Antisense transposon insertions into host genes trigger piRNA mediated immunity
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ABSTRACT:
PROVIDER: PRJNA1307507 | ENA |
REPOSITORIES: ENA
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Project description:Transposable elements pose a persistent threat to genome integrity, yet how host defense systems adapt to newly invading elements remains poorly understood. Here, we reveal how Drosophila melanogaster acquired PIWI-interacting RNA (piRNA)-mediated immunity against the recently invading endogenous retrovirus tirant. By integrating genetics, small RNA profiling, and population genomics, we identify two distinct modes of de novo piRNA biogenesis. The primary mechanism involves antisense insertions into the flamenco cluster, a well-established master locus for transposon control. Strikingly, we also find that antisense tirant insertions into 3′ UTRs of host genes robustly trigger piRNA production, a process driven by host gene transcription but independent of gene identity. These findings challenge prevailing models that link piRNA precursor specification to genomic origin or nuclear processing context. Instead, they uncover a flexible, general mechanism in which transposition into host gene exons represents a critical vulnerability for transposons: by generating chimeric antisense transcripts that are exported to the cytoplasm, transposons inadvertently initiate their own silencing, enabling rapid and adaptive genome defense against new invaders.
2025-08-21 | GSE305718 | GEO
Project description:Transposons evolve rapidly and can mobilize and trigger genetic instability. piRNAs silence these genome pathogens, but it is unclear how the piRNA pathway adapts to new transposons. In Drosophila piRNAs, encoded by heterochromatic clusters are maternally deposited in the embryo. Paternally inherited P-element transposons thus escape silencing and trigger a genetic instability and sterility. We show that this syndrome, termed P-M hybrid dysgenesis, also disrupts the piRNA biogenesis machinery and activates resident transposons. As dysgenic hybrids age, however, fertility is restored, P-elements are silenced, and P-element piRNAs are produced de novo. In addition, the piRNA biogenesis machinery is restored and resident elements are silenced. Significantly, new resident transposons insertions accumulate in piRNA clusters, and these new insertions are transmitted to progeny with high fidelity, produce novel piRNAs, and are associated with reduced transposition. P-M hybrid dysgenesis thus leads to heritable changes in chromosome structure that appear to enhance transposon silencing. 3 replicates of each sample (Har 2-4 days, w1 x Har 2-4 days, w1 x Har 21 days), total RNA samples hybridized to tiling array.
2011-12-23 | E-GEOD-31813 | biostudies-arrayexpress
Project description:Piwi-interacting RNAs (piRNAs) suppress transposon activity in animal germ cells. In the Drosophila ovary, primary Aubergine (Aub)-bound antisense piRNAs initiate the ping-pong cycle to produce secondary AGO3-bound sense piRNAs. This increases the number of secondary Aub-bound antisense piRNAs that can act to destroy transposon mRNAs. Here we show that Krimper (Krimp), a Tudor-domain protein, directly interacts with piRNA-free AGO3 to promote symmetrical dimethylarginine (sDMA) modification, ensuring sense piRNA-loading onto sDMA-modified AGO3. In aub mutant ovaries, AGO3 associates with ping-pong signature piRNAs, suggesting AGO3’s compatibility with primary piRNA loading. Krimp sequesters ectopically expressed AGO3 within Krimp bodies in cultured ovarian somatic cells (OSCs), in which only the primary piRNA pathway operates. Upon krimp-RNAi in OSCs, AGO3 loads with piRNAs, further showing the capacity of AGO3 for primary piRNA loading. We propose that Krimp enforces an antisense bias on piRNA pools by binding AGO3 and blocking its access to primary piRNAs.
2015-05-28 | GSE69293 | GEO
Project description:We sequenced insertion sites for the maize Mutator (Mu) transposon in leaf, root, endosperm, and pollen from Mu-active plants and Mu-inactive controls. Inherited insertions were identified using matched tissues, and then the abundance of de novo (post-zygotic) insertions was quantified and converted to variant allele frequencies (VAF). This dataset provides insight into the abundance of new transposon insertions within heterogeneous tissues and factors that shape mutation accumulation in multicellular organisms.
2025-05-09 | GSE279993 | GEO
Project description:Transposons evolve rapidly and can mobilize and trigger genetic instability. piRNAs silence these genome pathogens, but it is unclear how the piRNA pathway adapts to new transposons. In Drosophila piRNAs, encoded by heterochromatic clusters are maternally deposited in the embryo. Paternally inherited P-element transposons thus escape silencing and trigger a genetic instability and sterility. We show that this syndrome, termed P-M hybrid dysgenesis, also disrupts the piRNA biogenesis machinery and activates resident transposons. As dysgenic hybrids age, however, fertility is restored, P-elements are silenced, and P-element piRNAs are produced de novo. In addition, the piRNA biogenesis machinery is restored and resident elements are silenced. Significantly, new resident transposons insertions accumulate in piRNA clusters, and these new insertions are transmitted to progeny with high fidelity, produce novel piRNAs, and are associated with reduced transposition. P-M hybrid dysgenesis thus leads to heritable changes in chromosome structure that appear to enhance transposon silencing.
2011-12-23 | GSE31813 | GEO
Project description:Piwi-interacting RNAs (piRNAs) suppress transposon activity in animal germ cells. In the Drosophila ovary, primary Aubergine (Aub)-bound antisense piRNAs initiate the ping-pong cycle to produce secondary AGO3-bound sense piRNAs. This increases the number of secondary Aub-bound antisense piRNAs that can act to destroy transposon mRNAs. Here we show that Krimper (Krimp), a Tudor-domain protein, directly interacts with piRNA-free AGO3 to promote symmetrical dimethylarginine (sDMA) modification, ensuring sense piRNA-loading onto sDMA-modified AGO3. In aub mutant ovaries, AGO3 associates with ping-pong signature piRNAs, suggesting AGO3’s compatibility with primary piRNA loading. Krimp sequesters ectopically expressed AGO3 within Krimp bodies in cultured ovarian somatic cells (OSCs), in which only the primary piRNA pathway operates. Upon krimp-RNAi in OSCs, AGO3 loads with piRNAs, further showing the capacity of AGO3 for primary piRNA loading. We propose that Krimp enforces an antisense bias on piRNA pools by binding AGO3 and blocking its access to primary piRNAs. In order to investigate function of Krimp in piRNA pathway, sequencing of Piwi subfamily protein associated small RNAs was performed using adult Drosophila ovaries and Ovarian Somatic Cells (OSCs) depleted for Krimp or Aub.
2015-05-28 | E-GEOD-69293 | biostudies-arrayexpress
Project description:Drosophila Piwi-family proteins have been implicated in transposon control. Here, we examine piwi-interacting RNAs (piRNAs) associated with each Drosophila Piwi protein and find that Piwi and Aubergine bind RNAs that are predominantly antisense to transposons, whereas Ago3 complexes contain predominantly sense piRNAs. As in mammals, the majority of Drosophila piRNAs are derived from discrete genomic loci. These loci comprise mainly defective transposon sequences, and some have previously been identified as master regulators of transposon activity. Our data suggest that heterochromatic piRNA loci interact with potentially active, euchromatic transposons to form an adaptive system for transposon control. Complementary relationships between sense and antisense piRNA populations suggest an amplification loop wherein each piRNA-directed cleavage event generates the 5’ end of a new piRNA. Thus, sense piRNAs, formed following cleavage of transposon mRNAs, may enhance production of antisense piRNAs, complementary to active elements, by directing cleavage of transcripts from master control loci. Keywords: small RNA libraries from Drosophila ovaries
2007-03-08 | GSE6734 | GEO
Project description:The control of transposable element (TE) activity in germ cells provides genome integrity over generations. A distinct small RNA-mediated pathway utilizing Piwi-interacting RNAs (piRNAs) suppresses TE expression in gonads of metazoans. In the fly, primary piRNAs derive from so-called piRNA clusters, which are enriched in damaged repeated sequences. These piRNAs launch a cycle of TE and piRNA cluster transcript cleavages resulting in the amplification of piRNA and TE silencing. Using genome-wide comparison of TE insertions and ovarian small RNA libraries from two Drosophila strains, we found that individual TEs inserted into euchromatic loci form novel dual-stranded piRNA clusters. Formation of the piRNA-generating loci by active individual TEs provides a more potent silencing response to the TE expansion. Like all piRNA clusters, individual TEs are also capable of triggering the production of endogenous small interfering (endo-si) RNAs. Small RNA production by individual TEs spreads into the flanking genomic regions including coding cellular genes. We show that formation of TE-associated small RNA clusters can down-regulate expression of nearby genes in ovaries. Integration of TEs into the 3' untranslated region of actively transcribed genes induces piRNA production towards the 3'-end of transcripts, causing the appearance of genic piRNA clusters, a phenomenon that has been reported in different organisms. These data suggest a significant role of TE-associated small RNAs in the evolution of regulatory networks in the germline. The fractions of small RNAs (19-29 nt) from ovaries of y[1]; cn[1] bw[1] sp[1] line of Drosophila melanogaster were sequenced using Illumina HiSeq 2000.
2014-02-07 | E-GEOD-46105 | biostudies-arrayexpress
Project description:Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, PIWI proteins exert control over transposons. However, mammalian PIWI proteins, Miwi and Mili, partner with piRNAs that are depleted of repeat sequences, raising questions about a role for mammalian PIWIs in transposon control. A search for murine small RNAs that might program PIWI proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which PIWI catalyzes formation of piRNA 5’ ends. Mili mutants de-repress L1 and IAP and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression. Keywords: small RNA profile, piRNA
2007-04-20 | GSE7414 | GEO
Project description:The control of transposable element (TE) activity in germ cells provides genome integrity over generations. A distinct small RNA-mediated pathway utilizing Piwi-interacting RNAs (piRNAs) suppresses TE expression in gonads of metazoans. In the fly, primary piRNAs derive from so-called piRNA clusters, which are enriched in damaged repeated sequences. These piRNAs launch a cycle of TE and piRNA cluster transcript cleavages resulting in the amplification of piRNA and TE silencing. Using genome-wide comparison of TE insertions and ovarian small RNA libraries from two Drosophila strains, we found that individual TEs inserted into euchromatic loci form novel dual-stranded piRNA clusters. Formation of the piRNA-generating loci by active individual TEs provides a more potent silencing response to the TE expansion. Like all piRNA clusters, individual TEs are also capable of triggering the production of endogenous small interfering (endo-si) RNAs. Small RNA production by individual TEs spreads into the flanking genomic regions including coding cellular genes. We show that formation of TE-associated small RNA clusters can down-regulate expression of nearby genes in ovaries. Integration of TEs into the 3' untranslated region of actively transcribed genes induces piRNA production towards the 3'-end of transcripts, causing the appearance of genic piRNA clusters, a phenomenon that has been reported in different organisms. These data suggest a significant role of TE-associated small RNAs in the evolution of regulatory networks in the germline.
2014-02-07 | GSE46105 | GEO