2. Academic Validation
  3. Knockdown of METTL16 disrupts learning and memory by reducing the stability of MAT2A mRNA

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

  • Cell Death Discov. 2022 Oct 28;8(1):432. doi: 10.1038/s41420-022-01220-0.
Runjiao Zhang # 1 2,  Yizhou Zhang # 1 2 3,  Fangzhen Guo 1 2,  Guannan Huang 4,  Yan Zhao 1 2 5,  Bingyu Chen 1 2,  Chang Wang 1 2 3,  Chengran Cui 6,  Yichun Shi 6,  Sha Li 7 8 9,  Huixian Cui 10 11 12
Affiliations

Affiliations

  • 1 Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
  • 2 Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
  • 3 Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China.
  • 4 Department of Ultrasound, The Second Hospital of Hebei Medical University, 050000, Shijiazhuang, Hebei, China.
  • 5 School of Nursing, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
  • 6 Grade 2019, Basic Medicine, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
  • 7 Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. [email protected].
  • 8 Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. [email protected].
  • 9 Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China. [email protected].
  • 10 Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. [email protected].
  • 11 Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. [email protected].
  • 12 Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China. [email protected].
  • # Contributed equally.
PMID: 36307396 DOI: 10.1038/s41420-022-01220-0
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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