Zou Qianxing, Yang Lele, Shi Ruona, Qi Yuling, Zhang Xiaofei, Qi Huayu
CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510630, China.
Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510630, China.
iScience. 2021 Oct 30;24(12):103396. doi: 10.1016/j.isci.2021.103396. eCollection 2021 Dec 17.
Maintaining proteostasis is important for animal development. How proteostasis influences spermatogenesis that generates male gametes, spermatozoa, is not clear. We show that testis-specific paralog of ribosomal large subunit protein RPL39, RPL39L, is required for mouse spermatogenesis. Deletion of in mouse caused reduced proliferation of spermatogonial stem cells, malformed sperm mitochondria and flagella, leading to sub-fertility in males. Biochemical analyses revealed that lack of RPL39L deteriorated protein synthesis and protein quality control in spermatogenic cells, partly due to reduced biogenesis of ribosomal subunits and ribosome homeostasis. RPL39/RPL39L is likely assembled into ribosomes via H/ACA domain containing NOP10 complex early in ribosome biogenesis pathway. Furthermore, null mice exhibited compromised regenerative spermatogenesis after chemical insult and early degenerative spermatogenesis in aging mice. These data demonstrate that maintaining proteostasis is important for spermatogenesis, of which ribosome homeostasis maintained by ribosomal proteins coordinates translation machinery to the regulation of cellular growth.
维持蛋白质稳态对动物发育至关重要。蛋白质稳态如何影响产生雄性配子精子的精子发生尚不清楚。我们发现核糖体大亚基蛋白RPL39的睾丸特异性旁系同源物RPL39L是小鼠精子发生所必需的。在小鼠中缺失RPL39L会导致精原干细胞增殖减少、精子线粒体和鞭毛畸形，从而导致雄性生育力下降。生化分析表明，缺乏RPL39L会使生精细胞中的蛋白质合成和蛋白质质量控制恶化，部分原因是核糖体亚基的生物合成减少和核糖体稳态受损。RPL39/RPL39L可能在核糖体生物发生途径早期通过含有NOP10复合物的H/ACA结构域组装到核糖体中。此外，RPL39L基因敲除小鼠在化学损伤后再生精子发生受损，在衰老小鼠中精子发生早期退化。这些数据表明，维持蛋白质稳态对精子发生很重要，其中由核糖体蛋白维持的核糖体稳态将翻译机制与细胞生长调节相协调。
