{"doi":"10.1101/2022.09.20.508735","title":"Small molecule inhibition of multiple RNA binding proteins underlies Musashi-2 independent phenotypes","abstract":"ABSTRACT RNA binding proteins (RBPs) are key regulators of gene expression. Small molecules targeting these RBP-RNA interactions are a rapidly emerging class of therapeutics for treating a variety of diseases. Ro-08-2750 (Ro) is a small molecule inhibitor identified as a competitive inhibitor of Musashi(MSI)-RNA interactions. Here we show Ro potently inhibits adrenocortical steroidogenesis and viability independent of MSI2 in multiple cell lines. We identified Ro-interacting proteins using an unbiased proteome-wide approach and discovered it is broadly targeting RBPs. To confirm this finding, we leveraged the large-scale ENCODE data and found a subset of RBPs whose depletion phenocopies Ro inhibition. We conclude that Ro is a promiscuous inhibitor of multiple RBPs, many containing RRM1 domains. Moreover, we provide a general framework for validating the specificity and identifying targets of RBP inhibitors in a cellular context.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":311532,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"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":1007717,"name":"Marcin Piotr Sajek","orcid":"0000-0002-4115-4191","position":1,"is_corresponding":false},{"id":297836,"name":"Aaron Issaian","orcid":"0000-0001-9762-5098","position":2,"is_corresponding":false},{"id":761143,"name":"Amber Baldwin","orcid":"0000-0002-7346-3052","position":3,"is_corresponding":false},{"id":1008132,"name":"Evan Harrison","orcid":null,"position":4,"is_corresponding":false},{"id":761144,"name":"Elisabeth Murphy","orcid":"0009-0006-2588-1985","position":5,"is_corresponding":false},{"id":1007718,"name":"Miles E. Daniels","orcid":"0000-0002-7126-9168","position":6,"is_corresponding":false},{"id":822091,"name":"Julie Haines","orcid":null,"position":7,"is_corresponding":false},{"id":11001,"name":"Kirk C. Hansen","orcid":"0000-0001-5054-838X","position":8,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":9,"is_corresponding":false},{"id":558834,"name":"Neelanjan Mukherjee","orcid":"0000-0003-0017-1400","position":10,"is_corresponding":false},{"id":784703,"name":"Kathryn Walters","orcid":"0000-0001-6562-6889","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:28.480200Z","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":[]}