PXD048688-1

PXD048688 is an original dataset announced via ProteomeXchange.

Title	Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing
Description	The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and Adenosine Deaminase isoform switching. We found that A-to-I editing of Antizyme Inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.
HostingRepository	MassIVE
AnnounceDate	2025-09-28
AnnouncementXML	Submission_2025-09-28_10:52:14.341.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-18 07:59:08	ID requested
⏵ 1	2025-09-28 10:52:15	announced

Heruye SH, Myslinski J, Zeng C, Zollman A, Makino S, Nanamatsu A, Mir Q, Janga SC, Doud EH, Eadon MT, Maier B, Hamada M, Tran TM, Dagher PC, Hato T, Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing. J Clin Invest, 134(17):(2024) [pubmed]

submitter keyword: HEK293T, LC-MS/MS

Amber L. Mosley
contact affiliation	Indiana University School of Medicine
contact email	almosley@iu.edu
lab head
Emma Doud
contact affiliation	IUSM
contact email	edoud@iu.edu
dataset submitter

MassIVE dataset URI

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