Article

MIWI2 Is Essential for Spermatogenesis and Repression of Transposons in the Mouse Male Germline

Cold Spring Harbor Laboratory, Howard Hughes Medical Institute, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Developmental Cell (Impact Factor: 10.37). 04/2007; 12(4):503-14. DOI: 10.1016/j.devcel.2007.03.001
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ABSTRACT Small RNAs associate with Argonaute proteins and serve as sequence-specific guides for regulation of mRNA stability, productive translation, chromatin organization, and genome structure. In animals, the Argonaute superfamily segregates into two clades. The Argonaute clade acts in RNAi and in microRNA-mediated gene regulation in partnership with 21-22 nt RNAs. The Piwi clade, and their 26-30 nt piRNA partners, have yet to be assigned definitive functions. In mice, two Piwi-family members have been demonstrated to have essential roles in spermatogenesis. Here, we examine the effects of disrupting the gene encoding the third family member, MIWI2. Miwi2-deficient mice display a meiotic-progression defect in early prophase of meiosis I and a marked and progressive loss of germ cells with age. These phenotypes may be linked to an inappropriate activation of transposable elements detected in Miwi2 mutants. Our observations suggest a conserved function for Piwi-clade proteins in the control of transposons in the germline.

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    • "In model organisms like Drosophila and zebrafish, Piwi proteins and piRNAs are essential during both spermatogenesis and oogenesis (Ketting, 2011). Strikingly, none of the murine Piwi proteins affect female fertility (Carmell et al., 2007; Deng and Lin, 2002; Kuramochi-Miyagawa et al., 2004). Mouse oocytes do express Piwi proteins (Aravin et al., 2008; Ding et al., 2013; Lim et al., 2013), but only relatively minor amounts of piRNAs have been detected (Tam et al., 2008; Watanabe et al., 2008). "
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    ABSTRACT: Germ cells of most animals critically depend on piRNAs and Piwi proteins. Surprisingly, piRNAs in mouse oocytes are relatively rare and dispensable. We present compelling evidence for strong Piwi and piRNA expression in oocytes of other mammals. Human fetal oocytes express PIWIL2 and transposon-enriched piRNAs. Oocytes in adult human ovary express PIWIL1 and PIWIL2, whereas those in bovine ovary only express PIWIL1. In human, macaque, and bovine ovaries, we find piRNAs that resemble testis-borne pachytene piRNAs. Isolated bovine follicular oocytes were shown to contain abundant, relatively short piRNAs that preferentially target transposable elements. Using label-free quantitative proteome analysis, we show that these maturing oocytes strongly and specifically express the PIWIL3 protein, alongside other, known piRNA-pathway components. A piRNA pool is still present in early bovine embryos, revealing a potential impact of piRNAs on mammalian embryogenesis. Our results reveal that there are highly dynamic piRNA pathways in mammalian oocytes and early embryos.
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    • "Enigmatically, experiments on mouse and rat suggest that in mammals Piwi proteins and piRNAs are expressed mainly in the male germline. This is in line with the fact that male mice Piwi knockouts show increased transposon activity paired with sterility while females do not (Deng and Lin 2002; Kuramochi-Miyagawa et al. 2004; Carmell et al. 2007). On the other hand endo-siRNAs were observed to act in mouse oocytes (Tam et al. 2008; Watanabe et al. 2008), promoting the assumption that the siRNA-pathway took over piRNA-pathway function in the mammalian female germline. "
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    • "Of note, PIWI subfamilies of Argonaut proteins such as HIWI, HIWI2, HIWI3 and HILI have key functions in transposon silencing pathways. Moreover, several of these proteins are expressed in male gonad in specifically and showing biological functions in the germ line development (Carmell et al., 2007). Furthermore, any deficiency of these proteins maybe leads to aberrant male germ line cells development during spermatogenesis . "
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