PXD044382-2

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:47:28.346.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adil Muneer
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.

Dataset with its publication pending

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

Xian Chen
contact affiliation	University of North Carolina Chapel Hill
contact email	xianc@email.unc.edu
lab head
Adil Muneer
contact affiliation	University of North Carolina Chapel Hill
contact email	adil.muneer94@gmail.com
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/2023/10/PXD044382

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