The role of SUMO chains in nuclear foci formation and chromatin organization in Trypanosoma brucei procyclic forms

IRIBARREN, PA; DI MARZIO, LA; BERAZATEGUI, MA; DE GAUDENZI, JG; ALVAREZ, VE

Buenos Aires

Congreso; I Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Sociedad Argentina de Protozoología

SUMOylation is a post-translational modification conserved in eukaryotic organisms that involves the covalent attachment of the small ubiquitin-like protein SUMO to internal lysine residues in the target proteins. This tag usually alters the interaction surface of the modified protein and can be translated into changes in its biological activity, stability or subcellular localization, among other possible outputs. SUMO can be attached as a single moiety or in the case of the existence of internal aceptor sites in SUMO itself, it can lead to the formation of SUMO polymers. These chains have been shown to be important for proteasomal degradation as well as for the formation of subnuclear structures such us the synaptonemal complex in Saccharomyces cerevisiae or PML bodies in human cells.In this work, we have examined SUMO chain formation in the ancient protozoan parasite Trypanosoma brucei. Using a recently developed bacterial strain engineered to produce SUMOylated proteins we confirmed the ability of TbSUMO to form polymers and determined the type of linkage using site-directed mutational analysis. By generating transgenic procyclic parasites unable to form chains we demonstrated that although not essential for normal growth, SUMO polymerization determines the localization of the modified proteins at the nuclear periphery. In addition, FISH analysis of the telomeres showed a differential localization depending on the polySUMOylation abilities of the cells, and MNase accesibility assays revealed structural changes in the chromatin. A bioinformatic analysis showed that the T. brucei proteome contains about a hundred of good SUMO interactor candidates. Specifically, this proteins are sequences containing SUMO interactive motifs enriched in nuclear processes. Thus, our observations indicate that SUMO chains play an important role in establishing interaction platforms at the nuclear periphery likely contributing to chromatin organization.