iScience
Volume 24, Issue 12, 17 December 2021, 103396
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Article
Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

https://doi.org/10.1016/j.isci.2021.103396Get rights and content
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open access

Highlights

  • Rpl39l deletion causes reduced spermatogenesis and subfertility in male mice

  • SSC proliferation, mitochondria and sperm flagella compromised in Rpl39l–/– mice

  • Rpl39l deletion affects ribosomal LSU formation and protein quality control

  • Aberrant proteostasis affects spermatogenesis and regeneration

Summary

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.

Subject areas

Molecular biology
Male reproductive endocrinology
Developmental biology

Data and code availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository (www.iprox.org) (Ma et al., 2019) with the dataset identifier PXD029274. The processed LC-MS/MS data are included in Table S3. Proteins identified from GST pulled-down assays, related to Figure 4, Table S4. Differentially expressed proteins between Rpl39l null and wild type testes identified by LC-MS/MS, related to Figure 5, Table S5. Differentially expressed proteins in enriched mitochondria of Rpl39l null and wild type testes (FC > 2, p < 0.05), related to Figure 6. Original western blot images have been deposited at Mendeley and are publicly available as of the date of publication. The DOI is listed in the key resources table. Microscopy data reported in this paper will be shared by the lead contact upon request.

This study does not generate original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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