PXD042941-1

PXD042941 is an original dataset announced via ProteomeXchange.

Title	Antisense oligonucleotide-mediated inclusion of the TRA2β ultraconserved poison exon induces the expression of a lncRNA with anti-tumor effects
Description	Dysregulated expression of oncogenic splicing factors (SFs) occurs in human tumors in part through alterations in splicing of poison exons (PE), highly conserved exons that trigger RNA degradation. TRA2β is one such SF that undergoes PE suppression in tumor cells. Therefore, manipulation of TRA2β-PE can be a promising therapeutic strategy for cancer. Here, we demonstrate that low TRA2β-PE inclusion correlates with decreased patient survival across multiple tumor types. TRA2β-PE-targeting antisense oligonucleotides (ASOs) induce anti-cancer phenotypes and widespread transcriptomic alterations in cell culture models by causing both TRA2β protein knockdown and upregulation of TRA2β-PE-containing transcripts, which act as long-noncoding RNAs (lncRNAs) to sequester nuclear proteins. Finally, we demonstrate efficacy of TRA2β-PE-targeting ASOs in preclinical 3D organoid and in vivo patient-derived xenograft models. Together, this demonstrates that oncogenic SFs can be drugged using PE-targeting ASOs and elucidates a mechanism by which the TRA2β-PE acts both as a regulator of TRA2β protein expression and as a lncRNA that controls cancer cell growth.
HostingRepository	PRIDE
AnnounceDate	2024-12-20
AnnouncementXML	Submission_2024-12-20_12:40:08.547.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SungHee Park
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-13 05:46:42	ID requested
⏵ 1	2024-12-20 12:40:08	announced

Dataset with its publication pending

submitter keyword: Antisense oligonucleotide

poison exon

splicing factors

SR protein

TRA2-beta

alternative RNA splicing

breast cancer

splicing factor

triple negative breast cancer. RNA-binding proteins

patient-derived xenograft

organoid

RNA pulldown

mass spectrometry

Olga Anczukow
contact affiliation	The Jackson Laboratory For Genomic Medicine
contact email	olga.anczukow@jax.org
lab head
SungHee Park
contact affiliation	The Jackson Laboratory
contact email	sunghee.park@jax.org
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/2024/12/PXD042941

PRIDE project URI

• PRIDE
  1. PXD042941
     1. Label: PRIDE project
     2. Name: Antisense oligonucleotide-mediated inclusion of the TRA2β ultraconserved poison exon induces the expression of a lncRNA with anti-tumor effects