Staufen granules are recruited into Stress Granules in a cytoskeleton-dependent manner

G.L.BOCCACCIO

Campinas, San Pablo- Brasil

Congreso; IX Congreso Sociedad Iberoamericana de Biología Celular; 2004

Cytoplasmic mRNA granules are functional units for a variety of cellular events such as mRNA transport, silencing, activation and degradation. We found that the double stranded RNA binding proteins Staufen 1 and Staufen 2 form granules that contain ribosomes and associate to the cytoskeleton. Upon induction of heat shock or oxidative stress, Staufen granules remodelate into Stress Granules (SG), which are stress-induced organelles containing transiently silenced messengers. SGs are located in the nuclear periphery and remain attached to microtubules after a brief Triton extraction. We tested the effect of microtubule and microfilament-disrupting drugs on SG formation on primary cultures and cell lines and found that both treatments cause dramatic changes on SG assembly. Disruption of actin network induce the accumulation of a larger number of smaller SGs that remains dispersed throughout the cytoplasm. In contrast, disruption of microtubule network provokes the formation of normal-sized SGs which remains dispersed as well. Staufen is conserved among different organisms where it is required for microfilament and microtubule-dependent targeting of mRNAs granules. Our findings that Staufen molecules, are novel component of SGs and that the cytoskeleton is required for SG aggregation, suggest that Staufen may mediate motor recruitment for their clustering into SGs and likely, to allow relocation of mRNAs in response to different stimuli.   Supported by ANPCyT-Argentina; Fundación Antorchas-Argentina; NIH-USA and Wadsworth Foundation-USA