IMPACT OF POLYSTYRENE ON THE HUMAN RNA HELICASE DDX3X

Plastic pollution has increased over years, as a consequence of human activities. Environmental plastics undergo physical, chemical and biological degradation processes, resulting in micro and nano sizes. These particles pose a significant health risk because, at the nanoscale, they can enter human tissues and cells, potentially causing neuronal damage and inducing oxidative stress. Since nanoplastics exhibit neurotoxic effects, investigating their influence on the human RNA helicase DDX3X is of particular interest. DDX3X plays an important role during neurodevelopment, and DDX3X mutations are related to intellectual disability and autism spectrum disorders. DDX3X unwinds dsRNA upon ATP hydrolysis and is also involved in the assembly and disassembly of stress granules (SGs). Therefore, the aim of this study was to investigate the impact of polystyrene (PS) nanoplastics in vitro on DDX3X enzymatic activities and in its phase separation propensity. To evaluate these effects, helicase and ATPase enzymatic activities, phase separation assays, thioflavin T fluorescence measurements and dynamic light scattering analyses were performed. PS nanoplastics impaired the RNA helicase and ATPase activities of DDX3X, disrupted droplets formation during phase separation, and increased the propensity of protein aggregation. Collectively, these findings demonstrate that DDX3X is highly sensitive to PS nanoplastics, which may compromise protein functions during neurodevelopment. Further cellular studies will be performed to understand the consequences of reduced DDX3X enzymatic activities and the effect on the assembly and disassembly of SGs during PS exposure.

This work was supported by Brazilian Center for Research in Energy and Materials (CNPEM).