New Roles for Arginine Methylation in RNA Metabolism and Cancer

New Roles for Arginine Methylation in RNA Metabolism and Cancer

Détails

Titre: New Roles for Arginine Methylation in RNA Metabolism and Cancer
Auteur: Goulet, Isabelle
Résumé: 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.
Date: 2011
URI: http://hdl.handle.net/10393/20293
Superviseur: Côté, Jocelyn
Faculté: Médecine / Medicine
Degré: PhD

Fichier(s) constituant ce document :

Fichier(s) Taille Format
Goulet_Isabelle_2011_these.pdf 4.476Mb application/pdf Voir/Ouvrir

Cet article est disponible dans les collections suivantes

Détails


Nos coordonnées

Pavillon Morisset (carte)
65, rue Université
Ottawa ON Canada
K1N 6N5

Tél. 613-562-5800 (4563)
Fax 613-562-5195

ruor@uottawa.ca