PXD061192

PXD061192 is an original dataset announced via ProteomeXchange.

Title	ILF2 and ILF3 shield transcripts from RNA editing to enable human cell fate transitions
Description	Chromatin regulation and RNA processing are both fundamental for establishing cell identity, yet how they interact to direct cell fate remains unclear. To uncover factors that coordinate this interplay, we screened dual DNA- and RNA-binding proteins (DRBPs) and identified ILF2 and ILF3 as critical regulators of human cell fate. We show that ILF2 and ILF3 control human, but not mouse, gastrulation and maintain the self-renewal of adult progenitor cells across all three germ layers. Mechanistically, ILF2 and ILF3 interact with and inhibit the RNA-editing enzyme ADAR, which catalyzes adenosine-to-inosine conversion in primate-specific repetitive elements. Acute degradation of the ILF2-ILF3 complex triggers widespread RNA misediting and missplicing of transcripts encoding key cell fate regulators. These misedited transcripts are degraded, destabilizing the proteome and rewiring the epigenetic landscape of stem and progenitor cells. Our findings reveal a human-specific mechanism linking RNA processing to chromatin regulation and identify an evolutionary safeguard that prevents aberrant RNA editing and retrotransposon activation, enabling human cell fate transitions.
HostingRepository	PRIDE
AnnounceDate	2025-02-26
AnnouncementXML	Submission_2025-02-26_15:34:59.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joshua Coon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-25 13:17:50	ID requested
⏵ 1	2025-02-26 15:34:59	announced

Dataset with its publication pending

submitter keyword: hiPSC, LC-MS/MS

Joshua J. Coon
contact affiliation	1 Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA 2 Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, USA 3 Morgridge Institute for Research, Madison, WI, USA 4 National Center for Quantitative Biology of Complex Systems, Madison, WI, USA
contact email	jcoon@chem.wisc.edu
lab head
Joshua Coon
contact affiliation	University of Wisconsin - Madison, Morgridge Institute for Research
contact email	jcoon@chem.wisc.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/2025/02/PXD061192

PRIDE project URI

• PRIDE
  1. PXD061192
     1. Label: PRIDE project
     2. Name: ILF2 and ILF3 shield transcripts from RNA editing to enable human cell fate transitions