Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Arginine methylation-mediated FXR1 binding with RNAs in cancer cells

ABSTRACT: FXR1 is an RNA binding protein and it is post traslationally modified by a methyltrasferase to facilitate its RNA binding activity FXR1 is methylated by PRMT5, an arginine methyltransferase, to promote its stability and facilitate its association with mRNAs. Both genetic and small molecule PRMT5 inhibition failed to methylate recombinant as well as the endogenous FXR1, resulting in protein instability and downregulation of FXR1 target mRNA levels in HNSCC cells. To study the differentially regulated gene under the loss of PRMT5, we knocked- down the PRMT5 using shRNA and confirmed the transcript and protein levels using qRT PCR and immunoblot respectively.

ORGANISM(S): Homo sapiens

PROVIDER: GSE256352 | GEO | 2024/04/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Arginine methylation-mediated FXR1-G4 RNA binding in cancer cells

Project description:The RBP, FXR1, is overexpressed in many epithelial tumors containing a canonical RGG box domain. FXR1 controls post-transcriptional gene regulation through changes in mRNA turnover and translation of target genes. Here we show that arginine methyltransferase PRMT5- mediated specific arginine methylation of FXR1 increases its stability in cancer cells. FXR1-dependent gene signatures show decreased expression and instability of G4-rich sequences containing mRNAs such as CDKN1A, PLK2, TCN2, and TRAF4. Furthermore, structural features of FXR1 and G4-RNA interactions provide novel insights into the critical arginine amino acids of FXR1 essential for G4-RNA-binding and turnover activity. In addition, analysis of the eCLIP data provides various RNA targets and the G-rich sequence motifs of FXR1 in head and neck cancer cell line. Thus, our results indicate that PRMT5-mediated methylation of FXR1 binding with G4-RNAs favors mRNA stability and turnover, contributing to cancer cell growth and proliferation.

2024-04-08 | GSE252916 | GEO

Effect of depletion of FXR1 on gene expression in head and neck squamous cell carcinoma (HNSCC) cells

Project description:FXR1 is an essential RNA-binding protein. This chromosome 3q26-28 gene is overexpressed in many epithelial tumors. FXR1 controls the turnover and translation of multiple mRNAs and is involved in cellular transformation. We identified critical residues in the protein that are post-translationally modified. These regulate the stability of FXR1 protein, its RNA-binding function, cell growth, and proliferation. Here we show that PRMT5-mediated arginine methylation of FXR1 increases the protein's binding to G-quadruplex RNAs in vivo and controls their expression in cancer cells. Independent point mutations of specific arginine residues in the nuclear export signal (R386, R388) and arginine-glycine rich (R453, R455, R459) domains of FXR1 abrogate the RNA-binding in vitro. Genetic and small molecule inhibition of PRMT5 minimizes methylation and levels of FXR1 and suppresses oral tumor growth and proliferation. RNA-seq analyses of FXR1 KD cells show an increase in the expression of PLK2, TCN2, and TRAF4 along with FXR1’s well-known target CDKN1A. Like CDKN1A, these targets possess strong G4 sequences. FXR1 and G4-RNA interactions provide new insights into the molecular mechanism of FXR1 and its interaction with target mRNAs. Furthermore, an increased expression of FXR1 and PRMT5 is colocalized in cancer tissues, leading to a poor patient prognosis. Thus, our data demonstrate that PRMT5-mediated arginine methylation of FXR1 arginine residues in the NES and RGG domains plays a critical role in binding and controlling G4-RNAs, which encode tumor suppressors and promote cancer cell growth and proliferation.

2023-09-30 | GSE212760 | GEO

iCLIP of FXR1-WT and FXR1-V361P in HeLa cells

Project description:In the associated paper FXR1 is shown to package exceptionally long mRNAs in the cytoplasm and organizes them into an mRNP network. We performed iCLIP of FXR-WT and its mutant FXR1-V361P in HeLa cells where we knocked down endogenous FXR1 and replaced it with either GFP-tagged WT or V361P-mutant FXR1. The GFP-tagged proteins were immunoprecipitated using an anti-GFP antibody.

2024-11-01 | E-MTAB-13545 | biostudies-arrayexpress

iCLIP of FXR1-WT and FXR1-V361P in HeLa cells

Project description:iCLIP of FXR1-WT and FXR1-V361P in HeLa cells

| PRJEB70255 | ENA

Proteomics Profiling of Arginine Methylation Defines PRMT5 Substarate Specificity

Project description:Protein arginine methyltransferases (PRMTs) catalyze arginine methylation, an abundant post-translational modification occurring on both chromatin-bound and cytoplasmic proteins. Growing evidence supports the involvement of PRMT5, the major Type II PRMT, in pro-survival and differentiation pathways, important during development and to promote tumorigenesis. Thus, PRMT5 emerges as an attractive drug target and inhibitors are currently in clinical trials for cancer therapy. However, the knowledge of PRMT5 non-histone substrates is still limited, as are the dynamic changes in methylation levels upon its inhibition. Here, we employed a newly established pipeline coupling SILAC with methyl-peptides immuno-enrichment to globally profile arginine methylation following PRMT5 inhibition by GSK591 and adopted the heavy-methyl SILAC as orthogonal validation method to reduce false discovery rate. Then, in vitro methylation assays on a set of PRMT5 targets provided novel mechanistic insights into its strict preference to methylate arginine sandwiched between two neighbouring glycines (GRG). In conclusion, we identified novel PRMT5 substrates, thus providing the first proof of concept of the in vivo efficacy of PRMT5 inhibitor that impacts on arginine methylation beyond histones.

2019-04-10 | PXD009070 | Pride

Arginine methylation-mediated FXR1-G4 RNA binding in cancer cells

Project description:Arginine methylation-mediated FXR1-G4 RNA binding in cancer cells

| PRJNA1063237 | ENA

Arginine methylation-mediated FXR1 binding with RNAs in cancer cells

Project description:Arginine methylation-mediated FXR1 binding with RNAs in cancer cells

| PRJNA1079254 | ENA

PRMT5: a Novel Regulator of Hepatitis B Virus Replication and an Arginine Methylase of HBV Core

Project description:In the study, we identified protein arginine methyltransferase 5 (PRMT5) as a novel restriction factor of HBV replication. We have also demonstrated that PRMT5 can interact with the HBV core and methylate its arginine residues within arginine-rich domain. We identified two types of HBc post-translational modifications: arginine methylation and ubiquitination. While monomethylated HBc retains cytoplasmic localization, symmetric dimethylation is linked to serine phosphorylation and nuclear transport. Thus arginine methylation and ubiquitination are novel types of HBc post-translational modifications which add another level of complexity to the understanding of HBc function and regulation of HBV replication

2017-11-01 | PXD006828 | Pride

Fxr1 regulates sleep and synaptic homeostasis

Project description:Fxr1 regulates sleep and synaptic homeostasis

| PRJNA580288 | ENA

Transcriptome and translatome analysis of THP1 cells with doxycycline induced FXR1 Knockdown

Project description:FXR1 depletion in THP1 cells causes changes in polysome associated mRNAs. This leads to a distinct translatome in the cell.

2022-08-25 | GSE211933 | GEO