NAT10 Exacerbates Acute Renal Inflammation

What is it about?

N4-acetylcytidine has been identified as a novel mRNA modification catalysed by N-acetyltransferase 10 (NAT10) and regulated mRNA stability and translation efficiency. Here, we identified NAT10 as an important regulator for acute renal inflammation. By enhancing the ac4C acetylation of mRNAs of a range of key chemokines, including C-X-C motif chemokine ligand 1 (CXCL1) and C-C motif chemokine ligand 2 (CCL2), increases their stability, which in turn promotes the infiltration of macrophage and neutrophil cells, creating inflammatory microenvironment and exacerbating renal damage.

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Photo by julien Tromeur on Unsplash

Photo by julien Tromeur on Unsplash

Why is it important?

We identified NAT10 as an important regulator for acute renal inflammation. Our findings from ac4C-RIP-seq and RNA-seq analyses revealed that NAT10-mediated ac4C acetylation enhances the mRNA stability of a range of key chemokines, including C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1(CXCL1), promoting macrophage and neutrophil recruitment and accelerating renal inflammation. In addition, our newly identified NAT10 inhibitor Cpd-155, significantly reduces renal inflammation and injury. Thus, targeting the NAT10/CCL2/CXCL1 axis may present a promising therapeutic strategy for treating inflammatory kidney diseases.