Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ActD timecourse in HeLa cells, HeLa RNF219 KO cells, HeLa RNF219 KO cells overexpressing 3xFLAG-SBP-RNF219-WT or 3xFLAG-SBP-RNF219-mut

ABSTRACT: The evolutionarily conserved CCR4-NOT complex acts as a central player in the control of mRNA turnover and mediates accelerated mRNA degradation upon histone deacetylase (HDAC) inhibition. Here, we explored acetylation-induced changes in the composition of the CCR4-NOT complex by purification of the endogenously tagged scaffold subunit NOT1 and identified ring finger protein 219 (RNF219) as an acetylation-regulated cofactor. We provide evidence that RNF219 is an active RING-type E3 ubiquitin ligase which stably associates with the CCR4-NOT complex via the NOT9 module through a short linear motif located in the C-terminal low-complexity region of RNF219. Using a reconstituted six-subunit human CCR4-NOT complex, we demonstrate that RNF219 acts as an inhibitor of deadenylation. Accordingly, our transcriptome-wide mRNA half-life measurements reveal that RNF219 attenuates global mRNA turnover in cells, independently of its E3 ligase activity. Our results establish RNF219 as a negative regulator of CCR4-NOT-mediated mRNA deadenylation, whose loss upon HDAC inhibition contributes to accelerated mRNA turnover.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172019 | GEO | 2021/10/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of acetylation-regulated interactors of the human CCR4-NOT complex

Project description:The evolutionarily conserved CCR4-NOT complex acts as a central player in the control of mRNA turnover and mediates accelerated mRNA degradation upon histone deacetylase (HDAC) inhibition. Here, we explored acetylation-induced changes in the composition of the CCR4-NOT complex by purification of the endogenously tagged scaffold subunit NOT1 and identified ring finger protein 219 (RNF219) as an acetylation-regulated cofactor. We provide evidence that RNF219 is an active RING-type E3 ubiquitin ligase which stably associates with the CCR4-NOT complex via the NOT9 module through a short linear motif located in the C-terminal low-complexity region of RNF219. Using a reconstituted six-subunit human CCR4-NOT complex, we demonstrate that RNF219 acts as an inhibitor of deadenylation. Accordingly, our transcriptome-wide mRNA half-life measurements reveal that RNF219 attenuates global mRNA turnover in cells, independently of its E3 ligase activity. Our results establish RNF219 as a negative regulator of CCR4-NOT-mediated mRNA deadenylation, whose loss upon HDAC inhibition contributes to accelerated mRNA turnover.

2021-12-15 | PXD027237 | Pride

RIP-CHIP data from CNOT6L WT and KO hepatocytes

Project description:mRNA poly(A) tail plays a key role in post-transcriptional regulation of gene expression, including mRNA decay and translation. Deadenylation is a rate-limiting step in mRNA decay, which is catalyzed by the CCR4-NOT complex. To identify mRNAs associated with the CCR4-NOT complex, we have done RIP-CHIP (RNA-immunoprecipitation followed by DNA microarray) using primary hepatocytes from CNOT6L wild-type and knockout mice.

2019-03-29 | GSE62365 | GEO

Cnot3-dependent mRNA deadenylation safeguards the pluripotent state

Project description:Poly(A)-tail length and mRNA deadenylation play important roles in post-transcriptional gene regulation. Here, we report the regulation of mRNA expression, half-life, and polysome association in mouse embryonic stem cells by the Cnot3 subunit in the Ccr4-Not mRNA deadenylase complex.

2016-08-10 | GSE84953 | GEO

Effects of ERG knockdown on HeLa cells mRNA stability

Project description:Control of mRNA levels is a fundamental aspect in the regulation of gene expression and is achieved through a balance between mRNA synthesis and decay. E-twenty-six-related gene (Erg) proteins are canonical transcription factors whose described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function. ERG is recruited to mRNAs via its interaction with the RNA-binding protein RBPMS and promotes mRNA decay by binding to CNOT2, a component of the CCR4 deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, and whose decay during S-phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation.

2016-04-19 | GSE80395 | GEO

Transcriptome analysis of Arabidopsis mature pollen grains from wild type and heterozygous NOT1 mutants

Project description:In flowering plants, pollen development is under a dynamic and well-orchestrated transcriptional control, characterized by an early phase with high transcript diversity and a late post-mitotic phase skewed to a cell-type specific-transcriptome. Such transcriptional changes require a balance between synthesis and degradation of mRNA transcripts, the latter being initiated by deadenylation. The CCR4-NOT complex is the main evolutionary conserved deadenylase complex in eukaryotes, and its function is essential during germline specification in animals. We hypothesised that the CCR4-NOT complex might play a central role in mRNA turnover during microgametogenesis in Arabidopsis. Disruption of NOT1 gene, which encodes the scaffold protein of the CCR4-NOT complex, showed abnormal seed set. Genetic analysis failed to recover homozygous progeny and reciprocal crosses confirmed reduced transmission through the male and female gametophytes. Concordantly not1 embryo sacs showed delayed development and defects in embryogenesis. not1 pollen grains exhibited abnormal male germ unit configurations and failed to germinate. Transcriptome analysis of pollen from not1/+ mutants revealed that lack of NOT1 leads to an extensive transcriptional deregulation during microgametogenesis. Therefore, our work establishes NOT1 as an important player during gametophyte development in Arabidopsis.

2020-04-24 | GSE133490 | GEO

Spt6 association with RNAPII directs mRNA turnover during transcription

Project description:Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 interacts with elongating RNA polymerase II (RNAPII) via a tandem Src2 homology (tSH2) domain, but it is not known whether this particular interaction is required for the nucleosome reassembly activity of Spt6. Here, we show that Spt6 recruitment to genes and its nucleosome reassembly functions are largely independent of association with RNAPII. Instead, the Spt6-RNAPII association is required for post-transcriptional mRNA turnover. Mechanistically, association of Spt6 with RNAPII couples the Ccr4-Not complex to the transcribed regions of genes, which we show regulates the timely deadenylation and degradation of a broad range of mRNAs including those required for cell cycle progression. Thus, our findings reveal an unexpected control mechanism for mRNA turnover facilitated by a histone chaperone during transcription.

2018-04-18 | GSE111815 | GEO

Nanopore RNA sequencing in S. cerevisiae strains defective for decapping and deadenylation

Project description:RNA turnover in eukaryotes is triggered by decapping, believed to be activated mostly after deadenylation. To investigate simultaneous changes in RNA levels and poly(A) tail size we performed Nanopore RNA sequencing on total RNA extracted from S. cerevisiae strains in which the decapping enzyme Dcp2, or the deadenylation factors Ccr4 and Pop2 were depleted through an inducible degron system. Two fully independent replicate experiments were performed for wild type and the two mutant conditions.

2022-10-01 | GSE211782 | GEO

The Ccr4-Not complex monitors the translating ribosome for codon optimality

Project description:Control of messenger RNA (mRNA) decay rate is intimately connected to translation elongation, but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. We used a combination of cryo–electron microscopy, ribosome profiling, and mRNA stability assays to examine the recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site in Saccharomyces cerevisiae. This interaction occurred when the ribosome lacked accommodated A-site transfer RNA, indicative of low codon optimality. Loss of the interaction resulted in the inability of the mRNA degradation machinery to sense codon optimality. Our findings elucidate a physical link between the Ccr4-Not complex and the ribosome and provide mechanistic insight into the coupling of decoding efficiency with mRNA stability.

2020-04-16 | GSE144250 | GEO

The Ccr4-Not complex monitors the translating ribosome for codon optimality

2020-04-16 | GSE131408 | GEO

RNAi knock-down of CAF1-CCR4-NOT1 deadenylase complex or AGO1 in D. melanogaster S2 cells

Project description:miRNAs silence gene expression by repressing translation and/or by promoting mRNA decay. AGO1 is a key protein required for miRNA-mediated gene silencing. In animal cells, mRNA degradation of partially complementary miRNA targets occurs via deadenylation by the CAF1-CCR4-NOT1 deadenylase complex, followed by decapping and subsequent exonucleolytic digestion. To determine how generally miRNAs trigger deadenylation, we compared mRNA expression profiles in D. melanogaster cells depleted of AGO1, CAF1 or NOT1. We show that approximately 45% of AGO1-targets are regulated by both CAF1 and NOT1, indicating deadenylation is a widespread effect of miRNA regulation.<br><br>We employed RNA interference using long double-stranded RNAs to deplete cultured S2 cells of AGO1 (CG6671, 2 independent samples), CAF1 (CG5684, 2 independent samples), or NOT1 (CG1884, 3 independent samples). Further, we used Affymetrix oligonucleotide microarrays to analyze expression profiles in these samples. We included the following controls: mock RNAi treatment and GFP dsRNA treatment (3 and 2 independent samples, respectively).<br>

2008-12-03 | E-MEXP-1713 | biostudies-arrayexpress

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