The TDRD9-MIWI2 Complex Is Essential for piRNA-Mediated Retrotransposon Silencing in the Mouse Male Germline

Shoji, Masanobu; Tanaka, Takashi; Hosokawa, Mihoko; Reuter, M.; Stark, Alexander; Kato, Yuzuru; Kondoh, Gen; Okawa, Katsuya; Chujo, Takeshi; Suzuki, Tsutomu; Hata, Kenichiro; Martin, Sandra L.; Noce, Toshiaki; Kuramochi‐Miyagawa, Satomi; Nakano, Toru; Sasaki, Hidetada; Pillai, Ramesh S.; Nakatsuji, Norio; Chuma, Shinichiro

doi:10.1016/j.devcel.2009.10.012

Cited by 306 publications

(411 citation statements)

References 49 publications

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“…This phenotype was originally described for the methylationdeficient Dnmt3L mutant males (Bourc'his and Bestor, 2004), observed again in PIWI mutants (Carmell et al, 2007;Aravin et al, 2007b) and more recently recapitulated in mutations for proteins supporting the piRNA/ PIWI pathway, such as the Tudor domain-containing proteins TDRD1 and TDRD9 (Ollinger et al, 2008;Soper et al, 2008;Ma et al, 2009;Reuter et al, 2009;Shoji et al, 2009). Tudor domain-containing proteins assemble specialized RNA processing platforms in the cytoplasm of germ cells, to which they recruit PIWI proteins through their ability to bind symmetrically dimethylated arginines, a post-translational modification undergone by both MILI and MIWI2 (Aravin et al, 2009;Vagin et al, 2009;Wang et al, 2009;Shoji et al, 2009). As a whole, directed mutagenesis in mice has allowed the identification of nine proteins with a key role in safe guarding the male germline against TEs (Table 1 and Figure 1): Dnmt3L, Dnmt3A, MIWI2, MILI, Maelstrom (MAEL), TDRD1, TDRD9, GASZ and Tex19.1 (Testis expressed 19.1) (Ollinger et al, 2008;Soper et al, 2008;Ma et al, 2009).…”

Section: Te Silencing In the Germlinementioning

confidence: 99%

“…Contrary to flies and worms, which rely on the piRNA pathway but are devoid of genomic methylation, the mammalian germline combines both piRNA-induced degradation and DNA methylation to silence TEs. Their epistatic relationship explains why mutations in genes required for piRNA production, such as Mili, Miwi2, Tdrd1, Tdrd9 and Gasz, also affect the process of de novo methylation of TE elements in prospermatogonia (Carmell et al, 2007;Aravin et al, 2007b;Ma et al, 2009;Reuter et al, 2009;Shoji et al, 2009).…”

Section: Te Silencing In the Germlinementioning

confidence: 99%

“…Pi-bodies were recently shown to contain another important player of fetal piRNA biogenesis, the GASZ protein whose biochemical function is unknown (Germ cell protein with Ankyrin repeats, Sterile alpha motifs and Leucine Zipper) . Secondary antisense piRNAs are more prone to associate with MIWI2 proteins, which interact with other specialized Tudor proteins, TDRD9, and localize to distinct compartments called 'piP-bodies' (Aravin et al, 2009;Shoji et al, 2009). Exchange of sense and antisense piRNAs between pi-and piP-bodies intensifies and accelerates the degradation of TE transcripts, which eventually leads to the accumulation of TE-associated piRNAs in prospermatogonia.…”

Section: Te Silencing In the Germlinementioning

confidence: 99%

“…Females lacking any of the components mentioned above do not significantly reactivate TEs in their germline. It is noteworthy that Mili and Miwi2 mutant females are fertile even when harboring combined mutations (Carmell et al, 2007;Watanabe et al, 2008;Shoji et al, 2009). So what controls TE expression in oocytes?…”

Section: Te Silencing In the Germlinementioning

confidence: 99%

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Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

2010

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Retrotransposable elements comprise around 50% of the mammalian genome. Their activity represents a constant threat to the host and has prompted the development of adaptive control mechanisms to protect genome architecture and function. To ensure their propagation, retrotransposons have to mobilize in cells destined for the next generation. Accordingly, these elements are particularly well suited to transcriptional networks associated with pluripotent and germinal states in mammals. The relaxation of epigenetic control that occurs in the early developing germline constitutes a dangerous window in which retrotransposons can escape from host restraint and massively expand. What could be observed as risky behavior may turn out to be an insidious strategy developed by germ cells to sense retrotransposons and hold them back in check. Herein, we review recent insights that have provided a detailed picture of the defense mechanisms that concur toward retrotransposon silencing in mammalian genomes, and in particular in the germline. In this lineage, retrotransposons are hit at multiple stages of their life cycle, through transcriptional repression, RNA degradation and translational control. An organized cross-talk between PIWIinteracting small RNAs (piRNAs) and various nuclear and cytoplasmic accessories provides this potent and multilayered response to retrotransposon unleashing in early germ cells.

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Section: Te Silencing In the Germlinementioning

confidence: 99%

Section: Te Silencing In the Germlinementioning

confidence: 99%

Section: Te Silencing In the Germlinementioning

confidence: 99%

Section: Te Silencing In the Germlinementioning

confidence: 99%

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Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

2010

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“…The murine transposon-derived piRNAs share features with the Drosophila repeat-associated piRNAs and are also proposed to control transposable elements (Klattenhoff and Theurkauf 2008). In addition to PIWI proteins, other proteins such as GASZ, MOV10L1, Sun1, Tdrd9, and Tdrd1 are also required for biogenesis and/or stability of mouse piRNAs (Chi et al 2009;Ma et al 2009;Reuter et al 2009;Shoji et al 2009;Zheng et al 2010).…”

Section: Introductionmentioning

confidence: 99%

piRNA profiling during specific stages of mouse spermatogenesis

Gan

Lin²,

Zhang³

et al. 2011

RNA

111

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PIWI-interacting RNAs (piRNAs) are a class of small RNAs abundantly expressed in animal gonads. piRNAs that map to retrotransposons are generated by a ''ping-pong'' amplification loop to suppress the activity of retrotransposons. However, the biogenesis and function of other categories of piRNAs have yet to be investigated. In this study, we first profiled the expression of small RNAs in type A spermatogonia, pachytene spermatocytes, and round spermatids by deep sequencing. We then focused on the computational analysis of the potential piRNAs generated in the present study as well as other published sets. piRNAs mapping to retrotransposons, mRNAs, and intergenic regions had different length distributions and were differentially regulated in spermatogenesis. piRNA-generating mRNAs (PRMRs), whose expression positively correlated with their piRNA products, constituted one-third of the protein-coding genes and were evolutionarily conserved and enriched with splicing isoforms and antisense transcripts. PRMRs with piRNAs preferentially mapped to CDSs and 39 UTRs partitioned into three clusters differentially expressed during spermatogenesis and enriched with unique sets of functional annotation terms related to housekeeping activities as well as spermatogenesis-specific processes. Intergenic piRNAs were divided into 2992 clusters probably representing novel transcriptional units that have not been reported. The transcripts of a large number of genes involved in spermatogenesis are the precursors of piRNAs, and these genes are intricately regulated by alternative splicing and antisense transcripts. piRNAs, whose regulatory role in gene expression awaits to be identified, are clearly products of a novel regulatory process that needs to be defined.

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RNA Interference in Animals

Siomi¹

2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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The TDRD9-MIWI2 Complex Is Essential for piRNA-Mediated Retrotransposon Silencing in the Mouse Male Germline

Cited by 306 publications

References 49 publications

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

piRNA profiling during specific stages of mouse spermatogenesis

RNA Interference in Animals

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