PXD037092-3

PXD037092 is an original dataset announced via ProteomeXchange.

Title	Pharmacological perturbation of the phase-separating protein SMNDC1
Description	SMNDC1 is an essential splicing factor that, like its better-studied paralog SMN, binds to di-methylated arginines using its Tudor domain. The specific contributions of the SMNDC1 Tudor domain to protein-protein interactions, subcellular localization, and molecular function have not been studied in detail. Here, we perform such analysis and develop first small molecule inhibitors targeting the dimethyl arginine binding pocket of the SMNDC1 Tudor domain. We find that SMNDC1 localizes to phase-separated membraneless organelles that partially overlap with nuclear speckles. This condensation behavior is driven by the unstructured C-terminus, dependent on RNA interaction and can be recapitulated in vitro. Inhibitors of the protein’s Tudor domain drastically alter protein-protein interactions and subcellular localization, causing splicing changes at SMNDC1 dependent genes. These compounds will enable further pharmacological studies on the role of SMNDC1 in the regulation of nuclear condensates, gene regulation and cell identity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:29.366.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037092
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrea Rukavina
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-30 03:47:13	ID requested
1	2023-09-04 02:28:28	announced
2	2023-11-14 07:05:28	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:02:29	announced	2024-10-22: Updated project metadata.

10.6019/PXD037092;

10.1038/S41467-023-40124-0;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: pancreatic alpha cells,Tudor domain, small molecule inhibitor, NMR structure, nuclear speckles, splicing, chemical screening

Stefan Kubicek
contact affiliation	Stefan Kubicek Lab, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria
contact email	skubicek@cemm.oeaw.ac.at
lab head
Andrea Rukavina
contact affiliation	The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	arukavina@cemm.oeaw.ac.at
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/2023/09/PXD037092

PRIDE project URI

• PRIDE
  1. PXD037092
     1. Label: PRIDE project
     2. Name: Pharmacological perturbation of the phase-separating protein SMNDC1