The landscape of RNA binding proteins in mammalian spermatogenesis

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.

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Publication Details

Journal
Science
Published
2024-08-29
DOI
https://doi.org/10.1126/science.adj8172
Citations
24
Primary Topic
RNA Research and Splicing
Type
article
Field-Weighted Citation Impact
5.61
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article

The landscape of RNA binding proteins in mammalian spermatogenesis

Yue‐Qiu Tan, Qinghua Shi, Anastassios Vourekas, Tongyao Hu et al.
24 citations
Science
RNA Research and Splicing
5.61
article

The landscape of RNA binding proteins in mammalian spermatogenesis

Yue‐Qiu Tan, Qinghua Shi, Anastassios Vourekas, Tongyao Hu, Pinglan Yang, yuanyuan wang, Huicong Zhai, Yiqiang Cui, Ruoyu Yan, Mingyan Lin, Ting Ni, Zihan Yuan, Sen Ren, Bin Shen, Huanhuan Tan, Cuicui Wang, Ke Zheng, Cheng Wang, Yichun Guan, Xuejiang Guo, Lei Gao, Yiting Ye, Chen Tan, J. Xie, Zheng Sun, Yueshuai Guo, Lingxiu Tong, Qiuling Yue, Shenglin Han, Wei Li, Hao Zhang, Yanfeng Wang, Liya Liu, Xin Li, Chenyu Lu, Weixu Wang, Lan Ye, Yang Li, Gege Yuan, Wu Li, Yitong Yan, Lanlan Meng, Ge Lin, Wanyin Jiang
article en
24 citations

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.

ScienceVol. 386(6720)
Louisiana State University (US), University of Science and Technology of China (CN), Central South University (CN), Baylor College of Medicine (US), Fudan University (CN), Helmholtz Zentrum München (DE), Reproductive & Genetic Hospital CITIC-Xiangya (CN), Hefei National Center for Physical Sciences at Nanoscale (CN), Nanjing Drum Tower Hospital (CN), National Engineering Research Center of Human Stem Cells (CN), Fuzhou Maternity and Child Health Care Hospital (CN), Third Affiliated Hospital of Zhengzhou University (CN), Changzhou No.2 People's Hospital (CN), Huashan Hospital (CN), State Key Laboratory of Genetic Engineering, Nanjing Medical University (CN), Northwest A&F University (CN), Guangzhou Medical University (CN)
Openalex Percentile: Top 3%
RNA Research and Splicing
5.61
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