000277552 001__ 277552
000277552 005__ 20250406001041.0
000277552 0247_ $$2doi$$a10.1093/nar/gkaf176
000277552 0247_ $$2pmid$$apmid:40103230
000277552 0247_ $$2ISSN$$a0305-1048
000277552 0247_ $$2ISSN$$a0261-3166
000277552 0247_ $$2ISSN$$a1362-4954
000277552 0247_ $$2ISSN$$a1362-4962
000277552 0247_ $$2ISSN$$a1746-8272
000277552 0247_ $$2altmetric$$aaltmetric:175292558
000277552 037__ $$aDZNE-2025-00441
000277552 041__ $$aEnglish
000277552 082__ $$a570
000277552 1001_ $$aCorsi, Jessica$$b0
000277552 245__ $$aSmall molecule inhibitors of hnRNPA2B1-RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles.
000277552 260__ $$aOxford$$bOxford Univ. Press$$c2025
000277552 3367_ $$2DRIVER$$aarticle
000277552 3367_ $$2DataCite$$aOutput Types/Journal article
000277552 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1743582990_4325
000277552 3367_ $$2BibTeX$$aARTICLE
000277552 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000277552 3367_ $$00$$2EndNote$$aJournal Article
000277552 520__ $$aExtracellular vesicles (EVs) are cell-secreted membranous particles contributing to intercellular communication. Coding and noncoding RNAs can be detected as EV cargo, and RNA-binding proteins (RBPs), such as hnRNPA2B1, have been circumstantially implicated in EV-RNA sorting mechanisms. However, the contribution of competitive RBP-RNA interactions responsible for RNA-sorting outcomes is still unclear, especially for predicting the EV-RNA content. We designed a reverse proteomic analysis exploiting the EV-RNA to identify intracellular protein binders in vitro. Using cells expressing a recombinant hnRNPA2B1 to normalize competitive interactions, we prioritized a network of heterogeneous nuclear ribonucleoproteins and purine-rich RNA sequences subsequently validated in secreted EV-RNA through short fluorescent RNA oligos. Then, we designed a GGGAG-enriched RNA probe that efficiently interacted with a full-length human hnRNPA2B1 protein. We exploited the interaction to conduct a pharmacological screening and identify inhibitors of the protein-RNA binding. Small molecules were orthogonally validated through biochemical and cell-based approaches. Selected drugs remarkably impacted secreted EV-RNAs and reduced an RNA-dependent, EV-mediated paracrine activation of NF-kB in recipient cells. These results demonstrate the relevance of post-transcriptional mechanisms for EV-RNA sorting and the possibility of predicting the EV-RNA quality for developing innovative strategies targeting discrete paracrine functions.
000277552 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000277552 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000277552 650_7 $$2NLM Chemicals$$aHeterogeneous-Nuclear Ribonucleoprotein Group A-B
000277552 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000277552 650_7 $$2NLM Chemicals$$ahnRNP A2
000277552 650_7 $$2NLM Chemicals$$aNF-kappa B
000277552 650_7 $$2NLM Chemicals$$aSmall Molecule Libraries
000277552 650_2 $$2MeSH$$aHumans
000277552 650_2 $$2MeSH$$aExtracellular Vesicles: metabolism
000277552 650_2 $$2MeSH$$aHeterogeneous-Nuclear Ribonucleoprotein Group A-B: metabolism
000277552 650_2 $$2MeSH$$aHeterogeneous-Nuclear Ribonucleoprotein Group A-B: genetics
000277552 650_2 $$2MeSH$$aRNA: metabolism
000277552 650_2 $$2MeSH$$aRNA: genetics
000277552 650_2 $$2MeSH$$aProtein Binding
000277552 650_2 $$2MeSH$$aProteomics: methods
000277552 650_2 $$2MeSH$$aHEK293 Cells
000277552 650_2 $$2MeSH$$aNF-kappa B: metabolism
000277552 650_2 $$2MeSH$$aSmall Molecule Libraries: pharmacology
000277552 7001_ $$aSemnani, Pouriya Sharbatian$$b1
000277552 7001_ $$aPeroni, Daniele$$b2
000277552 7001_ $$aBelli, Romina$$b3
000277552 7001_ $$aMorelli, Alessia$$b4
000277552 7001_ $$aLassandro, Michelangelo$$b5
000277552 7001_ $$aSidarovich, Viktoryia$$b6
000277552 7001_ $$aAdami, Valentina$$b7
000277552 7001_ $$aValentini, Chiara$$b8
000277552 7001_ $$aCavallerio, Paolo$$b9
000277552 7001_ $$aGrosskreutz, Julian$$b10
000277552 7001_ $$aFabbiano, Fabrizio$$b11
000277552 7001_ $$aGrossmann, Dajana$$b12
000277552 7001_ $$0P:(DE-2719)2811732$$aHermann, Andreas$$b13
000277552 7001_ $$00000-0001-8845-6448$$aTell, Gianluca$$b14
000277552 7001_ $$00000-0002-9278-8960$$aBasso, Manuela$$b15
000277552 7001_ $$00000-0003-3379-2254$$aD'Agostino, Vito G$$b16
000277552 773__ $$0PERI:(DE-600)1472175-2$$a10.1093/nar/gkaf176$$gVol. 53, no. 5, p. gkaf176$$n5$$pgkaf176$$tNucleic acids research$$v53$$x0305-1048$$y2025
000277552 8564_ $$uhttps://pub.dzne.de/record/277552/files/DZNE-2025-00441%20SUP.zip
000277552 8564_ $$uhttps://pub.dzne.de/record/277552/files/DZNE-2025-00441.pdf$$yOpenAccess
000277552 8564_ $$uhttps://pub.dzne.de/record/277552/files/DZNE-2025-00441.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000277552 909CO $$ooai:pub.dzne.de:277552$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000277552 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811732$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000277552 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000277552 9141_ $$y2025
000277552 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-10
000277552 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000277552 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bNUCLEIC ACIDS RES : 2022$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-04-03T10:37:02Z
000277552 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-04-03T10:37:02Z
000277552 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000277552 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2024-04-03T10:37:02Z
000277552 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNUCLEIC ACIDS RES : 2022$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-10
000277552 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-10$$wger
000277552 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-10
000277552 9201_ $$0I:(DE-2719)1511100$$kAG Hermann$$lTranslational Neurodegeneration$$x0
000277552 980__ $$ajournal
000277552 980__ $$aVDB
000277552 980__ $$aUNRESTRICTED
000277552 980__ $$aI:(DE-2719)1511100
000277552 9801_ $$aFullTexts