The piRNA pathway sustains adult neurogenesis by reducing protein synthesis and cellular senescence
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182848 | GEO | 2021/08/30
REPOSITORIES: GEO
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Project description:Germ cells of most animals critically depend on piRNAs and Piwi proteins. Surprisingly, piRNAs in mouse oocytes are relatively rare and dispensable. We present compelling evidence for strong Piwi-piRNA expression in oocytes of other mammals. Human fetal oocytes express PIWIL2 and transposon-enriched piRNAs. Oocytes in adult human ovary express PIWIL1 and PIWIL2, while those in bovine ovary just express PIWIL1. In human, macaque and bovine ovaries we find piRNAs that resemble testis-borne pachytene piRNAs. Isolated bovine follicular oocytes were shown to contain abundant, relatively short piRNAs that preferentially target transposable elements. Using label-free quantitative proteome analysis we show that these maturing oocytes strongly and specifically express the thus-far uncharacterized PIWIL3 protein, alongside other known piRNA-pathway components. In bovine early embryos these piRNAs are still abundant, revealing a potential impact of piRNAs on mammalian embryogenesis. Our results reveal unexpected, highly dynamic piRNA pathways in mammalian oocytes and early embryos. Analyses of multiple small RNA libraries obtained from fetal/adult oocytes, cumulus cells, ovary, testis and 2-4 cell stage ivf embryos of multiple mammalian species.
2015-03-27 | E-GEOD-64942 | biostudies-arrayexpress
Project description:Germ cells of most animals critically depend on piRNAs and Piwi proteins. Surprisingly, piRNAs in mouse oocytes are relatively rare and dispensable. We present compelling evidence for strong Piwi-piRNA expression in oocytes of other mammals. Human fetal oocytes express PIWIL2 and transposon-enriched piRNAs. Oocytes in adult human ovary express PIWIL1 and PIWIL2, while those in bovine ovary just express PIWIL1. In human, macaque and bovine ovaries we find piRNAs that resemble testis-borne pachytene piRNAs. Isolated bovine follicular oocytes were shown to contain abundant, relatively short piRNAs that preferentially target transposable elements. Using label-free quantitative proteome analysis we show that these maturing oocytes strongly and specifically express the thus-far uncharacterized PIWIL3 protein, alongside other known piRNA-pathway components. In bovine early embryos these piRNAs are still abundant, revealing a potential impact of piRNAs on mammalian embryogenesis. Our results reveal unexpected, highly dynamic piRNA pathways in mammalian oocytes and early embryos.
2015-03-27 | GSE64942 | GEO
Project description:Purpose:To evaluate the effect of transient Global Cerebral Ischemia(tGCI) with Hypoxic Postconditioning (HPC) on piRNA expression profiles, piRNAs sequencing was performed. Methods: Total RNA of each sample (n=3 in each group) was prepared using Trizol reagent (Invitrogen), and the RNA quality and integrity were confirmed. 5’- and 3’-Adaptors were ligated to the obtained small RNA. Reverse transcription followed by PCR was used to create cDNA constructs. Subsequently, an about 150 bp fraction corresponding to approximate the adaptor-ligated constructs derived from the 30 nts piRNA fragment was excised and purified. The purified libraries were sequenced on Illumina HiSeq 2000 apparatus. The raw data were refined using cutadapt software (v1.9.1). After filtering out low quality reads and short reads (<15 nts), trimmed reads from all samples were pooled, and piano software was used to predict novel piRNAs. The trimmed reads were aligned to the merged rat piRNA databases (known piRNA from piRNABank plus the newly predicted piRNAs) using Novoalign software (v3.02.12) with at most one mismatch. PiRNA-binding transposon and targets were predicted by miranda software (v3.3a). piRNA-targets networks were plotted by cytoscape software (v2.8.0). Results: After tGCI, a total of 5574 piRNAs in CA1 was detected after 26 h of reperfusion. Of those, 12 were significantly upregulated compared with Sham rats (≥1.5-fold change, p<0.05), including 6 novel piRNAs. Of the 12 piRNAs, 4 showed ≥2-fold change. In comparison to tGCI group, 6 piRNAs in CA1 were significantly downregulated after HPC. Interestingly, the piRNAs rno_piR_000618, rno_piR_017990 and rno_piR_014971 were significantly changed in both tGCI and HPC groups Conclusions: In our study, we identified a cohort of piRNAs in CA1 of rats. Furthermore, we demonstrated directly contrast changes of piRNAs interacted with Piwil2 in CA1 after tGCI, as compared to those in HPC rats. Therefore, this study revealed that PIWI/piRNAs respond to ischemic brain damage and neuroprotection mediated by HPC. To the best of our knowledge, this is the first study ever on piRNAs associated with Piwil2 in cerebral ischemic tolerance.
2023-01-18 | GSE163298 | GEO
Project description:The piRNA pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. piRNAs are maternally deposited and required for proper transposon silencing in adult offspring. However, a long-standing question in the field is the precise function of maternally deposited piRNAs and its associated factors during embryogenesis. Here, we probe the spatio-temporal expression patterns of several piRNA pathway components during early stages of development. Amongst those, factors required for transcriptional gene silencing (TGS) showed ubiquitous abundance in somatic and pole cells throughout the first half of embryogenesis. We further analysed the transcriptomes of various embryo stages and correlated these with the presence of selected chromatin marks. We found that a number of transposon families show bursts of transcription during early embryonic stages. Transposons heavily targeted by maternally deposited piRNAs accumulated repressive chromatin marks following their spike in expression. Furthermore, depletion of maternally deposited Piwi protein in early embryos resulted in increased expression of transposons targeted by inherited piRNAs and was accompanied by a strong loss of repressive chromatin marks at coding sequences. Overall, our data suggests a pivotal role for the piRNA pathway in transposon defence during Drosophila embryogenesis in somatic cells.
2021-07-26 | PXD022409 | Pride
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:Small noncoding (snc) RNAs represent a growing family of transcripts that regulate key cellular processes, including mRNA degradation, translational repression and transcriptional gene silencing. Among these, the PIWI-interacting RNAs (piRNAs), a major class of sncRNAs initially identified in the germline of a variety of species, are now being found to be functionally active also in somatic cells. However, whether the Piwi/piRNA pathway is associated with fundamental biological processes, such as cell cycle progression, remains elusive. Here we investigated the possibility that piRNAs are expressed in liver and modulated during regenerative proliferation of this organ. To this aim, smallRNA-Seq was applied to identify and quantitate expression of these RNAs in rat liver before, during and after the wave of cell proliferation that follows partial hepatectomy (PH). Q-PCR analysis revealed the presence in rat liver of two PIWI (PIWI-Like) subfamily members (PIWIL2/HILI and, to a much lower level, PIWIL4/HIWI2) and other components of the piRNA biogenesis pathways, suggesting that this is present and functional in hepatocytes. Indeed, ~1400 piRNAs originally identified in rat and other mammalian germline cells are expressed in adult rat liver, including 72 that show timed changes in expression during cell cycle progression. Most piRNAs are up-regulated 24-48h after hepatectomy, a timing that corresponds to cell transition through the S phase, and return to basal levels by 168 h, when organ regeneration is completed and hepatocytes reach quiescence. These results indicate that the piRNA pathway is active in somatic cells and, more important, that it is subject to regulation during physiological processes, such as cell proliferation, when piRNAs may exert their regulatory functions on the cell genome and transcriptome. smallRNA-Seq was applied to identify and quantitate expression of RNAs in rat liver before and after partial hepatectomy (PH).
2014-06-17 | E-GEOD-55783 | biostudies-arrayexpress
Project description:PIWI-interacting RNAs (piRNAs) promote fertility in many animals. Yet, whether this is due to their conserved role in repressing repetitive elements (REs) or other functions remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets, but rather mediated by the epigenetic silencing of all the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway is sufficient to restore histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that the transgenerational silencing of histone genes contributes to the progressive loss of fertility in piRNA mutants and that coupling piRNAs and histone silencing may serve to maintain piRNAs production across evolution.
2019-12-11 | PXD012557 | Pride
Project description:Purpose：To identify piRNAs bound to Piwil2 in Sham,transient Global Cerebral Ischemia(tGCI) and transient Global Cerebral Ischemia(tGCI) with Hypoxic Postconditioning (HPC). Methods: Samples from CA1 subregion were lysed in 500 μl lysis buffer and centrifuged. After centrifugation, supernatant was incubated with monoclonal mouse antibody against Piwil2 (Santa Cruz, California, CA, USA), preincubated with Protein A/G Agarose. The beads were washed twice with lysis buffer. After quality check by Western blot, the RNA was extracted from the magnetic beads using Trizol reagent (Invitrogen). Then, the immunoprecipitated RNA was analyzed with piRNAs sequencing. Results: After tGCI, a total of 423 piRNAs interacted with Piwil2 in CA1 was upregulated after 26 h of reperfusion. Of the 423 piRNAs, 317 were significantly upregulated by more than 1.5-fold. Of the 317 piRNAs, 258 showed ≥2-fold change. Comparison between tGCI and HPC groups revealed that 401 piRNAs interacted with Piwil2 in CA1 were significantly downregulated after HPC, whereas only 7 piRNAs were found to be altered in all 3 groups studied (≥1.5-fold change). Conclusions: In our study, we identified a cohort of piRNAs in CA1 of rats. We demonstrated directly contrast changes of piRNAs interacted with Piwil2 in CA1 after tGCI, as compared to those in HPC rats. The results of the prediction showed that DNMT3A may be a potential common target of the 7 differentially expressed piRNAs interacted with Piwil2. Therefore, we focused on the expression of DNMT3A in CA1 after tGCI with or without HPC.
2023-01-18 | GSE163299 | GEO
Project description:Piwi-interacting RNAs (piRNAs) are genomically encoded small RNAs that engage Piwi Argonaute proteins to direct mRNA surveillance and transposon silencing. Despite advances in understanding piRNA pathways and functions, how the production of piRNA is regulated remains elusive. Here, using a genetic screen, we identify casein kinase II (CK2) as a factor required for piRNA pathway function. We show that CK2 is required for the localization of PRG-1 and for the proper localization of several factors that comprise the ‘upstream sequence transcription complex’ (USTC), which is required for piRNA transcription. Loss of CK2 impairs piRNA levels suggesting that CK2 promotes USTC function. We identify the USTC component twenty-one-U fouled-up 4 (TOFU-4) as a direct substrate for CK2. Our findings suggest that phosphorylation of TOFU-4 by CK2 promotes the assembly of USTC and piRNA transcription. Notably, during the aging process, CK2 activity declines, resulting in the disassembly of USTC, decreased piRNA production, and defects in piRNA-mediated gene silencing, including transposons silencing. These findings highlight the significance of posttranslational modification in regulating piRNA biogenesis and its implications for the aging process. Overall, our study provides compelling evidence for the involvement of a posttranslational modification mechanism in the regulation of piRNA biogenesis.
2024-07-01 | GSE239315 | GEO