The Cutoff protein regulates piRNA cluster expression and piRNA production in the<i>Drosophila</i>germline

Pane, Andrea; Jiang, Peng; Zhao, Dorothy Yanling; Singh, Mona; Schüpbach, Trudi

doi:10.1038/emboj.2011.334

Cited by 118 publications

(138 citation statements)

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“…The 21-nt small RNA production appears to be a common feature for a number of piRNA-producing loci (Czech et al 2008;Malone et al 2009;Pane et al 2011). cuff mutant analysis was shown to strongly affect 21-nt RNA production by a number of double-strand piRNA-producing loci, including the 42AB locus (Pane et al 2011;Le Thomas et al 2014). What mechanism could explain the 21-nt RNA dependence on the piRNA pathway?…”

Section: Discussionmentioning

confidence: 99%

“…It was shown further that production of these transgene-derived siRNAs by a female requires piRNA, but not siRNA, maternal inheritance, confirming that their appearance is downstream of piRNAs (Figure 2). The 21-nt small RNA production appears to be a common feature for a number of piRNA-producing loci (Czech et al 2008;Malone et al 2009;Pane et al 2011). cuff mutant analysis was shown to strongly affect 21-nt RNA production by a number of double-strand piRNA-producing loci, including the 42AB locus (Pane et al 2011;Le Thomas et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

“…piRNA-producing cluster transcription requires in most of the cases the presence of the HP1 paralog Rhino associated with Deadlock and Cutoff on the locus, forming the so-called RDC complex (Klattenhoff et al 2009;Pane et al 2011;Mohn et al 2014;Zhang et al 2014). In the cytoplasm, transcripts produced by the piRNA locus are sliced in an optically dense region surrounding the nucleus, called the nuage, and small RNAs (23-28 nt) loaded on Piwi or Aubergine proteins are produced (primary piRNAs).…”

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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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“…Nonetheless, two proteins in Drosophila, Rhino and Cutoff, were shown to be necessary for the production of dual-strand piRNA cluster transcripts [52,53]. Very recently, it was determined that Rhino (an HP1a homolog) recognizes piRNA clusters through chromatin interactions.…”

Section: Other Components Of Micro and Sirna Biogenesismentioning

confidence: 99%

From guide to target: molecular insights into eukaryotic RNA-interference machinery

Ipsaro

Joshua‐Tor

2015

Nat Struct Mol Biol

218

144

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Since its relatively recent discovery, RNA interference (RNAi) has emerged as a potent, specific, and ubiquitous means of gene regulation. Through a number of pathways that are conserved from yeast to humans, small non-coding RNAs direct molecular machinery to silence gene expression. In this review, we focus on mechanisms and structures that govern RNA silencing in higher organisms. In addition to highlighting recent advances, parallels and differences between RNAi pathways are discussed. Together, the studies reviewed herein reveal the versatility and programmability of RNA-induced Silencing Complexes (RISCs) and emphasize the importance of both upstream biogenesis and downstream silencing factors. Discovery and Biological Perspectives of RNA interferenceRNAi was first described by Fire and Mello in the 1990s when, in an attempt to use antisense RNA to down-regulate gene expression, they observed that double-stranded RNA (dsRNA) was more potent than sense or anti-sense RNA alone [1]. This seminal work boasted robust and specific gene knock down in addition to coining the term "RNA interference" (RNAi). Shortly beforehand, the discovery of individual regulatory RNAs in C. elegans hinted that small, non-coding RNAs might be a pervasive means of gene regulation in higher organisms [2,3]. In the following decade, with the mechanistic insight of Fire and Mello's work in hand, this idea was confirmed and it is now accepted that wellover 1,000 small RNAs are encoded in the human genome that may regulate over 60% of our genes [4,5]. It also became apparent that several seemingly disconnected phenomena are variations of RNAi-type pathways including co-suppression in plants, DNA elimination in Tetrahymena, and quelling in Neurospora [6]. The prevalence of RNAi is impressive and its importance is underscored by the fact that RNAi dysfunction is associated with numerous diseases and disorders including neurological maladies, cancers, and infertility.Shortly after the initial description of RNAi phenomenology, a burst of genetic, biochemical, biophysical, and bioinformatic efforts laid a strong foundation for identifying the molecular pathways, players, and parameters that govern silencing via RNAi. Work from Reprints and permissions information is available online at http://www.nature.com/reprints/index.html. HHMI Author ManuscriptHHMI Author Manuscript HHMI Author Manuscript numerous groups defined the molecular apparatus of RNAi as RISC (RNA-induced Silencing Complex), a ribonucleoprotein complex minimally comprised of a small singlestranded RNA (~20-31 nucleotides) and an Argonaute protein which serves as the effector molecule (reviewed in [7]). In this configuration, the loaded "guide" RNA acts as a specificity determinant that directs Argonaute and any other associated machinery to the target. The guide-loaded Argonaute platform underlies every example in the expansive array of known RNAi pathways in eukaryotes regardless of the source of the guide (structured loci, transposons, viral, etc.), the machinery ...

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The PIWI‐Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells

Sakakibara

Siomi

2017

BioEssays

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The PIWI-interacting RNA (piRNA) pathway, one of the major eukaryotic small RNA silencing pathways, is a genome surveillance system that silences selfish genes in animal gonads. piRNAs guide PIWI protein to target genes through Watson-Crick RNA-RNA base-parings. Loss of piRNA function causes genome instability, inducing failure in gametogenesis and infertility. Studies using fruit flies and mice as key experimental models have resulted in tremendous progress in understanding the mechanism underlying the piRNA pathway. Recent work using cultured silkworm germline cells has also expanded our knowledge of piRNA biogenesis in particular, since these silkworm cells are the only cells of germline origin that can be cultured. In this review, we describe elucidation of the piRNA pathway using cultured silkworm cells as an experimental model by focusing on recent work in biochemistry and structural biology. Earlier studies that made important contributions to the field are also described.

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The Cutoff protein regulates piRNA cluster expression and piRNA production in theDrosophilagermline

Cited by 118 publications

References 60 publications

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

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

From guide to target: molecular insights into eukaryotic RNA-interference machinery

The PIWI‐Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells

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