Dr. Clare Davies is a Professor of Cancer Cell Biology Department of Cancer and Genomic Sciences at the University of Birmingham.
Abstract
Arginine methylation, catalysed by PRMTs, is a common post-translational modification implicated in numerous cellular processes including DNA repair, RNA splicing, signalling and epigenetic gene expression. PRMT1 and PRMT5 are the main arginine methyltransferases in mammalian cells, with overexpression correlating with poor prognosis in numerous haematological and solid cancers. Although the first PRMT1 and PRMT pre-clinical inhibitor was only developed 5-10 years ago, progress to clinical trials has been rapid. Understanding the molecular and cellular roles of PRMT1 and PRMT5 in cancer will be key to clinical success.
In this seminar, she will present their most recent findings addressing this question that highlight a crosstalk between PRMT1/PRMT5, RNA biology and genome stability. Using proteomic approaches, they have identified a cytoplasmic RNA binding protein that is methylated by PRMT1 enabling it to moonlight within the nucleus promoting tolerance to replication stress. Additionally, they have previously assigned PRMT5 as a major regulator of breast cancer stem cell survival (PMID: 29262329)l. Now, they find that PRMT5 also promote chemoresistance via RNA splicing. These findings will be discussed in detail during the talk.