Transcriptomics

Dataset Information

63

Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery (BeadChip)


ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus  

SUBMITTER: Zahid Bonday   Leah Vardy  Shu X Teo  Julius Müller  Sanjeeb K Sahu  Wei C Mok  Ernesto Guccione  Marco Bezzi 

PROVIDER: E-GEOD-45269 | ArrayExpress | 2013-09-13

SECONDARY ACCESSION(S): GSE45269PRJNA193511

REPOSITORIES: GEO, ArrayExpress

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Publications

Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.

Bezzi Marco M   Teo Shun Xie SX   Muller Julius J   Mok Wei Chuen WC   Sahu Sanjeeb Kumar SK   Vardy Leah A LA   Bonday Zahid Q ZQ   Guccione Ernesto E  

Genes & development 20130901 17


The tight control of gene expression at the level of both transcription and post-transcriptional RNA processing is essential for mammalian development. We here investigate the role of protein arginine methyltransferase 5 (PRMT5), a putative splicing regulator and transcriptional cofactor, in mammalian development. We demonstrate that selective deletion of PRMT5 in neural stem/progenitor cells (NPCs) leads to postnatal death in mice. At the molecular level, the absence of PRMT5 results in reduced  ...[more]

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