DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

• Published in: Nature communications 2019-05, Vol.10 (1), p.2278-2278, Article 2278
• Main Authors: Legrand, Julien M. D., Chan, Ai-Leen, La, Hue M., Rossello, Fernando J., Änkö, Minna-Liisa, Fuller-Pace, Frances V., Hobbs, Robin M.
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/106; 13/31; 14/19; 38/15; 38/91; 631/136/2434/1822; 631/443/494; 631/532/2118; 64/60; 82/58; Animals; Cell cycle; Cell Cycle - genetics; Cell proliferation; Cell Proliferation - genetics; Cell self-renewal; Cell survival; Coculture Techniques; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DNA helicase; Embryo, Mammalian; Fertility; Fertility - genetics; Fibroblasts; Gene expression; Gene Expression Regulation - physiology; Genes; Germ cells; Humanities and Social Sciences; Maintenance; Male; Mice; Mice, Knockout; Models, Animal; multidisciplinary; Post-transcription; Primary Cell Culture; Promyelocytic Leukemia Zinc Finger Protein - metabolism; RNA helicase; RNA Splicing - physiology; Science; Science (multidisciplinary); Spermatogenesis; Spermatogenesis - genetics; Spermatogonia; Spermatogonia - metabolism; Splicing; Testis - cytology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09972-7

Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia. Sustained sperm production is dependent on activity of undifferentiated spermatogonia. Here, the authors demonstrate an essential role for RNA helicase DDX5 in maintenance of spermatogonia in adults through control of gene transcription plus RNA processing and export.