A Tudor-domain containing protein, SIMR-1, mediates silencing of piRNA target mRNAs by the Mutator Complex
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ABSTRACT:
PROVIDER: PRJNA575051 | ENA |
REPOSITORIES: ENA
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Project description:piRNAs play a critical role in the regulation of transposons and other germline genes. In Caenorhabditis elegans, silencing of piRNA target genes is mediated by the Mutator complex, which synthesizes high levels of siRNAs through the activity of an RNA-dependent RNA polymerase. However, how mRNAs recognized by the piRNA pathway are handed off to the Mutator pathway is unclear. Here, we identify the Tudor domain-containing protein, SIMR-1, as a key mediator of this handoff. Interestingly, SIMR-1 also localizes to distinct subcellular foci adjacent to P granules and Mutator foci, two phase-separated condensates that are the sites of piRNA-dependent mRNA recognition and Mutator complex-dependent siRNA amplification, respectively. Thus, our data suggests a role for multiple perinuclear condensates in organizing the piRNA pathway and promoting silencing by the Mutator complex.
2020-04-27 | GSE138220 | GEO
Project description:PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb. small RNA libraries were prepared from total RNA isolation of 8 different genotypes
2011-08-16 | E-GEOD-30955 | biostudies-arrayexpress
Project description:PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb.
2011-08-16 | GSE30955 | GEO
Project description:Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defence against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a novel piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile, and de-repress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter MIWI2 (PIWIL4). Cell culture studies with the insect orthologue of TDRD12 suggest a role for the multi-domain protein in mediating complex formation with other participants during secondary piRNA biogenesis. Total small RNA and immunoprecipitated small RNA were purified from mouse testis extract and Bmn4 cells for preparation of high-throughput sequencing libraries.
2013-11-04 | E-GEOD-50544 | biostudies-arrayexpress
Project description:Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defence against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a novel piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile, and de-repress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter MIWI2 (PIWIL4). Cell culture studies with the insect orthologue of TDRD12 suggest a role for the multi-domain protein in mediating complex formation with other participants during secondary piRNA biogenesis.
2013-11-04 | GSE50544 | GEO
Project description:Tudor domain containing 12 (TDRD12) is essential for secondary piRNA biogenesis in mice
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Project description:PIWI proteins and their associated small RNAs called PIWI-interacting RNAs (piRNAs) restrict transposon activity in animal gonads to ensure fertility. Distinct biogenesis pathways load piRNAs into the PIWI proteins MILI and MIWI2 in the mouse male embryonic germline. While most of MILI piRNAs derive via a slicer-independent pathway, a MILI slicer endonuclease-initiated pathway loads nuclear MIWI2 with a series of phased piRNAs. Tudor domain-containing 12 (TDRD12) and its interaction partner Exonuclease domain-containing 1 (EXD1) are required for loading MIWI2, but only Tdrd12 is essential for fertility, leaving us with no explanation for the physiological role of Exd1. Using an artificial piRNA precursor, we demonstrate that MILI-triggered piRNA biogenesis is greatly reduced in the Exd1 mutant. The situation deteriorates in the sensitized Exd1 mutant (Exd1-/-; Tdrd12+/-), where diminished MIWI2 piRNA levels de-repress LINE1 retrotransposons, causing infertility. Thus, EXD1 enhances slicing-triggered MIWI2 piRNA biogenesis via a functional interaction with TDRD12.
2018-09-27 | GSE119447 | GEO
Project description:23-29 nt Piwi-interacting RNAs (piRNAs) are crucial components of the ribonucleoprotein complexes which silence the most abundant class of mobile genetic elements in human genome, retrotransposons, in germline (germ) cells. In these cells, antisense piRNAs serve as RNA guides for Piwi proteins, base pairing with transposon RNAs which are subsequently cleaved by Piwi proteins. Germ cells belong to special class of stem cells which ultimately give rise to eggs and sperm and therefore, to next generations. Therefore, piRNAs protect next-generation genomes from devastating mutations caused by transposon insertions. Although, role of piRNAs in germ cells has been studied, functions of piRNAs and their associated proteins in somatic cells are not well understood. Importantly, Piwi proteins are expressed in the fruit fly Drosophila brain and are required for the silencing of transposable elements there, clearly indicating that Piwi-associated piRNAs are involved in this process in the brain. Furthermore, piRNAs have been implicated in the memory formation mechanisms in Aplysia brain. In addition to Piwi proteins, their associated partner, molecular scaffold Tudor protein, participates in piRNA biogenesis in germ cells and it is absolutely required for germline development. However, although tudor gene is expressed in the fly brain, its role in the central nervous system is not understood. In this study, we look at the role of Tudor as an essential player in piRNA biogenesis in Drosophila brain.
2020-11-27 | GSE149748 | GEO
Project description:Transposable elements are genomic parasites that expand within and spread between genomes. Piwi proteins control transposon activity, notably in the germline. These proteins recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step in this important genome immunity system. While the processing of piRNA precursors is an essential step in this process, many molecular details of this process remain unknown. We identify a novel endoribonuclease, PUCH, that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain (SLFNL) proteins, executes 5ï‚¢-end piRNA precursor cleavage. PUCH-mediated processing strictly requires an m7G-Cap and a Uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds piRNA precursors, and that this interaction enhances piRNA production in vivo. The identification of PUCH completes the C. elegans piRNA biogenesis repertoire and uncovers a novel type of RNA endonuclease formed by three SLFL proteins. Mammalian Slfn genes have been associated with immunity responses, exposing a novel molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.
2023-10-24 | PXD039502 | Pride
Project description:piRNA analysis of tudor[1] mutant Drosophila brain and ovaries
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