New Roles for Arginine Methylation in RNA Metabolism and Cancer

New Roles for Arginine Methylation in RNA Metabolism and Cancer

Show simple item record Goulet, Isabelle 2011-10-05T20:22:34Z 2011-10-05T20:22:34Z 2011 en_US 2011-10-05
dc.description.abstract Because it can expand the range of a protein’s interactions or modulate its activity, post-translational methylation of arginine residues in proteins must be duly coordinated and ‘decoded’ to ensure appropriate cellular interpretation of this biological cue. This can be achieved through modulation of the enzymatic activity/specificity of the protein arginine methyltransferases (PRMTs) and proper recognition of the methylation ‘mark’ by a subset of proteins containing ‘methyl-sensing’ protein modules known as ‘Tudor’ domains. In order to gain a better understanding of these regulatory mechanisms, we undertook a detailed biochemical characterization of the predominant member of the PRMT family, PRMT1, and of the novel Tudor domain-containing protein 3 (TDRD3). First, we found that PRMT1 function can be modulated by 1) the expression of up to seven PRMT1 isoforms (v1-7), each with a unique N-terminal region that confers distinct substrate specificity, and by 2) differential subcellular localization, as revealed by the presence of a nuclear export sequence unique to PRMT1v2. Second, our findings suggest that TDRD3 is recruited to cytoplasmic stress granules (SGs) in response to environmental stress potentially by engaging in methyl-dependent protein-protein interactions with proteins involved in the control of gene expression. We also found that arginine methylation may serve as a general regulator of overall SG dynamics. Finally, we uncovered that alteration of PRMT1, TDRD3, and global arginine methylation levels in breast cancer cells may be closely associated with disease progression and poor prognosis. Therefore, further studies into the pathophysiological consequences ensuing from misregulation of arginine methylation will likely lead to the development of novel strategies for the prevention and treatment of breast cancer. en_US
dc.language.iso en en_US
dc.subject Arginine methylation en_US
dc.subject Protein arginine methyltransferases en_US
dc.subject Protein arginine methyltransferase 1 en_US
dc.subject Tudor domain-containing proteins en_US
dc.subject TDRD3 en_US
dc.subject PRMT1 en_US
dc.subject Breast cancer en_US
dc.subject RNA metabolism en_US
dc.subject Stress granules en_US
dc.subject RNA processing en_US
dc.subject Tudor domain-containing protein 3 en_US
dc.subject Tudor domain en_US
dc.title New Roles for Arginine Methylation in RNA Metabolism and Cancer en_US
dc.type Thèse / Thesis en_US
dc.faculty.department Médecine cellulaire et moléculaire / Cellular and Molecular Medicine en_US
dc.contributor.supervisor Côté, Jocelyn
dc.embargo.terms immediate en_US PhD en_US doctorate en_US Médecine / Medicine en_US

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