Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

Qianxing Zou; Lele Yang; Ruona Shi; Yuling Qi; Xiaofei Zhang; Huayu Qi

doi:10.1016/j.isci.2021.103396

Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

iScience. 2021 Oct 30;24(12):103396. doi: 10.1016/j.isci.2021.103396. eCollection 2021 Dec 17.

Authors

Qianxing Zou^{1

2

3

4}, Lele Yang^{1

2

3}, Ruona Shi^{1

2

3

5}, Yuling Qi^{1

2

3

4

6}, Xiaofei Zhang^{1

2

3

4

6}, Huayu Qi^{1

2

3

4}

Affiliations

¹ CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510630, China.
² Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510630, China.
³ Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510630, China.
⁴ University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China.
⁶ Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou 510630, China.

Abstract

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 Rpl39l 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, Rpl39l 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.

Keywords: Developmental biology; Male reproductive endocrinology; Molecular biology.