PXD052658-1

PXD052658 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 01:00:11	ID requested
⏵ 1	2025-02-24 00:58:10	announced

10.6019/PXD052658;

submitter keyword: Extracellular vesicles (EVs), paracrine, hnRNPA2B1, RNA, high-throughput screening

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

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PRIDE project URI

• PRIDE
  1. PXD052658
     1. Label: PRIDE project
     2. Name: SMALL MOLECULE INHIBITORS OF HNRNPA2B1-RNA INTERACTIONS REVEAL A PREDICTABLE SORTING OF RNA SUBSETS INTO EXTRACELLULAR VESICLES