Translation-coupled sensing and degradation of RNA-protein crosslinks [Ribo-Seq: dataset_1]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA906951 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22462570.fastq.gz | Fastqsanger.gz | |||
| SRR22462571.fastq.gz | Fastqsanger.gz | |||
| SRR22462572.fastq.gz | Fastqsanger.gz | |||
| SRR22462573.fastq.gz | Fastqsanger.gz | |||
| SRR22462574.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Translation-coupled sensing and degradation of RNA-protein crosslinks [Ribo-Seq: dataset_2]
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Project description:Translation-coupled sensing and degradation of RNA-protein crosslinks
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Project description:Reactive aldehydes are abundant cytotoxic metabolites, which challenge homoeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA-DNA crosslinks cause cancer and bone marrow failure in Fanconi anemia, while covalent DNA-protein crosslinks require proteolytic repair to prevent liver tumours and premature ageing. Whether RNA damage contributes to the toxicity of aldehydes and whether cells possess mechanisms to resolve RNA-protein crosslinks (RPCs) in particular is unknown. Studying the specific consequences of aldehyde-induced RNA damage is challenging due to confounding induction of DNA damage. Here, we establish photoactivatable ribonucleosides as a tractable model system to study aldehyde-mimicking RNA damage in the absence of DNA damage. We find that RNA crosslinking damage causes translational stress by stalling elongating ribosomes, which causes cell death upon ZAKα-dependent activation of the ribotoxic stress response (RSR) and GCN2-dependent activation of the integrated stress response (ISR). Moreover, we discover the principles of a translation-coupled cellular quality control mechanism that targets RPCs. Collisions between translating ribosomes and crosslinked mRNA-binding proteins trigger their ubiquitylation and subsequent proteasomal degradation. Our findings reveal RNA damage and RPC formation as a central aspect of aldehyde-induced toxicity and establish a framework to study the cellular responses to these threats in mechanistic detail.
2023-11-13 | GSE219055 | GEO
Project description:Reactive aldehydes are abundant cytotoxic metabolites, which challenge homoeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA-DNA crosslinks cause cancer and bone marrow failure in Fanconi anemia, while covalent DNA-protein crosslinks require proteolytic repair to prevent liver tumours and premature ageing. Whether RNA damage contributes to the toxicity of aldehydes and whether cells possess mechanisms to resolve RNA-protein crosslinks (RPCs) in particular is unknown. Studying the specific consequences of aldehyde-induced RNA damage is challenging due to confounding induction of DNA damage. Here, we establish photoactivatable ribonucleosides as a tractable model system to study aldehyde-mimicking RNA damage in the absence of DNA damage. We find that RNA crosslinking damage causes translational stress by stalling elongating ribosomes, which causes cell death upon ZAKα-dependent activation of the ribotoxic stress response (RSR) and GCN2-dependent activation of the integrated stress response (ISR). Moreover, we discover the principles of a translation-coupled cellular quality control mechanism that targets RPCs. Collisions between translating ribosomes and crosslinked mRNA-binding proteins trigger their ubiquitylation and subsequent proteasomal degradation. Our findings reveal RNA damage and RPC formation as a central aspect of aldehyde-induced toxicity and establish a framework to study the cellular responses to these threats in mechanistic detail.
2023-11-13 | GSE240135 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-11-13 | GSE240136 | GEO
Project description:Reactive aldehydes are abundant cytotoxic metabolites, which challenge homoeostasis by crosslinking cellular macromolecules. Whether RNA damage contributes to the toxicity of aldehydes and whether cells possess mechanisms to resolve RNA-protein crosslinks (RPCs) in particular is unknown. Studying the specific consequences of aldehyde-induced RNA damage is challenging due to confounding induction of DNA damage. Here, we establish photoactivatable ribonucleosides as a tractable model system to study aldehyde-mimicking RNA damage in the absence of DNA damage. The aim of this phosphoproteome measurement is to elucidate the changes in phosphorylation sites upon RPC induction using the treatment with a photoactivatable-ribonucleoside-enhanced crosslinking (PAR-CL) by incubation with 4-thiouridine (4-SU) and subsequent crosslinking by UVA irradiation.
2023-11-13 | PXD038398 | Pride
Project description:The aim of the measurements was to investigate RNA damage and RNA-protein crosslinks (RPC) formation in the context of aldehyde-induced toxicity. For this, a photoactivatable-ribonucleoside-enhanced crosslinking (PAR-CL) strategy using 4-thiouridine (4-SU) and UVA-radiation was used. The submitted dataset contains data from LC-MS/MS measurements of crosslinks between proteins and poly-adenylated mRNAs (mRPCs). The measurements included the following six samples sets: Sample set 1 (9 runs = 3 conditions in 3 replicates): RPCs after formaldehyde (FA) and 4-SU + UVA treatment isolated using the protein-x-linked RNA extraction (XRNAX) protocol (doi:10.1016/j.cell.2018.11.004) Conditions: RPCs from untreated HAP1 =Ctrl RPCs from HAP1 treated with FA RPCs from HAP1 treated with 4-SU + UVA Sample set 2 (12 runs = 4 conditions in 3 replicates): mRPCs after 4-SU + UVA treatment using poly-A pulldown Conditions: mRPCs from untreated HAP1=Ctrl mRPCs from HAP1 treated with UVA but without 4-SU (0h after irradiation) mRPCs from HAP1 treated with 4-SU but without UVA mRPCs from HAP1 treated with 4-SU + UVA (0h after irradiation) Sample set 3 (24 runs = 6 conditions in 4 replicates): mRPCs after 4-SU + UVA and Ub-E1i treatment using poly-A pulldown Conditions: mRPCs from HAP1 treated with 4-SU + UVA (0h, 0.5h and 1h after irradiation) mRPCs from HAP1 treated with 4-SU + UVA and Ub-E1i (0h, 0.5h and 1h after irradiation) Sample set 4 (24 runs = 6 conditions in 4 replicates): mRPCs after 4-SU + UVA and MG132 treatment isolated using poly-A pulldown Conditions: mRPCs from HAP1 treated with 4-SU + UVA (0h, 0.5h and 1h after irradiation) mRPCs from HAP1 treated with 4-SU + UVA and MG132 (0h, 0.5h and 1h after irradiation) Sample set 5 (24 runs = 6 conditions in 4 replicates): mRPCs after 4-SU + UVA and ANS treatment using isolated poly-A pulldown Conditions: mRPCs from HAP1 treated with 4-SU + UVA (0h, 0.5h and 1h after irradiation) mRPCs from HAP1 treated with 4-SU + UVA and ANS (0h, 0.5h and 1h after irradiation) Sample set 6 (24 runs = 6 conditions in 4 replicates ): mRPCs after 4-SU+UVA in AAVS1 control and RNF14 KO cells using poly-A pulldown mRPCs from HAP1 AAVS1 control cells (clone #6) treated with 4-SU+UVA (0h, 0.5h and 1h after irradiation) mRPCs from HAP1 RNF15 KO cells (clone #15) treated with 4-SU+UVA (0h, 0.5h and 1h after irradiation) Abbreviations: 4-SU: 4-thiouridine ANS: Anisomycine, a translation elongation inhibitor FA: Formaldehyde MG132: proteasome-inhibitor mRPCs: crosslinks between proteins and poly-adenylated mRNAs isolated by Poly-A pulldown RPCs: crosslinks between proteins and RNA isolated by XRNAX Ub-E1i: ubiquitin E1 inhibitor (E1i, TAK-243) UVA: Ultraviolet A
2023-11-03 | PXD038332 | Pride
Project description:PxP-MS (Purification of x-linked Proteins coupled to Mass Spectrometry) was used to assess the role of CSB in DNA-protein crosslink repair. The CSB protein is a sensor that can detect stalled RNA polymerases at sites of DNA damage, thereby triggering transcription-coupled repair mechanisms. DPCs were induced in WT and CSB knock-out RPE1 cells using a pulse of formaldehyde. To identify crosslinked proteins that specifically require CSB for repair, DNA-protein crosslinks were isolated from cells using PxP either directly after formaldehyde exposure or following a chase in drug-free media and identified by mass spectrometry.
2024-02-15 | PXD047668 | Pride
Project description:OGR1 is a pH sensing G protein-coupled receptor involved in intestinal homeostasis and inflammation. Up-regulation of genes, mediated by OGR1, in response to extracellular acidification were enriched for inflammation, immune response, actin cytoskeleton and cell adhesion pathways. Microarray profiling was performed to compare global gene expression of Ogr1 KO and WT residential peritoneal macrophages in response to an acidic pH shift (pH 6.7, 24 h)
2015-04-12 | E-GEOD-60295 | biostudies-arrayexpress
Project description:OGR1 is a pH sensing G protein-coupled receptor involved in intestinal homeostasis and inflammation. Up-regulation of genes, mediated by OGR1, in response to extracellular acidification were enriched for inflammation, immune response, actin cytoskeleton and cell adhesion pathways.
2015-04-12 | GSE60295 | GEO