PXD074388

PXD074388 is an original dataset announced via ProteomeXchange.

Title	Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8
Description	The type I interferon (IFN) response is the main innate immune pathway against viruses in mammals. This pathway must be tightly regulated to prevent viral spread while avoiding excessive immune responses. Here, we show that inactivation of the double stranded RNA (dsRNA)-binding protein DGCR8 unleashes the IFN response in human cells. We demonstrate that DGCR8 restricts the accumulation of endogenous dsRNA originating from protein-coding mRNAs that harbour transposable elements (TEs), primarily Alu. We propose that DGCR8 binding to TE-rich mRNAs is essential to resolve dsRNA structures, and in its absence, accumulated dsRNA signals through the RIG-I-like signalling pathway triggering the IFN response. This mechanism is relevant to conditions where DGCR8 expression levels are altered, including the 22q11.2 deletion syndrome (22qDS). Supporting this, we show that 22qDS-derived cells exhibit an exacerbated type I IFN response which inversely correlated with DGCR8 levels. All these together demonstrate the importance of suppressing endogenous TE-dsRNA accumulation to prevent unwanted immune activation and associated disease pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2026-02-12
AnnouncementXML	Submission_2026-02-12_05:19:26.506.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Witteveldt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-12 04:48:24	ID requested
⏵ 1	2026-02-12 05:19:27	announced

Dataset with its publication pending

submitter keyword: interferon response, transposable elements, 22qDS, human, dsRNA,Dgcr8, stem cells, mouse, PA-1

Sara Macias
contact affiliation	Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, UK
contact email	Sara.Maciasribela@ed.ac.uk
lab head
Jeroen Witteveldt
contact affiliation	The University of Edinburgh
contact email	jeroen.witteveldt@ed.ac.uk
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/2026/02/PXD074388

PRIDE project URI

• PRIDE
  1. PXD074388
     1. Label: PRIDE project
     2. Name: Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8