Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole-genome CRISPR screen to identify regulators of cold-shock protein RBM3

ABSTRACT: Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 induction during cooling remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217789 | GEO | 2023/05/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size

Project description:The goal of this study was to identify changes in muscle gene expression that may contribute to loss of adaptability of old muscle. Muscle atrophy was induced in young adult (6-month) and old (32-month) male Brown Norway/F344 rats by two weeks of hind limb suspension (HS) and soleus muscles were analyzed by cDNA microarrays. We conclude that a cold shock response may be part of a compensatory mechanism in muscles undergoing atrophy to preserve remaining muscle mass and that RBM3 may be a therapeutic target to prevent muscle loss.

2008-07-23 | GSE12087 | GEO

Cold-induced protein RBM3 regulates neocortical development via Yap1 in maternal hypothermia

Project description:Next-generation sequencing (NGS) has revolutionized systems-based analysis of gene expression. The goals of this study are to compare the different transcripts between control or RBM3 knockdown in the neural stem cells when the maternal hypothermia was induced.

2017-09-27 | GSE104300 | GEO

Whole-genome CRISPR screen to identify regulators of cold-shock protein RBM3

Project description:Whole-genome CRISPR screen to identify regulators of cold-shock protein RBM3

| PRJNA900543 | ENA

TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection.

Project description:Increasing levels of the cold-shock protein, RNA-binding motif 3 (RBM3), either through cooling or by ectopic over-expression, prevents synapse and neuronal loss in mouse models of neurodegeneration. To exploit this process therapeutically requires an understanding of mechanisms controlling cold-induced RBM3 expression. Here, we show that cooling increases RBM3 through activation of TrkB via PLCγ1 and pCREB signaling. RBM3, in turn, has a hitherto unrecognized negative feedback on TrkB-induced ERK activation through induction of its specific phosphatase, DUSP6. Thus, RBM3 mediates structural plasticity through a distinct, non-canonical activation of TrkB signaling, which is abolished in RBM3-null neurons. Both genetic reduction and pharmacological antagonism of TrkB and its downstream mediators abrogate cooling-induced RBM3 induction and prevent structural plasticity, whereas TrkB inhibition similarly prevents RBM3 induction and the neuroprotective effects of cooling in prion-diseased mice. Conversely, TrkB agonism induces RBM3 without cooling, preventing synapse loss and neurodegeneration. TrkB signaling is, therefore, necessary for the induction of RBM3 and related neuroprotective effects and provides a target by which RBM3-mediated synapse-regenerative therapies in neurodegenerative disorders can be used therapeutically without the need for inducing hypothermia.

| S-EPMC7893816 | biostudies-literature

HNRNPH1 is required for rhabdomyosarcoma cell growth and survival

Project description:Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-year survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-year survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in 3 cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was dramatically reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a striking reduction in tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data show that HNRNPH1 may be an important molecular target for the development of future RMS therapy.

2018-02-02 | GSE104559 | GEO

RNA-binding protein RBM3 negatively regulates innate lymphoid cells (ILCs) and lung inflammation

Project description:Innate lymphoid cells (ILCs) promote lung inflammation in diseases such as asthma through cytokine production. RNA-binding proteins (RBPs) are critical post-transcriptional regulators of cellular function though the role of RBPs in innate lymphoid cells is unknown. Here, we demonstrate that RNA-binding motif 3 protein (RBM3) is one of the most highly expressed RBPs in Thy1.2+ lung ILCs after fungal allergen challenge and is further induced by epithelial cytokines TSLP and IL-33 in both human and mouse ILCs. Single (rbm3-/-) and double (rbm3-/-rag2-/-) knockout mice exposed via the airway to the asthma-associated fungal allergen Alternaria alternata displayed increases in eosinophilic lung inflammation and ILC activation compared to control mice. In addition to increased Th2 cytokine production, rbm3-/- ILCs produced elevated IL-17A. The negative regulation by RBM3 in ILC responses was direct as purified rbm3-/- ILCs were hyperinflammatory in vitro and in vivo after stimulation with IL-33. Transcriptomic analysis by RNA-sequencing of rbm3-/- lung ILCs showed increased type 2 and 17 cytokines as well as global expression differences in critical cytokines, receptors, transcription factors, and survival transcripts compared with WT ILCs. Importantly, these transcript changes were independent of the numbers of AU-rich elements (AREs) which RBM3 is known to bind. Thus, regulation of ILC responses by RNA-binding proteins offers novel mechanistic insight into lung ILC biology and ILC-driven inflammatory diseases.

2021-01-01 | GSE155330 | GEO

HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.

Project description:Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator. Splicing analysis revealed that moderate hypothermia significantly represses the inclusion of a poison exon, which, when retained, targets the mRNA for nonsense-mediated decay. Importantly, we show that HNRNPH1 mediates this cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon. Our study provides novel mechanistic insights into the regulation of RBM3 and provides further targets for neuroprotective therapeutic strategies.

| S-EPMC10350819 | biostudies-literature

Heterozygous Hnrnph1 deletion decreases methamphetamine reinforcement, reward, and dopamine release and opposing changes in synaptosomal mitochondrial protein levels

Project description:Individual variation in the addiction liability of amphetamines can be explained, in part, by heritable genetic factors. We recently identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying variance in the locomotor stimulant response to methamphetamine in mice. The functional consequences of Hnrnph1 mutation on MA reward and reinforcement and the mechanisms by which Hnrnph1 alters methamphetamine sensitivity are unknown but could involve functional perturbations in dopamine neurotransmission. Here, we showed that mice with a heterozygous mutation in the first coding exon of Hnrnph1 (H1+/-) exhibited reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference. Accordingly, H1+/- mice showed a robust decrease in methamphetamine-induced dopamine release in the nucleus accumbens with no change in baseline dopamine levels, dopamine transporter levels, or dopamine uptake. Surprisingly, immunohistochemical and immunoblot staining of midbrain dopaminergic neurons and their forebrain projections for tyrosine hydroxylase did not reveal any obvious changes in intensity or numbers of cells stained or in the number of forebrain TH-positive puncta. Finally, we observed a two-fold increase in hnRNP H protein in the striatal synaptosme of H1+/- mice; proteomic analysis identified an increased abundance of several mitochondrial complex I and V proteins. We conclude that H1+/- deficits in behavior are associated with blunted MA-induced dopamine release and an upregulation of synaptic mitochondrial proteins.

2019-07-29 | MSV000084149 | MassIVE

HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion

| S-SCDT-10_15252-EMBJ_2022113168 | biostudies-other

Pre-clinical and clinical studies on the role of RBM3 in muscle-invasive bladder cancer: longitudinal expression, transcriptome-level effects and modulation of chemosensitivity

Project description:Background: The response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is impaired in up to 50% of patients due to chemoresistance, with no predictive biomarkers in clinical use. RNA-binding motif protein 3 (RBM3) has emerged as a putative modulator of chemotherapy response but has a hitherto unrecognized role in MIBC. Methods: Tumour-specific RBM3 protein expression was assessed via immunohistochemistry in paired transurethral resection of the bladder (TURB) specimens, cystectomy specimens and lymph node metastases from 145 patients. The effect of RBM3 suppression on chemosensitivity was examined in RT4 and T24 cells in vitro. RNA-sequencing was applied to compare gene expression profiles between siRBM3-treated and control cells. Findings: RBM3 protein expression was significantly higher in TURB compared to cystectomy specimens but showed consistency between primary tumours and lymph node metastases. High tumour-specific RBM3 expression was significantly associated with a reduced risk of recurrence in NAC treated patients. In T24 cells, which displayed higher RBM3 levels than RT4 cells, RBM3 silencing conferred a decreased sensitivity to cisplatin and gemcitabine. RNA-sequencing revealed potential involvement of RBM3 in facilitating cell cycle progression, in particular G1/S-phase transition, and initiation of DNA replication. Interpretation: The presented data highlight the predictive value of RBM3 in MIBC, which could, if prospectively validated, improve treatment stratification of patients with this aggressive disease.

2022-01-11 | GSE167558 | 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