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

Runjiao Zhang, Yizhou Zhang, Fangzhen Guo, Guannan Huang, Yan Zhao, Bingyu Chen, Chang Wang, Chengran Cui, Yichun Shi, Sha Li, Huixian Cui

2022Cell Death Discovery25 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

Gene knockdownHippocampal formationLong-term potentiationDendritic spineSynaptic plasticityMorris water navigation taskDownregulation and upregulationNeuroscienceCell biologyMessenger RNAChemistryPsychologyBiologyBiochemistryReceptorGeneApoptosisRNA modifications and cancerEpigenetics and DNA MethylationCancer-related gene regulation