小柯机器人

南京医科大学沙家豪等研究人员合作发现，一个雄性生殖细胞特有的核糖体控制雄性的生育能力。相关论文于2022年12月14日在线发表在《自然》杂志上。

研究人员报告了一个具有专门新生多肽出口通道的核糖体——Ribosome^ST，它与雄性生殖细胞特异性蛋白RPL39L组装在一起，这是核心核糖体（Ribosome^Core）蛋白RPL39的旁系同源物。小鼠体内Ribosome^ST的缺失会导致精子形成缺陷，从而导致生育能力大幅下降。研究人员对来自小鼠肾脏和睾丸核糖体的单颗粒冷冻电镜结构的比较表明，与Ribosome^Core相比，Ribosome^ST具有一个具有不同大小和电荷状态的核糖体多肽出口通道。Ribosome^ST主要通过共翻译方式调控雄性生殖细胞特异性蛋白子集的折叠，这些蛋白对精子的形成至关重要。此外，研究人员发现Ribosome^ST的专门功能不能被Ribosome^Core取代。总之，这种精子特异性核糖体的鉴定应极大地扩展人们对核糖体功能和哺乳动物蛋白质表达模式的组织特异性调节的理解。

据介绍，核糖体是高度复杂的翻译机器，已被证明在调节蛋白质合成方面具有异质性。雄性生殖细胞的发育涉及精子形成过程中复杂的翻译调节。然而，目前仍不清楚精子形成过程中的翻译是否由一个特定的核糖体完成。

附：英文原文

Title: A male germ-cell-specific ribosome controls male fertility

Author: Li, Huiling, Huo, Yangao, He, Xi, Yao, Liping, Zhang, Hao, Cui, Yiqiang, Xiao, Huijuan, Xie, Wenxiu, Zhang, Dejiu, Wang, Yue, Zhang, Shu, Tu, Haixia, Cheng, Yiwei, Guo, Yueshuai, Cao, Xintao, Zhu, Yunfei, Jiang, Tao, Guo, Xuejiang, Qin, Yan, Sha, Jiahao

Issue&Volume: 2022-12-14

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.

DOI: 10.1038/s41586-022-05508-0

Source: https://www.nature.com/articles/s41586-022-05508-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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