piRNA-mediated transgenerational inheritance of an acquired trait

Abstract

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.

piRNAs: from biogenesis to function

“…A lack of maternal piRNAs against the paternally contributed active transposable element is thus the cause of the dysgenic phenotype. Interestingly, this phenotype in the progeny can be rescued by aging of mothers lacking the transposable element: aged female ancestors are able to generate a sufficient amount of piRNAs from heterochromatic remnants of the element via the secondary ping-pong cycle and can thereby provide protection to their progeny (Grentzinger et al, 2012).…”

Small but sturdy: small RNAs in cellular memory and epigenetics

“…3B; Bucheton 1979;Bingham et al 1982;Rubin et al 1982). Recent studies revealed that derepression of the TE in a dysgenic cross correlates with the absence of cognate piRNAs targeting this element, thereby implicating a failure of piRNA-mediated silencing as a primary reason for element activation (Brennecke et al 2008;Khurana et al 2011;Grentzinger et al 2012). Similar to the crosses with the lacZ transgene described above, the genotypes of the progeny in the two crosses are identical, pointing to the involvement of a maternally transmitted epigenetic signal that is required to produce piRNAs targeting the element.…”

The capacity of target silencing by Drosophila PIWI and piRNAs

“…Piwi proteins and piRNAs are best known to suppress transposable elements (TEs) in animal germ cells, as supported by TE transcript up-regulation in Piwi pathway mutants (Aravin et al 2004;Kalmykova et al 2005;Saito et al 2006;Vagin et al 2006), a genetic role in hybrid dysgenesis studies (Brennecke et al 2008;Chambeyron et al 2008;Khurana et al 2011;Grentzinger et al 2012), and perfect complementarity between piRNA sequences and TE coding transcripts (Juliano et al 2011;Siomi et al 2011). In Drosophila, the precursors to TE-associated piRNAs can begin as long singlestranded transcripts from loci that trap TE relics in a biased orientation so that transcription generates piRNAs complementary to TEs (Brennecke et al 2007;Lau et al 2009a;Malone et al 2009).…”