南京医科大学郑科、郭雪江、林明焰等在研究中取得进展。他们揭示了哺乳动物精子发生过程中RNA结合蛋白（RBP）图谱。2024年8月29日出版的《科学》发表了这项成果。

研究人员利用RNA相互作用组捕获技术研究了小鼠雄性生殖细胞，并建立了一个以精子发生过程中多层动态变化为特征的RBP图谱。对RNA交联肽的捕获表明，谷氨酸-精氨酸（ER）基序-一种存在于卷曲螺旋中的残基进化多聚酶元件-增强了其宿主RBPs的RNA结合能力。

在NONO（含非POU结构域的八聚体结合蛋白）中缺失这一元件会导致有丝分裂到减数分裂的转变出现缺陷，原因是NONO与RNA的相互作用受到了影响。对1000多名男性不育患者进行的全基因组测序揭示了RBPs在男性不育这一人类遗传结构中的重要作用，并确定了风险ER基序变体。

据悉，尽管RNA结合蛋白的研究范围不断扩大，但人们对哺乳动物睾丸中的RBP还缺乏系统了解，而睾丸是最复杂的组织转录组之一。

附：英文原文

Title: The landscape of RNA-binding proteins in mammalian spermatogenesis

Author: Yang Li, 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, Chenyu Lu, Xin Li, Jie Xie, Gege Yuan, Yiqiang Cui, Bin Shen, Cheng Wang, Yichun Guan, Wei Li, Qinghua Shi, Ge Lin, Ting Ni, Zheng Sun, Lan Ye, Anastasios Vourekas, Xuejiang Guo, Mingyan Lin, Ke Zheng

Issue&Volume: 2024-08-29

Abstract: 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.

DOI: adj8172

Source: https://www.science.org/doi/10.1126/science.adj8172