The Translation Repressor Smaug forms Stress Granule-like Foci.

MARÍA V. BAEZ; GRACIELA L. BOCCACCIO.

San Francisco DC, USA, (2005)

Congreso; ASCB 45th annual meeting,; 2005

American Society for Cell Biology

Cytoplasmic events depending on RNA binding proteins contribute to the fine-tuning of gene expression. 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 and deadenylation of maternal mRNAs by independent mechanisms, and the yeast homologue Vts1 stimulates degradation of SRE-containing messengers. Two homologous genes are present in the mammalian genome. Here we show that hSmaug 1, encoded in human chromosome 14, represses the translation of reporter transcripts carrying SRE motifs, without affecting transcripts levels. When expressed in fibroblasts, hSmaug 1 forms cytoplasmic granules that contain polyadenylated mRNA. After treatment with the polysome-stabilizing drug cycloheximide, granules containing transfected hSmaug 1 disappears almost completely. In contrast, puromycin, which inhibits translation by disrupting polysomes, provokes the opposite effect, hSmaug 1 granules became more numerous and remarkably larger. Similar to stress granules, hSmaug1 foci frequently contain the RNA binding proteins Staufen, TIAR, TIA-1 and HuR. Transfected Smaug 1 foci are distinct from degradation foci, as they exclude GW182, Dcp 1 and XRN 1. We found that the murine protein mSmaug 1 is expressed in the central nervous system and that it is abundant in post-synaptic densities, a subcellular region where translation is tightly regulated by synaptic stimulation. These results suggest a role for mammalian Smaug 1 in RNA granule formation and translation regulation in neurons.