NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of mRNA in ischemic stroke.

Although a single nucleotide polymorphism for -acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA 4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice.