Academic journal article Genetics

Paramutation in Drosophila Requires Both Nuclear and Cytoplasmic Actors of the piRNA Pathway and Induces Cis-Spreading of piRNA Production

Academic journal article Genetics

Paramutation in Drosophila Requires Both Nuclear and Cytoplasmic Actors of the piRNA Pathway and Induces Cis-Spreading of piRNA Production

Article excerpt

GENOMES 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 (Sato and Siomi 2013; Weick and Miska 2014). piRNA biogenesis in the germline involves a nuclear and a cytoplasmic step. In the nucleus, 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). Further, piRNAs loaded on Piwi enter the nucleus and target euchromatic TE copies to induce their transcriptional repression via heterochromatin formation, which involves HP1 (Wang and Elgin 2011; Sienski et al. 2012; Le Thomas et al. 2013; Rozhkov et al. 2013). In contrast, piRNAs loaded on Aubergine remain in the nuage and target homologous transcripts being exported from the nucleus, which are produced by both homologous TE copies and the piRNA locus. 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). How Rhino is addressed to a piRNA-producing locus is still unclear.

In Drosophila, in contrast to Caenorhabditis elegans (Ruby et al. 2006; Batista et al. 2008), the production of piRNAs by a piRNA locus in the germline does not appear to be only genetically determined, i.e., no specific sequence motif or structure has been identified that is sufficient to promote piRNA production by DNA adjacent to this sequence. Conversely, using piRNA-producing loci that repress P-transposable elements (Ronsseray et al. 1996), it was shown that maternal transmission of piRNAs together with the piRNA locus can stimulate production of piRNAs by paternally inherited Pelements scattered through the genome (Brennecke et al. 2008). In addition, analysis of ageing effects on I-transposable element repression capacities showed that the amount of I-homologous piRNAs in adult ovaries is correlated to the amount of homologous piRNAs deposited in embryos (Grentzinger et al. 2012). Furthermore, it was shown that de novo, long-term activation of a piRNA locus can be achieved in Drosophila by maternal transmission of homologous piRNAs, without transmission of the initial piRNA donor locus. …

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