PXD052658 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | SMALL MOLECULE INHIBITORS OF HNRNPA2B1-RNA INTERACTIONS REVEAL A PREDICTABLE SORTING OF RNA SUBSETS INTO EXTRACELLULAR VESICLES |
Description | Extracellular 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. |
HostingRepository | PRIDE |
AnnounceDate | 2025-02-24 |
AnnouncementXML | Submission_2025-02-24_00:58:10.350.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD052658 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Romina Belli |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-05-29 01:00:11 | ID requested | |
⏵ 1 | 2025-02-24 00:58:10 | announced | |
Publication List
Keyword List
submitter keyword: Extracellular vesicles (EVs), paracrine, hnRNPA2B1, RNA, high-throughput screening |
Contact List
Vito G. D'Agostino |
contact affiliation | Laboratory of Biotechnology and Nanomedicine, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123, Trento, Italy |
contact email | vito.dagostino@unitn.it |
lab head | |
Romina Belli |
contact affiliation | University of Trento |
contact email | romina.belli@unitn.it |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052658
- Label: PRIDE project
- Name: SMALL MOLECULE INHIBITORS OF HNRNPA2B1-RNA INTERACTIONS REVEAL A PREDICTABLE SORTING OF RNA SUBSETS INTO EXTRACELLULAR VESICLES