Separation of stem cell maintenance and transposon silencing functions of Piwi protein

Klenov, Mikhail S.; Sokolova, Olesya; Yakushev, E. Y.; Stolyarenko, Anastasia D.; Mikhaleva, Elena A.; Lavrov, Sergey; Гвоздев, В. А.

doi:10.1073/pnas.1106676108

Cited by 172 publications

(185 citation statements)

References 56 publications

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“…These congruent findings across species underscore the distinct and conserved nuclear function of Piwi proteins that is independent of their slicer activity. There are multiple lines of evidence supporting the notion that transposon silencing is regulated by the Piwi-piRNA complex in the nucleus (8,28). The association of Piwi with chromatin and with epigenetic factors offers an attractive model for transposon repression via an epigenetic mechanism guided by piRNA sequence-specific recognition of the target transposon sequences (17,18).…”

Section: Discussionmentioning

confidence: 98%

“…Piwi proteins are paralogs of Argonaute proteins, sharing the same domain architecture and the property of binding small noncoding RNAs (2)(3)(4)(5)(6). Argonaute proteins bind to small interfering RNAs (siRNAs) or microRNAs (miRNAs) and are effectors of RNA interference (RNAi) and miRNA pathways; conversely, Piwi proteins bind to Piwi-interacting RNAs (piRNAs) and are involved in the piRNA pathway in both the germ line and soma during gametogenesis (1,7,8).…”

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confidence: 99%

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Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity

Darricarrère

Liu

Watanabe

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The Piwi protein subfamily is essential for Piwi-interacting RNA (piRNA) biogenesis, transposon silencing, and germ-line development, all of which have been proposed to require Piwi endonuclease activity, as validated for two cytoplasmic Piwi proteins in mice. However, recent evidence has led to questioning of the generality of this mechanism for the Piwi members that reside in the nucleus. Drosophila offers a distinct opportunity to study the function of nuclear Piwi proteins because, among three Drosophila Piwi proteins-called Piwi, Aubergine, and Argonaute 3-Piwi is the only member of this subfamily that is localized in the nucleus and expressed in both germ-line and somatic cells in the gonad, where it is responsible for piRNA biogenesis and regulatory functions essential for fertility. In this study, we demonstrate beyond doubt that the slicer activity of Piwi is not required for any known functions in vivo. We show that, in transgenic flies with the DDX catalytic triad of PIWI mutated, neither primary nor secondary piRNA biogenesis is detectably affected, transposons remain repressed, and fertility is normal. Our observations demonstrate that the mechanism of Piwi is independent of its in vitro endonuclease activity. Instead, it is consistent with the alternative mode of Piwi function as a molecule involved in the piRNA-directed guidance of epigenetic factors to chromatin.small RNA | RNase H fold | transposable element | sterility

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity

Darricarrère

Liu

Watanabe

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…4B). Again, we did not detect any significant differences in the enrichment of Cold Spring Harbor Laboratory Press on May 10, 2018 -Published by genome.cshlp.org Downloaded from trimethylated histone 3 lysine 9 (H3K9me3) (P > 0.05), which has been reported to be associated with piRNA cluster transcription (Rangan et al 2011); in the enrichment of dimethylated histone 3 lysine 4 (H3K4me2; P > 0.05), which has been described as a mark of transcriptionally active chromatin (Klenov et al 2011); or in the enrichment of RNA polymerase II (P > 0.05), which might reflect the transcription level of a genomic region.…”

Section: Ping-pong Amplification Can Occur Between Defective I-elemenmentioning

confidence: 99%

piRNA-mediated transgenerational inheritance of an acquired trait

et al. 2012

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The maintenance of genome integrity is an essential trait to the successful transmission of genetic information. In animal germ cells, piRNAs guide PIWI proteins to silence transposable elements (TEs) in order to maintain genome integrity. In insects, most TE silencing in the germline is achieved by secondary piRNAs that are produced by a feed-forward loop (the pingpong cycle), which requires the piRNA-directed cleavage of two types of RNAs: mRNAs of functional euchromatic TEs and heterochromatic transcripts that contain defective TE sequences. The first cleavage that initiates such an amplification loop remains poorly understood. Taking advantage of the existence of strains that are devoid of functional copies of the LINE-like I-element, we report here that in such Drosophila ovaries, the initiation of a ping-pong cycle is exclusively achieved by secondary I-element piRNAs that are produced in the ovary and deposited in the embryonic germline. This unusual secondary piRNA biogenesis, detected in the absence of functional I-element copies, results from the processing of sense and antisense transcripts of several different defective I-element. Once acquired, for instance after ancestor aging, this capacity to produce heterochromatic-only secondary piRNAs is partially transmitted through generations via maternal piRNAs. Furthermore, such piRNAs acting as ping-pong initiators in a chromatin-independent manner confer to the progeny a high capacity to repress the I-element mobility. Our study explains, at the molecular level, the basis for epigenetic memory of maternal immunity that protects females from hybrid dysgenesis caused by transposition of paternally inherited functional I-element.

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“…Numerous studies have highlighted a role for Piwi in silencing transposons in Drosophila gonads (Kalmykova et al 2005;Saito et al 2006;Pelisson et al 2007;Yin and Lin 2007;Gangaraju et al 2011;Klenov et al 2011;Sokolova et al 2011). However, these have been based on genetic mutants, which lose Piwi function in both the germline and somatic compartments with consequent severe effects on ovary morphology.…”

Section: Cell Type-specific Knockdown Of Piwi Proteinmentioning

confidence: 99%

Multiple roles for Piwi in silencing Drosophila transposons

Hammell²,

2013

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Silencing of transposons in the Drosophila ovary relies on three Piwi family proteins-Piwi, Aubergine (Aub), and Ago3-acting in concert with their small RNA guides, the Piwi-interacting RNAs (piRNAs). Aub and Ago3 are found in the germ cell cytoplasm, where they function in the ping-pong cycle to consume transposon mRNAs. The nuclear Piwi protein is required for transposon silencing in both germ and somatic follicle cells, yet the precise mechanisms by which Piwi acts remain largely unclear. We investigated the role of Piwi by combining cell typespecific knockdowns with measurements of steady-state transposon mRNA levels, nascent RNA synthesis, chromatin state, and small RNA abundance. In somatic cells, Piwi loss led to concerted effects on nascent transcripts and transposon mRNAs, indicating that Piwi acts through transcriptional gene silencing (TGS). In germ cells, Piwi loss showed disproportionate impacts on steady-state RNA levels, indicating that it also exerts an effect on post-transcriptional gene silencing (PTGS). Piwi knockdown affected levels of germ cell piRNAs presumably bound to Aub and Ago3, perhaps explaining its post-transcriptional impacts. Overall, our results indicate that Piwi plays multiple roles in the piRNA pathway, in part enforcing transposon repression through effects on local chromatin states and transcription but also participating in germ cell piRNA biogenesis.

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Separation of stem cell maintenance and transposon silencing functions of Piwi protein

Cited by 172 publications

References 56 publications

Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity

Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity

piRNA-mediated transgenerational inheritance of an acquired trait

Multiple roles for Piwi in silencing Drosophila transposons

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