Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FUS KO mRNA sequencing and anti-FUS RNA immunoprecipitation sequencing

ABSTRACT: The aim of our study is to identify the role of FUS in shaping the transcriptome. RNA-seq of two FUS KO clones was performed and compared to wt; for each, four replicates were sequenced. RNA molecules associated with the FUS protein were determined by means of a RNA immuno-precipitation, followed by high-throughput sequencing. Total RNA was used as a control. SH-SY5Y cells were used for both experiments. RNA-seq: 4 wt samples, 4 A4 KO samples, 4 A5 KO samples. RIP-seq: 1 input control sample, 3 anti-FUS IP replicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Oliver Muehlemann

PROVIDER: E-GEOD-71812 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants.

Reber Stefan S Stettler Jolanda J Filosa Giuseppe G Colombo Martino M Jutzi Daniel D Lenzken Silvia C SC Schweingruber Christoph C Bruggmann Rémy R Bachi Angela A Barabino Silvia Ml SM Mühlemann Oliver O Ruepp Marc-David MD

The EMBO journal 20160601 14

Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to mi ...[more]

PMID: 27252488

Similar Datasets

Mutant FUS triggers age-dependent synaptic impairment in presymptomatic ALS-FUS mice (CLIP-seq)

Project description:FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNA, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages. Despite apparently unaltered synaptic organization, RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS relocalization to the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.

2021-03-05 | E-MTAB-9211 | biostudies-arrayexpress

Identification of FUS RNA targets in HeLa cells

Project description:We identified a landscape of FUS-binding RNA targets in HeLa cells. The majority of the FUS binding sites are in introns of pre-mRNAs and less are in exons and untranslated regions. Significant FUS binding in introns flanking cassette exons, long intron (>100kb) containing transcripts and noncoding RNAs were detected in our study. We specifically determined the function of FUS in regulating the alternative splicing of cassette exons. The top FUS-associated cassette exon is exon 7 of the pre-mRNA of FUS itself. We demonstrated that FUS is a repressor of its own exon 7 splicing. FUS autoregulates its own protein levels by exon 7 alternative splicing and nonsense mediated decay. Moreover, Amyotrophic Lateral Sclerosis (ALS) linked FUS mutants are deficient in FUS autoregulation. CLIP-seq of FUS in HeLa cells

2013-12-16 | E-GEOD-50178 | biostudies-arrayexpress

Identification of in vivo, conserved, FUS RNA binding sites and the impact of FUS on the neuronal transcriptome

Project description:FUS, an RNA binding protein was recently implicated in Amyotrophic Lateral Sclerosis (ALS). ALS is a fatal neurodegenerative disease. We report the identification of the conserved neuronal RNA targets of FUS and the assessment of the impact of FUS depletion on the neuronal transcriptome. We identified that FUS regulates splicing of conserved intron containing transcripts. FUS retains or excludes the conserved intron by binding to them. Identification of FUS neuronal targets using normal human brain samples and mouse neurons

2013-01-25 | E-GEOD-43308 | biostudies-arrayexpress

Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_Stability]

Project description:TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3â untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).

2016-07-05 | E-GEOD-77704 | biostudies-arrayexpress

HITS-CLIP analysis of FUS in lineage-committed cells.

Project description:In the present study, we performed HITS-CLIP analysis for FUS using mouse brain to extensively characterize tits RNA-binding sites and functional roles in RNA metabolisms. We identified preferential binding of FUS to stem-and-loop structures but without any discernible consensus motifs. FUS was preferentially bound to introns and 3' untranslated regions, but the exon/intron boundaries were mostly devoid of FUS-tags. Analysis of position-dependence of FUS-binding sites in regulating inclusion and skipping of exons disclosed that FUS is bound broadly around the alternatively spliced exons. Among them, however, noticeable CLIP-tags were observed in the downstream introns. We also noticed that FUS occasionally binds to the antisense strands in the promoter regions. Global analysis of CLIP-tags and expression profiles revealed that binding of FUS to the promoter antisense regions downgregulates transcription of the sense strand. HITS-CLIP (High Throughput Sequencing after Crosslinking and Immunoprecipitation) experiments targeting FUS in mouse cerebrums derived from 12-week-old C57BL/6 mice

2012-07-26 | E-GEOD-37190 | biostudies-arrayexpress

A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy - PART 3

Project description:Mutations in proteins like FUS which cause Amyotrophic Lateral Sclerosis (ALS) result in the aberrant formation of stress granules while ALS-linked mutations in other proteins impede elimination of stress granules. Repeat expansions in C9ORF72, the major cause of ALS, reduce C9ORF72 levels but how this impacts stress granules is uncertain. Here, we demonstrate that C9ORF72 associates with the autophagy receptor p62 and controls elimination of stress granules by autophagy. This requires p62 to associate via the Tudor protein SMN with proteins, including FUS, that are symmetrically arginine-methylated by PRMT5. Mice lacking p62 accumulate arginine-methylated proteins and alterations in FUS-dependent splicing. Finally, patients with C9ORF72 repeat expansions accumulate symmetric arginine dimethylated proteins which co-localize with p62. This suggests that C9ORF72 initiates a cascade of ALS-linked proteins (C9ORF72, p62, SMN, FUS) to recognize stress granules for degradation by autophagy and hallmarks of a defect in this process are observable in ALS patients.

2018-07-25 | PXD009760 | Pride

RNA-seq to investigate the phase separation-dependent FUS RNA interactome

Project description:The protein Fused in Sarcoma undergoes liquid-liquid phase separation. To investigate whether this phase transition alters the RNA interactome we purified phase-separated FUS droplets and soluble FUS from HEK 293T cells transfected with GFP-tagged WT FUS or P525L FUS. Phase separated FUS was purified by fluorescence-activated particle sorting (droplets) and soluble FUS by co-Immunoprecipitation (IP) respectively followed by isolation of co-purified RNA. Here we show that phase separation affects the RNA interactome of FUS.

2021-06-23 | E-MTAB-8456 | biostudies-arrayexpress

Mutant FUS triggers age-dependent synaptic impairment in presymptomatic ALS-FUS mice (RNA-seq)

2021-03-05 | E-MTAB-9212 | biostudies-arrayexpress

The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia

Project description:Fusion proteins involving the ETS factor ERG have been associated with multiple cancers such as Ewing's sarcoma and prostate cancer. In acute myeloid leukemias harboring t(16;21) another ERG fusion protein is expressed, FUS-ERG. Here, we found that this FUS-ERG oncofusion protein acts in the context of a heptad of proteins (ERG, FLI1, GATA2, LYL1, LNMO2, RUNX1 and TAL1) central to proper expression of genes involved in maintaining a stem cell hematopoietic phenotype. Moreover, in t(16;21) FUS-ERG co-occupies genomic regions bound by the nuclear receptor heterodimer RXR-RARA inhibiting target gene expression and interfering with hematopoietic differentiation. All-Trans Retinoic Acid treatment of t(16;21) cells as well as FUS-ERG knock down alleviate the myeloid differentiation block. Together, the results suggest that FUS-ERG acts as a transcriptional repressor of the retinoic acid signaling pathway. Cell lines were used for RNA extraction for RNA-seq and ChIP experiments for ChIP-seq.

2015-06-23 | E-GEOD-60477 | biostudies-arrayexpress

Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]

Project description:TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3â?? untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).

2016-07-05 | E-GEOD-77702 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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