PXD044382-1

PXD044382 is an original dataset announced via ProteomeXchange.

Title	Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation
Description	We report a novel translation-regulatory function of G9a, a histone methyltransferase and well-understood transcriptional repressor, in promoting hyperinflammation and lymphopenia; two hallmarks of endotoxin tolerance (ET)-associated chronic inflammatory complications. Using multiple approaches, we demonstrate that G9a interacts with multiple translation regulators during ET, particularly the N6-methyladenosine (m6A) RNA methyltransferase METTL3, to co-upregulate expression of certain m6A-modified mRNAs that encode immune-checkpoint and anti-inflammatory proteins. Mechanistically, G9a promotes m6A methyltransferase activity of METTL3 at translational/post-translational level by regulating its expression, its methylation, and its cytosolic localization during ET. Additionally, from a broader view extended from the G9a-METTL3-m6A translation regulatory axis, our translatome proteomics approach identified numerous “G9a-translated” proteins that unite the networks associated with inflammation dysregulation, T cell dysfunction, and systemic cytokine response. In sum, we identified a previously unrecognized function of G9a in protein-specific translation that can be leveraged to treat ET-related chronic inflammatory diseases.
HostingRepository	PRIDE
AnnounceDate	2023-10-20
AnnouncementXML	Submission_2023-10-20_14:40:38.094.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AdilMuneer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-05 01:02:12	ID requested
⏵ 1	2023-10-20 14:40:38	announced
2	2023-11-14 07:47:28	announced	2023-11-14: Updated project metadata.

submitter keyword: inflammation, m6A, endo-toxin tolerance,G9a, translation, METTL3

XianChen
contact affiliation	University of North Carolina Chapel Hill
contact email	xianc@email.unc.edu
lab head
AdilMuneer
contact affiliation	University of North Carolina Chapel Hill
contact email	adil.muneer94@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044382
     1. Label: PRIDE project
     2. Name: Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation