Ptbp2 Controls an Alternative Splicing Network Required for Cell Communication during Spermatogenesis.
Ptbp2 Controls an Alternative Splicing Network Required for Cell Communication during Spermatogenesis.
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DOI：
10.1016/j.celrep.2017.05.089
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发表时间：
2017-06-20
期刊：
影响因子：
8.8
通讯作者：
Licatalosi DD
中科院分区：
文献类型：
--
作者：
Hannigan MM;Zagore LL;Licatalosi DD
选择性剪接在发育中起着重要作用。值得注意的是，与大多数完整组织相比，生精细胞表达更多的选择性剪接RNA，然而这些RNA的调控仍不清楚。在这里，我们的特点选择性剪接景观在精子发生过程中，并揭示了一个重要的功能，RNA结合蛋白Ptbp 2在这个高度调节的发展计划。我们发现，Ptbp 2控制着一个涉及细胞粘附，迁移和极性的基因网络，这表明Ptbp 2的剪接调节对于生殖细胞与支持细胞（精子发生所需的多功能体细胞）的通讯至关重要。事实上，Ptbp 2-消融在生殖细胞中导致的F-actin细胞骨架在Sertoli细胞的解体，表明选择性剪接调节是必要的细胞串扰在生殖细胞发育。总的来说，这些数据描绘了一个选择性剪接调控网络精子发生，控制它的剪接因子，其在生殖支持通信的生物学重要性。Hannigan等人描述了精子发生过程中的选择性剪接景观，并揭示了Ptbp 2在这种时间调节中的重要作用。此外，Ptbp 2的剪接调控是生殖细胞发育过程中正确调控贩运和细胞极性基因以及细胞通讯所必需的。
Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues, however regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis, and reveal an essential function for the RNA binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis). Indeed, Ptbp2-ablation in germ cells resulted in disorganization of the F-actin cytoskeleton in Sertoli cells, indicating that alternative splicing regulation is necessary for cellular crosstalk during germ cell development. Collectively, the data delineate an alternative splicing regulatory network essential for spermatogenesis, the splicing factor that controls it, and its biological importance in germ-Sertoli communication. Hannigan et al. characterize the alternative splicing landscape during spermatogenesis and reveal an essential role for Ptbp2 in this temporal regulation. Moreover, splicing regulation by Ptbp2 is required for proper regulation of trafficking and cell polarity genes, and cell communication during germ cell development.
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