Mammalian Smaug, a member of a novel family of RNA binding proteins, is a translational repressor in neurons

MARÍA V BAEZ,; CLAUDIA C. LEISHMAN; GRACIELA L BOCCACCIO

Los Cocos, Cordoba Argentina

Congreso; VIII Taller Argentino de Neurociencias; 2006

Mammalian Smaug, a member of a novel family of RNA binding proteins, is a translational repressor in neuronsMaría V Baez, Claudia C. Leishman and Graciela L BoccaccioFundación Instituto Leloirmbaez@leloir.org.ar   Mechanisms for translational regulation contributing to synapse formation and plasticity include among others, CPEB-mediated poly(A) elongation, use of internal ribosome entry sites and modulation of the availability and activity of general factors for protein synthesis. In addition, a number of RNA-binding proteins, including Staufen, Survival Motor Neuron (SMN), fragile X mental retardation protein (FMRP), and ELAV family members, thought to be involved in regulation of gene expression, are present in dendrites and post-synaptic sites. Sterile Alpha Motif (SAM)-containing RNA binding proteins constitute a novel family of post-transcriptional regulators that recognize a specific RNA sequence motif known as Smaug Recognition Element (SRE). The Drosophila member of this family, dSmaug, triggers the translational repression of maternal mRNAs and the yeast orthologue Vts1 stimulates degradation of SRE-containing messengers. Two orthologous genes are present in the mammalian genome, that we named Smaug1 (mouse and human chromosome 14) and Smaug2 (mouse chromosome 7 and human chromosome 19). We found that human Smaug1 (hSmaug1) represses the translation of reporter transcripts carrying SRE motifs without affecting their stability, as judged by real time PCR assays. When expressed in fibroblasts, hSmaug1 forms cytoplasmic granules that contain polyadenylated mRNAs and are different from degradation foci also known as P bodies or GW bodies. Biochemical analysis indicated that both neuronal murine Smaug1 and hSmaug1 transfected into fibroblast, are present in 20S particles, in accordance with a role for these molecules in translation initiation blockage. We found that the murine protein mSmaug1 is expressed in hippocampal rodent neurons during late neuritogenesis and localizes at body cell cytoplasm and dendrites. Furthermore, we found that mSmaug1 is abundant in post-synaptic densities, a subcellular region where translation is regulated by synaptic stimulation. Our results suggest the SRE-Smaug system as a novel mechanism for translational control in neurons. A survey of neuronal messengers containing SREs in data bases yielded a reduced number of mRNAs encoding distinct functions. Some of them are localized at the dendritic compartment, and thus, it seems possible that Smaug contributes to their regulation. This hypothesis and whether Smaug is controlled by synaptic activity remains to be confirmed.   Supported by NIH and Wadsworth Foundation (USA), and ANPCyT and CONICET (Argentina).