TY - JOUR T1 - Bisphenol A promotes stress granule assembly and modulates the integrated stress response JF - bioRxiv DO - 10.1101/673194 SP - 673194 AU - Marta M. Fay AU - Daniella Columbo AU - Cecelia Cotter AU - Chandler Friend AU - Shawna Henry AU - Megan Hoppe AU - Paulina Karabelas AU - Corbyn Lamy AU - Miranda Lawell AU - Sarah Monteith AU - Christina Noyes AU - Paige Salerno AU - Jingyi Wu AU - Hedan Mindy Zhang AU - Paul J. Anderson AU - Nancy Kedersha AU - Pavel Ivanov AU - Natalie G. Farny Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/17/673194.abstract N2 - Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of >92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA causes stress granules (SGs) in human cells. A common estrogen derivative, β-estradiol, does not trigger SGs, indicating the mechanism of SG induction is not via the ER pathway. We also tested other structurally related environmental contaminants including the common BPA substitutes BPS and BPF, the industrial chemical 4-nonylphenol (4-NP) and structurally related compounds 4-EP and 4-VP, and the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The variable results from these related compounds suggest that structural homology is not a reliable predictor of the capacity of a compound to cause SGs. Also, we demonstrate that BPA acts primarily through the PERK pathway to generate canonical SGs. Finally, we show that chronic exposure to a low physiologically relevant dose of BPA disrupts SG assembly by inhibiting SGs upon additional acute stress. Our work identifies additional effects of BPA beyond endocrine disruption that may have consequences for human health. ER -