PXD064630-1

PXD064630 is an original dataset announced via ProteomeXchange.

Title	Elongator is required for pattern recognition receptor and type I interferon signaling in macrophages.
Description	Innate immune detection of pathogens by macrophages requires a rapid and large scale mobilisation of cellular resources towards an appropriate immune response, mainly involving altered protein expression. Pathogen recognition is mediated by pattern recognition receptor (PRR) sensing of conserved microbial patterns, a prototypical example being recognition of LPS by TLR4. This leads to induction of pro-inflammatory cytokines, chemokines and type I interferons (IFN Is) which together mobilise appropriate anti-pathogen responses. IFN Is signal to transcription of IFN-stimulated genes (ISG) which encode numerous anti-viral proteins. Many studies have contributed to a detailed understanding of transcriptional regulation of mRNA during such responses, however much less is known about the contribution of protein complexes required for mRNA translation. Here we examine the role of the evolutionarily conserved elongator complex in PRR signaling in macrophages. Elongator modifies tRNAs at U34 to facilitate more efficient wobble interactions between tRNAs and mRNA codons. In macrophages, deletion of Elp3, the catalytic subunit of elongator, led to an impaired PRR-IFN I-ISG signaling axis. The ELP3-dependent LPS-stimulated proteome was enriched with proteins involved in PRR activation of IRFs and in IFN signalling. Specifically, ELP3 was required for expression of key transcription factors regulating this axis, for TYK2-dependent IFN-I signaling and for IRF3 activation for some, but not all, PRRs. Importantly, ELP3 was also necessary for innate immune gene induction following virus infection. These data reveal specific roles for elongator in PRR signaling and illustrate the underappreciated importance of translational regulation in optimal anti-pathogen innate immune responses.
HostingRepository	PRIDE
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2025-12-21_17:42:06.626.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Corinna Grünke
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 07:15:25	ID requested
⏵ 1	2025-12-21 17:42:07	announced

Murphy J, Baran M, Gr, ü, nke C, Haas D, Barber G, Pichlmair A, Bowie AG, Elongator is required for pattern recognition receptor and type I interferon signaling in macrophages. J Biol Chem, 301(12):110916(2025) [pubmed]

10.1016/j.jbc.2025.110916;

submitter keyword: Innate immunity

interferon

interferon regulatory factor (IRF)

lipopolysaccharide (LPS)

macrophage

pattern recognition receptor (PRR)

STAT transcription factor

Toll-like receptor 4 (TLR4)

virus

elongator

Andreas Pichlmair
contact affiliation	Technical University of Munich
contact email	andreas.pichlmair@tum.de
lab head
Corinna Grünke
contact affiliation	Technical University of Munich
contact email	corinna.gruenke@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064630
     1. Label: PRIDE project
     2. Name: Elongator is required for pattern recognition receptor and type I interferon signaling in macrophages.