Smaug1-silencing foci located at synapses respond to aynaptic stimuli

MARIA V. BAEZ; CLAUDIA C. LEISHMAN; GRACIELA L. BOCCACCIO

Bariloche, Rio Negro, Argentina

Congreso; ICGEB and EURASNET meetings on "Gene Expression and RNA processing" and "Cell Biology, Signaling and Alternative Splicing"; 2007

ICGEB y EURASNET

Certain neuronal mRNAs localize in dendrites and synapsis as silenced ribonucleoparticles (RNPs) whose translation is activated upon synaptic stimulation. Sterile Alpha Motif (SAM)-containing RNA binding proteins constitute a novel family of post-transcriptional silencers that recognize a specific RNA sequence motif, the Smaug Recognition Element (SRE). Two orthologous genes carrying a SAM domain, that we named Smaug1 and Smaug2, are present in the mammalian genome. We have previously shown that Smaug1 represses translation of SRE-containing reporters, without affecting their stability. Biochemical analysis indicated that Smaug1 is present in particles that exclude ribosomal subunits, in accordance with a role in translation initiation blockage (JBC, 2005). Here we show that Smaug1 expression in cultured hippocampal neurons temporally correlates with that of synaptic markers. In mature neurons, Smaug 1 forms foci that are different from FMRP and SMN granules and that colocalize with PB markers. Smaug1 foci are disrupted by cycloheximide and enhanced by puromycin, a hallmark of silencing foci. Furthermore, Smaug1 foci located at synapses disassemble upon synaptic stimulation, suggesting the release of previously silenced mRNAs. Our results suggest that Smaug1 is a novel postranscriptional regulator relevant to synaptogenesis and/or synaptic plasticity. A survey of neuronal messengers containing SRE in databases yielded a reduced number of mRNAs encoding distinct functions. Some of them localize at the dendritic compartment, and thus, it seems possible that Smaug1 contributes to their regulation. This hypothesis and whether Smaug1 is controlled by synaptic activity remains to be investigated.                                                               Supported by NIH (USA);University of Buenos Aires, ANPCyT and CONICET (Argentina).