The landscape of RNA binding proteins in mammalian spermatogenesis

• 成果类型: Article
• 署名作者: Li, Yang; Wang, Yuanyuan; Tan, Yue-Qiu; Yue, Qiuling; Guo, Yueshuai; Yan, Ruoyu; Meng, Lanlan; Zhai, Huicong; Tong, Lingxiu; Yuan, Zihan; Li, Wu; Wang, Cuicui; Han, Shenglin; Ren, Sen; Yan, Yitong; Wang, Weixu; Gao, Lei; Tan, Chen; Hu, Tongyao; Zhang, Hao; Liu, Liya; Yang, Pinglan; Jiang, Wanyin; Ye, Yiting; Tan, Huanhuan; Wang, Yanfeng; Lu, Chenyu; Li, Xin; Xie, Jie; Yuan, Gege; Cui, Yiqiang; Shen, Bin; Wang, Cheng; Guan, Yichun; Li, Wei; Shi, Qinghua; Lin, Ge; Ni, Ting; Sun, Zheng; Ye, Lan; Vourekas, Anastasios; Guo, Xuejiang; Lin, Mingyan; Zheng, Ke
• 署名单位: Nanjing Medical University; Nanjing Medical University; Central South University; Nanjing University; Northwest A&F University - China; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Nanjing Medical University; Zhengzhou University; Guangzhou Medical University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Fudan University; Fudan University; Baylor College of Medicine; Louisiana State University System; Louisiana State University; Nanjing Medical University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12195
• DOI: 10.1126/science.adj8172
• 发表日期: 2024-10-25
• 关键词: spermatogonial stem-cells; messenger-rna; structural basis; chromatoid body; gene-expression; bound proteome; identification; transcriptome; RECOGNITION; domains

摘要

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.