Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting PRMT1-mediated SRSF1 Methylation to Suppress Exon Inclusion within Oncogenic Transcripts and Breast Tumorigenesis

ABSTRACT: Targeting PRMT1-mediated SRSF1 Methylation to Suppress Exon Inclusion within Oncogenic Transcripts and Breast Tumorigenesis

PROVIDER: PRJNA873704 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR21202891_1.fastq.gz	Fastqsanger.gz
	SRR21202891_2.fastq.gz	Fastqsanger.gz
	SRR21202892_1.fastq.gz	Fastqsanger.gz
	SRR21202892_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

Targeting PRMT1-mediated SRSF1 Methylation to Suppress Exon Inclusion within Oncogenic Transcripts and Breast Tumorigenesis

Project description:PRMT1 is highly expressed in breast tumors, and has been suggested to play a vital role in breast tumorigenesis, but the underlying molecular mechanisms remain to be fully characterized. Here, we reveal that PRMT1 exhibits a wide-spreading role in RNA alternative splicing based on transcriptome analysis, with a preference for exon inclusion in a large cohort of oncogenic genes. Profiling PRMT1 methylome reveals that the arginine/serine-rich splicing factor SRSF1 is heavily arginine-methylated by PRMT1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and PRMT1-induced exon inclusion. In breast tumors, the overexpression of PRMT1 is associated with high levels of SRSF1 arginine methylation and aberrant exon inclusion in those oncogenic genes. Accordingly, PRMT1-mediated SRSF1 methylation and exon inclusion events are found to be critical for the malignant behaviors of breast cancer cells. Furthermore, we identified and characterized a selective PRMT1 inhibitor iPRMT1, which is potent in inhibiting PRMT1-mediated SRSF1 methylation and exon inclusion events, and breast cancer cell growth both in vitro and in vivo. Combination treatment with iPRMT1 and inhibitor targeting SRSF1 phosphorylation, SPHINX31 or SRPIN340, exhibits synergistic effects on suppressing breast cancer cell growth, strengthening the cross-talk between arginine methylation and phosphorylation in SRSF1. In conclusion, our data uncover a key mechanism underlying PRMT1-mediated gene alternative splicing, demonstrating targeting PRMT1 has great potential to treat breast cancer in clinic.

2023-10-02 | GSE212049 | GEO

Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion [RNA-seq]

Project description:RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we evaluated 718 human RBPs with tethered function luciferase-based splicing reporter assays to identify 58 candidates, including known splicing factors such as RBFOX and serine-arginine proteins. We performed enhanced CLIP, RNA-seq, and affinity purification-mass spectrometry to investigate a subset of the 11 candidates with no prior association with splicing. Integrative analysis of these assays indicated the surprising roles of TRNAU1AP, SCAF8, and RTCA in modulating hundreds of endogenous splicing events. We also leveraged our tethering assays and top candidates to identify potent and compact exon inclusion activation domains for splicing modulation applications. Using identified domains, we engineered programmable fusion proteins which outperformed current artificial splicing factors at manipulating inclusion of reporter and endogenous exons. Altogether, our tethering approach characterized the ability of RBPs to induce exon inclusion and yielded new molecular parts for programmable splicing control.

2023-09-25 | GSE232598 | GEO

Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion [eCLIP-seq]

2023-09-25 | GSE232597 | GEO

Identification of alternative splicing events regulated by the splicing factor SRSF1 using data from exon-junction microarray technologies

Project description:Analysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA 9 samples from three independent experiments using A549 cells transfected with lipofectamine alone, scramble siRNA or SRSF1 siRNA

2013-12-18 | E-GEOD-53410 | biostudies-arrayexpress

TDP-43 represses cryptic exon inclusion in FTD/ALS gene UNC13A

Project description:TDP-43 represses cryptic exon inclusion in FTD/ALS gene UNC13A

| PRJNA758574 | ENA

N6-Methyladenosine mediates alternative intron/exon inclusion in the nascent transcriptome

Project description:N6-Methyladenosine mediates alternative intron/exon inclusion in the nascent transcriptome

| PRJNA647274 | ENA

inclusion body myositis

Project description:We investigated the gene and exon espression profiling in muscle biopsies of patients affected by inclusion body myosistis, polymyositis and in normal muscle controls

2014-02-02 | E-MTAB-2141 | biostudies-arrayexpress

Analysis of RNA from primary hepatocytes from hepatocyte-specific SRSF1 knockout mice vs. WT

Project description:RNA from primary hepatocyte cultures from three 3-month-old SRSF1HKO mice compared to RNA from three 3-month-old WT mice for changes in exon utilization and gene expression. SRSF1 KO vs. WT, three replicates each.

2015-05-01 | E-GEOD-57020 | biostudies-arrayexpress

Toxoplasma gondii arginine methyltransferase 1 (PRMT1) regulates parasite counting during tachyzoite cell division

Project description:PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. We generated T. gondii mutants lacking PRMT1 (∆prmt1) by deletion of the PRMT1 gene. ∆prmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the complemented strain ∆prmt::PRMT1mRFP. PRMT1 localizes primarily in the cytoplasm with enrichment at the centrosome, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, ∆prmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole genome expression profiling demonstrated differences in expression of cell cycle regulated genes in ∆prmt1 relative to the complemented ∆prmt1::PRMT1mRFP and parental wild-type strains, but these changes did not correlate with a specific block in cell cycle. Although PRMT1’s primary biological function was previously proposed to be methylation of histones, our genetic studies suggest that the most critical function of PRMT1 is within the centrosome as a regulator of daughter cell counting to assure the proper replication of the parasite. RNA samples were isolated in triplicates from RH-hxgprt parent strain (W), PRMT1 knockout (K) strain and PRMT1 knockout strain complemented with RFP-tagged PRMT1 protein (C). Parasites were grown for 32h at 37C. Samples were hybridized to the Toxoplasma gondii Affymetrix microarray (ToxoGeneChip: http://ancillary.toxodb.org/docs/Array-Tutorial.html). Hybridization data was preprocessed with Robust Multi-array Average (RMA) and normalized using per chip and per gene median polishing and analyzed using the software package GeneSpring GX (Agilent Technologies).

2015-09-18 | E-GEOD-73177 | biostudies-arrayexpress

N6-Methyladenosine mediates alternative intron/exon inclusion in the nascent transcriptome [4sU-seq]

Project description:N6-Methyladenosine mediates alternative intron/exon inclusion in the nascent transcriptome [4sU-seq]

| PRJNA647276 | ENA