IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Smaug1-mediated repression is independent from aggregation and involves deadenylation
Autor/es:
PASCUAL M; THOMAS MG; FERNANDEZ-ALVAREZ AJ; IZAURALDE E; BOCCACCIO GL
Lugar:
Buenos Aires
Reunión:
Congreso; SAIB (Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular); 2013
Institución organizadora:
SAIB (Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular)
Resumen:
Local protein synthesis at the synapse is important
for synapse remodelling and memory formation. Mammalian Smaug1 (mSmaug1) is an
mRNA repressor specifically expressed in mature neurons, where it forms mRNA
silencing foci, termed S-foci, involved in synaptic plasticity. The
S-foci respond to stimulation by dissolving and releasing transcripts to
allow translation, the CamKII alpha mRNA among others (Baez et al., JCB, 2011;
Pascual et al., CIB 2012) (Baez and Boccaccio, JBC 2005). We previously found
that a conserved D domain is required for mSmaug1 aggregation. Here we show
that lack of the D domain does not affect repression in an MS2 tethering assay,
thus suggesting that aggregation is not necessary for translation silencing and
opening the possibility that RNA recognition is facilitated by Smaug
aggregation. The molecular mechanism for Smaug1-mediated repression is unknown
and we performed a co-IP screen for several components of the two major
deadenylation pathway: the CCR4/NOT/POP and the PAN2/PAN3 complexes. We found
that several molecules of these complexes are recruited to the S-foci,
suggesting that Smaug1 mediates deadenylation. We also found that Ago1 is
recruited to the S-foci,
indicating a role for the miRNA pathway in mSmaug1-mediated repression. We are
currently studying the biological relevance of Smaug1 aggregation in Zebrafish
models.