RNAi pathways repress reprogramming of C. elegans germ cells during heat stress
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ABSTRACT:
PROVIDER: PRJNA555613 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11034887_1.fastq.gz | Fastqsanger.gz | |||
| SRR11034887_2.fastq.gz | Fastqsanger.gz | |||
| SRR11034888_1.fastq.gz | Fastqsanger.gz | |||
| SRR11034888_2.fastq.gz | Fastqsanger.gz | |||
| SRR11034889_1.fastq.gz | Fastqsanger.gz |
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Project description:Repression of cellular reprogramming in germ cells is critical to maintaining cell fate and fertility. When germ cells mis-express somatic genes they can be directly converted into other cell types, resulting in loss of totipotency and reproductive potential. Here we show that RNAi pathways play a key role in maintaining germline gene expression and totipotency after heat stress. By examining transcriptional changes that occur in mut-16 mutants, that lack a key protein in the RNAi pathway, at elevated temperatures we found that soma-specific genes are mis-expressed in germ cells. This trend was also observed in hrde-1 mutants, which fail to direct transcriptional silencing of RNAi-targeted genes. These findings indicate that the RNAi pathway plays a key role in preventing aberrant expression of somatic genes in the germline during heat stress. This regulation likely occurs in part through the maintenance of germline chromatin by the nuclear RNAi pathway.
2020-03-06 | GSE134573 | GEO
Project description:Repression of cellular reprogramming in germ cells is critical to maintaining cell fate and fertility. When germ cells mis-express somatic genes they can be directly converted into other cell types, resulting in loss of totipotency and reproductive potential. Identifying the molecular mechanisms that coordinate these cell fate decisions is an active area of investigation. Here we show that RNAi pathways play a key role in maintaining germline gene expression and totipotency after heat stress. By examining transcriptional changes that occur in mut-16 mutants, lacking a key protein in the RNAi pathway, at elevated temperature we found that genes normally expressed in the soma are mis-expressed in germ cells. Furthermore, these genes displayed increased chromatin accessibility in the germlines of mut-16 mutants at elevated temperature. These findings indicate that the RNAi pathway plays a key role in preventing aberrant expression of somatic genes in the germline during heat stress. This regulation occurs in part through the maintenance of germline chromatin, likely acting through the nuclear RNAi pathway. Identification of new pathways governing germ cell reprogramming is critical to understanding how cells maintain proper gene expression and may provide key insights into how cell identity is lost in some germ cell tumors.
| S-EPMC7192617 | biostudies-literature
Project description:Germ granules are biomolecular condensates that promote germ cell totipotency in most, if not all, animals. In C. elegans, MEG-3 and MEG-4 are two intrinsically disordered proteins that are redundantly required for the phase separations that drive germ granule assembly in germline blastomeres. Here, we show that animals lacking MEG-3/4 exhibit defects in dsRNA-mediated gene silencing (RNAi) that are due, at least in part, to defects in systemic RNAi. Interestingly, these RNAi defects are transgenerationally disconnected from meg-3/4 genotype: RNAi defects do not arise until 5-9 generations after animals become mutant for meg-3/4, and RNAi defects persist for 9-11 generations after meg-3/4 genotype is restored to wild type. Similar non-Mendelian patterns of inheritance are associated with other mutations that disrupt germ granule formation, indicating that germ granule disruption is the likely cause of genotype/phenotype disconnects. Loss of germ granules is associated with the production of aberrant populations of endogenous siRNAs, which, remarkably, are propagated for ≅10 generations in wild-type descendants of animals that lacked germ granules. sid-1, which encodes a factor required for systemic RNAi in C. elegans, is inappropriately and heritably silenced by aberrantly expressed sid-1 endogenous siRNAs, suggesting that transgenerational silencing of sid-1 likely underlies the heritable defect in RNAi. We conclude that one function of germ granules is to organize RNA-based epigenetic inheritance pathways and that failure to assemble germ granules has consequences that persist across many generations.
2019-08-08 | GSE134683 | GEO
Project description:Post-transcriptional control of mRNAs by RNA-binding proteins (RBPs) has a prominent role in the regulation of gene expression. RBPs interact with mRNAs to control their biogenesis, splicing, transport, localization, translation, and stability. Defects in such regulation can lead to a wide range of human diseases from neurological disorders to cancer. Many RBPs are conserved between Caenorhabditis elegans and humans, and several are known to regulate apoptosis in the adult C. elegans germ line. How these RBPs control apoptosis is, however, largely unknown. Here, we identify mina-1(C41G7.3) in a RNA interference-based screen as a novel regulator of apoptosis, which is exclusively expressed in the adult germ line. The absence of MINA-1 causes a dramatic increase in germ cell apoptosis, a reduction in brood size, and an impaired P granules organization and structure. In vivo crosslinking immunoprecipitation experiments revealed that MINA-1 binds a set of mRNAs coding for RBPs associated with germ cell development. Additionally, a system-wide analysis of a mina-1 deletion mutant compared to wild type, including quantitative proteome and transcriptome data, hints to a post-transcriptional regulatory RBP network driven by MINA-1 during germ cell development in C. elegans. In particular, we found that the germline-specific Argonaute WAGO-4 protein levels are increased in the mina-1 mutant background. Phenotypic analysis of double mutant mina-1;wago-4 revealed that contemporary loss of MINA-1 and WAGO-4 strongly rescues the phenotypes observed in the mina-1 mutant background. To strengthen this functional interaction, we found that upregulation of WAGO-4 in mina-1 mutant animals causes hypersensitivity to exogenous RNAi. Our comprehensive experimental approach allowed us to describe a phenocritical interaction between two RBPs controlling germ cell apoptosis and exogenous RNAi. These findings broaden our understanding of how RBPs can orchestrate different cellular events such as differentiation and death in C. elegans.
2021-09-08 | PXD011625 | Pride
Project description:We resport the changes in gene expression occuring after heat exposure in C. elegans with low s-adenosylmethionine, or RNAi of two H3K4 methyltransferases Using a C. elegans model of low SAM, we previously found that transcriptional responses response to a bacterial pathogen failed and these bacterial-response genes did not show normal H3K4me3 close to the transcriptional start sites, (Ding et al. 2015 Cell Metabolism). We also found the HMT set-16/MLL was required for full induction, whereas set-2/SET1 appeared dispensable (Ding et al. 2015 Cell Metabolism). We hypothesized that animals with low SAM might fail to transcriptionally respond to stress and that the HMTs may also have distinct roles in modulating stress responses. In our present study, we set out to compare induction of transcriptional responses and survival upon stress exposure between C. elegans with reduced SAM (sams-1(RNAi)) and animals with limited H3K4me3 function, set-2/SET1, and set-16/MLL RNAi. Because distinct stresses may rely on different transcriptional activation mechanisms, we also compared whole-genome expression patterns in three stresses: pathogenic bacteria (PA14), xenotoxic (R24) and heat in response to each RNAi.
2018-10-20 | GSE121510 | GEO
Project description:Environmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena, particularly in animals, are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. At the organismal level, this pathway plays a transgenerational role in maintaining the germline immortality when C. elegans is under a mild heat stress. However, the underlying molecular mechanism is unknown. In this study, we performed a 12-generation temperature-shift experiment (15˚C->23˚C->15˚C) using the wild type (N2) and a mutant strain that lacks the germline-specific nuclear AGO protein HRDE-1/WAGO-9. We found that the temperature-sensitive mortal germline (Mrt) phenotype of the hrde-1 mutant is reversible, indicating a transgenerational cumulative but also reversible nature of the underlying molecular cause. By taking the whole-genome RNA and chromatin profiling approaches, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes, predominantly in or near LTR retrotransposons. Strikingly, for some of these elements, the heat stress-induced transcription becomes progressively activated in the hrde-1 mutant over several generations under heat stress. Furthermore, the effect of heat stress-induced transcription activation is heritable for at least two generations after the heat stress. Interestingly, the siRNA expression of these genes tend to be heat-inducible in the wild type animals, but not in the hrde-1 mutant, suggesting a role of siRNAs in repressing heat-inducible elements. Our study revealed a novel phenomenon of transgenerational feed-forward transcriptional activation, which is normally repressed in the wild type C. elegans by the germline nuclear RNAi pathway. It also provides a new paradigm to study epigenetic circuitry that connects the environment and gene regulation in the germline.
2016-02-01 | GSE74404 | GEO
Project description:Environmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena, particularly in animals, are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. At the organismal level, this pathway plays a transgenerational role in maintaining the germline immortality when C. elegans is under a mild heat stress. However, the underlying molecular mechanism is unknown. In this study, we performed a 12-generation temperature-shift experiment (15˚C->23˚C->15˚C) using the wild type (N2) and a mutant strain that lacks the germline-specific nuclear AGO protein HRDE-1/WAGO-9. We found that the temperature-sensitive mortal germline (Mrt) phenotype of the hrde-1 mutant is reversible, indicating a transgenerational cumulative but also reversible nature of the underlying molecular cause. By taking the whole-genome RNA and chromatin profiling approaches, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes, predominantly in or near LTR retrotransposons. Strikingly, for some of these elements, the heat stress-induced transcription becomes progressively activated in the hrde-1 mutant over several generations under heat stress. Furthermore, the effect of heat stress-induced transcription activation is heritable for at least two generations after the heat stress. Interestingly, the siRNA expression of these genes tend to be heat-inducible in the wild type animals, but not in the hrde-1 mutant, suggesting a role of siRNAs in repressing heat-inducible elements. Our study revealed a novel phenomenon of transgenerational feed-forward transcriptional activation, which is normally repressed in the wild type C. elegans by the germline nuclear RNAi pathway. It also provides a new paradigm to study epigenetic circuitry that connects the environment and gene regulation in the germline.
2016-02-01 | GSE74403 | GEO
Project description:Environmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena, particularly in animals, are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. At the organismal level, this pathway plays a transgenerational role in maintaining the germline immortality when C. elegans is under a mild heat stress. However, the underlying molecular mechanism is unknown. In this study, we performed a 12-generation temperature-shift experiment (15˚C->23˚C->15˚C) using the wild type (N2) and a mutant strain that lacks the germline-specific nuclear AGO protein HRDE-1/WAGO-9. We found that the temperature-sensitive mortal germline (Mrt) phenotype of the hrde-1 mutant is reversible, indicating a transgenerational cumulative but also reversible nature of the underlying molecular cause. By taking the whole-genome RNA and chromatin profiling approaches, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes, predominantly in or near LTR retrotransposons. Strikingly, for some of these elements, the heat stress-induced transcription becomes progressively activated in the hrde-1 mutant over several generations under heat stress. Furthermore, the effect of heat stress-induced transcription activation is heritable for at least two generations after the heat stress. Interestingly, the siRNA expression of these genes tend to be heat-inducible in the wild type animals, but not in the hrde-1 mutant, suggesting a role of siRNAs in repressing heat-inducible elements. Our study revealed a novel phenomenon of transgenerational feed-forward transcriptional activation, which is normally repressed in the wild type C. elegans by the germline nuclear RNAi pathway. It also provides a new paradigm to study epigenetic circuitry that connects the environment and gene regulation in the germline.
2016-02-01 | GSE74399 | GEO
Project description:RNA interference (RNAi) is a conserved gene silencing process that exists in diverse organisms to protect genome integrity and regulate gene expression. In C. elegans, the majority of RNAi pathway proteins localize to perinuclear, phase-separated germ granules, which are comprised of sub-domains referred to as P granules, Mutator foci, Z granules, and SIMR foci. However, the protein components and function of the newly discovered SIMR foci are unknown. Here we demonstrate that HRDE-2 localizes to SIMR foci and interacts with the germline nuclear RNAi Argonaute HRDE-1. Furthermore, HRDE-1 also localizes to SIMR foci, dependent on HRDE-2, but only in its small RNA unbound state. This germ granule localization is critical to promote the small RNA binding specificity of HRDE-1 and, in the absence of HRDE-2, HRDE-1 exclusively loads CSR-class 22G-RNAs rather than WAGO-class 22G-RNAs, resulting in H3K9me3 deposition on CSR-target genes. Thus, our study demonstrates that HRDE-2 is critical to ensure that the correct small RNAs are used to guide nuclear RNA silencing in the C. elegans germline.
2023-07-27 | MSV000092546 | MassIVE
Project description:Male germ cells are sensitive to heat stress and testes must be maintained outside the body for optimal fertility. However, no germ cell intrinsic mechanism that protects from heat has been reported. Here, we identify the germ cell specific Golgi glycoprotein MGAT4D as a protector of male germ cells from heat stress. Mgat4d is highly expressed in spermatocytes and spermatids. Unexpectedly, when the Mgat4d gene was inactivated globally or conditionally in spermatogonia, or mis-expressed in spermatogonia, spermatocytes or spermatids, neither spermatogenesis nor fertility were affected. On the other hand, when males were subjected to mild heat stress of the testis (43 °C for 25 min), germ cells with inactivated Mgat4d were markedly more sensitive to the effects of heat stress, and transgenic mice expressing Mgat4d were partially protected from heat stress. Bioinformatics analyses of microarray data from heat stressed versus control germ cells showed that germ cells lacking Mgat4d generally mounted a similar heat shock response to control germ cells, but could not maintain that response. Several pathways activated by heat stress in wild type were induced to a lesser extent in Mgat4d[−/−] heat-stressed germ cells (NFκB response, TNF and TGFβ signaling, Hif1α and Myc genes). Thus, the Golgi glycoprotein MGAT4D is a novel, intrinsic protector of male germ cells from heat stress.
2020-02-24 | GSE137307 | GEO