Seminar: Michael Lund Nielsen, theme Cancer development and immune defence

Systematic and quantitative analysis of the human arginine methylome

17 September 2015 10:00 hrs. - 11:00 hrs.
Hippocrates room, route 77
Systematic and quantitative analysis of the human arginine methylome

Michael Lund Nielsen, Center for Protein Research, Copenhagen, Denmark


Michiel Vermeulen & Nina Hubner, Dept. of Molecular Biology, RIMLS

17-09-2015 10:00:0017-09-2015 11:00:00Europe/AmsterdamSystematic and quantitative analysis of the human arginine methylome Hippocrates room, route

Remarks / more information:

undefinedPost-translational modifications (PTMs) greatly increase the complexity of proteins far beyond the combinatorial possibilities of the twenty amino acids. As a result, the ability to characterize and identify PTM patterns in cells, tissues and organisms on a proteome-wide scale has become important to better understand the molecular details of the individual PTMs and their associated enzymes. Arginine methylation is a PTM that increases the structural diversity of proteins and modulates their function in living cells. Methylation of the arginine side-chain is catalyzed by protein arginine methyltransferases (PRMTs), many of which are able to generate both omega-N-methylarginine (MMA; arginine mono-methylation) and asymmetric/symmetric N,N-dimethylarginine (ADMA/SDMA; arginine di-methylation) on target proteins. Although discovered 50 years ago, protein methylation has predominantly been studied as a mechanism of epigenetic regulation of histones, while reports describing arginine methylation on non-histone proteins has only started to emerge in recent years. Here we describe an improved proteomic strategy for proteome-wide characterization of arginine methylation in human cells. Using the developed methodology we identify 9.000 arginine methylation sites on >3.300 human proteins, demonstrating that arginine methylation is a wide-spread modification similar to phosphorylation and ubiquitylation. Using RNAi experiments of various PRMT enzymes we are able to characterize the specific substrates targeted by these enzymes using quantitative proteomics. Collectively our proteomics strategy allows for novel insights into the human arginine methylome. 

Key publications

  • Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p. Nature Communications, 2015
  • Specificity and commonality of the phosphoinositide-binding proteome analyzed by quantitative mass spectrometry. Cell Reports; 6:578-91, 2014.
  • Proteome-wide identification of poly(ADP-Ribosyl)ation targets in different genotoxic stress responses. Molecular Cell. 24; 52:272-85, 2013.

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