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Title: Characterization of The Role of Protein Arginine Methyltransferase 5 (PRMT5) in Mammalian Development
Keywords: PRMT5, arginine, methylation, development, splicing, MDM4
Issue Date: 24-Jan-2014
Citation: MARCO BEZZI (2014-01-24). Characterization of The Role of Protein Arginine Methyltransferase 5 (PRMT5) in Mammalian Development. ScholarBank@NUS Repository.
Abstract: The tight control of gene expression at the level of both transcription and post-transcriptional RNA processing is essential for mammalian development and altered in a multitude of human pathologies. We here investigate the role of protein arginine methyltransferase 5 (PRMT5), a putative splicing regulator and transcriptional cofactor, of high-interest to the cancer and drug discovery fields, yet of unclear function during mammalian development. We demonstrate, by combining in vivo studies in conditional mouse models and high-throughput techniques such as RNA-sequencing, that PRMT5 role is critical during mouse organogenesis and it is essential for proliferating cells homeostasis mostly by ensuring correct pre-mRNA processing. Moreover, we uncover a non-canonical, DNA damage independent mechanism of p53 response activation. This mechanism relies on the alternative splicing of the Mdm4 pre-mRNA and could be exploited for anti-cancer therapy.
Appears in Collections:Ph.D Theses (Open)

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