Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increase in harmful R-loops associates with different alterations in mRNP composition

ABSTRACT: Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insights into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose stoichiometry is important for limiting R-loop accumulation and, consequently, preventing DNA damage. Notably, Rim4 and She2 are overrepresented in mRNPs assembled in the absence of THO. Additionally, we found that an excess of Dis3 impairs exosome function, promoting R-loops, particularly from non-coding RNAs, that causes genomic instability. Our results indicate that mRNP assembly is a precise process that when perturbed by changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may have important implications for understanding the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast) Saccharomyces Cerevisiae

SUBMITTER: Guillaume CHEVREUX

LAB HEAD: Ana G. Rondón

PROVIDER: PXD057248 | Pride | 2025-06-13

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	1317004-1.raw	Raw
	1317004-10.raw	Raw
	1317004-11.raw	Raw
	1317004-12.raw	Raw
	1317004-2.raw	Raw

Items per page:

1 - 5 of 16

Similar Datasets

R-loops are marks for histone H3 Ser10 phosphorylation and chromatin compaction

Project description:R-loops are transcription by-products that may constitute a threat to genome integrity. In addition to specific enzymes to remove them, eukaryotes rely on a number of mRNP biogenesis factors such as the THO complex, to prevent co-transcriptional R-loop formation. We show in Saccharomyces cerevisiae that R-loops are tightly and specifically linked with histone H3-Ser10 phosphorylation (H3S10P), a mark of chromatin condensation. Importantly, ChIP-chip analyses reveal a clear H3S10P accumulation at the pericentromeric chromatin during the G1-phase of the cell cycle only in R loop-accumulating yeast strains but not in those non-accumulating R-loops, and a significantly higher accumulation during S-phase. Such a difference can also be detected in a number of genes along the genome. ChIP-chip studies were perfomed with antibodies against Histone H3 and the phosphorylated Histone H3 at Serine10 in the yeast S. cerevisiae.

2013-11-13 | E-GEOD-46627 | biostudies-arrayexpress

Expression data from Saccharomyces cerevisiae strains deleted for different subunits of the THO/TREX complex

Project description:THO/TREX is a conserved nuclear complex that functions in mRNP biogenesis at the interface of transcription-RNA export with a key role in preventing transcription-associated genome instability. We used microarrays to analyze the impact of different THO/TREX mutations on gene expression and found that THO-Sub2 deletions have a high functional impact on highly expressed, long and G+C-rich genes regardless of gene function.

2011-06-29 | GSE24802 | GEO

Expression data from Saccharomyces cerevisiae strains deleted for different subunits of the THO/TREX complex

2011-06-28 | E-GEOD-24802 | biostudies-arrayexpress

R-loops are marks for histone H3 Ser10 phosphorylation and chromatin compaction

2013-11-13 | GSE46627 | GEO

Expression data from Saccharomyces cerevisae strains deleted for the RNA-binding hnRNP Npl3

Project description:Transcription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and some heterogeneous nuclear ribonucleoproteins (hnRNPs) mutants. We used microarrays to the global impact of Npl3 in gene expression and found that Npl3 deletion has a functional impact in highly-expressed, long and G+C rich genes regardless of gene function. S. cerevisiae strains were grown in YPD liquid culture, total RNA was isolated and hybridized on Affymetrix microarrays.

2013-11-15 | E-GEOD-50186 | biostudies-arrayexpress

UAP56/DDX39b is a major co-transcriptional RNA-DNA helicase that unwinds harmful R loops genome-wide

Project description:Non-scheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R loop accumulation. One mechanism relies on the conserved THO complex in association with co-transcriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R loop removal. We show that UAP56 depletion causes R loop accumulation, R loop-mediated genome instability and replication fork stalling. We demonstrate an RNA-DNA helicase activity in UAP56 and that its overexpression suppresses R loops and genome instability induced by depleting 5 different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA-DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful co-transcriptional RNA structures that otherwise would block transcription and replication.

2020-05-25 | GSE127979 | GEO

Expression data from Saccharomyces cerevisae strains deleted for the RNA-binding hnRNP Npl3

2013-11-15 | GSE50186 | GEO

Harmful R loops are prevented via different cell cycle specific mechanisms

Project description:R loops induce transcription-replication (T-R) conflicts, but recent reports have suggested that R-loops are caused by T-R conflicts. Identifying how R loops are generated is crucial to know how transcription compromise genome integrity. Genome-wide analyses of conditional yeast mutants reveal that transcription factors, such as the THO complex. prevents R loop formation in G1 and S-phase, whereas the Sen1 DNA-RNA helicase prevents them only in S-phase. Interestingly, damage accumulates asymmetrically downstream of the RF in sen1 cells but symmetrically in the hpr1 THO mutant. Our results unambiguously indicate that: R loops forms co-transcriptionally independently of DNA replication; THO is a general and cell-cycle independent safeguard against R loops, and Sen1, in contrast to previously believed, is an S-phase-specific R loop resolvase. These conclusions have important implications for the mechanism of R loop formation and the role of other factors reported to impact on R loop homeostasis

2021-07-22 | GSE159870 | GEO

Expression data from Saccharomyces cerevisiae strains deleted for the THSC/TREX-2 subunits Thp1, Sac3 and Sus1

Project description:Transcription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and the NPC-associated THSC/TREX-2 complex. We used microarrays to analyze the global impact of THSC/TREX-2 in gene expression and found that Thp1 and Sac3 depletion has a functional impact in highly-expressed, long and G+C-rich genes regardless of their function

2014-10-08 | GSE56702 | GEO

ChIP-chip data of Npl3-Myc and Rrm3-Flag in wild-type and npl3∆ cells

Project description:Transcription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and some heterogeneous nuclear ribonucleoproteins (hnRNPs) mutants. Here we show that yeast npl3∆ cells show genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells.

2013-11-15 | GSE50185 | 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