PXD054780

PXD054780 is an original dataset announced via ProteomeXchange.

Title	A Comprehensive Interrogation of Mirror-Image L-RNA-Protein Interactome Reveals Key Mechanisms of L-RNA Cytotoxicity
Description	L-Oligonucleotides (ONs), the synthetic enantiomer of native D-nucleic acids, are being increasingly utilized for the development of diverse biomedical technologies, including molecular imaging tools, diagnostic biosensors, and aptamer-based therapeutics. Nevertheless, our understanding of how L-ONs behave in living systems falls far short of native D-ONs. In particular, despite the potential for an abundant L-ON-protein interactome, the extent to which L-ONs bind to endogenous proteins and the consequences of these interactions are unknown, posing a major hurdle towards engineering functional L-ONs with predictable intracellular behaviours. Towards closing this knowledge gap, we now report the first comprehensive characterization of L-ON–protein interactome, revealing that a wide-range nuclear proteins have the potential to bind L-RNA, especially those containing the common RNA recognition motif (RRM). Importantly, by focusing our study on cytotoxic L-RNA sequences, our data reveal key L-RNA–protein interactions that contribute to L-RNA cytotoxicity. Furthermore, we show that introducing 2-O-methyl modifications into cytotoxic L-RNA can decrease its cytotoxicity through reducing L-RNA–protein interactions, thereby demonstrating that a well-established strategy for mitigating the cytotoxic effects of antisense ONs (ASOs) can be translated across the chiral mirror. Overall, these findings greatly deepen our understanding of the intracellular behavior of L-ONs and provide valuable guidance for the future development of safe and effective L-ON-based biomedical technologies.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-13_16:31:53.395.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaomei He
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-10 21:52:51	ID requested
⏵ 1	2025-03-13 16:31:53	announced

Dataset with its publication pending

submitter keyword: L-oligonucleotides • Spiegelmers • cytotoxicity • SILAC • protein binding

Yinsheng Wang
contact affiliation	Department of Chemistry, University of California, Riverside, California, 92521-0403, USA
contact email	yinsheng@ucr.edu
lab head
Xiaomei He
contact affiliation	East Carolina University
contact email	xiaomeih@ucr.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/03/PXD054780

PRIDE project URI

• PRIDE
  1. PXD054780
     1. Label: PRIDE project
     2. Name: A Comprehensive Interrogation of Mirror-Image L-RNA-Protein Interactome Reveals Key Mechanisms of L-RNA Cytotoxicity