Knockdown of METTL16 disrupts learning and memory by reducing the stability of MAT2A mRNA

Abstract N6-methyladenosine (m 6 A) is abundant in the mammalian brain and is considered to have a wide range of effects on learning and memory. Here, we found that the upregulated methyltransferase-like protein 16 (METTL16) in the hippocampal tissues of Morris water maze (MWM)-trained mice contributed to improved memory formation and hippocampal synaptic plasticity. Mechanismly, METTL16 promoted the expression of methionine adenosyltransferase 2A (MAT2A) by the m 6 A methylation of the MAT2A mRNA-3′UTR-end to increase its stability, and this involved in improving hippocampal global m 6 A levels, plasticity of dendritic spine, learning and memory. This study provides a new perspective to explore the regulatory mechanisms of m 6 A for learning and memory.