Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs [RNA-seq]

Clinically used small molecules has been predicted to off-target to RNAs. However, the extend of this interaction is small molecule cancer therapeutics has not been characterized. Here, we screened for anticancer smalll molecules for their RNA interactions and uncovered widespread RNA off-targeting. Cisplatin was found to be one among the RNA binders. We used it as a model agent to identify the specific transcripts it interact with. To accomplish this, we developed Plat-RNAseq, a click-chemistry-mediated transcriptome-wide assay. Our results revealed that cisplatin binding was enriched at guanine-rich regions capable of forming RNA G-quadruplexes (rG4s) .We found that the recruitment of cisplatin to rG4s partially contributed to its cytotoxicity, revealing a noncanonical mechanism of action for this widely used chemotherapeutic agent. RNA seq was performed to catalogue all non-ribosomal RNAs present in A2780 cells. Overall design: A2780 cells were treated with 10 µM cisplatin 24 hours. RNA was collected and rRNA depleted library was constructed. The objective of the experiment was to identify non-ribosomal RNAs expressed in A2780 cells in basal and cisplatin-treated conditions.