Drosophila non-gonadal PIWI protein Aubergine regulates regenerative stem cell proliferation and tumourigenesis in the adult intestine [ncRNA-seq]
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PROVIDER: PRJNA1066367 | ENA |
REPOSITORIES: ENA
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Project description:Drosophila non-gonadal PIWI protein Aubergine regulates regenerative stem cell proliferation and tumourigenesis in the adult intestine
| PRJNA1066364 | ENA
Project description:Drosophila non-gonadal PIWI protein Aubergine regulates regenerative stem cell proliferation and tumourigenesis in the adult intestine [RNA-seq]
| PRJNA1066368 | ENA
Project description:Somatic stem cells are executors of physiological and pathological proliferation of adult self-renewing tissues, such as the intestine. The actions of intestinal stem cells (ISCs) rely on the integration of cell intrinsic and niche-derived signals, which are necessary to achieve a balanced response to the multiple stimuli that constantly challenge tissue homeostasis and organismal health. Disruption of such balance is causative of age-associated tissue dysfunction and hyperproliferative conditions, including inflammation and cancer. The highly conserved PIWI-interacting RNAs (piRNAs) biosynthesis pathway, also known as the PIWI pathway, has been classically studied in the Drosophila germline for its role in the repression of transposable elements (TEs) and the regulation of germline stem cell homeostasis. Recent reports have emerged on a role of Piwi, the founding member of the pathway, in the maintenance of ISC homeostasis in the adult Drosophila midgut. The implications of these findings regarding a general role of the PIWI pathway and piRNAs in the intestine remain to be addressed. Here, we characterise a cell autonomous role of the PIWI family protein Aubergine (Aub) in ISCs. We show that, while dispensable for homeostatic self-renewal of the midgut, inducible Aub is essential to regulate ISC proliferation following acute damage of the intestinal epithelium and in oncogenic settings. Our work suggests that the role of Aub in ISCs is independent of its piRNAs regulatory function. Instead, Aub drives ISC proliferation through the induction of regenerative stem cell factors Myc and Sox21a, and through the initiation of protein translation by the eukaryotic initiation factor 3 complex (eIF3). In summary, our results discover a role of Aub in damage induced proliferation of the adult Drosophila intestine involving the regulation of major regenerative signalling pathways and the protein translation machinery. Furthermore, we present genetically distinct hyperplastic settings fostering a role of Aub as an intestinal tumour promoter or suppressor.
2024-12-29 | GSE253621 | GEO
Project description:Somatic stem cells are executors of physiological and pathological proliferation of adult self-renewing tissues, such as the intestine. The actions of intestinal stem cells (ISCs) rely on the integration of cell intrinsic and niche-derived signals, which are necessary to achieve a balanced response to the multiple stimuli that constantly challenge tissue homeostasis and organismal health. Disruption of such balance is causative of age-associated tissue dysfunction and hyperproliferative conditions, including inflammation and cancer. The highly conserved PIWI-interacting RNAs (piRNAs) biosynthesis pathway, also known as the PIWI pathway, has been classically studied in the Drosophila germline for its role in the repression of transposable elements (TEs) and the regulation of germline stem cell homeostasis. Recent reports have emerged on a role of Piwi, the founding member of the pathway, in the maintenance of ISC homeostasis in the adult Drosophila midgut. The implications of these findings regarding a general role of the PIWI pathway and piRNAs in the intestine remain to be addressed. Here, we characterise a cell autonomous role of the PIWI family protein Aubergine (Aub) in ISCs. We show that, while dispensable for homeostatic self-renewal of the midgut, inducible Aub is essential to regulate ISC proliferation following acute damage of the intestinal epithelium and in oncogenic settings. Our work suggests that the role of Aub in ISCs is independent of its piRNAs regulatory function. Instead, Aub drives ISC proliferation through the induction of regenerative stem cell factors Myc and Sox21a, and through the initiation of protein translation by the eukaryotic initiation factor 3 complex (eIF3). In summary, our results discover a role of Aub in damage induced proliferation of the adult Drosophila intestine involving the regulation of major regenerative signalling pathways and the protein translation machinery. Furthermore, we present genetically distinct hyperplastic settings fostering a role of Aub as an intestinal tumour promoter or suppressor.
2024-12-29 | GSE253624 | GEO
Project description:In Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis. small RNA libraries were prepared from Piwi immuno-precipitates of five different genotypes
2010-10-03 | E-GEOD-23560 | biostudies-arrayexpress
Project description:In Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis.
2010-10-04 | GSE23560 | GEO
Project description:Silencing of transposons in the Drosophila ovary relies on three Piwi-family proteins, Piwi, Aubergine (Aub), and Ago3, acting in concert with their small RNA guides, the piRNAs. Aub and Ago3 are found in the germ cell cytoplasm, where they function in the ping-pong cycle to consume transposon mRNAs. The nuclear Piwi protein is required for transposon silencing in both germ and somatic follicle cells, yet the precise mechanisms by which Piwi acts remain largely unclear. We investigated the role of Piwi by combining cell-type specific knockdowns with measurements of steady state transposon mRNA levels, nascent RNA synthesis, and small RNA abundance. In somatic cells, Piwi loss lead to concerted effects on nascent transcripts and transposon mRNAs, indicating that Piwi acts through transcriptional gene silencing (TGS). In germ cells, Piwi loss showed disproportionate impacts on steady state RNA levels, indicating that it also exerts an effect on post-transcriptional gene silencing (PTGS). Piwi knockdown affected levels of germ cell piRNAs presumably bound to Aub and Ago3, perhaps explaining its post-transcriptional impacts. Overall, our results indicate that Piwi plays multiple roles in the piRNA pathway, in part enforcing transposon repression through effects on transcription but also participating in germ cell piRNA biogenesis.
2013-02-09 | GSE43360 | GEO
Project description:In Drosophila, Piwi proteins associate with Piwi-interacting RNAs (piRNAs) and protect the germline genome by silencing mobile genetic elements. This defense system acts in germline and gonadal somatic tissue to preserve germline development. Genetic control for these silencing pathways varies greatly between tissues of the gonad. Here, we identified Vreteno (Vret), a novel gonad-specific protein essential for germline development. Vret is required for piRNA-based transposon regulation in both germline and somatic gonadal tissues. We show that Vret, which contains Tudor domains, associates physically with Piwi and Aubergine (Aub), stabilizing these proteins via a gonad-specific mechanism, absent in other fly tissues. In the absence of vret, Piwi-bound piRNAs are lost without changes in piRNA precursor transcript production, supporting a role for Vret in primary piRNA biogenesis. In the germline, piRNAs can engage in an Aub/Argonaute 3 (AGO3)-dependent amplification in the absence of Vret, suggesting that Vret function can distinguish between primary piRNAs loaded into Piwi/Aub complexes and piRNAs engaged in the amplification cycle. We propose that Vret acts at an early step in primary piRNA processing where it plays an essential role in transposon regulation. These studies show that vreteno (vret) has a role in germline development and primary piRNA regulation in Drosophila. Transposable element expression profiles from Drosophila ovaries mutant for vreteno, piwi and aubergine were compared using genome-wide mRNA expression profiling by Affymetrix GeneChip arrays (Drosophila 2.0). Key targets were validated by qPCR experiments.
2011-09-28 | E-GEOD-30360 | biostudies-arrayexpress
Project description:This study examines the population of transcripts associated with the Xenopus Piwi proteins, Xiwi and Xili, from X.laevis and X.tropicalis. RIP-seq, CLIP-seq, piRNA-seq, and mRNA-seq datasets were integrated to determine how the Xenopus Piwi proteins where using piRNAs and binding interactions to associate with transcripts in gonadal cells.
2015-11-10 | GSE63228 | GEO
Project description:Silencing of transposons in the Drosophila ovary relies on three Piwi-family proteins, Piwi, Aubergine (Aub), and Ago3, acting in concert with their small RNA guides, the piRNAs. Aub and Ago3 are found in the germ cell cytoplasm, where they function in the ping-pong cycle to consume transposon mRNAs. The nuclear Piwi protein is required for transposon silencing in both germ and somatic follicle cells, yet the precise mechanisms by which Piwi acts remain largely unclear. We investigated the role of Piwi by combining cell-type specific knockdowns with measurements of steady state transposon mRNA levels, nascent RNA synthesis, and small RNA abundance. In somatic cells, Piwi loss lead to concerted effects on nascent transcripts and transposon mRNAs, indicating that Piwi acts through transcriptional gene silencing (TGS). In germ cells, Piwi loss showed disproportionate impacts on steady state RNA levels, indicating that it also exerts an effect on post-transcriptional gene silencing (PTGS). Piwi knockdown affected levels of germ cell piRNAs presumably bound to Aub and Ago3, perhaps explaining its post-transcriptional impacts. Overall, our results indicate that Piwi plays multiple roles in the piRNA pathway, in part enforcing transposon repression through effects on transcription but also participating in germ cell piRNA biogenesis. Piwi function in transcriptional and post-transcriptional transposon silencing was probed using deep-sequencing of small RNAs, steady-state and nascent transcripts, and DNA associated with H3K9me3 chromatin mark. In all cases comparison of two samples was performed: Tj- or nos-driven knock down of piwi to respective knock down of white gene (control sample). RNA-seq dataset has two replicates.
2013-02-09 | E-GEOD-43360 | biostudies-arrayexpress