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

METTL16 的敲低会降低 MAT2A mRNA 的稳定性,从而破坏学习和记忆

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

Abstract

N6-methyladenosine (m6A) 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 m6A methylation of the MAT2A mRNA-3'UTR-end to increase its stability, and this involved in improving hippocampal global m6A levels, plasticity of dendritic spine, learning and memory. This study provides a new perspective to explore the regulatory mechanisms of m6A for learning and memory.

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