RNA processing in the male germline: Mechanisms and implications for fertility

Legrand, Julien M. D.; Hobbs, Robin M.

doi:10.1016/j.semcdb.2017.10.006

Cited by 32 publications

(29 citation statements)

References 159 publications

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“…1d). Next, we observed DDX5 expression localised to the nuclei of GFRα1-positive (self-renewing, A s and A pr ) 3 , SOX3-positive (committed progenitor, A al ) 8 , and c-KIT-positive (differentiating) 1,9 spermatogonia, with GILZ used as a broad spermatogonial marker 37 (Fig. 1a, e).…”

Section: Resultsmentioning

confidence: 86%

“…The balance between stem cell self-renewal and differentiation can be regulated through extrinsic stimuli, including growth factors produced in a supportive niche, as well as cell intrinsic factors such as transcription factors and post-transcriptional gene regulatory mechanisms. The mammalian testis is an example of such a tissue where tightly co-ordinated transcriptional and post-transcriptional mechanisms harmonise to ensure lifelong maintenance of fertility through the continual production of mature spermatozoa 1 .…”

Section: Introductionmentioning

confidence: 99%

“…During spermatogenesis, undifferentiated spermatogonia undergo mitotic divisions followed by induction of differentiation that ultimately results in production of meiotic spermatocytes. After two meiotic reduction divisions, round spermatids are formed that undergo significant morphological changes during a process known as spermiogenesis to ultimately produce haploid spermatozoa 1 . The entire process of spermatogenesis occurs within seminiferous tubules of the testis and is supported by Sertoli cells, essential somatic components that produce GDNF, a growth factor critical for spermatogonial maintenance 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Besides regulation at the transcriptional level, periods of transcriptional quiescence occurring in spermatogenesis during meiotic homologous recombination and spermiogenesis necessitates post-transcriptional regulation of gene expression 1 . Numerous regulators of alternative pre-mRNA splicing, mRNA export and stability, as well as translational control have been shown to be essential for timely gene expression during spermatogenesis 1 . The RNA-binding protein NANOS2 maintains the undifferentiated state of spermatogonia by recruiting differentiation-associated mRNAs to ribonucleoprotein complexes and inhibiting their translation 19 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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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Section: Resultsmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Spermatogenesis is a highly regulated process with many genes tightly controlling the different maturation steps (Legrand and Hobbs 2017) and playing a role in the sperm's fertility potential (Jodar et al 2015). Our study in 190 samples suggests that the sperm quality parameters that we assessed are independent of the amount of RNA recoveredas a proxy of RNA loadper sperm cell.…”

Section: Discussionmentioning

confidence: 78%

A technical assessment of the porcine ejaculated spermatozoa for a sperm-specific RNA-seq analysis

Gòdia

Mayer

Nafissi

et al. 2018

Systems Biology in Reproductive Medicine

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FPKM: fragments per kilobase of transcript per million mapped reads; KRT1: keratin 1; miRNA: micro-RNA; miscRNA: miscellaneous RNA; Mt rRNA: mitochondrial ribosomal RNA; Mt tRNA: mitochondrial transference RNA; OAZ3: ornithine decarboxylase antizyme 3; ORT: osmotic resistance test; piRNA: Piwi-interacting RNA; PRM1: protamine 1; PTPRC: protein tyrosine phosphatase receptor type C; rRNA: ribosomal RNA; snoRNA: small nucleolar RNA; snRNA: small nuclear RNA; SRR: sperm recovery rate; tRNA: transfer RNA.

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CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing

Wang,

Cai,

et al. 2024

Advanced Science

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The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis.

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RNA processing in the male germline: Mechanisms and implications for fertility

Cited by 32 publications

References 159 publications

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

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

A technical assessment of the porcine ejaculated spermatozoa for a sperm-specific RNA-seq analysis

CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing

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