The landscape of RNA binding proteins in mammalian spermatogenesis
Yang Li, yuanyuan wang, yuanyuan wang, Yue‐Qiu Tan, Qiuling Yue, Yueshuai Guo, Ruoyu Yan, Lanlan Meng, Huicong Zhai, Lingxiu Tong, Zihan Yuan, Wu Li, Cuicui Wang, Shenglin Han, Sen Ren, Yitong Yan, Weixu Wang, Lei Gao, Chen Tan, Tongyao Hu, Hao Zhang, Liya Liu, Pinglan Yang, Wanyin Jiang, Yiting Ye, Huanhuan Tan, Yanfeng Wang, Yanfeng Wang, Chenyu Lu, Xin Li, J. Xie, Gege Yuan, Yiqiang Cui, Bin Shen, Cheng Wang, Yichun Guan, Wei Li, Qinghua Shi, Ge Lin, Ting Ni, Zheng Sun, Lan Ye, Anastassios Vourekas, Xuejiang Guo, Mingyan Lin, Ke Zheng
Abstract
Despite continuous expansion of the RNA binding protein (RBP) world, there is a lack of systematic understanding of RBPs in the 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-cross-linked 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.