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PXD052658-1

PXD052658 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSMALL MOLECULE INHIBITORS OF HNRNPA2B1-RNA INTERACTIONS REVEAL A PREDICTABLE SORTING OF RNA SUBSETS INTO EXTRACELLULAR VESICLES
DescriptionExtracellular vesicles (EVs) are cell-secreted membranous particles contributing to intercellular communication. Coding and non-coding RNAs are widely detected as EV cargo, and RNAbinding 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 and used cells expressing a recombinant hnRNPA2B1 to normalize competitive interactions. Interestingly, we prioritized heterogeneous nuclear ribonucleoproteins in networks including RAB proteins and recognizing purine-rich RNA sequences representing a subset of previously identified EXO motifs. A screening campaign using a full-length human hnRNPA2B1 protein and a synthetic purine-rich RNA probe brought to small molecule inhibitors orthogonally validated through biochemical and cell-based approaches. Selected drugs effectively interfered with a post-transcriptional layer impacting secreted EV-RNAs, reducing the vesicular pro-inflammatory miR-221 while counteracting the hnRNPA2B1- or TDP43Q331K-dependent paracrine activation of NF-kB in EV 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.
HostingRepositoryPRIDE
AnnounceDate2025-02-24
AnnouncementXMLSubmission_2025-02-24_00:58:10.350.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD052658
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRomina Belli
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-29 01:00:11ID requested
12025-02-24 00:58:10announced
Publication List
10.6019/PXD052658;
Keyword List
submitter keyword: Extracellular vesicles (EVs), paracrine, hnRNPA2B1, RNA, high-throughput screening
Contact List
Vito G. D'Agostino
contact affiliationLaboratory of Biotechnology and Nanomedicine, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123, Trento, Italy
contact emailvito.dagostino@unitn.it
lab head
Romina Belli
contact affiliationUniversity of Trento
contact emailromina.belli@unitn.it
dataset submitter
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Dataset FTP location
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