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@ARTICLE{Corsi:277552,
      author       = {Corsi, Jessica and Semnani, Pouriya Sharbatian and Peroni,
                      Daniele and Belli, Romina and Morelli, Alessia and
                      Lassandro, Michelangelo and Sidarovich, Viktoryia and Adami,
                      Valentina and Valentini, Chiara and Cavallerio, Paolo and
                      Grosskreutz, Julian and Fabbiano, Fabrizio and Grossmann,
                      Dajana and Hermann, Andreas and Tell, Gianluca and Basso,
                      Manuela and D'Agostino, Vito G},
      title        = {{S}mall molecule inhibitors of hn{RNPA}2{B}1-{RNA}
                      interactions reveal a predictable sorting of {RNA} subsets
                      into extracellular vesicles.},
      journal      = {Nucleic acids research},
      volume       = {53},
      number       = {5},
      issn         = {0305-1048},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2025-00441},
      pages        = {gkaf176},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Extracellular Vesicles: metabolism /
                      Heterogeneous-Nuclear Ribonucleoprotein Group A-B:
                      metabolism / Heterogeneous-Nuclear Ribonucleoprotein Group
                      A-B: genetics / RNA: metabolism / RNA: genetics / Protein
                      Binding / Proteomics: methods / HEK293 Cells / NF-kappa B:
                      metabolism / Small Molecule Libraries: pharmacology /
                      Heterogeneous-Nuclear Ribonucleoprotein Group A-B (NLM
                      Chemicals) / RNA (NLM Chemicals) / hnRNP A2 (NLM Chemicals)
                      / NF-kappa B (NLM Chemicals) / Small Molecule Libraries (NLM
                      Chemicals)},
      cin          = {AG Hermann},
      ddc          = {570},
      cid          = {I:(DE-2719)1511100},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40103230},
      doi          = {10.1093/nar/gkaf176},
      url          = {https://pub.dzne.de/record/277552},
}