Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [PacBio Sequel IIe]

ABSTRACT: PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [PacBio Sequel IIe]

PROVIDER: PRJNA1228633 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [PacBio Sequel IIe]

Project description:Protein Arginine Methyltransferase 5 (PRMT5) is a key regulator of gene expression and RNA splicing, with its therapeutic potential demonstrated through synthetic lethality in MTAP-deleted cancers. Emerging evidence also suggests that MYC-driven or p53 wild-type tumors may be more sensitive to PRMT5 inhibition, though the underlying mechanisms remain unclear. Virus-positive Merkel cell carcinoma (MCC) serves as an ideal model to explore this question, as it is driven by the MYC paralog MYCL, and most virus-positive MCCs retain wild-type p53. In this study, we investigated PRMT5’s impact on the Tip60-EP400 complex, given MCC’s reliance on the interaction between MYCL and this complex. We used second-generation sequencing (Illumina) to characterize PRMT5-mediated bulk gene expression and long-read RNA sequencing (PacBio Iso-Seq) to analyze PRMT5-mediated alternative splicing. The mechanism underlying PRMT5 deficiency's selective impact on specific splice sites while leaving others unaffected remains unclear. Our findings suggest that PRMT5-mediated methylation of SRSF1 enhances its recruitment to m6A-modified RNA, ensuring proper splicing of Tip60 and maintaining Tip60-EP400 activity. In contrast, PRMT5 inhibition disrupts this recruitment, leading to widespread splicing defects, including both exon skipping and intron retention. These results provide new insights into PRMT5’s role in splicing regulation in cancer cells and may have broader implications for targeting splicing dysregulation in MYC-driven cancers.

2025-08-20 | GSE290569 | GEO

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [JNJvsDMSO_raw]

2025-08-20 | GSE290105 | GEO

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion

Project description:PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion

| PRJNA1228975 | ENA

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [JNJvsDMSO_raw]

Project description:PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion [JNJvsDMSO_raw]

| PRJNA1226215 | ENA

PRMT5-mediated SRSF1 methylation promotes virus-positive Merkel cell carcinoma tumorigenesis by increasing Tip60 exon inclusion

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-08-20 | GSE290609 | GEO

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

Comparative Transcriptional Profiling of human Merkel cells and Merkel Cell Carcinoma

Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCV+ Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and down-regulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. Two-conditions experiment, MCV vs Normal Merkel Cell. Biological replicates : 4 MCV (Cy5), 1 control = pool of Normal Merkel cells from 3 liftings

2014-01-01 | E-GEOD-50434 | biostudies-arrayexpress

TIP60 complex

Project description:TIP60 complex

| PRJNA312375 | ENA

Comparative Transcriptional Profiling of Human Merkel cells and Merkel Cell Carcinoma

Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCPyV(+) Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and downregulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy.

2014-01-01 | GSE50434 | GEO

Characterization of human Merkel cells and their response to Merkel cell polyomavirus

Project description:Merkel cells are epidermal mechanoreceptor cells responsible for the perception of gentle touch. Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer. Although MCC histologically resembles Merkel cells, the cell of origin for MCC is unknown. MCC frequently contains integrated Merkel cell polyomavirus (MCPyV), a small DNA tumor virus with widespread prevalence. Whether MCPyV can transform Merkel cells is unknown. Here, we describe the isolation and long-term expansion of human Merkel cells from neonatal foreskin. We validated the expression of several Merkel cell-related factors by RNASeq, and assessed the ultrastructure by electron microscopy. Culture of Merkel cell preparations on an artificial basement membrane promoted the formation of structures containing both Merkel and non-Merkel cell populations. To determine whether Merkel cells were susceptible to transformation, we expressed tumor-derived MCPyV T antigens and additional oncogenes. We were unable to demonstrate tumorigenesis in immunodeficient mice, but were able to detect T antigen expression from excised cells weeks after implantation. These results highlight that foreskin-isolated Merkel cells can be propagated extensively, sustain expression of MCPyV T antigens, but are not susceptible to transformation by MCPyV, suggesting that Merkel cells from non-glabrous skin may not be a cell of origin for MCC.

2017-04-01 | GSE79657 | 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