Protein Arginine Methylation

TOPICAL COLLECTIONS

Guest Editors

Dalia Barsyte-Lovejoy

University of Toronto

Dr. Barsyte-Lovejoy is an Assistant Professor at the Department of Pharmacology and Toxicology and Principal Investigator at the Structural Genomics Consortium. She received an undergraduate degree in biology from Vilnius University, Lithuania and a PhD in molecular biology from the University of Manchester, UK where she focused on stress response and ageing regulation. She went on to do her postdoctoral training at the University of Manchester, Dr Andy Sharrocks' lab and at the Ontario Cancer Institute, Canada in Dr Linda Penn’s lab, working on transcription factor and kinase signaling, recognition modes, oncogenic programs, and epigenetics. Dr. Barsyte-Lovejoy’s research focuses on understanding how epigenetic regulators control cell survival, death, and adaptation. Epigenetic enzymes that methylate lysine/arginine residues on histones, transcription, splicing or repair factors, chaperones, and signaling proteins provide additional levels of functional regulation profoundly impacting the biological systems. Using the chemical probe, small molecule compounds that modulate epigenetic regulators, we are investigating the cellular functions of these proteins and their potential to become therapeutic targets in diseases such as cancer. Notable recent contributions include: characterizing small molecule arginine methyltransferase inhibitor compounds and cellular functions of PRMT enzymes (Eram et al 2016; Bonday et al 2018; Szewczyk et al 2020), studying lysine methyltransferases and their substrates (Barsyte-Lovejoy et al, 2014; Bromberg et al 2017) and targeting methylation readers in chromatin and cancer biology (Grebien et al 2015; He et al 2017; Bottcher et al 2019).

Tiziana Bonaldi

European Institute of Oncology

Tiziana Bonaldi is Group Leader at the Department of Experimental Oncology of the European Institute of Oncology, where she has been directing the Giovanni Armenise-Harvard Foundation Laboratory on “Quantitative proteomics to study regulation of gene expression through chromatin structure and dynamics” since 2008. Following training in Biology at the University of Milan, she obtained her PhD degree in Molecular and Cellular Biology, San Raffaele Scientific Institute in Milan (Italy), working in the laboratory of chromatin dynamics under the supervision of Prof. Marco E. Bianchi. In 2003, she was awarded a long-term EMBO fellowship and joined the laboratory of Prof. Axel Imhof at the Department of Molecular Biology Dpt. of the Ludwig Maximillians University of Munich (Germany). She then followed this with her second post-doctoral research, carried out in the Department of Proteomics and Signal Transduction headed by Prof. Matthias Mann at the Max Planck Institute of Biochemistry in Martinsried (Germany). Her notable recent research contributions include The analysis of Chromatin composition in a locus –specific manner (Soldi and Bonaldi, 2013); The Accurate profiling of hPTMS by MS from clinical samples (cells, fresh frozen and FFPE-tissues) (Noberini et al. 2015); The systematic and quantitative analysis of the methyl-proteome (Bremang et al., 2013); Drug targets deconvolution screening by chemo-proteomics (Colzani et al, 2014); and The comprehensive analysis of microRNA effect on gene expression during cancer progression (Mihailovich et al., 2015).

Collection Overview

Protein arginine methylation is a widespread posttranslational modification. Over ten PRMT (protein arginine methyltransferase) enzymes have been described, and over 4000 substrate proteins detected so far as arginine monomethylated, symmetrically or asymmetrically dimethylated. Arginine methylation controls a broad range of biological processes such as histone methylation in transcription, splicing factor function/stability, as well as RNA binding protein, signaling molecule, translation associated factor function, and many others. Recent reagents and technologies are allowing further characterization of PRMT enzymes, quantitation of methylation, and assigning methylated substrates to a particular PRMT. These advances have brought a greater understanding of the downstream biological processes and mechanistic aspects of arginine methylation.

Examples of the methods to be included will range from in vitro PRMT activity, and substrate characterization, an overview of cell-based assays, antibody reagents, and selective inhibitor tool compounds use. Systematic proteome-wide arginine methylation is currently identified by liquid chromatography tandem mass spectrometry methods that rely on various mass tags. Several PRMTs have profound and unique splicing process regulatory effects that are determined by RNAseq differential splicing analysis methods. The biological outcomes of arginine methylation and its resulting cellular phenotypes, such as genome stability, stress response, and RNA binding protein function and localization will be included. Recent data indicates that arginine methylation regulates the phase separation of intrinsically disordered proteins that often are highly arginine methylated. This methods collection will capture the basic methods of investigating arginine methylation on proteome and genome-wide scale as well as an individual assessment of substrates and phenotypes.