敲低METTL16会通过降低MAT2A mRNA的稳定性来破坏学习和记忆。

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

Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.

Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.

Cell Death Discov. 2022 Oct 28;8(1):432. doi: 10.1038/s41420-022-01220-0.

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

N6-甲基腺苷（mA）在哺乳动物大脑中含量丰富，被认为对学习和记忆有广泛影响。在此，我们发现，在经过莫里斯水迷宫（MWM）训练的小鼠海马组织中，上调的类甲基转移酶16（METTL16）有助于改善记忆形成和海马突触可塑性。机制上，METTL16通过对甲硫氨酸腺苷转移酶2A（MAT2A）mRNA 3'UTR末端进行mA甲基化来促进MAT2A的表达，以增加其稳定性，这参与提高海马整体mA水平、树突棘可塑性、学习和记忆。本研究为探索mA对学习和记忆的调控机制提供了新视角。