Ontology highlight
ABSTRACT:
PROVIDER: PRJNA917260 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22949401.fastq.gz | Fastqsanger.gz | |||
| SRR22949402.fastq.gz | Fastqsanger.gz | |||
| SRR22949403.fastq.gz | Fastqsanger.gz | |||
| SRR22949404.fastq.gz | Fastqsanger.gz | |||
| SRR22949405.fastq.gz | Fastqsanger.gz |
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Project description:5-Fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5-FU on the expression and export of small RNAs into small extracellular vesicles (sEVs) and regulation of post-transcriptional small RNA modifications (PTxMs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell-cell communication. PTxMs on cellular and extracellular small RNAs provide yet another layer of gene regulation. We found that treatment of colorectal cancer (CRC) cells with 5-FU represses sEV export of miRNA and snRNA-derived RNAs, but promotes export of snoRNA-derived RNAs. Strikingly, 5-FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5-FU exposure led to increased levels of cellular small RNAs containing a variety of methyl-modified bases. Our results suggest that 5-FU exposure leads to altered expression, base modification, and mislocalization of sEV small RNAs.
2024-09-18 | GSE255876 | GEO
Project description:5-Fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5-FU on the expression and export of small RNAs into small extracellular vesicles (sEVs) and regulation of post-transcriptional small RNA modifications (PTxMs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell-cell communication. PTxMs on cellular and extracellular small RNAs provide yet another layer of gene regulation. We found that treatment of colorectal cancer (CRC) cells with 5-FU represses sEV export of miRNA and snRNA-derived RNAs, but promotes export of snoRNA-derived RNAs. Strikingly, 5-FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5-FU exposure led to increased levels of cellular small RNAs containing a variety of methyl-modified bases. Our results suggest that 5-FU exposure leads to altered expression, base modification, and mislocalization of sEV small RNAs.
2024-09-18 | GSE255875 | GEO
Project description:Pseudouridine synthases (PUSs) catalyze the isomerization of uridine (U)-to-pseudouridine (Ψ) and have emerging roles in development and disease. How PUSs adapt gene expression under stress remains mostly unexplored. We identify an unconventional role for the Ψ “writer” PUS10 impacting intracellular innate immunity. Using Pus10 knock-out mice, we uncover cell-intrinsic upregulation of interferon (IFN) signalling, conferring resistance to inflammation in vivo. Pus10 loss alters tRNA-derived small RNAs (tdRs) abundance, perturbing translation and endogenous retroelements expression. We found one of the differentially expressed tDRs is derived from tRNA glycine (tDR Gly). To delinate the tDR Gly interactome, we employed an optimized pull-down strategy using PUS10 KO cells followed by data-independent acquisition-based quantitative mass spectrometry analysis.
2025-05-27 | PXD061235 | Pride
Project description:Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation. In C. elegans, inherited small RNA precursors have poly (UG) tails, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs and their precursors. We also detect substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) in Arabidopsis pollen, and piwi-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are localized to sperm cells, and we found that PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that Exportin-t is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.
2024-04-29 | PXD042662 | Pride
Project description:Pseudouridine is an isomer of uridine and is the most common RNA modification in both procaryotes and eucaryotes. It is found in ribosomal, transfer, and other structural RNA as well as in some mRNA and non-coding RNA. We have found abundant pseudouridine in small RNA and their precursors in Arabidopsis.
2023-08-07 | GSE230228 | GEO
Project description:Pseudouridine (Ψ) is an isomer of uridine found in ribosomal, transfer and other structural RNAs as well as in some mRNAs and non-coding RNAs, but is difficult to detect in short RNA sequences. Using modified techniques we found Ψ in microRNAs (miRNAs) and their precursors from mammalian and plant cells, primarily at the 5ʹ terminus of the mature miRNA. Small RNAs targeting transposons in reproductive cells (piRNA in testis and easiRNA in pollen) were highly enriched for Ψ, indicating a potential role in epigenetic inheritance. In pollen, pseudouridylated small RNAs were produced by RNA polymerase IV and were localized to sperm cells, as were miRNAs with terminal Ψ. We show that pseudouridylated easiRNAs from pollen contribute to imprinting and the triploid block (chromosome dosage-dependent epigenetic lethality) via the activity of PAUSED/HEN5, the plant homolog of Exportin-t. Exportin-t is required for nuclear export of pseudouridylated tRNA, and we found that PSD is required for cell-cell transport of small RNA in the germline.
2023-08-07 | GSE229986 | GEO
Project description:Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation. In C. elegans, these inherited small RNAs have poly (UG) tails, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we developed novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs and their precursors. We also detected substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) in Arabidopsis pollen, and PIWI-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are produced by RNA polymerase IV and localized to sperm cells. We found that PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ synthase and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that PSD is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. We propose that Ψ has a conserved role in marking inherited small RNAs in the germline.
2023-08-07 | GSE230359 | GEO
Project description:We report RBS-Seq, a new RNA bisulfite sequencing method enabling the sensitive and simultaneous detection of m5C, pseudouridine, and m1A at single-base resolution transcriptome-wide. For each, we detect ‘signature’ base mismatches (for m5C and m1A), or 1-2 base deletions (for pseudouridine) structurally explained by ribose ring-opened pseudouridine-mono-bisulfite adducts. Our profiles for pseudouridine reveal clear signatures at known sites in tRNAs and rRNAs, and provide hundreds of new targets in non-coding RNAs and mRNAs. However, our results diverge greatly from prior work, suggesting ~10-fold fewer m5C sites, and the absence of substantial m1A in mRNAs.
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Project description:In an effort to produce a mouse model of Mitochondrial Myopathy with Lactic acidosis and Sideroblastic Anemia (MLASA), we knocked out the gene for Pseudouridine synthase 1 (PUS1), an enzyme that modifies uridine to pseudouridine in many cytoplasmic and mitochondrial tRNAs, as well as other cellular RNAs. The Pus1-/- mice are viable, are born at the expected Mendelian frequency, and are non-dysmorphic. The PUS1 mRNA and certain pseudouridine modifications are absent in cytoplasmic and mitochondrial tRNAs in the Pus1-/- mice. The Pus1-/- mice display reduce exercise capacity at 14 weeks, with alterations in muscle morphology, histology, and physiology. Red gastrocnemius muscle from Pus1-/- mice shows reduced number and size of mitochondria and reduced Cytochrome C oxidase activity. Two-condition, two-color experiment: Mouse wild type PUS1 and homozygous mutant PUS1 M1-skeletal muscle (red, slow) tissue samples: 4 biological replicates each.
2016-05-16 | E-GEOD-77821 | biostudies-arrayexpress