Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Atypical K6-linked ubiquitylation marks toxic RNA-protein crosslinks induced by formaldehyde

ABSTRACT: Atypical K6-linked ubiquitylation marks toxic RNA-protein crosslinks induced by formaldehyde

PROVIDER: PRJNA933609 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23400936_1.fastq.gz	Fastqsanger.gz
	SRR23400936_2.fastq.gz	Fastqsanger.gz
	SRR23400937_1.fastq.gz	Fastqsanger.gz
	SRR23400937_2.fastq.gz	Fastqsanger.gz
	SRR23400938_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Atypical K6-linked ubiquitylation marks toxic RNA-protein crosslinks induced by formaldehyde

Project description:Reactive aldehydes are produced during cellular metabolism and can accumulate in specific tissues particularly when aldehyde clearance mechanisms are impaired. Reactive aldehydes induce DNA-DNA and DNA-protein crosslinks (DPCs) that are repaired by different DNA repair pathways. Cellular toxicity of endogenous formaldehyde has been attributed to the damage of the genomic DNA and consequent inhibition of transcription. However, whether damage to other cellular macromolecules and interference with additional metabolic processes contributes to formaldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces toxic RNA-protein crosslinks (RPCs) in mRNA that inhibit translation and induce a specific RPC stress response pathway that is characterized by linkage-specific ubiquitylation. RPCs in the mRNA are recognized by stalling ribosomes and marked by K6-linked ubiquitylation that promotes their clearance by the ubiquitin-dependent unfoldase VCP.

2023-09-01 | GSE225044 | GEO

K6-Linked Ubiquitylation Marks Formaldehyde-Induced RNA–Protein Crosslinks for Resolution

Project description:Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA–protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-Between-RING E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.

2023-11-13 | PXD038655 | Pride

K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

Project description:Reactive aldehydes induce the formation of RNA-protein crosslinks (RPCs), RPCs in the mRNA stall the ribosome and inhibit translation, RPCs are K6-linked ubiqutylated by RBR-type E3 ligase RNF14, RPCs are resolved in a UBXN1-VCP/p97-dependent manner

2023-11-03 | GSE240625 | GEO

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

Project description:VCP is an evolutionary conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells. We demonstrate that inhibition of VCP perturbs cellular ubiquitylation and increases ubiquitylation of a different subset of proteins compared to proteasome inhibition. VCP inhibition globally upregulates K6-linked ubiquitylation that is dependent on the HECT-type ubiquitin E3 ligase HUWE1. We report ~450 putative VCP substrates, many of which function in nuclear processes, including gene expression, DNA repair and cell cycle. Moreover, we identify that VCP regulates the level and activity of the transcription factor c-Myc.

2018-02-08 | GSE107313 | GEO

K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

Project description:K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

| PRJNA1004331 | ENA

Identification of formaldehyde-induced DNA-protein crosslinks by PxP-MS

Project description:Compromised enzymatic actions, reactive metabolites, and various chemotherapeutics cause toxic covalent DNA-protein crosslinks (DPCs). Failure to repair DPCs results in genomic instability, premature aging, and tumorigenesis. However, understanding the principles underlying DPC formation and repair has been hampered by a lack of methodologies to study DPCs in human cells. Here, we developed a technique for the Purification of x-linked Proteins (PxP), which allows identification and tracking of enzymatic and nonenzymatic DPCs. By combining PxP with quantitative proteomics, we investigated the nature of DPCs induced by formaldehyde.

2023-01-20 | PXD026654 | Pride

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

2018-02-09 | PXD003936 | Pride

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

Project description:Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

| PRJNA419745 | ENA

RNF14-dependent atypical ubiquitylation promotes translation-coupled resolution of RNA-protein crosslinks.

Project description:Reactive aldehydes are abundant endogenous metabolites that challenge homeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA damage requires repair to prevent cancer and premature aging, but it is unknown whether cells also possess mechanisms that resolve aldehyde-induced RNA lesions. Here, we establish photoactivatable ribonucleoside-enhanced crosslinking (PAR-CL) as a model system to study RNA crosslinking damage in the absence of confounding DNA damage in human cells. We find that such RNA damage causes translation stress by stalling elongating ribosomes, which leads to collisions with trailing ribosomes and activation of multiple stress response pathways. Moreover, we discovered a translation-coupled quality control mechanism that resolves covalent RNA-protein crosslinks. Collisions between translating ribosomes and crosslinked mRNA-binding proteins trigger their modification with atypical K6- and K48-linked ubiquitin chains. Ubiquitylation requires the E3 ligase RNF14 and leads to proteasomal degradation of the protein adduct. Our findings identify RNA lesion-induced translational stress as a central component of crosslinking damage.

| S-EPMC10783637 | biostudies-literature

Translation-coupled sensing and degradation of RNA-protein crosslinks [Ribo-Seq: dataset_1]

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data