An Epigenetic Role for Maternally Inherited piRNAs in Transposon Silencing

Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory (CSHL), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Science (Impact Factor: 33.61). 12/2008; 322(5906):1387-92. DOI: 10.1126/science.1165171
Source: PubMed


In plants and mammals, small RNAs indirectly mediate epigenetic inheritance by specifying cytosine methylation. We found that small RNAs themselves serve as vectors for epigenetic information. Crosses between Drosophila strains that differ in the presence of a particular transposon can produce sterile progeny, a phenomenon called hybrid dysgenesis. This phenotype manifests itself only if the transposon is paternally inherited, suggesting maternal transmission of a factor that maintains fertility. In both P- and I-element-mediated hybrid dysgenesis models, daughters show a markedly different content of Piwi-interacting RNAs (piRNAs) targeting each element, depending on their parents of origin. Such differences persist from fertilization through adulthood. This indicates that maternally deposited piRNAs are important for mounting an effective silencing response and that a lack of maternal piRNA inheritance underlies hybrid dysgenesis.

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    • "Because these embryos have no fully onset transcription (Vlassova et al. 1991; Pritchard and Schubiger 1996), their small RNAs and Piwi proteins are essentially the same of the maternal germ cells (Harris and Macdonald 2001; Megosh et al. 2006; Brennecke et al. 2008; Le Thomas et al. 2014). A similar scenario was found for D. melanogaster (Brennecke et al. 2008). At early embryogenesis, the maternally inherited piRNAs and piwi proteins could be leading elements in the process of defining heterochromatic domains (Sentmanat et al. 2013). "
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    Chromosome Research 09/2015; DOI:10.1007/s10577-015-9480-x · 2.48 Impact Factor
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    • "et al., 2013; Siomi et al., 2011). In this view, Aub-bound, maternally deposited antisense piRNAs must initiate ping-pong amplification, leading to the accumulation of Ago3-bound sense piRNAs (Brennecke et al., 2008; Le Thomas et al., 2014). Pingpong amplification of Ago3-bound piRNAs would then serve to ensure a sufficient supply of guides for Piwi. "
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    ABSTRACT: In Drosophila ovarian germ cells, PIWI-interacting RNAs (piRNAs) direct Aubergine and Argonaute3 to cleave transposon transcripts and instruct Piwi to repress transposon transcription, thereby safeguarding the germline genome. Here, we report that RNA cleavage by Argonaute3 initiates production of most Piwi-bound piRNAs. We find that the cardinal function of Argonaute3, whose piRNA guides predominantly correspond to sense transposon sequences, is to produce antisense piRNAs that direct transcriptional silencing by Piwi, rather than to make piRNAs that guide post-transcriptional silencing by Aubergine. We also find that the Tudor domain protein Qin prevents Aubergine's cleavage products from becoming Piwi-bound piRNAs, ensuring that antisense piRNAs guide Piwi. Although Argonaute3 slicing is required to efficiently trigger phased piRNA production, an alternative, slicing-independent pathway suffices to generate Piwi-bound piRNAs that repress transcription of a subset of transposon families. This alternative pathway may help flies silence newly acquired transposons for which they lack extensively complementary piRNAs. Copyright © 2015 Elsevier Inc. All rights reserved.
    Molecular cell 09/2015; 59(5):819-30. DOI:10.1016/j.molcel.2015.08.007 · 14.02 Impact Factor
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    • "Much less clear is how this process is initiated during development. In this respect, maternally deposited piRNAs (especially those bound to Aub) (Brennecke et al. 2008) that are enriched in developing primordial germ cells of the embryo are likely to play a central role in kick-starting the ping-pong cycle but also in defining the target spectrum of nuclear Piwi. How primary piRNA biogenesis in Drosophila ovarian somatic cells is steered to piRNA cluster transcripts and a subset of cellular mRNAs is a central, unresolved question . "
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