MassIVE MSV000093887

Complete Public PXD048688

Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing

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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. [doi:10.25345/C5VX06D89] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: HEK293T ; LC-MS/MS

Contact

Principal Investigators:
(in alphabetical order) 		Amber L. Mosley, Indiana University School of Medicine, USA
Submitting User: edoud

Publications

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. Epub 2024 Sep 3.

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