PXD070432

PXD070432 is an original dataset announced via ProteomeXchange.

Title	A Molecular Clamp Targeting the TOE1:Sm Complex Imparts Tunable Regulation of Splicing
Description	Small nuclear RNAs (snRNAs) are required for the structure and function of the spliceosome. The RNA exonuclease TOE1 trims and matures the 3’ ends of snRNAs, but how this post-transcriptional process contributes to spliceosome activity remains poorly understood. Here we report a potent and selective covalent ligand that targets TOE1 specifically when bound to the Sm complex. We find that this compound acts as a “molecular clamp”, dramatically stabilizing TOE1 interactions with the Sm complex and triggering excessive trimming of snRNA 3’ termini in cells. We show that this over-trimming activity is tunable by factors that include the expression levels of TOE1 and auxiliary splicing regulators like SNRPB2, which create synthetic lethality interactions with TOE1 ligands that alter splicing and impair cancer cell growth. Our findings demonstrate the feasibility of chemically modulating spliceosome function through targeting the processing of its snRNA components, which may have broad therapeutic implications for splicing-related diseases.
HostingRepository	PRIDE
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-11_14:13:44.763.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haoxin Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-06 21:20:48	ID requested
⏵ 1	2025-11-11 14:13:45	announced

Dataset with its publication pending

submitter keyword: cancer, snRNA,human, TOE1

Benjamin Cravatt
contact affiliation	Professor and Gilula Chair of Chemical Biology Department of Chemistry The Scripps Research Institute
contact email	cravatt@scripps.edu
lab head
Haoxin Li
contact affiliation	The Scripps Research Institute
contact email	haoxinli@scripps.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/2025/11/PXD070432

PRIDE project URI

• PRIDE
  1. PXD070432
     1. Label: PRIDE project
     2. Name: A Molecular Clamp Targeting the TOE1:Sm Complex Imparts Tunable Regulation of Splicing