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 (m 1 A) is an RNA modification that can affect gene expression and RNA stability. The m 1 A landscape and potential functions of m 1 A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m 1 A modification in normal and OGD/R-treated mouse neurons and the effect of m 1 A on diverse RNAs. We investigated the m 1 A landscape in primary neurons, identified m 1 A-modified RNAs, and found that OGD/R increased the number of m 1 A RNAs. m 1 A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA-RNA binding proteins (RBPs) interactions and circRNA translation. We showed that m 1 A 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 m 1 A-regulatory specificity. Systematic analysis of the m 1 A 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.