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Series GSE212760 Query DataSets for GSE212760
Status Public on Sep 30, 2023
Title Effect of depletion of FXR1 on gene expression in head and neck squamous cell carcinoma (HNSCC) cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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.   
 
Overall design To investigate the cooperative functionFXR1 in the HNSCC cell lines in which FXR1 has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and KD cells with Biological triplicates.
 
Contributor(s) Majumder M, Palanisamy V, Berto S
Citation(s) 38709899
Submission date Sep 06, 2022
Last update date Jul 08, 2024
Contact name Stefano Berto
E-mail(s) berto@musc.edu
Phone 4696626889
Organization name Medical University of South Carolina
Department Neuroscience
Lab BE208
Street address 68 President Street
City Charleston
State/province SC
ZIP/Postal code 29403
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (6)
GSM6544988 UMSCC74B cells, Control 1
GSM6544989 UMSCC74B cells, Control 2
GSM6544991 UMSCC74B cells, Control 3
Relations
BioProject PRJNA877224

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE212760_FXR1_Counts.txt.gz 208.0 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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