Hannigan Molly M, Zagore Leah L, Licatalosi Donny D
Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.
Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.
Cell Rep. 2017 Jun 20;19(12):2598-2612. doi: 10.1016/j.celrep.2017.05.089.
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 filamentous actin (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.
可变剪接在发育过程中起着至关重要的作用。值得注意的是，与大多数全组织相比，生精细胞表达更多的可变剪接RNA；然而，这些RNA的调控机制仍不清楚。在这里，我们描绘了精子发生过程中的可变剪接图谱，并揭示了RNA结合蛋白Ptbp2在这个高度调控的发育程序中的重要功能。我们发现Ptbp2控制着一个涉及细胞黏附、迁移和极性的基因网络，这表明Ptbp2的剪接调控对于生殖细胞与支持细胞（精子发生所必需的多功能体细胞）之间的通讯至关重要。事实上，生殖细胞中Ptbp2的缺失导致支持细胞中丝状肌动蛋白（F-肌动蛋白）细胞骨架紊乱，这表明可变剪接调控对于生殖细胞发育过程中的细胞间相互作用是必要的。总的来说，这些数据描绘了一个对精子发生至关重要的可变剪接调控网络、控制它的剪接因子及其在生殖细胞-支持细胞通讯中的生物学重要性。
