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
  • 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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