Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility
| Autor: | Yannick Romero, Henrik Kaessmann, Maria Warnefors, Christelle Borel, Adem Bilican, Lee B. Smith, Céline Zimmermann, Serge Nef, Noora Kotaja |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Ribonuclease III Sexual Reproduction Small interfering RNA Physiology Organogenesis lcsh:Medicine RNA-binding protein Spermatocyte Mice Animal Cells Gene expression Testis Ribonuclease III/genetics/metabolism ddc:576.5 Cell Cycle and Cell Division RNA Small Interfering lcsh:Science Mice Knockout Multidisciplinary biology RNA-Binding Proteins Spermatozoa Meiosis medicine.anatomical_structure Cell Processes Cellular Types Germ cell Research Article Testes Development Infertility Male/genetics/metabolism ta3111 microRNA medicine Animals RNA-Binding Proteins/genetics/metabolism Spermatogenesis Infertility Male Spermatogenesis/genetics Spermatozoa/metabolism lcsh:R Biology and Life Sciences Cell Biology Molecular biology Fertility Germ Cells Testis/metabolism biology.protein Fertility/genetics lcsh:Q Physiological Processes Organism Development Dicer Developmental Biology |
| Zdroj: | PLoS ONE PLOS ONE, Vol. 9, No 9 (2014) P. e107023 Zimmermann, C, Romero, Y, Warnefors, M, Bilican, A, Borel, C, Smith, L B, Kotaja, N, Kaessmann, H & Nef, S 2014, ' Germ Cell-Specific Targeting of DICER or DGCR8 Reveals a Novel Role for Endo-siRNAs in the Progression of Mammalian Spermatogenesis and Male Fertility ', PLoS ONE, vol. 9, no. 9, e107023, pp. e107023 . https://doi.org/10.1371/journal.pone.0107023 PLoS ONE, Vol 9, Iss 9, p e107023 (2014) PLoS One, vol. 9, no. 9, pp. e107023 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0107023 |
| Popis: | Small non-coding RNAs act as critical regulators of gene expression and are essential for male germ cell development and spermatogenesis. Previously, we showed that germ cell-specific inactivation of Dicer1, an endonuclease essential for the biogenesis of micro-RNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), led to complete male infertility due to alterations in meiotic progression, increased spermatocyte apoptosis and defects in the maturation of spermatozoa. To dissect the distinct physiological roles of miRNAs and endo-siRNAs in spermatogenesis, we compared the testicular phenotype of mice with Dicer1 or Dgcr8 depletion in male germ cells. Dgcr8 mutant mice, which have a defective miRNA pathway while retaining an intact endo-siRNA pathway, were also infertile and displayed similar defects, although less severe, to Dicer1 mutant mice. These included cumulative defects in meiotic and haploid phases of spermatogenesis, resulting in oligo-, terato-, and azoospermia. In addition, we found by RNA sequencing of purified spermatocytes that inactivation of Dicer1 and the resulting absence of miRNAs affected the fine tuning of protein-coding gene expression by increasing low level gene expression. Overall, these results emphasize the essential role of miRNAs in the progression of spermatogenesis, but also indicate a role for endo-siRNAs in this process. |
| Databáze: | OpenAIRE |
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