IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SMAUG 1 AGGREGATION MEDIATES mRNA SILENCING FOCI FORMATION
Autor/es:
PASCUAL M; THOMAS MG; HABIF M; BAEZ MV; BOCCACCIO GL
Lugar:
Iguazú
Reunión:
Simposio; Symposium of Gene expression and RNA processing; 2011
Institución organizadora:
ICGB
Resumen:
Mammalian Smaug1 is a repressor of mRNAs carrying specific motifs termed Smaug-Recognition-Element (SRE) (Baez and Boccaccio, JBC 2005). We found Smaug 1 is expressed in mature neurons and regulates synaptogenesis. Smaug1 forms mRNA silencing foci (S-foci) associated to the post-synapses that respond to synaptic stimulation dissolving and releasing transcripts to allow their translation. S-foci are distinct from PBs, stress granules, or any other previously described neuronal RNA granule. Smaug 1 also forms mRNA silencing foci when expressed in cell lines, suggesting that neuronal factors are not required. Both in neurons and in cell lines, S-foci are in contact with PBs, suggesting a functional link between these foci. Here we show by RNAi strategies against key PB components that Smaug1 aggregation does not require PB integrity. Instead, Smaug1-mediated mRNA repression induces PB assembly. We analyzed the Smaug1 domains involved in aggregation. We found that a construct lacking the RNA binding domain forms foci, suggesting that Smaug1 aggregation is independent of its repressor activity. Smaug1 aggregation requires two conserved regions, a D domain located at the N-terminus, and the C-terminal region, which includes a PHAT domain. Co-tranfection experiments suggest homotypical interactions between D and PHAT domains. The relevance of foci formation in Smaug1- mediated repression and how aggregation is controlled by synaptic stimulation remain to be investigated. Supported by University of Buenos Aires, ANPCyT and CONICET (Argentina). MV. Baez and GL Boccaccio, 2005, J Biol Chem, vol 280, page 43131-43140.