Can Human Canonical Glutathione S-Transferases Act as RNA-Binding Proteins?

Glutathione S-transferase (GST) is an enzyme superfamily of particular interest for human health with many functional roles, and it is involved in several cancer types. Under cell stress conditions, their concentrations can increase by up to 10% of cell protein content. Recently, a study describing the landscape of RNA-binding proteins in mammalian spermatogenesis reported evidence of canonical GST–RNA interactions in three mouse mu GSTs. Prompted by this, we searched for available databases and found that RBP2GO, which collects candidate RNA-binding proteins (RBPs) detected in recent human proteomic studies, also lists a few human GST–RNA interactions, without any molecular details. To highlight the molecular features of the GST–RNA interaction, we applied recently developed predictors of RNA–binding sites and validated the results with AutoDock Vina, a docking program that computes binding affinity. Overall, our findings support the notion that a GST–RNA interaction can exist and suggest a potential overlap between RNA binding sites and residues responsible for binding glutathione (GSH), which is the most common GST substrate. Our computational analysis supports the notion that human GSTs can bind RNA that shares the binding region with the glutathione-binding pocket.