IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The translational repressor Smaug forms mRNA-silencing foci and induces PB formation
Autor/es:
THOMAS MG; HABIF M; PASCUAL M; LUCHELLI L; BAEZ MV; MASCHI D; BOCCACCIO GL
Lugar:
Heidelberg. Alemania
Reunión:
Conferencia; EMBL Conference: The Complex Life of mRNA: From Synthesis to Decay; 2010
Institución organizadora:
EMBL
Resumen:
Drosophila Smaug is a post-transcriptional repressor that defines a novel family of RNA-binding proteins. Both Drosophila Smaug and mammalian Smaug 1 form mRNA silencing foci and repress the translation of reporter mRNAs carrying specific motifs termed Smaug-Recognition-Element (SRE) (Baez and Boccaccio, JBC 2005). Smaug 1 is restricted to mature neurons, and Smaug 1 silencing foci (S-foci) are located at dendritic spines. Smaug1 knockdown alters the number and size of synapses, and impairs synaptic stimulation, as indicated by a reduced induction of the activity marker ARC upon repetitive depolarization. S-foci reversibly disassemble upon neuron depolarization, releasing mRNAs to allow their translation. Pharmacological studies indicate that S-foci dissolution requires NMDAR receptor activation and PI3K signalling. All this suggests that S-foci regulate local translation, thus affecting synapse plasticity. S-foci are distinct from other neuronal RNA granule hitherto described and are in contact with PBs. The PB structural components Hedls or RCK/p54 are not required for S-foci formation. Smaug 1 expression induces the formation of PBs in cells that lack PB upon knockdown of PB structural components. A Smaug 1 construct that lack the RNA binding domain forms aggregates that do not behave as silencing foci, as they are not in equilibrium with polysomes, and this construct is not able to induce PBs. Smaug 1 aggregation domains map at the N-terminus. We conclude that S-foci formation is not the consequence of mRNA silencing, and that PBs are induced as a consequence of Smaug1-mediated silencing. Whether PI3K directly regulates Smaug 1 aggregation domains thus governing S-foci formation and mRNA release upon synaptic stimulation remains to be investigated.