Grant: Travel Awards - Institute Community Support

Stress granules (SGs) are large, cytoplasmic, protein-RNA complexes that play major roles in modulation of gene expression and cellular homeostasis. SG formation protects cells under unfavourable conditions. Cells that are incapable of forming SGs are more vulnerable to stresses than cells that are capable of forming SGs. Many proteins that are associated with SGs play a critical role in the formation of SGs, and the absence of one or more of these proteins make the cells less efficient in SG assembly and more sensitive to stress. The transcription and translation regulation factor YB-1 is recruited to SGs, but its exact function in SG formation is not clear. We demonstrate that siRNA-mediated downregulation of YB-1 led to a significant reduction in the efficiency of SG assembly in two sarcoma cell lines, U2OS and Rh-30. We also found that si-YB-1 cells with an inefficient stress granule formation were more sensitive to stress induced by arsenite or H2O2 compared to si-control cells. YB-1 influences SG assembly via two distinct mechanisms. First, it acts as a scaffold protein to recruit mRNA and other associated RNA-binding proteins into SGs. Second, YB-1 regulates the translation of important SG proteins G3BP1 and TIA-1, controlling their availability during SG assembly. Taken together, YB-1 is critical in SG formation and cell survival.