Typical 2-cys peroxiredoxins regulate stress granule formation

MARCELO PEREZ PEPE; MARTIN ARAN; LORENA B BENSEÑOR; RICARDO WOLOSIUK; GRACIELA L BOCCACCIO

Buenos Aires

Congreso; Argentinian Society of Biochemistry and Molecular Biology Research; 2013

SAIB

Stress granules (SGs) are cytoplasmic accretions that form transiently in all cell types undergoing acute stress. SGs contain mRNAs trapped in abortive translation initiation complexes and RNA-binding proteins involved in reprogramming mRNA translation and decay and are linked to pathogenic protein aggregates (Thomas et al., Cell Sig 2011). SG assembly and disassembly depends on: I) destabilization of polysomes (Thomas et al., MBoC 2005, JCS 2009). II) Retrograde transport by dynein and bicaudal (Loschi et al., JCS 2009) III) Aggregation through specific proteins IV) Disolution and dispersion mediated by stress-induced chaperones and kinesin (Loschi et al., JCS 2009; Thomas et al., CS 2011). In a high-throughput RNAi-screen in Drosophila S2R+ cells we identified 32 positive regulators and 15 inhibitors of SG formation (Perez-Pepe et al, PLoS ONE 2012). In addition, we investigate the role of the typical 2-Cys Peroxiredoxins (2C-Prx), which are peroxidases with stress-regulated chaperone and kinase activities. In addition, 2C-Prxs bind RNA and associate to ribosomes under normal conditions. We find that 2C-Prxs facilitate SG formation upon oxidative stress induction. Both reduced and overoxidized Prxs are excluded from SGs. Collectively, these results suggest that Prx peroxidase or chaperone activities are involved in SG regulation.