Topaz1 , an essential gene for murine spermatogenesis, down-regulates the expression of numerous testis-specific long non-coding RNAs - Archive ouverte HAL Access content directly
Preprints, Working Papers, ... Year : 2021

Topaz1 , an essential gene for murine spermatogenesis, down-regulates the expression of numerous testis-specific long non-coding RNAs

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Abstract

Spermatogenesis involves coordinated processes, including meiosis, to produce functional gametes. We previously reported Topaz1 as a germ cell-specific gene highly conserved in vertebrates. Topaz1 knockout males are sterile with testes that lack haploid germ cells because of meiotic arrest after prophase I. To better characterize Topaz1 −/− testes, we used RNA-sequencing analyses at two different developmental stages (P16 and P18). The absence of TOPAZ1 disturbed the expression of genes involved in microtubule and/or cilium mobility, which was consistent with testicular histology showing the disruption of microtubules and centrosomes. Moreover, a quarter of P18 dysregulated genes are long non-coding RNAs (lncRNAs), and three of them are testis-specific and located in spermatocytes, their expression starting between P11 and P15. The suppression of one of them, 4930463O16Rik , did not alter fertility although sperm parameters were disturbed and sperm concentration fell. The transcriptome of P18- 4930463O16Rik −/− testes was altered and the molecular pathways affected included microtubule-based processes, the regulation of cilium movement and spermatogenesis. The absence of TOPAZ1 protein or 4930463O16Rik produced the same enrichment clusters in mutant testes despite a contrasted phenotype on male fertility. In conclusion, TOPAZ1 appeared to stabilize the expression of numerous lncRNAs. Its suppression is not essential for fertility but required during the terminal differentiation of male gametes. Author Summary The Topaz1 gene was initially characterized during the initiation of meiosis in the sheep fetal ovary. In order to determine its function, a KO of the murine gene was performed. In this species, only males were sterile and spermatogenesis was blocked before the first meiotic division. Here, we show that cytoskeletal elements are markedly disturbed in mutant testes, indicating that these elements play an important function in spermatogenesis. While the mitotic spindle of spermatogonia was normal, the meiotic spindle of spermatocytes was hemi-spindle-shaped and the homologous chromosome pairs could position themselves on the equatorial plate. In addition, lncRNAs account for 25% of genes whose expression in testes varies significantly in the absence of Topaz1 . This suggests a key role for these factors in spermatogenesis. Largely testis-specific, they may be involved in spermatogenesis and play a more or less critical role in mouse fertility, which probably also depends on their redundancies.
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hal-03805272 , version 1 (07-10-2022)

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Manon Chadourne, Elodie Poumerol, Luc Jouneau, Bruno Passet, Johan Castille, et al.. Topaz1 , an essential gene for murine spermatogenesis, down-regulates the expression of numerous testis-specific long non-coding RNAs. 2022. ⟨hal-03805272⟩
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