PXD059977-1

PXD059977 is an original dataset announced via ProteomeXchange.

Title	Silencing of double stranded RNA sensing is required for early embryonic development
Description	The type I interferon (IFN) response is inactive during early mammalian development and becomes functional only after gastrulation. As a result, the totipotent and pluripotent embryonic stages remain susceptible to pathogens, including viruses. Here, we demonstrate that pluripotent mouse embryonic stem cells (mESCs) suppress the RIG-I-like receptor sensing pathway by silencing the expression of the dsRNA sensor MDA5. This silencing is necessary to avoid the recognition of dsRNAs of endogenous origin, which accumulate in mESCs. Reintroducing MDA5 results in recognition of these endogenous dsRNAs and triggers the activation of the IFN response through IRF3. The production of IFN alters the differentiation ability of mESCs, and affects the pluripotency gene expression program, as shown by epigenetic, transcriptomic and proteomic analyses. These findings are conserved in zebrafish, where MDA5 is also expressed at later developmental stages. Similarly, zebrafish lack earlystage IFN activation, and dsRNA-mediated signalling results in developmental defects. Altogether, we conclude that silencing the RIG-I-like receptor pathway during early development is widely conserved and is essential to prevent aberrant immune recognition of endogenous dsRNAs, safeguarding normal development.
HostingRepository	PRIDE
AnnounceDate	2025-09-26
AnnouncementXML	Submission_2025-09-26_05:25:26.780.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zicong Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-20 07:00:02	ID requested
⏵ 1	2025-09-26 05:25:27	announced

Dataset with its publication pending

submitter keyword: Chromatin-associated proteomics

MDA5

Pluripotency stem cells

Sara Macias
contact affiliation	Institute of Immunology and Infection Research, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, EH9 3FL, Edinburgh, United Kingdom
contact email	Sara.Maciasribela@ed.ac.uk
lab head
Zicong Liu
contact affiliation	Radboud Universiteit Nijmegen
contact email	zicong.liu@ru.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059977
     1. Label: PRIDE project
     2. Name: Silencing of double stranded RNA sensing is required for early embryonic development