Claudio
通讯作者：
Sette, Claudio
影响因子：
7.7
作者：
Felipe-Medina, Natalia;Caburet, Sandrine;Pendas, Alberto M.
通讯作者：
Pendas, Alberto M.