{"doi":"10.1101/2022.07.18.500496","title":"Pervasive Transcriptome Interactions of Protein-Targeted Drugs","abstract":"The off-target toxicity of drugs targeted to proteins imparts substantial health and economic costs. Proteome interaction studies can reveal off-target effects with unintended proteins; however, little attention has been paid to intracellular RNAs as potential off targets that may contribute to toxicity. To begin to assess this, we developed a reactivity-based RNA profiling (RBRP) methodology, and applied it to uncover transcriptome interactions of a set of FDA-approved small-molecule drugs in vivo. We show that these protein-targeted drugs pervasively interact with the human transcriptome and can exert unintended biological effects on RNA function. In addition, we show that many off-target interactions occur at RNA loci associated with protein binding and structural changes, allowing us to generate hypotheses to infer the biological consequences of RNA off-target binding. The results suggest that rigorous characterization of drugs' transcriptome interactions may help assess target specificity and potentially avoid toxicity and clinical failures.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297389,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":492084,"name":"Willem A. Velema","orcid":"0000-0003-0257-2734","position":1,"is_corresponding":false},{"id":985985,"name":"Yujeong Lee","orcid":null,"position":2,"is_corresponding":false},{"id":329317,"name":"Lu Xiao","orcid":"0000-0003-1934-4711","position":3,"is_corresponding":false},{"id":985404,"name":"Michael G. Mohsen","orcid":"0000-0001-7400-9196","position":4,"is_corresponding":false},{"id":985405,"name":"Anna M. Kietrys","orcid":"0000-0002-8725-9079","position":5,"is_corresponding":false},{"id":329319,"name":"Eric T. Kool","orcid":"0000-0002-7310-2935","position":6,"is_corresponding":false},{"id":454755,"name":"Linglan Fang","orcid":"0000-0003-2637-090X","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}