MOLECULAR DETERMINANTS OF SMAUG1 AGGREGATION

MARÍA GABRIELA THOMAS; MALENA PASCUAL; MARTÍN HABIF; GRACIELA LIDIA BOCCACCIO

Buenos Aires, Argentina

Congreso; SAIB-49th Annual Meeting - Argentine Society for Biochemistry and Molecular Biology; 2013

Mammalian Smaug1 (mSmaug1) is a novel translational repressor specific of the post-synapse of mature neurons. mSmaug1 knockdown provokes the formation of immature synapses and impairs the response to synaptic stimulation (Baez et al., JCB 2011; Pascual et al., CIB 2012). Both Drosophila Smaug and mSmaug1 repress the translation of reporter mRNAs carrying specific motifs termed Smaug- recognition-Element (SRE) and form mRNA silencing foci termed S-foci (Baez and Boccaccio, JBC 2005). Self-aggregation is a common feature of RNA-binding proteins involved in mRNA-silencing and here we investigated the mSmaug1 domains involved in S-foci formation. We found that mSmaug1 aggregation is independent of RNA binding and requires two conserved regions, a D domain located at the N-terminus and the C terminal region. Co-tranfection experiments suggest that both regions interact homotypically thus facilitating mSmaug1 oligomerization. Aggregation of the Drosophila molecule requires the conserved D domain and is further facilitated by a QN-rich domain that is absent from the vertebrate molecule, likely due to its inherent toxicity. Co-transfection of dSmaug and mSmaug1 constructs indicates that the homotypic interaction of the D-domain is specie-specific. We are currently studying the relevance of mSmaug1 aggregation to the repressor activity.