piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis

Mohn, Fabio; Handler, Dominik; Brennecke, Julius

doi:10.1126/science.aaa1039

Cited by 335 publications

(527 citation statements)

References 38 publications

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“…Primary piRNAs are processed from single-stranded RNA precursors, which are transcribed mostly from chromosomal loci consisting mainly of remnants of TE sequences, termed piRNA clusters (14). In D. melanogaster, the cleavage of primary piRNA precursors and generation of 5′ end of mature piRNAs were recently linked to Zucchini endonuclease (Zuc) activity (15)(16)(17)(18). The cleaved precursor is loaded into Piwi family Argonaute proteins Piwi or Aubergine (Aub) and then trimmed by a still-unknown nuclease to reach its final length, which can vary from 24 to 30 nt.…”

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confidence: 99%

piRNA pathway is not required for antiviral defense in Drosophila melanogaster

Petit

Mongelli

Frangeul

et al. 2016

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

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Since its discovery, RNA interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. In insects, the small interfering RNA (siRNA) pathway is the major antiviral response. In recent years, the Piwi-interacting RNA (piRNA) pathway also has been implicated in antiviral defense in mosquitoes infected with arboviruses. Using Drosophila melanogaster and an array of viruses that infect the fruit fly acutely or persistently or are vertically transmitted through the germ line, we investigated in detail the extent to which the piRNA pathway contributes to antiviral defense in adult flies. Following virus infection, the survival and viral titers of Piwi, Aubergine, Argonaute-3, and Zucchini mutant flies were similar to those of wild type flies. Using next-generation sequencing of small RNAs from wild type and siRNA mutant flies, we showed that no viral-derived piRNAs were produced in fruit flies during different types of viral infection. Our study provides the first evidence, to our knowledge, that the piRNA pathway does not play a major role in antiviral defense in adult Drosophila and demonstrates that viral-derived piRNA production depends on the biology of the host–virus combination rather than being part of a general antiviral process in insects.

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confidence: 99%

piRNA pathway is not required for antiviral defense in Drosophila melanogaster

Petit

Mongelli

Frangeul

et al. 2016

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

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“…Figure 3C shows that, as early as generation 3, the three types of G 0 maternal inheritance resulted in strong production of small RNAs covering the entire BX2 P{lacW} transgene length. Thus, partially homologous paramutations are associated with rapid and stable spreading of piRNA production by nonhomologous sequences of the targets, similarly to what was found for target transgenes (Muerdter et al 2011;Olovnikov et al 2013;Han et al 2015;Mohn et al 2015) or transposable elements (Shpiz et al 2014).Further, the paramutagenicity of P-1152 BX2*, RS3 BX2*, and P-1152+RS3 BX2* females was tested. Figure 4 shows that maternal transmission of cytoplasm produced by these females, combined to paternal transmission of a BX2 naive locus, resulted in female progeny showing strong trans-silencing properties.…”

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confidence: 71%

“…One possibility is that P{lacW} siRNA production results from the fact that both sense and antisense RNAs, produced by this dualstrand cluster, are concentrated locally due to the piRNA machinery, for example in the nuage, leading to occurrence of double-strand RNAs, which can further be processed by Dcr-2. The piRNA mutants tested could alter the production of the piRNAs associated with Piwi, which are produced downstream of the ping-pong amplification step (Han et al 2015;Mohn et al 2015), and consequently reduce a positive feedback in the nucleus of these piRNAs (Mohn et al 2014). This would reduce deposition of Rhino at several piRNA, producing loci (Mohn et al 2014) and thus affect dual-strand transcription of the BX2 locus, abolish the sense and antisense RNA concentration step, and siRNA production as well.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the TSE capacities of the BX2* paramutated locus were shown to be completely impaired by loss of function of aubergine (aub) involved in the piRNA ping-pong step, whereas they were insensitive to loss of function of Dicer-2 (Dcr-2) involved in the siRNA pathway . This suggested that the 21 nt would not be necessary for BX2* silencing capacities.We thus performed deep sequencing of ovarian small RNAs of mutant females for aub and Dcr-2 and extended the analysis to rhino (rhi) and cutoff (cuff), which are nuclear actors involved in piRNA loci noncanonical transcription (Mohn et al 2014;Zhang et al 2014), and to zucchini (zuc), which is involved in the cleavage of piRNA precursors and secondary piRNAs in the cytoplasm (Ipsaro et al 2012;Nishimasu et al 2012;Voigt et al 2012;Han et al 2015;Mohn et al 2015). All these genes are located, as BX2 is, on chromosome 2.…”

mentioning

confidence: 99%

“…This produces secondary piRNAs loaded on Aubergine or Ago3, other PIWI proteins (Weick and Miska 2014;Iwasaki et al 2015) and results in a piRNA amplification process called ping-pong amplification (Brennecke et al 2007;Gunawardane et al 2007). Finally, piRNA loaded on Piwi can also be produced downstream of the ping-pong amplification step by a slicing process that can spread on targeted RNA, increasing both piRNA quantity and diversity (Han et al 2015;Mohn et al 2015;Siomi and Siomi 2015). Upstream of this complex machinery, the presence of Rhino on the piRNA-producing locus is particularly important since it appears sufficient to promote processing of transcripts by the piRNA machinery (Klattenhoff et al 2009;Zhang et al 2014).…”

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confidence: 99%

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Paramutation inDrosophilaRequires Both Nuclear and Cytoplasmic Actors of the piRNA Pathway and InducesCis-spreading of piRNA Production

et al. 2015

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Transposable element activity is repressed in the germline in animals by PIWI-interacting RNAs (piRNAs), a class of small RNAs produced by genomic loci mostly composed of TE sequences. The mechanism of induction of piRNA production by these loci is still enigmatic. We have shown that, in Drosophila melanogaster, a cluster of tandemly repeated P-lacZ-white transgenes can be activated for piRNA production by maternal inheritance of a cytoplasm containing homologous piRNAs. This activated state is stably transmitted over generations and allows trans-silencing of a homologous transgenic target in the female germline. Such an epigenetic conversion displays the functional characteristics of a paramutation, i.e., a heritable epigenetic modification of one allele by the other. We report here that piRNA production and trans-silencing capacities of the paramutated cluster depend on the function of the rhino, cutoff, and zucchini genes involved in primary piRNA biogenesis in the germline, as well as on that of the aubergine gene implicated in the ping-pong piRNA amplification step. The 21-nt RNAs, which are produced by the paramutated cluster, in addition to 23-to 28-nt piRNAs are not necessary for paramutation to occur. Production of these 21-nt RNAs requires Dicer-2 but also all the piRNA genes tested. Moreover, cytoplasmic transmission of piRNAs homologous to only a subregion of the transgenic locus can generate a strong paramutated locus that produces piRNAs along the whole length of the transgenes. Finally, we observed that maternally inherited transgenic small RNAs can also impact transgene expression in the soma. In conclusion, paramutation involves both nuclear (Rhino, Cutoff) and cytoplasmic (Aubergine, Zucchini) actors of the piRNA pathway. In addition, since it is observed between nonfully homologous loci located on different chromosomes, paramutation may play a crucial role in epigenome shaping in Drosophila natural populations.KEYWORDS gene regulation; trans-generational epigenetics; noncoding small RNAs; mobile DNA; Drosophila G ENOMES must confront the presence of a large fraction of mobile DNA whose activity can result in severe deleterious effects on chromosome stability and gametogenesis. In the germline of animals, a system of genomic traps exists into which any transposable element (TE) can insert, thereby generating loci that contain a catalog of potentially dangerous sequences that have to be repressed (Brennecke et al. 2007;Pane et al. 2011;Iwasaki et al. 2015). In the Drosophila melanogaster germline, most of these loci are transcribed in both directions (dual-strand clusters) and undergo noncanonical transcription and RNA processing (Mohn et al. 2014;Zhang et al. 2014). This results in production of noncoding small RNAs having the capacity to target the transcripts of the homologous, potentially active, TE copies scattered throughout the genome. These small RNAs are called PIWI-interacting RNAs (piRNAs) and repress TE activity at both the transcriptional and post-transcriptional levels (Sa...

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Non‐gonadal expression of piRNAs is widespread across Arthropoda

Yamashita,

Komenda,

Miłodrowski

et al. 2024

FEBS Letters

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PIWI‐interacting RNAs (piRNAs) were discovered in the early 2000s and became known for their role in protecting the germline genome against mobile genetic elements. Successively, piRNAs were also detected in the somatic cells of gonads in multiple animal species. In recent years, piRNAs have been reported in non‐gonadal tissues in various arthropods, contrary to the initial assumptions of piRNAs being exclusive to gonads. Here, we performed an extensive literature review, which revealed that reports on non‐gonadal somatic piRNA expression are not limited to a few specific species. Instead, when multiple studies are considered collectively, it appears to be a widespread phenomenon across arthropods. Furthermore, we systematically analyzed 168 publicly available small RNA‐seq datasets from diverse tissues in 17 species, which further supported the bibliographic reports that piRNAs are expressed across tissues and species in Arthropoda.

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piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis

Cited by 335 publications

References 38 publications

piRNA pathway is not required for antiviral defense in Drosophila melanogaster

piRNA pathway is not required for antiviral defense in Drosophila melanogaster

Paramutation inDrosophilaRequires Both Nuclear and Cytoplasmic Actors of the piRNA Pathway and InducesCis-spreading of piRNA Production

Non‐gonadal expression of piRNAs is widespread across Arthropoda

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