METTL3-mediated N(6)-methyladenosine mRNA modification enhances long-term memory consolidation.
METTL3-mediated N(6)-methyladenosine mRNA modification enhances long-term memory consolidation.
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METTL3介导的N6-甲基腺苷mRNA修饰增强长期记忆巩固
DOI：
10.1038/s41422-018-0092-9
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发表时间：
2018-11
期刊：
影响因子：
44.1
通讯作者：
Wang XJ
中科院分区：
文献类型：
--
作者：
Zhang Z;Wang M;Xie D;Huang Z;Zhang L;Yang Y;Ma D;Li W;Zhou Q;Yang YG;Wang XJ
长时记忆的形成对人类和动物的学习能力和社会行为是至关重要的，但其潜在的机制在很大程度上还不清楚。我们发现，海马区依赖的记忆巩固的有效性是由METTL3调节的，METTL3是一种RNA N6-甲基腺苷(M6A)甲基转移酶，通过促进神经元早期反应基因的翻译来调节。这种作用依赖于METTL3的m6A甲基转移酶功能。在小鼠海马区耗尽METTL3会降低记忆巩固能力，但如果给予足够的训练或恢复METTL3的m6A甲基转移酶功能，则可以获得不受影响的学习结果。野生型小鼠海马区METTL3的丰度与学习效能呈正相关，METTL3的过度表达显著增强了长期记忆巩固。这些发现揭示了RNA m6A修饰在调节长期记忆形成中的直接作用，也表明个体之间的记忆效能差异可以通过重复学习来补偿。
The formation of long-term memory is critical for learning ability and social behaviors of humans and animals, yet its underlying mechanisms are largely unknown. We found that the efficacy of hippocampus-dependent memory consolidation is regulated by METTL3, an RNA N6-methyladenosine (m6A) methyltransferase, through promoting the translation of neuronal early-response genes. Such effect is exquisitely dependent on the m6A methyltransferase function of METTL3. Depleting METTL3 in mouse hippocampus reduces memory consolidation ability, yet unimpaired learning outcomes can be achieved if adequate training was given or the m6A methyltransferase function of METTL3 was restored. The abundance of METTL3 in wild-type mouse hippocampus is positively correlated with learning efficacy, and overexpression of METTL3 significantly enhances long-term memory consolidation. These findings uncover a direct role of RNA m6A modification in regulating long-term memory formation, and also indicate that memory efficacy difference among individuals could be compensated by repeated learning.
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影响因子：
48
作者：
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通讯作者：
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影响因子：
64.8
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影响因子：
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影响因子：
16.2
作者：
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影响因子：
64.8
作者：
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