A PUTATIVE ROLE FOR THE DOUBLE-STRANDED RNA-BINDING PROTEIN STAUFEN 1 IN STRESS GRANULES´ PHYSIOLOGY. Martínez Tosar, Leandro J. and Boccaccio, Graciela L.

MARTÍNEZ TOSAR, LEANDRO J.; BOCCACCIO, GRACIELA L.

Pinamar, Argentina

Congreso; XLI reunión SAIB; 2005

Eukaryotic cells respond to stress by dramatically altering mRNA metabolism in phenomena such as localization, translational state and decay rates. The most studied event involved in these changes is the assembly of stress granules (SG). We have shown previously that under oxidative stress, mammalian Staufen 1 undergoes aggregation in SG (Thomas et al. MBC 2005). The colocalization of Staufen 1 with SG markers was also demonstrated in many different stress conditions and cell types, and thus the possibility for an active role in the stress response was suggested. In this work we show that cell lines overexpressing Staufen 1 fail to assemble SG, in response to different stressors. However, phosphorilation of eIF2-a  –a required event in the stress response  cascade, and in SG formation–  is normal in Staufen 1 overexpressing cells, suggesting a downstream action of Staufen. We used several constructs bearing deletions, isolated double-stranded RNA-binding domains (dsRBDs) and oligomeric domains, to identify the protein region(s) responsible for SG inhibition. This study presents the first physiological evidence of a role for Staufen 1 in the regulation of SG assembly.