PXD065769-1

PXD065769 is an original dataset announced via ProteomeXchange.

Title	5′-triphosphate guanosine RNAs recruit GTP-binding proteins to suppress RIG-I/IFN type I signalling
Description	The interferon (IFN) response is crucial for antiviral activity, but its overstimulation can lead to a wide range of autoimmune disorders. The cytoplasmic pattern recognition receptor RIG-I detects viral double stranded RNAs (dsRNAs) and endogenous polymerase III transcripts carrying a 5′-triphosphate (5′-ppp) or 5′-diphosphate (5′-pp) moiety, triggering phosphorylation of IRF3 and IFN immune response. While many viral RNAs initiate with 5′-ppp-adenosine (5′-pppA) and most endogenous Pol III transcripts in higher eukaryotes start with 5′-ppp-guanosine (5′-pppG), no apparent reason for this bias has been identified so far. Here we demonstrate that dsRNAs initiating with 5′-pppA trigger stronger RIG-I/IFN response than those starting with 5′-pppG. We show that several GTP-binding proteins interact preferentially with 5′-pppG RNAs. Finally, supplementation with guanosine, but not adenosine, which rapidly increases intracellular concentrations of GTP and ATP respectively, eliminates the difference in immunogenicity between 5′-pppG and 5′-pppA RNAs. Our findings suggest that 5′-pppG RNAs may enable certain RNA viruses and Pol III transcripts to limit detection by innate immune receptors. These results offer new insights into the sequence-dependent activation of the RIG-I/IFN pathway and have important implications for both antiviral immunity and the role of Pol III-derived RNAs in autoimmune diseases.
HostingRepository	PRIDE
AnnounceDate	2026-05-07
AnnouncementXML	Submission_2026-05-07_04:32:33.397.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacek Szymanski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-03 17:50:12	ID requested
⏵ 1	2026-05-07 04:32:34	announced

Dataset with its publication pending

submitter keyword: None

Gracjan Michlewski
contact affiliation	International Institute of Molecular and Cell Biology, Laboratory of RNA-Protein Interactions - Dioscuri Centre, Warsaw, Poland
contact email	gmichlewski@iimcb.gov.pl
lab head
Jacek Szymanski
contact affiliation	International Institute of Molecular and Cell Biology in Warsaw, Poland
contact email	jszymanski@iimcb.gov.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065769
     1. Label: PRIDE project
     2. Name: 5′-triphosphate guanosine RNAs recruit GTP-binding proteins to suppress RIG-I/IFN type I signalling