4.8 Article

A male germ-cell-specific ribosome controls male fertility

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NATURE
卷 612, 期 7941, 页码 726-+

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NATURE PORTFOLIO
DOI: 10.1038/s41586-022-05508-0

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  1. National Key RD Program [2018YFC1003500, 2018YFA0106900, 2021YFC2700200]
  2. National Natural Science Foundation of China [31890784, 31830043]

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A sperm-specific ribosome with a specialized nascent polypeptide exit tunnel has been identified in mice, which plays a crucial role in regulating protein folding during sperm formation.
Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis(1,2). Male germ cell development involves complex translational regulation during sperm formation(3). 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, Ribosome(ST), that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (Ribosome(Core)) protein RPL39. Deletion of Ribosome(ST) 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 Ribosome(ST) features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with Ribosome(Core). Ribosome(ST) 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 Ribosome(ST) were not replaceable by Ribosome(Core). 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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