Despite continuous expansion of the RNA-binding protein (RBP) world, there is a lack of systematic understanding of RBPs in mammalian testis, which harbors one of the most complex tissue transcriptomes. We adapted RNA interactome capture to mouse male germ cells, building an RBP atlas characterized by multiple layers of dynamics along spermatogenesis. Trapping of RNA-crosslinked peptides showed that the glutamic acid-arginine (ER) patch, a residue-coevolved polyampholytic element present in coiled-coils, enhances RNA binding of its host RBPs. Deletion of this element in NONO (non-POU domain-containing octamer-binding protein) led to a defective mitosis-to-meiosis transition due to compromised NONO-RNA interactions. Whole-exome sequencing of over 1000 infertile men revealed a prominent role of RBPs in the human genetic architecture of male infertility and identified risk ER patch variants.

中文翻译：

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哺乳动物精子发生中 RNA 结合蛋白的景观


尽管 RNA 结合蛋白 （RBP） 世界不断扩大，但对哺乳动物睾丸中的 RBP 缺乏系统的认识，而哺乳动物睾丸拥有最复杂的组织转录组之一。我们将 RNA 相互作用组捕获适应小鼠雄性生殖细胞，构建了一个 RBP 图谱，其特征是沿精子发生多层动力学。RNA 交联肽的捕获表明，谷氨酸-精氨酸 （ER） 贴片是一种存在于卷曲螺旋中的残基共进化的两性溶解元件，可增强其宿主 RBP 的 RNA 结合。由于 NONO-RNA 相互作用受损，在 NONO（不含 POU 结构域的八聚体结合蛋白）中缺失该元件导致有丝分裂到减数分裂转变有缺陷。对 1000 多名不育男性的全外显子组测序揭示了 RBPs 在男性不育症的人类遗传结构中的突出作用，并确定了风险 ER 斑片变异。