A male germ-cell-specific ribosome controls male fertility

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 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, 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.