The landscape of m 1 A modification and its posttranscriptional regulatory functions in primary neurons.

Cerebral ischaemia‒reperfusion injury (IRI), during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (mA) is an RNA modification that can affect gene expression and RNA stability. The mA landscape and potential functions of mA modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) mA modification in normal and OGD/R-treated mouse neurons and the effect of mA on diverse RNAs. We investigated the mA landscape in primary neurons, identified mA-modified RNAs, and found that OGD/R increased the number of mA RNAs. mA modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA-RNA binding proteins (RBPs) interactions and circRNA translation. We showed that mA modification mediates the circRNA/lncRNA‒miRNA-mRNA competing endogenous RNA (ceRNA) mechanism and that 3' untranslated region (3'UTR) modification of mRNAs can hinder miRNA-mRNA binding. Three modification patterns were identified, and genes with different patterns had intrinsic mechanisms with potential mA-regulatory specificity. Systematic analysis of the mA landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA modification and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases.