Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14460862.fastq.gz | Fastqsanger.gz | |||
| SRR14460863.fastq.gz | Fastqsanger.gz | |||
| SRR14460864.fastq.gz | Fastqsanger.gz | |||
| SRR14460865.fastq.gz | Fastqsanger.gz | |||
| SRR14460866.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Functional genomic analyses of exopolysaccharide-producing Streptococcus thermophilus ASCC 1275 in response to shifts in milk fermentation conditions
| MSV000083741 | MassIVE
Project description:Central to genotoxic responses is their ability to sense highly specific signals to activate the appropriate repair response. We previously reported that the activation of the ASCC-ALKBH3 repair pathway is exquisitely specific to alkylation damage in human cells. Yet the mechanistic basis for the selectivity of this pathway was not immediately obvious. Here, we demonstrate that RNA but not DNA alkylation is the initiating signal for this process. Aberrantly methylated RNA is sufficient to recruit ASCC, while an RNA dealkylase suppresses ASCC recruitment during chemical alkylation. In turn, recruitment of ASCC during alkylation damage, which is mediated by the E3 ubiquitin ligase RNF113A, suppresses transcription and R-loop formation. We further show that alkylated pre-mRNA is sufficient to activate RNF113A E3 ligase in vitro in a manner dependent on its RNA binding Zn-finger domain. Together, our work identifies an unexpected role for RNA damage in eliciting a specific response to genotoxins.
2021-02-01 | GSE158090 | GEO
Project description:Anal squamous cell carcinoma (ASCC) is an infrequent tumor. Since 70s, treatment of stages II-III consists on a combination of 5-fluorouracil (5FU), mitomycin C (MMC), and radiotherapy. The aim of this study is the identification of biomarkers that allow personalized treatment and improvement of therapeutic outcomes. Forty-six tumor paraffin samples from ASCC patients were analyzed by whole-exome sequencing. Single nucleotide polymorphisms and copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied using BRB Array Tool and Kaplan-Meier analyses. Obtained findings were validated in an independent retrospective cohort of 101 ASCC patients with stages I-III from eleven hospitals within the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD) using qPCR Copy Number Assays. GEMCAD validation cohort was also analyzed using mass spectrometry proteomics to assess the biological features of these tumors.
2023-04-26 | PXD037816 | Pride
Project description:Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy that is linked to high-risk Human papillomavirus (HPV) infection. It is often preceded by precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). The incidence of ASCC varies across populations, with heightened risk in HIV-positive individuals. In a previous study, we characterized the anal microbiome in high-risk HIV-exposed MSM and TGW subjects. We revealed oncogenic viromes and pertinent bacterial species associated with anal SILs. Our current investigation aimed to delineate transcriptomic and metatranscriptomic changes during the progression from precancerous lesions to ASCC. We collected 70 anal tissue samples across various lesion stages (LGSIL, HGSIL, and ASCC). Our metatranscriptomic analysis revealed that Fusobacterium nucleatum, F. gonidiaformans, Bacteroides fragilis, Campylobacter ureolyticus, and Cribacterium bergeronii were more prevalent in ASCC than in precancerous lesions. These bacterial species contributed with gene encoding enzymes (e.g.: Acca, glyQ, eno, pgk and por) and oncoproteins (FadA and dnaK) revealing potential new markers for diagnosis or treatment approaches. Our unsupervised transcriptome analysis identified two distinct sample clusters based on histological diagnosis, immune infiltrate, HIV and HPV status, and pathway activities such as immune activation, cell cycle, and antiviral signaling that recapitulate the natural history of anal cancer progression. Mutations were observed affecting KMT2C (30%), PIK3CA (21%), EP300 (21%) and NOTCH1 (13%) cancer driver genes among ASCC but also in precancerous lesions. Our study provides insights into the molecular mechanisms governing anal cancer progression, offering valuable information that may help to stratify HGSIL cases with low- or high-risk progression to the malignant stages.
2024-08-04 | GSE253560 | GEO
Project description:Translation is initiated by binding of the eIF4F complex to the 5' cap of the mRNA, which is followed by scanning of the initiation codon by scanning ribosomes. Here we demonstrate that the ASC-1 complex (ASCC), which was previously shown to promote the dissociation of colliding 80S ribosomes, associates with the scanning ribosomes to regulate translation initiation. Sel-TCP-seq analysis revealed that ASCC3, a subunit of ASCC with a helicase domain, localizes predominantly to the 5' untranslated region of mRNAs. Knockdown of ASCC3 resulted in reduced translation efficiency associated with reduced 43S preinitiation complex (PIC) loading and a reduced speed of scanning ribosomes. In addition, depletion of the ubiquitin ligase ZNF598, a sensor of collided 80S ribosomes, also reduces the PIC loading and speed of scanning ribosomes. Our results have thus revealed that ASCC is required not only for dissociation of colliding 80S ribosomes, but also for efficient translation initiation by scanning ribosomes.
2023-03-31 | GSE186502 | GEO
Project description:Activating signal co-integrator complex (ASCC) supports diverse genome maintenance and gene expression processes. Its ASCC3 subunit is an unconventional nucleic acid helicase, harboring tandem Ski2-like NTPase/helicase cassettes crucial for ASCC functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regulation remain unresolved. Here, we present cryogenic electron microscopy, DNA-protein cross-linking/mass spectrometry as well as in vitro and cellular functional analyses of the ASCC3-ASC1/TRIP4 sub-module of ASCC. Unlike the related spliceosomal SNRNP200 RNA helicase, ASCC3 can thread substrates through both helicase cassettes. ASC1 docks on ASCC3 via a zinc finger domain and stimulates the helicase by positioning a C-terminal ASC1-homology domain next to the C-terminal helicase cassette of ASCC3, likely assisting the DNA exit. ASC1 binds ASCC3 mutually exclusively with the dealkylase, ALKBH3, directing ASCC for specific ASCC-dependent processes. Our findings define ASCC3-ASC1/TRIP4 as a tunable motor module of ASCC that encompasses two cooperating ATPase/helicase units functionally expanded by ASC1/TRIP4.
2023-03-06 | PXD036106 | Pride
Project description:Translation of damaged mRNA can lead to ribosome stalling, thereby producing incomplete proteins toxic to the cell. The mechanism of ribosome-associated quality control (RQC) disassembles stalled ribosomes through the actions of the ASC-1 complex (ASCC). Here, we show that some reagents that chemically damage RNA, such as ultraviolet light (UV), cause ribosome stalling, which leads to accumulation of the ASC-1 complex (ASCC) on stalled ribosomes and stable interaction of the ASCC3 helicase with RNA. In contrast, the ASCC was not similarly affected by emetine or anisomycin-induced ribosome stalling. Our work identified two different types of stalled ribosome. Ribosomes arrested by emetine or anisomycin are transient as they are resolved by the ASCC. Whereas the ASCC fails to split some stalled ribosomes, such as those induced by UV, resulting in long-lived stalled ribosome complexes. We show that ribosome stalling activates the G1/S and G2/M cell cycle checkpoints with long-lived stalled ribosomes causing prolonged checkpoint activation. Thus, the cell adjusts this adaptive survival response to match the nature of the stalled ribosome.
2022-02-07 | PXD023861 | Pride
Project description:Translation of damaged mRNA can lead to ribosome stalling, thereby producing incomplete proteins toxic to the cell. The mechanism of ribosome-associated quality control (RQC) disassembles stalled ribosomes through the actions of the ASC-1 complex (ASCC). Here, we show that some reagents that chemically damage RNA, such as ultraviolet light (UV), cause ribosome stalling, which leads to accumulation of the ASC-1 complex (ASCC) on stalled ribosomes and stable interaction of the ASCC3 helicase with RNA. In contrast, the ASCC was not similarly affected by emetine or anisomycin-induced ribosome stalling. Our work identified two different types of stalled ribosome. Ribosomes arrested by emetine or anisomycin are transient as they are resolved by the ASCC. Whereas the ASCC fails to split some stalled ribosomes, such as those induced by UV, resulting in long-lived stalled ribosome complexes. We show that ribosome stalling activates the G1/S and G2/M cell cycle checkpoints with long-lived stalled ribosomes causing prolonged checkpoint activation. Thus, the cell adjusts this adaptive survival response to match the nature of the stalled ribosome.
2022-02-07 | PXD023976 | Pride
Project description:Translation of damaged mRNA can lead to ribosome stalling, thereby producing incomplete proteins toxic to the cell. The mechanism of ribosome-associated quality control (RQC) disassembles stalled ribosomes through the actions of the ASC-1 complex (ASCC). Here, we show that some reagents that chemically damage RNA, such as ultraviolet light (UV), cause ribosome stalling, which leads to accumulation of the ASC-1 complex (ASCC) on stalled ribosomes and stable interaction of the ASCC3 helicase with RNA. In contrast, the ASCC was not similarly affected by emetine or anisomycin-induced ribosome stalling. Our work identified two different types of stalled ribosome. Ribosomes arrested by emetine or anisomycin are transient as they are resolved by the ASCC. Whereas the ASCC fails to split some stalled ribosomes, such as those induced by UV, resulting in long-lived stalled ribosome complexes. We show that ribosome stalling activates the G1/S and G2/M cell cycle checkpoints with long-lived stalled ribosomes causing prolonged checkpoint activation. Thus, the cell adjusts this adaptive survival response to match the nature of the stalled ribosome.
2022-02-07 | PXD023978 | Pride
Project description:Translation of damaged mRNA can lead to ribosome stalling, thereby producing incomplete proteins toxic to the cell. The mechanism of ribosome-associated quality control (RQC) disassembles stalled ribosomes through the actions of the ASC-1 complex (ASCC). Here, we show that some reagents that chemically damage RNA, such as ultraviolet light (UV), cause ribosome stalling, which leads to accumulation of the ASC-1 complex (ASCC) on stalled ribosomes and stable interaction of the ASCC3 helicase with RNA. In contrast, the ASCC was not similarly affected by emetine or anisomycin-induced ribosome stalling. Our work identified two different types of stalled ribosome. Ribosomes arrested by emetine or anisomycin are transient as they are resolved by the ASCC. Whereas the ASCC fails to split some stalled ribosomes, such as those induced by UV, resulting in long-lived stalled ribosome complexes. We show that ribosome stalling activates the G1/S and G2/M cell cycle checkpoints with long-lived stalled ribosomes causing prolonged checkpoint activation. Thus, the cell adjusts this adaptive survival response to match the nature of the stalled ribosome.
2022-02-07 | PXD023878 | Pride