{"doi":"10.1007/s12079-021-00646-y","title":"CD47 interactions with exportin-1 limit the targeting of m7G-modified RNAs to extracellular vesicles","abstract":"Abstract CD47 is a marker of self and a signaling receptor for thrombospondin-1 that is also a component of extracellular vesicles (EVs) released by various cell types. Previous studies identified CD47-dependent functional effects of T cell EVs on target cells, mediated by delivery of their RNA contents, and enrichment of specific subsets of coding and noncoding RNAs in CD47 + EVs. Mass spectrometry was employed here to identify potential mechanisms by which CD47 regulates the trafficking of specific RNAs to EVs. Specific interactions of CD47 and its cytoplasmic adapter ubiquilin-1 with components of the exportin-1/Ran nuclear export complex were identified and confirmed by coimmunoprecipitation. Exportin-1 is known to regulate nuclear to cytoplasmic trafficking of 5’-7-methylguanosine (m 7 G)-modified microRNAs and mRNAs that interact with its cargo protein EIF4E. Interaction with CD47 was inhibited following alkylation of exportin-1 at Cys 528 by its covalent inhibitor leptomycin B. Leptomycin B increased levels of m 7 G-modified RNAs, and their association with exportin-1 in EVs released from wild type but not CD47-deficient cells. In addition to perturbing nuclear to cytoplasmic transport, transcriptomic analyses of EVs released by wild type and CD47-deficient Jurkat T cells revealed a global CD47-dependent enrichment of m 7 G-modified microRNAs and mRNAs in EVs released by CD47-deficient cells. Correspondingly, decreasing CD47 expression in wild type cells or treatment with thrombospondin-1 enhanced levels of specific m 7 G-modified RNAs released in EVs, and re-expressing CD47 in CD47-deficient T cells decreased their levels. Therefore, CD47 signaling limits the trafficking of m 7 G-modified RNAs to EVs through physical interactions with the exportin-1/Ran transport complex.","journal":"Journal of Cell Communication and Signaling","year":2021,"id":172117,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365747,"name":"Alejandra Cavazos Saldana","orcid":null,"position":1,"is_corresponding":false},{"id":470115,"name":"Abdel Elkahloun","orcid":"0000-0002-1749-740X","position":2,"is_corresponding":false},{"id":554321,"name":"Jennifer D. Petersen","orcid":"0000-0003-1107-8535","position":3,"is_corresponding":false},{"id":695991,"name":"Anush Arakelyan","orcid":null,"position":4,"is_corresponding":false},{"id":707703,"name":"Satya P. Singh","orcid":"0000-0003-3159-3622","position":5,"is_corresponding":false},{"id":261931,"name":"Lisa M. Jenkins","orcid":"0000-0003-1245-1338","position":6,"is_corresponding":false},{"id":708279,"name":"Bethany Kuo","orcid":null,"position":7,"is_corresponding":false},{"id":707704,"name":"Bianca Reginauld","orcid":"0000-0003-2183-1789","position":8,"is_corresponding":false},{"id":708280,"name":"David G. Jordan","orcid":null,"position":9,"is_corresponding":false},{"id":356751,"name":"Andy D. Tran","orcid":"0000-0002-2388-7121","position":10,"is_corresponding":false},{"id":494123,"name":"Weiwei Wu","orcid":"0000-0003-4260-2803","position":11,"is_corresponding":false},{"id":481127,"name":"Joshua Zimmerberg","orcid":"0000-0002-1707-3789","position":12,"is_corresponding":false},{"id":344429,"name":"Leonid Margolis","orcid":"0000-0002-1960-1928","position":13,"is_corresponding":false},{"id":318082,"name":"David D. Roberts","orcid":"0000-0002-2481-2981","position":14,"is_corresponding":false},{"id":322438,"name":"Sukhbir Kaur","orcid":"0000-0003-0513-6225","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"34841476","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":[]}