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Title

Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility

Authors
Zimmermann, Céline
Romero, Yannick
Warnefors, Maria
Bilican, Adem
Smith, Lee B
Kotaja, Noora
Kaessmann, Henrik
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Published in PLOS ONE. 2014, vol. 9, no. 9, p. e107023
Abstract 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.
Keywords AnimalsFertility/geneticsInfertility, Male/genetics/metabolismMaleMiceMice, KnockoutRNA, Small InterferingRNA-Binding Proteins/genetics/metabolismRibonuclease III/genetics/metabolismSpermatogenesis/geneticsSpermatozoa/metabolismTestis/metabolism
Identifiers
PMID: 25244517
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Article (Published version) (2.1 MB) - public document Free access
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Research group Mécanismes moléculaires et génétiques du développement sexuel (778)
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ZIMMERMANN, Céline et al. Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility. In: PLOS ONE, 2014, vol. 9, n° 9, p. e107023. https://archive-ouverte.unige.ch/unige:86819

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Deposited on : 2016-09-06

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