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Publication : DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice.

First Author  Wang Z Year  2024
Journal  Development Volume  151
Issue  13 PubMed ID  38953252
Mgi Jnum  J:361552 Mgi Id  MGI:7859596
Doi  10.1242/dev.202579 Citation  Wang Z, et al. (2024) DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice. Development 151(13)
abstractText  Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.
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