Engineering Human PEG10-based Nanoparticles for RNA Self-packaging, Delivery and Cancer Therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE331505 | GEO | 2026/06/13
REPOSITORIES: GEO
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Project description:Engineering Human PEG10-based Nanoparticles for RNA Self-packaging, Delivery and Cancer Therapy
| PRJNA1468507 | ENA
Project description:The prevailing dogma that approximately 50% of our genome is “junk” DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed “domestication of transposable elements” and the majority of these genes have been found to be essential for the existence of the organism. One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years. Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification.
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Project description:During mammalian spermiogenesis, the majority of the nucleosomes packaging the male haploid genome are replaced by protamines to produce a highly compact chromatin architecture that is critical to male fertility. We have carried out a genomewide survey of murine spermatozoal chromatin using a micrococal nuclease approach to characterise the DNA sequences that remain packaged by histones.
2009-06-09 | GSE15941 | GEO
Project description:During mammalian spermiogenesis, the majority of the nucleosomes packaging the male haploid genome are replaced by protamines to produce a highly compact chromatin architecture that is critical to male fertility. We have carried out a genomewide survey of human spermatozoal chromatin using both a salt and micrococal nuclease approach to characterise the DNA sequences that remain packaged by histones.
2009-06-09 | GSE12088 | GEO
Project description:Viruses package host RNAs in their virions which are associated with a range of functions in the viral life cycle. Previous transcriptomic profiling on host RNA packaging were mostly focused on retroviruses. Which host RNAs are packaged in other viruses at the transcriptome level has not been thoroughly examined. Here we apply both small RNA and large RNA sequencing of SARS-CoV-2 virions from six individual isolates in Vero cell cultures to profile packaging of host RNAs in a coronavirus and to explore SARS-CoV-2 genomic RNA modifications. We find selective packaging of specific tRNAs, tRNA fragments and signal recognition particle RNA into SARS-CoV-2 virions. Virions from all individual clones package the same set of host RNAs, suggesting a common mechanism of selective packaging. We estimate that a SARS-CoV-2 virion contains up to 1 SRP RNA and 4 tRNA molecules. We identify tRNA modification differences between the virion-packaged tRNAs and those in the uninfected host cells. Furthermore, we find subgenomic viral RNAs in the virions, and uncharacterized candidate modifications in the SARS-CoV-2 genomic RNA. Our results reveal an under-explored aspect of viral-host interaction that may be explored for viral therapeutics.
2022-03-06 | GSE182883 | GEO
Project description:The goal of this study was to determine transcriptional changes in HEK293 cells upon overexpression of various forms of Paternally Expressed Gene 10, or PEG10. Cells were transfected either with control, or with PEG10 gag, gag-pol, or isolated NC fragment constructs and RNA isolated for RNA-Seq analysis.
2023-03-29 | GSE227789 | GEO
Project description:The prevailing dogma that approximately 50% of our genome is “junk” DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed “domestication of transposable elements” and the majority of these genes have been found to be essential for the existence of the organism. One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years. Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification.
2019-03-22 | GSE122216 | GEO
Project description:Rhodobacter capsulatus produces a gene transfer agent (GTA) called RcGTA. RcGTA is a phage-like particle that packages R. capsulatus DNA and transfers it to other R. capsulatus cells. Low-resolution techniques suggested RcGTA packages random DNA. Analysis of the RcGTA terminase sequence revealed a distant relationship to the phage T4 terminase protein, which can also perform sequence-independent packaging. We quantified the relative frequency of packaging for each gene in the genome by hybridization of DNA from RcGTA particles to an R. capsulatus microarray. All genes were found within the RcGTA particles, and random packaging was observed at a genome-wide scale. However, the genes encoding the RcGTA particle were under-packaged compared to other regions. Single-cell expression analysis demonstrated that RcGTA gene expression is not uniform within a culture. We propose a mechanism by which high levels of RcGTA gene transcription in the most active RcGTA producing cells hinders access of the packaging machinery to these genes, which causes a reduction in their packaging frequency. This sub-population gene expression phenomenon likely explains the lack of observed cell lysis in RcGTA producing cultures. DNA extracted from within RcGTA particles produced by DE442, an RcGTA overproducer, was hybridized to an Affymetrix genechip custom array in order to quantify the relative frequency with which any given gene was packaged within the particles. These data were MAS5 normalized. An underlying packaging bias was suspected to be transcription related, so these frequencies were compared to expression levels within the population, as determined by hybridization of late-stationary RNA samples of DE442 and of the wildtype (SB1003) to the same custom array. These data were RMA normalized.
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Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC.
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Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC.
2015-01-05 | GSE59984 | GEO