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

Julien M. D. Legrand, Ai-Leen Chan, Hue M. La, Fernando J. Rossello, Minna-Liisa Änkö, Frances V. Fuller-Pace, Robin M. Hobbs (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Article number2278
Pages (from-to)1-21
Number of pages21
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 23 May 2019

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spermatogenesis
Spermatogonia
maintenance
Spermatogenesis
Genes
Maintenance
genes
Cells
RNA Helicases
knockout mice
Cell proliferation
fertility
Gene expression
splicing
gene expression
Transcription Factors
cdc Genes
Knockout Mice
Germ Cells
Fertility

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Legrand, Julien M. D. ; Chan, Ai-Leen ; La, Hue M. ; Rossello, Fernando J. ; Änkö, Minna-Liisa ; Fuller-Pace, Frances V. ; Hobbs, Robin M. / DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia. In: Nature Communications. 2019 ; Vol. 10, No. 1. pp. 1-21.
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abstract = "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.",
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DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia. / Legrand, Julien M. D.; Chan, Ai-Leen; La, Hue M.; Rossello, Fernando J.; Änkö, Minna-Liisa; Fuller-Pace, Frances V.; Hobbs, Robin M. (Lead / Corresponding author).

In: Nature Communications, Vol. 10, No. 1, 2278, 23.05.2019, p. 1-21.

Research output: Contribution to journalArticle

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