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| 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
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| 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.
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| 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.
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| 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
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| Lab |
Ernesto Guccione
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| Street address |
61 Biopolis Drive
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| City |
Singapore |
| ZIP/Postal code |
138673 |
| Country |
Singapore |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| 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 |
|
| Relations |
| BioProject |
PRJNA193512 |
| SRA |
SRP019782 |
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