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Abstract
Arginine methylation is a post-translational modification that has been implicated in a plethora of cellular processes. It is evolutionarily conserved and may play a role in human diseases such as cancers and cardiovascular diseases. Despite intense research, there are many facets of arginine methylation that are yet to be elucidated. This includes its predominance in the proteome, the methyltransferases which catalyse the methylation and its functional role. The major aims of this thesis are to identify additional arginine-methylated proteins and their methylarginine sites in the simple eukaryote, S. cerevisiae. To this end, a variety of techniques, including gene deletion analyses, immunoprecipitations, tandem mass spectrometry and proteome arrays were used. We identified a total of 217 arginine-methylated proteins, of which 209 are novel, and validated a total of 15 proteins. This discovery is a significant advance over the 19 methylarginine-containing proteins in S. cerevisiae currently described in the literature. In addition, throughout this thesis, evidence of unidentified arginine methyltransferases was found. When the biological functions of the 217 identified proteins were analysed, we confirmed biological processes for which arginine methylation had been previously implicated (e.g. RNA processing, translation) as well as entirely novel biological processes (e.g. protein folding and tRNA aminoacylation). This observation falls within the growing body of evidence that arginine methylation is important for many aspects of cellular physiology. Finally, we also explore the possibility of the interplay between arginine methylation and phosphorylation.