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

GSE310424 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/02/23 Platform GPL34284
Summary
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.
Published in
Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs
Krishnaraj A, Wei X, Thakral R et al. · bioRxiv : the preprint server for biology 2025 · PMID 41509293 · doi:10.64898/2025.12.20.694502
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Also filed as BioProject PRJNA1365924 and SRA study SRP646689. Searching any of these in the dataset finder brings you back here.

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