Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nrf2 Mediates RNA Splicing Through Physical Association with the Survival Of Motor Neuron (SMN) Complex and Transcriptional Activation of the SMN1 Gene In Non-Small Cell Lung Cancer

ABSTRACT: The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) signal pathway is frequently deregulated in human cancers. The critical functions of NRF2 other than transcriptional activation in cancers remain largely unknown. Here, we uncovered a previously unrecognized role of Nrf2 in RNA splicing via regulating survival of motor neuron protein (SMN). Here, we performed next-generation high throughput global RNA-sequencing of siNrf2-C27 and siGFP-C5, which are stable NRF2-knockdown and control cell lines derived from A549 NSCLC cells, respectively To investigate whether NRF2 plays any role in RNA splicing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164720 | GEO | 2022/10/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

Project description:Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

2021-03-31 | GSE150760 | GEO

Comparison of the transcriptomic impact of NRF2 depletion with that of NUAK1 depletion in SW480 colorectal cancer cells

Project description:The intent of the experiment is to determine how much of NRF2 (NFE2L2)-dependent transcription requires NUAK1 upstream. SW480 cells were transfected with siRNA targeting either NRF2, NUAK1 or non-targeting control, and harvested for analysis by RNA-SEQ 48hrs after transfection. mRNA was analysed by Illumina paired-end RNA-SEQ

2018-02-19 | E-MTAB-6264 | biostudies-arrayexpress

Identification of Novel NRF2-Regulated Genes by ChIPSeq

Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high-confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRAhas implications for response to retinoid treatments and adipogenesis. In mouse 3T3-L1 cells SFN treatment affected Rxra expression early in adipogenesis and knockdown of Nrf2 delayed Rxra expression, both leading to impaired adipogenesis. ChIP-Seq analysis of NRF2 binding sites in human lymphoblastoid cells treated with sulforaphane or vehicle

2012-06-18 | E-GEOD-37589 | biostudies-arrayexpress

Expression data from KEAP1 overexpression and NRF2 siRNA knockdown of A549 NSCLC cell

Project description:KEAP1 overexpressed and NRF2 siRNA knockdown A549 NSCLC cells were used to identify downstream genes of NRF2 pathway separately and by combinatorial analysis. We used triplicate microarrays of transfected A549 cells with mKeap1-GFP for overexpression, siRNAs targeting NRF2 for knockdown and siGFP as control respectively. As a result, we identified several genes which are involved in cancer metabolic functions in these cells. We used microarrays to identify the gene downregulated in both KEAP1 overexpressed and NRF2 siRNA knockdown A549 NSCLC cells and found a subset of downregulated genes which are involved in metabolic functions.

2017-08-02 | GSE94393 | GEO

Gain of toxic function by long-term SMN overexpression in the sensory-motor circuit.

Project description:The neurodegenerative disease spinal muscular atrophy (SMA) is a leading genetic cause of infant death caused by deficiency in the survival motor neuron (SMN) protein. Currently approved SMA treatments aim to restore SMN, but the potential for expression of SMN beyond physiological levels is a unique feature of AAV9-SMN gene therapy. Here, we show that long-term AAV9-mediated SMN overexpression in mouse models induces dose-dependent, late-onset motor dysfunction associated with loss of proprioceptive synapses and neurodegeneration. Mechanistically, aggregation of overexpressed SMN in the cytoplasm of motor circuit neurons sequesters components of small nuclear ribonucleoproteins (snRNPs), leading to splicing dysregulation and widespread transcriptome abnormalities with prominent signatures of neuroinflammation and innate immune response. Thus, long-term SMN overexpression can interfere with its normal activity in RNA regulation and trigger SMA-like pathogenic events through toxic gain of function mechanisms. These unanticipated, SMN-dependent and neuron-specific liabilities of AAV9-SMN warrant further evaluation of the long-term safety of gene therapy in SMA.

2021-02-01 | GSE149391 | GEO

Transgenic expression of Nrf2 in the mouse

Project description:NFE2L2, nuclear factor, erythroid 2 like 2 (Nrf2), is a transcription factor that protects cells through maintaining a homeostatic redox state during stress. Constitutive expression of Nrf2 (CaNrf2-TG) was previously shown to be pathological to the heart over time. We tested a hypothesis that the cardiac-specific expression of full length Nrf2 (mNrf2-TG) would moderately increase the basal antioxidant defense, triggering a pro-reductive environment leading to adaptive cardiac remodeling.

2022-05-09 | GSE202298 | GEO

RNA-seq of microglia and monocyte-derived cells in Nrf2 knockout and wild-type mice after induced intracerebral hemorrhage or sham treatment

Project description:Secondary injury causes death and dependence after spontaneous intracerebral haemorrhage (ICH). Having found that ICH is associated with activation of genes regulated by the transcription factor Nrf2, particularly in mononuclear myeloid cells (for example, monocyte-derived cells (MdC) and microglia), we sought to determine the importance of Nrf2 to mononuclear myeloid cell responses and their impact on ICH pathology. We used intrastriatal injection of collagenase to induce ICH in both wild-type mice, and knockout mice with Cx3cr1-Cre-mediated excision of Nrf2 (Nfe2l2) exon 5.

2024-08-13 | E-MTAB-14324 | biostudies-arrayexpress

ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP

Project description:The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease ALS, is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and reduce interaction with U1-snRNP. Correspondingly, global RNA analysis reveals a mutant-dependent loss of splicing activity, with ALS-linked mutants failing to reverse changes caused by loss of wild-type FUS/TLS. Furthermore, a common FUS/TLS mutant-associated RNA splicing signature is identified in ALS patient fibroblasts. Taken together, our studies establish potentially converging disease mechanisms in ALS and spinal muscular atrophy, with ALS-causative mutants acquiring properties representing both gain (dysregulation of SMN) and loss (reduced RNA processing mediated by U1-snRNP) of function. RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Generation sequencing (RASL-seq) method was used for analyzing alternative splicing changes. Oligonucleotide probes are designed to anneal to the exon-exon junctions. The probe library was assembled to assess 5530 unique alternative splicing events, most of which were exon inclusion or skipping, with a minority for alternative 5’- or 3’- splice sites. The splicing changes were compared among groups of reducing FUS/TLS or SMN levels, or expressing various FUS mutations to determine the loss versus gain of FUS/TLS function on splicing regulation.

2015-02-10 | E-GEOD-64078 | biostudies-arrayexpress

Role of SMN Protein in regulating the transcription and alternative splicing of Pulmonary Vascular Remodeling-Related Genes in HPASMCs

Project description:To explore the effect of SMN protein on alternative splicing of multiple genes in human pulmonary artery smooth muscle cells (HPASMCs), we used shRNA specifically against the SMN to knock down the expression of SMN protein.Human primary pulmonary artery smooth muscle cells (hPASMCs) of donors were obtained from China Center for Type Culture Collection (Wuhan, Hubei, China).

2024-03-15 | GSE261233 | GEO

Differential pre-mRNA defects in fission yeast carrying a temperature degron allele of the SMN gene

Project description:The SMA disease results from deletions or mutations in the “survival of motor neuron” (SMN1) gene. The SMN protein plays an essential role in the biogenesis of spliceosomal snRNPs but the link between a defect in this process and specific splicing inhibition is not known. Here, we report the construction of a temperature degron (td) allele of the S. pombe SMN protein and show that its depletion at 37°C affects snRNPs stability and splicing. In addition, the function of the tdSMN allele in snRNPs assembly is affected already at 25°C suggesting a deleterious effect of the tag at this temperature. Remarkably, using S. pombe tiling arrays and RT-PCR validation tests, we report that splicing is altered differentially in the tdSMN cells at permissive temperature. Our results suggest that the defects observed in tdSMN fission yeast cells mimic splicing deficits observed in SMN-deficient metazoan cells.

2010-04-22 | GSE17010 | 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