Cell Death Discovery (Oct 2022)

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

DOI
https://doi.org/10.1038/s41420-022-01220-0
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 14

Abstract

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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.