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| 001 | 277552 | ||
| 005 | 20250406001041.0 | ||
| 024 | 7 | _ | |a 10.1093/nar/gkaf176 |2 doi |
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| 024 | 7 | _ | |a 0305-1048 |2 ISSN |
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| 024 | 7 | _ | |a 1746-8272 |2 ISSN |
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| 037 | _ | _ | |a DZNE-2025-00441 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Corsi, Jessica |b 0 |
| 245 | _ | _ | |a Small molecule inhibitors of hnRNPA2B1-RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles. |
| 260 | _ | _ | |a Oxford |c 2025 |b Oxford Univ. Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1743582990_4325 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Extracellular 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. |
| 536 | _ | _ | |a 353 - Clinical and Health Care Research (POF4-353) |0 G:(DE-HGF)POF4-353 |c POF4-353 |f POF IV |x 0 |
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| 650 | _ | 7 | |a Heterogeneous-Nuclear Ribonucleoprotein Group A-B |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA |0 63231-63-0 |2 NLM Chemicals |
| 650 | _ | 7 | |a hnRNP A2 |2 NLM Chemicals |
| 650 | _ | 7 | |a NF-kappa B |2 NLM Chemicals |
| 650 | _ | 7 | |a Small Molecule Libraries |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Extracellular Vesicles: metabolism |2 MeSH |
| 650 | _ | 2 | |a Heterogeneous-Nuclear Ribonucleoprotein Group A-B: metabolism |2 MeSH |
| 650 | _ | 2 | |a Heterogeneous-Nuclear Ribonucleoprotein Group A-B: genetics |2 MeSH |
| 650 | _ | 2 | |a RNA: metabolism |2 MeSH |
| 650 | _ | 2 | |a RNA: genetics |2 MeSH |
| 650 | _ | 2 | |a Protein Binding |2 MeSH |
| 650 | _ | 2 | |a Proteomics: methods |2 MeSH |
| 650 | _ | 2 | |a HEK293 Cells |2 MeSH |
| 650 | _ | 2 | |a NF-kappa B: metabolism |2 MeSH |
| 650 | _ | 2 | |a Small Molecule Libraries: pharmacology |2 MeSH |
| 700 | 1 | _ | |a Semnani, Pouriya Sharbatian |b 1 |
| 700 | 1 | _ | |a Peroni, Daniele |b 2 |
| 700 | 1 | _ | |a Belli, Romina |b 3 |
| 700 | 1 | _ | |a Morelli, Alessia |b 4 |
| 700 | 1 | _ | |a Lassandro, Michelangelo |b 5 |
| 700 | 1 | _ | |a Sidarovich, Viktoryia |b 6 |
| 700 | 1 | _ | |a Adami, Valentina |b 7 |
| 700 | 1 | _ | |a Valentini, Chiara |b 8 |
| 700 | 1 | _ | |a Cavallerio, Paolo |b 9 |
| 700 | 1 | _ | |a Grosskreutz, Julian |b 10 |
| 700 | 1 | _ | |a Fabbiano, Fabrizio |b 11 |
| 700 | 1 | _ | |a Grossmann, Dajana |b 12 |
| 700 | 1 | _ | |a Hermann, Andreas |0 P:(DE-2719)2811732 |b 13 |
| 700 | 1 | _ | |a Tell, Gianluca |0 0000-0001-8845-6448 |b 14 |
| 700 | 1 | _ | |a Basso, Manuela |0 0000-0002-9278-8960 |b 15 |
| 700 | 1 | _ | |a D'Agostino, Vito G |0 0000-0003-3379-2254 |b 16 |
| 773 | _ | _ | |a 10.1093/nar/gkaf176 |g Vol. 53, no. 5, p. gkaf176 |0 PERI:(DE-600)1472175-2 |n 5 |p gkaf176 |t Nucleic acids research |v 53 |y 2025 |x 0305-1048 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/277552/files/DZNE-2025-00441%20SUP.zip |
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