1. Academic Validation
  2. A male germ-cell-specific ribosome controls male fertility

A male germ-cell-specific ribosome controls male fertility

  • Nature. 2022 Dec;612(7941):725-731. doi: 10.1038/s41586-022-05508-0.
Huiling Li # 1 Yangao Huo # 2 3 Xi He # 1 Liping Yao # 1 Hao Zhang # 4 Yiqiang Cui # 1 Huijuan Xiao # 1 Wenxiu Xie 1 Dejiu Zhang 2 5 Yue Wang 1 Shu Zhang 1 Haixia Tu 1 Yiwei Cheng 1 Yueshuai Guo 1 Xintao Cao 2 5 Yunfei Zhu 1 Tao Jiang 2 5 Xuejiang Guo 6 Yan Qin 7 8 Jiahao Sha 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
  • 2 CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 School of Life Science and Engineering, Foshan University, Guangdong, China.
  • 4 Gusu School, Nanjing Medical University, Nanjing, China.
  • 5 University of Chinese Academy of Sciences, Beijing, China.
  • 6 State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. [email protected]
  • 7 CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [email protected]
  • 8 University of Chinese Academy of Sciences, Beijing, China. [email protected]
  • 9 State Key Laboratory of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China. [email protected]
  • # Contributed equally.
Abstract

Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis1,2. Male germ cell development involves complex translational regulation during sperm formation3. However, it remains unclear whether translation during sperm formation is performed by a specific ribosome. Here we report a ribosome with a specialized nascent polypeptide exit tunnel, RibosomeST, that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (RibosomeCore) protein RPL39. Deletion of RibosomeST in mice causes defective sperm formation, resulting in substantially reduced fertility. Our comparison of single-particle cryo-electron microscopy structures of ribosomes from mouse kidneys and testes indicates that RibosomeST features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with RibosomeCore. RibosomeST predominantly cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. Moreover, we found that specialized functions of RibosomeST were not replaceable by RibosomeCore. Taken together, identification of this sperm-specific ribosome should greatly expand our understanding of ribosome function and tissue-specific regulation of protein expression pattern in mammals.

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