|
| 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 (BeadChip) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| 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 Prmt5F/F, and Prmt5 depleted Prmt5F/FNes (Nestin-Cre) Neural Stem/Progenitors Cells (NPCs). The final cRNA samples were hybridized to Illumina MouseRef-8 V2 arrays in quadruplicates.
|
| |
|
| Contributor(s) |
Bezzi M, Teo SX, Müller J, Mok WC, Sahu SK, Vardy L, Bonday Z, Guccione E |
| Citation(s) |
24013503 |
| Submission date |
Mar 18, 2013 |
| Last update date |
Jun 14, 2018 |
| 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) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (8)
|
|
| 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 |
PRJNA193511 |
Less...
More...