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Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs [CUT&TAG]

GSE310421 Homo sapiens Genome binding/occupancy 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. We developed Plat-RNAseq, a click-chemistry-mediated transcriptome-wide assay to map transcriptome-wide interaction of cisplatin. Our results revealed that cisplatin binding was enriched at guanine-rich regions capable of forming RNA G-quadruplexes (rG4s). To test the relationship with RNA-DNA hybrid R-loop structures and cisplatin-RNA interaction, we used CUT&Tag experiment using S9.6 R-loop specfic antibody. This result revealed an increased cisplatin interacitn on R-loop engaged RNAs.
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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Direct links to NCBI, no account and no request form: the whole study as GSE310421_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1365914 and SRA study SRP646676. Searching any of these in the dataset finder brings you back here.

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