Cisplatin Destabilizes RNA : DNA Hybrid Structures and Inhibits RNA Function in a CRISPR Model System

Abstract

AbstractRNA has received enormous attention as a biomolecule in the fields of medicine, public health, and biotechnology. Over the last decade, various types of RNA molecules have been exploited as valuable drug targets by different classes of pharmaceutical agents in combating infections and diseases. In this work, we have investigated the binding of Cisplatin to RNA within double stranded RNA : DNA hybrid structures. UV melting and Isothermal Titration Calorimetry studies reveal that Cisplatin binding leads to destabilization of hybrid duplex likely due to Cisplatin‐RNA adduct formation. Gel electrophoretic analysis using an in vitro CRISPR‐Cas9 model system shows that Cisplatin binding to guide RNA leads to a concentration‐dependent reduction in target DNA cleavage.