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Series GSE45284 Query DataSets for GSE45284
Status Public on Sep 13, 2013
Title Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery (RNA-Seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Protein Arginine MethylTransferase 5 (PRMT5) is known to mediate epigenetic control on chromatin and to functionally regulate components of the splicing machinery. In this study we show that selective deletion of PRMT5 in different organs leads to cell cycle arrest and apoptosis. At the molecular level, PRMT5 depletion results in reduced methylation of Sm proteins, aberrant constitutive splicing and in the Alternative Splicing (AS) of specific mRNAs. We identify Mdm4 as one of these mRNAs, which due to its weak 5’-Donor site, acts as a sensor of splicing defects and transduces the signal to activate the p53 response, providing a mechanistic explanation of the phenotype observed in PRMT5 conditional knockout mice. Our data demonstrate a key role of PRMT5, together with p53, as guardians of the transcriptome. This will have fundamental implications in our understanding of PRMT5 activity, both in physiological conditions, as well as pathological conditions, including cancer and neurological diseases.
Overall design Total RNA was extracted from control and Prmt5 depleted Neural Stem/Progenitors Cells (NPCs) and Mouse Embryonic Fibroblasts (MEFs). Prmt5 depleted cells were treated with 4-OHT 24 hours before splitting to induce PRMT5 knockout and final libraries were sequenced in triplicates on Illumina HiSeq 2000.
Contributor(s) Bezzi M, Teo SX, Müller J, Mok WC, Sahu SK, Vardy L, Bonday Z, Guccione E
Citation(s) 24013503
Submission date Mar 19, 2013
Last update date May 15, 2019
Contact name Julius Müller
Organization name A*Star Singapore
Department IMCB
Lab Ernesto Guccione
Street address 61 Biopolis Drive
City Singapore
ZIP/Postal code 138673
Country Singapore
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (12)
GSM1100740 NPC_wt_rep1
GSM1100741 NPC_wt_rep2
GSM1100742 NPC_wt_rep3
This SubSeries is part of SuperSeries:
GSE45285 Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery
BioProject PRJNA193512
SRA SRP019782

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Supplementary file Size Download File type/resource
GSE45284_MEF_cuffdiff.txt.gz 2.5 Kb (ftp)(http) TXT
GSE45284_MEF_mats.txt.gz 5.9 Kb (ftp)(http) TXT
GSE45284_NPC_cuffdiff.txt.gz 49.8 Kb (ftp)(http) TXT
GSE45284_NPC_mats.txt.gz 21.0 Kb (ftp)(http) TXT
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Processed data are available on Series record

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